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"Increased genitourinary fistula rate after bevacizumab in\nrecurrent cervical cancer patients initially treated with definitive\nradiochemotherapy and image-guided adaptive brachytherapy\n",
"Alina Sturdza! - Sandra Hofmann · Marlene Kranawetter - Stephan Polterauer4. Christoph Grimm -\nMichael Krainer Christian Kirisits' · Richard Pötter' Alexander Reinthaller. Richard Schwameis\n",
"Zusammenfassung\n",
"these 6 patients with fistulae, 5 (83%) had undergone pre-\nvious invasive procedures after the diagnosis of RecCC and\nI patient had undergone pelvic re-irradiation: 3/6 patients\nhad developed a local recurrence. No other risk factors for\nfistula formation were identified.\n",
"Conclusion In patients with RecCC after definitive ra-\ndiochemotherapy including IGABT, the addition of BEV\nto CHT may increase the risk for GU fistula formation,\nparticularly after invasive pelvic procedures. Future clin-\nical studies are required to identify predictors for fistula\nformation to subsequently improve patient selection for the\naddition of BEV in the RecCC setting.\n",
"Keywords Avastin - Radiotherapy Chemotherapy\nCervical cancer Toxicity\n",
"Erhöhte urogenitale Fistelrate nach Bevacizumab\nbei Patientinnen mit rezidiviertem\nZervixkarzinom nach primärer Behandlung mit\ndefinitiver Radiochemotherapie und\nbildgesteuerter adaptiver Brachytherapie\n",
"Abstract\n",
"Background and purpose Patients with recurrent cervical\ncancer (RecCC) who received definitive radiochemotherapy\nincluding image-guided adaptive brachytherapy (IGABT)\nas primary treatment are currently treated in our institution\nwith palliative intent by chemotherapy (CHT) combined\nwith bevacizumab (BEV). We aim to evaluate the risk of\ngastrointestinal (GINgenitourinary (GU) fistula formation\nin these patients.\n",
"Materials and methods Data of 35 consecutive patients\nwith RecCC treated initially with radiochemotherapy and\nIGABT were collected. Known and presumed risk fac-\ntors associated with fistula formation were evaluated. Fis-\ntula rate was compared between patients receiving CHT or\nCHT+BEV.\n",
"Results Of the 35 patients, 25 received CHT and 10 patients\nreceived CHT+BEv. Clinical characteristics were compara-\nble. Fistulae were reported in 6 patients: two fistulae (8%)\nin the CHT group, four (40%) in the CHT+BEV group.\nGU fistula occurred in the CHT+BEV group only (3/4). Of\n",
"Hintergrund und Ziel Patientinnen mit Rezidiv eines Zer-\nvixkarzinoms (RecCC), die primär eine bildgesteuerte ad-\naptive Brachytherapie (IGABT) und kombinierte Radioche-\nmotherapie (RCHT) erhalten hatten, werden derzeit in un-\nserem Institut mit einer Kombination aus Chemotherapie\n(CHT) und Bevacizumab (BEV) behandelt. Ziel dieser Stu-\ndie war es, das Risiko für das Auftreten gastrointestina-\nler (GI) sowie urogenitaler (GU) Fisteln unter CHT sowie\nCHT + BEV zu analysieren.\n",
"Patienten und Methode In diese retrospektive Datenanalyse\nwurden insgesamt 35 konsekutive Patientinnen mit RecCC,\n"
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"Patients\n",
"containing regimes. Since 2014, the use of bevacizumab\n(BEV) in combination with systemic CHT for the treat-\nment of recurrent or metastatic cervical cancer has become\ncommon. It has been shown that the addition of BEV was\nassociated with a significant increase in progression-free\nand overall survival [9]. However, it has also been reported\nthat CHT+BEV is associated with an increased risk of fis-\ntula formation when compared to CHT alone in patients\nwith cervical cancer [10], even in the absence of radia-\ntion treatment. In a subset analysis of the Gynecologic On-\ncology Group trial (GOG 240) published in abstract form\n[11], it was observed that among the patients who devel-\noped GI vaginal fistula, 100% had received prior pelvic\nradiation, some including standard brachytherapy. How-\never, little is known about the risk factors for fistula for-\nmation in the presence of BEV. This study aims to evaluate\nwhether patients with RecCC treated initially by concurrent\nradiochemotherapy and IGABT have an increased risk for\nGI and GU fistula formation after CHT+BEV treatment.\n",
"Materials and methods\n",
"die primär mit RCHT und IGABT behandelt worden wa-\nren, inkludiert. Klinisch-pathologische Risikofaktoren für\ndas Auftreten einer Gl- sowie GU-Fistel wurden erhoben.\nDie Raten an Fistelbildungen in der CHT-Gruppe und in\nder Gruppe mit CHT + BEV wurden verglichen.\n",
"Ergebnisse Von 35 Patientinnen erhielten 25 eine CHT\nund 10 CHT + BEV. Insgesamt wurde bei 6 Patientinnen\neine Fistel diagnostiziert, davon 2 in der Gruppe mit CHT\n(8%) und 4 in der mit CHT + BEV (40%). GU-Fisteln\nentwickelten sich ausschließlich in der Gruppe mit CHT +\nBEV (3/4; 75 %). Von den 6 Patientinnen (83 %) mit Fistel-\nbildung hatten 5 eine vorangehende invasive diagnostische\nAbklärung und 1 Patientin wurde einer neuerlichen Radio-\ntherapie unterzogen. Ein Lokalrezidiv hatten 3/6 Patientin-\nnen entwickelt. Weitere Risikofaktoren für die Entwicklung\neiner Fistel konnten nicht identifiziert werden.\n",
"Schlussfolgerung Die zusätzliche Gabe von BEV zur CHT\nbei RecCC-Patienten, die primär mit IGABT und RCHT\nbehandelt wurden, könnte möglicherweise zu einer erhöh-\nten Rate an GU-Fisteln führen. Zukūnftige Studien soll-\nten Risikofaktoren für Fistelbildung untersuchen, um eine\ngründliche Patientenselektion für die Gabe von BEV bei\nRecCC zu ermöglichen.\n",
"Schlüsselwörter Avastin Strahlentherapie -\nChemotherapie · Zervixkarzinom Toxizität\n",
"For patients with locally advanced cervical cancer (LACC),\nconcurrent radiochemotherapy including brachytherapy\n(BT) is the standard therapy, leading to good oncologic\nresults [1-31. The reported absolute risk of developing\ngrade 3-4 (G3-4) genitourinary (GU) or gastrointestinal\n(GI) fistulae through definitive radiation therapy including\nstandard BT with dose prescription to point A is around 9%\n(overall G3-4 toxicity 30%) [4]. Within the last few years,\nmodern radiotherapy techniques have been introduced into\nthe treatment of LACC. These include magnetic resonance\n(MR) image-guided adaptive brachytherapy (IGABT) [5]\nwith dose prescription individualised to the target at the\ntime of BT. In a recently published cohort of 731 patients,\nthe overall actuarial rate of G3-4 GI and GU toxicity af-\nter definitive radiochemotherapy and IGABT was 11% at\n5 years [6, 18]. A previous publication from our centre on\n156 patients in whom systematic 1GABT was performed\nreported only 2/156 fistula events [5]. Despite excellent\noverall local tumour control results, several series [5, 7,\n8] still observed relatively high rates of distant recur-\nrences after 1GABT, especially in patients with advanced\nstage (stage IlI/IV) and/or nodal disease [6]. These distant\nmetastases require cytotoxic treatment.\n",
"Patients with recurrent cervical cancer (RecCC), depend-\ning on the site of relapse (local, distant), have been treated\nby systemic chemotherapy (CHT), typically with paclitaxel-\n",
"Consecutive patients diagnosed with RecCC who were\ntreated between 2009 and 2014 in our institution were\nenrolled in this study. Clinical data were obtained using\navailable tumour databases and by electronic chart re-\nview. The 2009 International Federation of Gynecology\nand Obstetrics (FIGO) classification system was used [12).\nEligible patients had recurrence of a formerly locally ad-\nvanced cervical cancer that had been initially treated by\ndefinitive concurrent radiochemotherapy including IGABT\nin our institution. Patients treated initially with surgery or\nthose with primary metastatic disease were not eligible.\n",
"Tumour status was assessed, the presence of GU and\nGI fistula identified, and survival and follow-up times were\nrecorded. Risk factors for fistula development including\ncomorbidities (diabetes, arterial hypertension, peripheral\nvascular disease, thromboembolic events), previously per-\nformed bowel surgery, minor interventions/biopsy/major\npelvic surgery after RecCC and number of treatment cycles\nwere documented.\n",
"The primary endpoint was to document the frequency of\nfistula events in both groups (CHT or CHT+BEV) in this\nmono-institutional series.\n",
"The Ethics Committee of our institution gave approval\nprior to initiation of the study (IRB approval number:\n1996/2015). All patients consented to treatment according\nto institutional guidelines, as well as to anonymized assess-\nments and analysis of data and outcome of therapy. Records\nwere anonymized and de-identified prior to analysis.\n"
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"Treatment\n",
"Initial treatmenr\n",
"All patients received definitive concurrent radiochemother-\napy. Radiotherapy consisted of extemal beam radiotherapy\n(EBRT) concurrent with weekly cisplatin-based CHT (usu-\nally cisplatin 5 x 40 mg/m body surface area) and IGABT.\nThe maximally allowed duration of radiation therapy was\n50 days in total.\n",
"External beam radiotherapy\n",
"EBRT was delivered using three-dimensional conformal\ntechniques or intensity-modulated radiation therapy. The\nclinical target volume (CTV) iradiated through EBRT con-\nsisted of the tumour, entire uterus, bilateral parametria, up-\nper vagina (if no vaginal involvement had been present) and\nthe pelvic lymph nodes. In case of lymph node involvement\nof the common iliac or para-aortic (PAN) lymph nodes (as\ndiagnosed by positron-emission tomography/CT (PET-CT}\nor laparoscopic staging lymphadenectomy), para-aortic ra-\ndiotherapy was performed. The prescribed dose was 45 Gy\nat 1.8 Gy per fraction. Grossly involved lymph nodes, if not\nsurgically remowed, were treated with an additional boost\n(range 55-60 Gy).\n",
"Image-guided adaptive brachytherapy\n",
"Systematically, MRI-based IGABT was performed in all\npatients diagnosed with LACC with definitive intent. The\nhigh-risk CTV (HRCTV) and/or the intermediate-risk\nCTV (IRCTV) was contoured according to Gyn GEC-\nESTRO Recommendations I [13]. Organs at risk (OARS)\nwere contoured: rectum, sigmoid colon and urinary blad-\nder. Dose-volume histogram (DVH) parameters for the\nHRCTV, IRCTV and OARS were calculated and reported\naccording to Gyn GEC-ESTRO Recommendations II [14].\nDose prescription for target and dose constraints for OARS\nwere applied according to our institutional guidelines [51.\nOur planning aim was 285 Gy to 90% of the HRCTV (D).\nThis total EQD2 (equivalent dose in 2 Gy per fraction) from\nEBRT and BT was calculated using an alß of 10 Gy for\ntumour (EQD210) and 3 Gy for OARS (EQD2;) [15].\n",
"Follow-up\n",
"All patients were followed-up in a joint programme by a gy-\nnaecologic oncologist and a radiation oncologist specialised\nin gynaecologic malignancies. Regular follow-up included\nclinical examination, blood analysis and imaging. Complete\nremission after initial treatment was defined as the absence\nof disease in the cervix (uterus), upper vagina, parametrium\n",
"and regional lymph nodes, as verificd by clinical examina-\ntion, abdominal and thoracie imaging, and biopsy as appro-\npriate. Patients were followed-up every 3 to 4 months for\nthe first 3 years, every 6 months for the following 2 years\nand annually up to 10 years and beyond thereafter. Fol-\nlow-up was performed at our institution using standardized\nquestionnaires and assessment forms.\n",
"If recurrent disease was suspected, restaging by CT scans\nof the thorax and abdomen as well as MRI of the pelvis was\nperformed, Whenever possible, recurrent disease was con-\nfirmed by biopsy and PET-CT was additionally performed.\n",
"Recurrence treatment\n",
"Chemotherapy/bevacizumab\n",
"Within this study, all patients were treated by either CHT or\nCHT+BEV. In addition, salvage surgery was performed in\nselected cases. CHT consisted of paclitaxel in combination\nwith cisplatin (n = 18), with carboplatin (n = 2), or with\ntopotecan (n = 5). Alternatively, selected patients received\ncisplatin in combination with topotecan (n = 9) or carbo-\nplatin with docetaxel (n = 1). CHT was administered until\nprogression, complete response or treatment-limiting toxic-\nity occurred. Starting 2013, most patients received BEV in\naddition to CHT (n= 10). Thereafter, patients were again\nfollowed-up according to the institution's follow-up pro-\ngram. In a few cases, salvage surgery or radiotherapy of\nmetastases was performed in the presence of oligometas-\ntases in lung, liver or periaortic nodes.\n%3!\n%3D\n",
"Statistical analysis\n",
"Time-to-event analyses were computed using the Ka-\nplan-Meier method and log-rank test, with and IBM\nSPSS 23.0 for MAC (SPSS 23.0, IBM Inc., Armonk,\nNY, USA). Time intervals for survival analyses were cal-\nculated from the date of biopsy to the date of event or last\nfollow-up. Patients lost to follow-up were censored at the\ntime of last follow-up.\n",
"Descriptive statistic values are given as mean (standard\ndeviation, SD). T-tests and y' tests were used to compare pa-\ntients' characteristics and risk factors for fistula formation\nbetween groups. P-values <0.05 were considered statisti-\ncally significant. Overall survival was analysed using the\nlog-rank test.\n",
"Results\n",
"A total of 35 patients were included in this study. Pa-\ntients' and treatment characteristics are shown in Table 1.\nThere were no fistulae at the time of relapse diagnostic.\n"
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"\"Table 1\nfor the whole group (N = 35)\nand broken down by subsoquent\ntreatment, i. e. chemotherapy\nonly or chemotherapy plus\nhevacizumab\nPatient characteristics\n",
null
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"CHT chemotherapy. BEV bevacizumab, ECOG Eastern Cooperative Oncology Group. Gl gastrointestinal.\nEBRT external beam radiotherapy. IMRT intensity-modulated radiotherapy. VMAT volumetrie-modulated arc\ntherapy, LN lymph node, RecCC recurent cervical cancer, BT IC intracavitary only brachytherapy\n",
null,
"\"Table 1 Patient characteristics\nfor the whole group (N = 35)\nand broken down by subsoquent\ntreatment, i. e. chemotherapy\nonly or chemotherapy plus\nhevacizumab (Continued)\n",
"At the time of recurrence, 2 patients had persistent local\ndisease (incomplete remission), 1 patient had local recur-\n",
"rence (which was treated with palliative re-irradiation) and\n3 patients had systemic recurrence (Table 3).\n",
"All 6 patients with fistula formation had undergone an\ninvasive procedure or palliative pelvic radiation prior to or\nduring the systemic palliative treatment (Table 3). In the\nCHT group the events occurred subsequent to a posterior\nvaginal wall biopsy (P5) and after pelvic re-imradiation (P3).\nIn this group, a further 10 of the remaining 23 patients\nhad undergone an invasive procedure but did not develop\nfistula (Table 1). In the CHT+BEV group, 4/4 patients with\nevents (100%) had undergone at least a minimally invasive\nprocedure (i. e. ureter stenting) and only 1/6 patients (17%)\ndid not develop an event after an invasive procedure.\n",
"We found no association between radiation dose to the\ntarget or the reported DVH parameters for OARS and the\nrate of fistula (Table 4).\n",
"Within the cohort, median follow-up was 11 months\n(range 0-50 months) and overall survival time from the date\nof diagnosis of RecCC was 8 months (2-27 months) and\n26 months (5-87 months) from diagnosis of primary dis-\nease. Fistula formation had no significant impact on overall\nsurvival (p = 0.317).\n",
"CHT was received by 25 patients and 10 patients received\nCHT+BEV. Patient characteristics and treatment modali-\nties in the both groups were similar. All 10 patients in the\nCHT +BEV group had undergone interstitial IGABT as op-\nposed to 21/25 in the CHT group (p = 0.18).\n",
"Table 2 provides treatment details of the therapy at first\ndiagnosis and the number of events analysed according to\nthe type of treatment at recurrence. No statistically signifi-\ncant difference in radiation dose (90.4 Gy vs. 89.4 Gy. p =\n0.353) or number of CHT cycles at RecCC (5.1 vs. 6.4, p=\n0.403) was observed between treatment groups.\n",
"A total of six fistulae were recorded (patient tumour and\ntreatment details in Table 3: PI-6). In the CHT+BEV group.\na significantly higher rate of fistula formation (4/10 pa-\ntients, 40%) was observed compared to the CHT only group\n(2/25 patients, 8%; p= 0.043).\n",
"GU fistula formation was noticed only in the CHT+BEV\ngroup (3/10 patients), of which two were grade 2 and one\nwas grade 3 requiring surgical intervention [16]. Addition-\nally, a grade 3 rectovaginal fistula was documented in this\ngroup (P2). In the CHT only group, both events were recto-\nvaginal fistula grade 3. For all patients with G3 rectovaginal\nfistula a functional colostomy was performed. For the G3\nGU fistula, an ileal conduit was necessary.\n"
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"CHT chemotherapy. BEV bevacizumab. BT brachytherapy, HRCTV high-risk clinical target volume.\nD90 dose to 90% of the HRCTV, SD standard deviation, IC intracavitary only. ICAS intracavitary and\ninterstitial brachytherapy, D2ec dase to 2ec volume of the respective organ (ie: rectum, sigmoid, bowel\nblackler)\n",
null,
"\"Table 2 Treatment character-\nisties at the time of recurrence,\ndose-volume parameters (DVH)\nat the time of the initial definitive\ntreatment and number of events\nbased on the type of treatment\nfor recurrent disease\n",
"Discussion\n",
"In this study, patients receiving a combination of CHT and\nBEV for the treatment of RecCC had a significantly higher\nrisk for fistula formation than patients receiving CHT alone\n(40 vs. 8%). We observed a notably higher rate of GU fistula\nin patients treated with CHT+BEV (30% vs, none). The rate\nof rectovaginal fistula was similar in the two groups (10 vs.\n8%).\n",
"Previously published studies reported an overall fistula\n(>grade 2) formation rate of 8.6% (GI vaginal) and 3.2%\nGI perforation in 218 patients with preliminary metastatic\nor recurrent cervical cancer treated in the CHT+BEV arm\n[17] of the GOG 240 study (hrst data freeze). Furthermore.\nthe rate of fistula (any grade) formation was even higher\n(12.6%) during CHT+BEV treatment if only patients with\nprior radiochemotherapy were considered [11]. Overall,\nGOG 240 reported an increased incidence of 6% of fistula\nformation (second data freeze) [9). It is not clear how many\npatients had received definitive radiochemotherapy includ-\ning IGABT in the GOG 240 cohort. In our cohort, only\npatients who received definite IGABT plus radiochemother-\napy as initial treatment were included. Therefore, our cohort\nis the first one comparing CHT and CHT+BEV in LACC\npatients previously treated with definitive radiochemother-\napy and IGABT.\n",
"All patients who developed fistulae in our cohort had\nundergone a minor intervention (5/6, 83%; repeated ureter\nstenting, biopsy or pelvic re-irradiation) or a major pelvic\nsurgery (1/6, 17%). This is in accordance with the observa-\ntion of Feddock el al. [19], who associated pelvic radiation\nand invasive procedures with 8.2% fistula formation, even\nin the absence of CHT + BEV, In the CHT group, 43%\n(10/23) of the non-event patients had undergone an inter-\nvention, while in the CHT+BEV only group, 17% (1/6)\nhad undergone an invasive pelvic procedure and did not de-\nvelop a fistula. This may suggest that BEV in the presence\nof an invasive pelvic procedure may trigger GU fistula for-\nmation. There are case reports in literature suggesting that\na combination of perioperative BEV administration and an\ninvasive procedure could result in fistula formation. Aor-\ntooesophageal fistula rupture or colovesical fistula during\ntreatment including BEV due to metastatic colorectal can-\ncer have been reported in case studies [25]. One other report\ndescribes two late-onset pulmonary fistulae after resection\nof pulmonary metastasis from colorectal cancer following\nperioperative CHT with BEV [26]. An increased risk of\nbowel perforation or fistula formation for patients with re-\ncurrent epithelial ovarian cancer treated with BEV has been\nobserved (24, 27, 28].\n",
"Although not statistically significant due to the limited\nnumber of patients and events, one may observe the fact that\n3/6 patients with fistulae had a local recurrence (2 patients\n"
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"CHT chemotherapy, BEV bevacizumab. BT brachytherapy, HRCTV high-risk elinical target volume, FIGO Federation of Gynecology and Obstetrics, D90 dose to 90% of the HRCTV, DO.lec dose\nto 0. lcc volume of the respective organ (i.e: rectum, sigmoid, bowel, bladder). D2ee dose to 2ee volume of the respective organ (i.e rectum, sigmoid, bowel, bladder)\n",
"Table 3 Tumour and treatment characteristics of the patients with events (fistula formation\n"
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"CHT chemotherapy. REV bevacizumab, HRCTV high-risk clinical target volume. D90 dase to 90% of the\nHRCTV, OAR organ at risk, D0.lec dose to 0. lce volume of the respective organ (i.e: rectum, sigmoid,\nhowel, bladder), D2er dose to 2ec volume of the respective organ (i.e: rectum, signmoid, bowel, bladder)\ntest\nt-test\n",
null,
"\"Table 4 Mean tradiation dose\nfor HRCTV and OARS ac-\ncording to fistula status (dose\n- volume parameters (DVH)\npatients and Gy)\n",
"CHT+BEV is administered to RecCC patients without\ncurative intent. The quality of life in this palliative set-\nting is of particular importance and should have a sub-\n",
"stantial influence on the selection of therapy. Interestingly,\nwhile GOG 240 reported an increased rate of fistula in the\nCHT+BEV group, the quality of life was not decreased in\nthis group. Other reports show that fistula formation leads\nto a substantial reduction in quality of life [23]. Therefore,\npatient-reported outcomes, as used in GOG 240, might not\nbe appropriate to determine the detrimental effect of fistula\nformation on quality of life.\n",
"Based on our observations, we suggest that when fac-\ning persistent disease or local recurrence, with or with-\nout systemic disease, caution should be used in prescribing\nCHT+BEV. This combination should be offered only after\nthoroughly informing the patients about the high probabil-\nity of developing fistula, especially GU fistula. Prudence\nshould also be used when facing ureteral stent change or\nother pelvic interventions, which are common in patients\nwith RecCC.\n",
"Admittedly, the shorteomings of this study have to be\nconsidered. This was a retrospective data analysis of a small\npatient cohort from a single institution. The limited number\nof patients included in this report impaired statistical anal-\nysis and multivariate models were not feasible. However,\ngiven the lack of published data and increasing number of\npatients who are possibly candidates for this treatment, we\nwant to raise awareness about the potential risks of using\nBEV in addition to CHT in the setting of pelvic RecCC and\nrelated interventions.\n",
"never achieved complete local remission and I had a local\nrecurrence).\n",
"We could not detect any association between comorbidi-\nties, radiation dose, performance status or previously per-\nformed bowel surgery prior to the diagnosis of RecCC and\na higher rate of fistula formation. Our findings are in ac-\ncordance with previously published reports (201. In a study\nincluding 30 patients with FIGO stage IVA (with bladder\norland rectal infiltration) undergoing radiochemotherapy,\nthe 5-year fistula-free survival rate was 64%, but no prog-\nnostic variables were identified. Although all the patients\nin the CHT +BEV group underwent interstitial IGABT as\nopposed to 84% in the CHT group, the use of interstitial\nimplants is not statistically correlated to the occurrence of\nfistula when BEV is added to the treatment of RecCC (p =\n0.18). Moreover, recent literature shows that primarily use\nof advanced IGABT, especially interstitial implants, does\nnot increase late toxicity when compared to intracavitary\ntherapy only [18].\n",
"Recent studies suggest that only intermediate- and high-\nrisk RecCC patients show a survival benefit when receiving\nCHT+BEV [21). These patients have 2-3 (intermediate-)\nand 4-5 (high-risk) risk factors from: black race, perfor-\nmance status 1, pelvic disease, prior cisplatin and progres-\nsion-free interval <365 days. Hence, patient selection is\ncrucial with respect to side effects and complications. Sev-\neral approaches were performed to identify biomarkers to\npredict the effect of BEV on an individual basis [22]. How-\never, no predictive biomarker has been established thus far.\n"
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"Conclusion\n",
"Until larger studies are available, based on our observa-\ntions in this small cohort, and given the overall survival\nbenefit [9], CHT+BEV should probably be offered mainly\nto patients with local control and systemic recurrences. Fu-\nture clinical studies are required to identify predictive and\nprognostic factors for fistula formation, in order to improve\npatient selection for CHT+BEV in the setting of RecCC.\n",
"Acknowledgements Open access funding provided by Medical Uni-\nversity of Vienna.\n",
"Conflict of interest A Sturdza. S. Hofmann, M. Kranawetter,\nS. Polterauer, C. Grimm. M. Krainer, C. Kirisits, R. Potter,\nA. Reinthaller and R. Schwameis declare that they have no competing\ninterests.\n",
"Open Access This article is distributed under the terms of the\nCreative Commons Attribution 4.0 Intemational License (htip://\ncreativecommons.org/licenves/by/4.V), which permits unrestricted\nuse, distribution, and reproduction in any medium, provided you give\nappropriate credit to the original authoris) and the source, provide a\nlink t0 the Creative Commons license, and indicate if changes were\nmade.\n",
"References\n",
"Perez CA, Grigsby PW. Chao KS. Mutch DG. Locket MA (1998)\nTumor size, irradiation dose, and long-tem outcome of carcinoma\nof uterine cervix. Int J Radiat Oncol Biol Phys 41:307-317\n2. Eifel PJ, Jhingran A, Brown J. Levenback C, Thames H (2006)\nTime course and outeome of central recumence after radiation ther-\napy for carcinoma of the cervix. Int J Gynecol Cancer 16:1106-1111\n3. Chemoradiotherapy for Cervical Cancer Meta-Analysis Collabora-\ntion (2008) Reducing uncertainties about the effects of chemora-\ndiotherapy for cervical cancer: a systematic review and meta-anal-\nysis of individual patient data from 18 randomized trials. Joumal\nof clinical oncology: official joumal of the American Society of.\nI Clin Oncol 26:5802-5812\n4. Kizer NT, Thaker PH, Gao F. Zighelboim I, Powell MA, Raker JS\net al (2011) The efects of body mass index on complications and\nsurvival outcomes in patients with cervical carcinoma undergoing\ncurative chemoradiation therapy. Cancer 117:948-956\n5. Potter R. Georg P, Dimopoukas JC, Grimm M. Berger D. Nesvacil\nNet al (2011) Clinical outcome of protocol based image (MRI)\nguided adaptive brachytherapy combined with 3D conformal ra-\ndiotherapy with or without chemotherapy in patients with locally\nadvanced cervical cancer. Radiother Oncol 100:116-123\n6. Sturdza A. Potter R. Fokdal LU, Haie-Meder C. Tan LT, Maze-\nron R et al (2016) Image guided brachytherapy in locally advanced\ncervical cancer: Impruved pelvic control and survival in RetroEM-\nBRACE, a malticenter cohort study. Radiother Oncol. doi: 10.1016\nj.radone. 2016.03.011\n7. Gill BS, Kim H, Houser CJ, Kelley JL. Sukumvanich P. Ed-\nwards RP et al (2015) MRI-guided high-dose-rate intracavitary\nbrachytherapy for treatment of cervical cancer: the University of\nPittsburgh experience. Int J Radiat Oncol Biol Phys 91:540-547\n8. Castelnau-Marchand P. Chargari C. Maroun P. Dumas I. Del Campo\nER, Cao Ket al (201S) Clinical outcomes of definitive chemoradia-\nlion followed by intracavitary pulsed-dose rate image-guidkd adap-\ntive brachytherapy in locally advanced cervical cancer. Gynecol\nOncol 139:288-294\n",
"detta LM et al (2014) Inproved survival with bevacizumab in ad-\nvanced cervical cancer. N Engl J Med 370:734-743\n10. Burger RA, Brady MF. Bookman MA, Monk BJ, Walker JL. Home-\nsley HD et al (2014) Risk factors for GI adverse events in a phase II\nrandomized trial of bevacizumab in first-line therapy of advanced\novarian cancer: A Gynecologic Oncology Groap Study. Journal of\nelinical oncology : official joumal of the American Society of. Clin\nOncol 32:1210-1217\nI1. Willmott LJ (2014) Gastrointestinal and Genitourinary Fistulae in\nWomen Treated with Chemotherapy with and without Bevacizumab\nfor Advanced and Recurrent Cervical Cancer. International Gyne-\ncologic Cancer Society, Melbourne (A NRG Oncology - Gyneco-\nlogic Group Ancillary Data Study 15th Biennial Meeting of the In-\nternational Gynecologic Cancer Society)\n12. Benedet JL. Bender H. Jones H 3rd, Ngan HY, Pecorelli S (2000)\nFIGO staging classifications and clinical practice guidelines in the\nmanagement of gynecokogic cancers. FIGO Committee on Gyne-\ncologic Oncology. Int J Gynaecol Obstet 70:209-262\n13. Haie-Meder C. Potter R. Van Limbergen E. Briot E, De Brabandere\nM. Dimopoulos J et al (2005) Recommendations from Gynaecolog-\nical (GYN) GEC-ESTRO Warking Group (I) concepts and terms in\n3D image based 3D treatment planning in cervix cancer brachyther-\napy with emphasis on MRI assessment of GTV and CTV. Radiother\nОпсol 74.235-245\n14. Potter R. Haie-Meder C, Van Limbergen E, Barillot L De Braban-\ndere M. Dimopoukos J et al (2006) Recommendations from gy-\nnaecological (GYN) GEC ESTRO working group (11): concepts\nand terms in 3D image-based treatment planning in cervix cancer\nbrachytherapy-3D dose volume parameters and aspects of 3D im-\nage-hased anatomy, radiation physics, radiobiology. Radkol Oncol\n78:67-77\n15. Bentzen SM, Dorr W, Gahbauer R. Howell RW, Joiner MC, Jones\nBet al (2012) Bioeffect modeling and equieffective dose concepts\nin radiation oncology - terminology, quantities and units. Radiol\nOncol 105:266-268\n16. CTEP (20006) Common Terminology Criteria for Adverse Events\nv3.0 (CTCAE)\n17. Tewari KS (2014) Abstract LBA26 - final overall survival analysis\nof the phase III randomized trial of chemotherapy with and withoum\nhevacizumah for advanced cervical cancer: a NRG oncalogy - Gy-\nnecalogic Oncology Group Stady. European Society for Medical\nOncology, Madrid\n18. Fokdal L. Sturdza A. Mazeron R. Haie-Meder C. Tan LT, Gillbam\nCet al (2016) Image guided adaptive brachytherapy with combined\nintracavitary and interstitial technique improves the therapeutic ra-\ntio in locally advanced cervical cancer: Analysis from the retroEM-\nBRACE study. Radiol Oncol. doi:10. 1016/j.radonc.2016.03.020\n19. Feddock J, Randall M. Kudrimoti M, Baldwin L, Shah P. Weiss Het\nal (2014) Impact of post-radiation biopsies on development of fis-\ntulac in patients with cervical cancer. Gynecol Oncol 133:263-267\n20. Biewenga P. Mutsaerts MA, Stalpers LJ, Buist MR. Schilthais MS.\nvan der Velden J (2010) Can we predict vesicovaginal or rectovagi-\nnal fistula formation in patients with stage IVA cervical cancer? Int\nJ Gynecol Cancer 20:471-475\n21. Tewari KS, Sill MW, Monk BJ, Penson RT, Long HJ 3rd, Poveda A\net al (2015) Prospective validation of pooled prognostie factors in\nwomen with advanced cervical cancer treated with chemotherapy\nwith/without bevacizumab: NRG oncology/GOG study. Clin Can-\ncer Res 21:5480-5487\n22. Gonzalez-Vacarezza N. Alonso I, Amoyo G, Martinez J. De An-\ndres F. Llerena A et al (2016) Predictive biomarkers candidates\nfor patients with metastatic colorectal cancer treated with beva-\ncizumab-containing regimen. Drug Metabol Personal Ther. doi:10.\n"
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"23. Mohr S. Brandner S, Mueller MD. Dreher EF. Kuhn A (2014) Sex-\nual function after vaginal and abdominal fistula repair. Am J Obstet\nGynecol 211:74.el-74.ct\n24. Cohn DE, Kim KH, Resnick KE, O'Malley DM, Straughn IM J.\n(2011) At what cost does a potential sarvival advantage of beva-\ncizumab make sense for the primary treatment of ovarian cancer?\nA cost-effectiveness analysis. J Clin Oncol 29:1247-1251\n25. Koda T. Koike J. Masuhara H, Kurihara A. Shiokawa H, Ushigome\nMet al (2016) A case of Aortoesophageal fistula rupture due to de-\nscending thoracic aortic dissection with recurent colon cancer dur-\ning chemotherapy containing bevacizumab. Gan To Kagaku Ryoho\n43(12):1815-1817\n26. Kanzaki R. Shintani Y, Inoue M, Kawaumara T, Funaki S. Minami\nM. Okumura M (2017) Late-onset pulmonary fistula after resection\nof pulmonary metastasis from colorectal cancer following periop-\n",
"crative chemotherapy with bevacizumab. Ann Thorac Cardiovas\nSurg. doi: 10.5761/ates.er. 16-00117\n27. Richardson DL, Backes FJ, Hurt JD, Seamon LG, Copeland LJ.\nFowler JM, Cohn DE O'Malley DM (2010) Which factors pre-\ndict bowel complications in patients with recurrent epithelial\novarian cancer being treated with bevacizumub? Gynecol Oncol\n1181)47-51\n28. Burger RA, Brady MF. Bookman MA, Monk BJ, Walker JL. Home-\nsley HD, Fowler J, Greer BE, Boente M. Fleming GF. Lim PC,\nRuhin SC. Katsamata N, Liang SX (2014) Risk factors for Gl ad-\nverse events in a phase III randomized trial of hevacizumab in first-\nline therapy of advanced ovarian cancer: A Gynecologic Oncolaogy\nGroup Study. J Clin Oncol 32(12):1210-1217. doi:10.1200VICO.\n2013.53.6524\n"
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"Open Access\n",
"Improving access to skilled facility-based\ndelivery services: Women's beliefs on\nfacilitators and barriers to the utilisation of\nmaternity waiting homes in rural Zambia\n",
"Cephas Sialubanje\", Karlijn Massar\", Marit S. G. van der Pijl, Elisa Maria Kirch, Davidson H. Hamer\nand Robert A. C. Ruiter\n",
"Abstract\n",
"Background: Maternity waiting homes (MWHS) are aimed at improving access to facility-based skilled delivery\nservices in rural areas. This study explored women's experiences and beliefs concerning utilisation of MWHS in rural\nZambia. Insight is needed into women's experiences and beliefs to provide starting points for the design of public\nhealth interventions that focus on promoting access to and utilisation of MWHS and skilled birth attendance\nservices in rural Zambia.\n",
"Methods: We conducted 32 in-depth interviews with women of reproductive age (15-45 years) from nine health.\ncentre catchment areas. A total of twenty-two in-depth interviews were conducted at a health care facility with a\nMWH and 10 were conducted at a health care facility without MWis. Women's perspectives on MWHS, the\ndecision-making process regarding the use of MWHS, and factors affecting utilisation of MWHS were explored\n",
"Results: Most women appreciated the important role MWHS play in improving access to skilled birth attendance\nand improving maternal health outcomes. However several factors such as women's lack of decision-making\nautonomy, prevalent gender inequalities, low socioeconomic status and socio-cultural norms prevent them from\nutilising these services. Moreover, non availability of funds to buy the requirements for the baby and mother to use\nduring labour at the clinic, concerns about a relative to remain at home and take care of the children and concerms\nabout the poor state and lack of basic social and healthcare needs in the MWHS - such as adequate sleeping space,\nbeddings, water and sanitary services, food and cooking facilities as well as failure by nurses and midwives to visit\nthe mothers staying in the MWHS to ensure their safety prevent women from using MWHS.\n",
"Conclusion: These findings highlight important targets for interventions and suggest a need to provide women\nwith skills and resources to ensure decision-making autonomy and address the prevalent gender and cultural norms\nthat debase their Social status, Moreover, there is need to consider provision of basic social and healthcare needs\nSuch as adequate sleeping space, beddings, water and sanitary services, food and cooking facilities, and ensuring\nthat nurses and midwives conduct regular visits to the mothers staying in the MWHS.\n",
"Keywords: Matermal health, Facility-based delivery services, Maternity waiting home, Kalomo, Zambia\n"
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"Background\n",
"Globally, around 287 000 women die annually from pre-\nventable pregnancy and childbirth-related complications\n(1, 2). Almost all (99 %) of the maternal deaths occur in\ndeveloping countries and more than 50 % occur in sub-\nSaharan Africa (2, 3). Zambia is one of the sub-Saharan\nAfrican countries with a high maternal mortality ratio\n(MMR) at 398 deaths per 100 000 live births (4]. Most\nof the maternal deaths and morbidity have been shown\nto be associated with behavioural risk factors such as\nlow or non utilisation of skilled birth attendance. Skilled\nbirth attendance is considered to be the most important\nintervention for ensuring optimal maternal and newborn\nhealth outcomes (5). Many maternal and perinatal deaths\ncould be prevented if all women delivered their babies in\nfacilities with adequate resources and staffing that are pro-\nviding a high quality of medical care [6).\n",
"The proportion of women who receive skilled birth at-\ntendance is still low in Zambia [4). Many women (53 %)\nstill give birth at home and most (62 %) do not receive\nassistance from skilled birth attendants. However, stud-\nies have shown that most women who give birth at home\nexpress willingness to give birth at the clinic (7-9). For\nexample, a study by Stekelenburg et al [9] showed that,\nalthough most pregnant women (94 %) indicated they\nwould prefer to give birth in a health centre, only 54 % ac-\ntually did (9).\n",
"Rural-urban disparities have been reported in the util-\nisation of skilled birth attendance services. For example,\nthe United Nations (UN) report [10] showed that, in sub\nSub-Saharan Africa, less than half (50 %) of the women\nin rural areas received skilled attendance at birth com-\npared to over 80 % in urban areas. In Zambia, only 30 %\nof the women in rural areas are attended to by a skilled\nprovider compared with 80 % of the births in urban\nwomen [4). Several reasons have been reported for the\nlow utilisation of skilled birth attendance services in the\nrural areas. For example, studies conducted in Zambia\n(6-9, 11] showed that, in addition to limited access to\nhealthcare facilities due to physical and logistical barriers\nsuch as long distances to health facilities and high trans-\nportation costs, poor quality of services due to low mid-\nwifery staffing levels and a lack of medical equipment\nfor emergence obstetric care, are important reasons pre-\nventing pregnant women in rural areas from accessing\nskilled birth attendance. Further, Sialubanje et al [7. 8)\nshowed that nurses' disrespectful attitude towards preg-\nnant women, pregnant women's negative attitude to-\nwards healthcare services due to the low quality of\nservices women receive at the clinic, social norms re-\ngarding childbirth and indirect costs of buying baby re-\nquirements or food while staying in a health care facility\nare important reasons for pregnant women in rural\nareas to refrain from accessing skilled birth attendance,\n",
"Mitigating these barriers could improve the utilisation.\nof skilled birth attendance services (7, 8, 12).\n",
"To overcome physical and logistical barriers such as\nlong distances and high transportation costs to healthcare\nfacilities faced by women living in rural areas, maternity\nwaiting homes (MWHS) have been established in many de-\nveloping countries, including Zambia [13-15). The World\nHealth Organisation (WHO) has defined MWHS as \"resi-\ndential facilities, located near a qualified medical establish-\nment, where women living far from the healthcare facility\nand those with high-risk pregnancies can wait for their de-\nlivery and be transferred to a nearby medical facility shortly\nbefore delivery, or earlier, should complications arise\" (15).\n",
"Studies investigating the effectiveness of the MWHS\nhave reported positive results. For example, studies from\nEthiopia (16), Zimbabwe (17]. Liberia (18] and Eritrea\n[19] as well as a WHO report [15) showed that MWHS\nimproved pregnant women's access to healthcare facilities,\nled to an increase in the number of women receiving\nskilled birth attendance, and reduced maternal mortality\nin the area and improved maternal and new born health\noutcomes among women who stayed in the MWHS dur-\ning the last period of their pregnancy. The report [15] also\nshowed that MWHS were essential in the management of\nwomen with high-risk pregnancies. Moreover, a study\nconducted in rural Zambia (20] comparing women using\nMWHS and those who did not use them showed that, al-\nthough women using MWHS had higher maternal risk\nfactors (83 %) compared to those who did not use MW'Hs\n(53 %), there were no differences in maternal outcomes\nbetween the two groups after delivery, suggesting that\nMWHS were effective in reducing maternal mortality.\n",
"Qualitative studies exploring women's perceptions to-\nwards MWHS show that most women had a positive at-\ntitude towards MWHS and expressed willingness to stay\nin them while waiting for labour.\n",
"Regarding women's perceptions about utilisations of\nMWHS, qualitative studies show that women's views\ndiffer. For example, in their study conducted in Kalabo\ndistrict, Zambia, Stekelenburg et al [9| reported that\nmost respondents (97 %) expressed willingness to stay in\na MWH If it were available. Similarly, a study evaluating\na community trial on MWHS in Liberia (18] showed that\ntraditional midwives participating in the study believed\nthat MWHS provided a safe environment for pregnant\nwomen preparing for delivery, allowed them to stay\nclose to the healthcare facilities and helped them rest be-\nfore giving birth. The study also showed that, compared\nto the communities without MWHS, those with MWHS\nexperienced a significant increase in the number of\nbirths from baseline to post-intervention. In contrast to\nthese positive views, a study from Ghana (21] reported\nlow utilisation of MWHS due to various factors includ-\ning the cost associated with staying in a MWH, the\n"
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"hardship of staying away from home and the absence of\nhealth personnel in healthcare facilities (21, 22).\n",
"Little research on women's perceptions towards MWHS\nhas been conducted. Study findings from other countries\nmay not be applicable to the rural Zambian context.\nWomen's experiences and opinions regarding utilisation\nof the MWHS may differ from one geographical, socio-\ncultural and economic context to another. The purpose of\nthis study, therefore, is to explore women's experiences\nand beliefs concerning utilisation of MWHS in rural\nZambia. Insight is needed into women's experiences and\nbeliefs to provide starting points for the design of public\nhealth interventions that focus on enhancing access to\nand utilisation of skilled birth attendance services in rural\nZambia, by promoting the use of MWHS.\n",
"Methods\n",
"Study design\n",
"The study was qualitative in design and used in-depth\ninterviews (IDIS) to provide a detailed understanding of\nthe women's experiences and beliefs concerning utilisa-\ntion of MWHS in Kalomo district. The Tropical Diseases\nResearch Centre Ethics Review Committee and the Min-\nistry of Health Research and Ethics Committee in\nZambia granted ethical approval.\n",
"Study setting\n",
"The study was conducted in Kalomo district, located\n360km south of the capital Lusaka, and covering a total\nsurface area of 15 000 km'. It has an estimated population\nof 275, 779 [23) with an annual growth rate of 4.4 %. Most\nof the population (92 %) live in rural areas with subsist-\nence farming and cattle rearing being the major economic\nactivities. The district is one of the poorest in the country,\nwith more than 70 % of its population living on less than a\ndollar per day [24). Administratively, the district is divided\ninto three constituencies, four chiefdoms and twenty polit-\nical wards. The health system in the district comprises two\nhospitals, thirty-four health centres and several health\nposts. Furthermore, only 52 % of the health care facilities\nhave access to reliable electricity [25] The district is one of\nthe rural districts in the country with low maternal health-\ncare service utilisation rates, where less than 30 % of the\nwomen receive assistance from a skilled birth attendant in\na health facility, compared with 80 % of the births in urban\nwomen 14, 7, 8, 25]. The main players in the maternal\nhealth programmes are the Ministry of Health, missionar-\nies, non-governmental organisations, community leaders\nand various community-based health agents, including\ntraditional birth attendants.\n",
"Study population and sampling techniques\n",
"The study participants were selected from the women of\nreproductive age (aged between 15 and 45 years) who-\n",
"had given birth within one year prior to the study and\nwere visiting the local health centre for their children's\nroutine under five clinics. To be eligible to participate in\nthe interview, women must have had resided in the area\nfor more than six months; those who had lived there for\nless than six months were excluded because the investi-\ngators thought these women would not have had enough\nlocal experience on utilisation of MWHS in the area. In\naddition, women aged below 15 and above 45 years were\nexcluded from participation.\n",
"Selection of study participants was done using a pur-\nposeful homogeneous sampling technique. This tech-\nnique was used in order to select respondents with\nsimilar experience regarding utilisation of MWHS and\nchildbirth services, while, at the same time, allowing\nfor recruitment of respondents with different charac-\nteristics in terms of their age, number of children,\nmarital status, and education level, which helped pro-\nvide insight into the similarities and differences in their\nexperiences (26, 27).\n",
"To begin with, all the ten health centres with a MWH\nin the district were identified and included in the re-\nsearch with the help of the district managers at the Dis-\ntrict Medical Office. In addition, five (5) out of a total\ntwenty five health centres without a MWH were also\npurposefully selected and included in the study.\n",
"A month prior to the interview, the principal investi-\ngator contacted respective health centre in-charges to in-\nform them about the study. Due to logistical challenges, it\nwas not possible to hold meetings with respective health\ncentre in-charges. Instead, they were contacted by phone\nand the purpose and objective of the study were discussed\nin detail. The health centre in-charges were then asked to\ninform the mothers attending the under five clinics about\nthe study and to explain its purpose and objectives-, that\nis, the study aimed to gain insight into their experience\nand knowledge about MWHS in their areas, how the deci-\nsions for pregnant to use the service were made and what\nthey thought were the main factors affecting utilisation of\nthe service. This information was shared by health centre\nin-charges during the health promotion sessions oon-\nducted by nurses and midwives during each under five\nclinic visit, and involved all the women attending the\nunder five clinics on a particular day. Women who were\nwilling to participate in the study were advised on the\ninterview date and were asked to retum to the clinic for\nthe interview on an agreed upon date. The date for the\ninterview was set by the health centre in-charge and then\ncommunicated to the research team through the principal\ninvestigator.\n",
"Data collection\n",
"The IDIS were conducted from the second week of\nMarch, 2014 to the end of May, 2014 and lasted for ten\n"
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"weeks. The research team travelled to the health centre\non the day of the interview. To ensure privacy and confi-\ndentiality, each IDI was conducted in a quiet place, out-\nside health centre premises, normally under a tree for\nshade and lasted between 30 and 50 min. The IDIS were\nconducted in Tonga, the local language in the area.\nBefore each IDI, written consent was obtained from each\nparticipant by requesting them to read and sign the con-\nsent form, which was translated into the local language.\nResearch assistants read the consent form aloud for those\nwho could not read.\n",
"After obtaining consent, research assistants requested\neach respondent to complete a short demographic ques-\ntionnaire which included questions such as the respon-\ndent's age, number of children, marital status, level of\neducation, occupation, level of income, estimated walk-\ning time to the clinic, place of delivery for the youngest\nchild, history of complications during the previous deliv-\nery, and use of a MWH. The last question was only ap-\nplicable for the respondents located at a health care\nfacility with a MWH. After completing the questionnaire,\nthe interviews were conducted. Each IDI was facilitated by\ntwo trained research assistants using a semi-structured\ninterview guide which was translated into Tonga. One re-\nsearch assistant conducted the interview, while the second\none recorded using a digital voice recorder. The principal\ninvestigator attended interviews at random to ensure the\ndata collection protocol was consistently followed by the\nresearch team members.\n",
"A total of 32 IDIS were conducted in 9 health centres,\n22 of whom were interviewed in 7 health centres with a\nMWH, and 10 were interviewed in 2 health care facil-\nities without a MWH, although 10 health centres with\nMWHS and 5 health centres without MWHS were ini-\ntially identified to be included in the study. After 15\ninterviews involving respondents from five health cen-\ntres with MWHS, and 10 interviews from health centres\nwithout MWHS, data saturation was achieved; that is,\nno more substantial information was obtained. At this\npoint, the research team decided to stop the interviews\nand, thus, leave out the remaining selected health cen-\ntres. Rather, they decided to only conduct the interviews\nin the two mission-owned health centres with MWHS in\nthe district. The rationale for this decision was to obtain\nextra insight into the study from these respondents be-\ncause, compared to the MWHS in the other health facil-\nities in the district, MWHS in the mission facilities were\nof better quality and provided better social services such\nas a larger sleeping space, mattresses, beds and blankets.\nIn addition, the facilities had better cooking facilities and\nsanitary conditions with piped water. Seven (7) extra re-\nspondents were interviewed from these two health cen-\ntres, giving a total of 32 respondents. The age of the\nrespondents ranged between 17 and 44 years old.\n",
"Research instrument\n",
"A semi-structured interview guide was developed that\nhad three pre-determined themes. The first theme fo-\ncused on women's perspectives and experience regarding\nMWHS and its role to improve facility-based skilled\nbirth attendance, and included questions on women's\nexperience regarding utilisation of MWHS. For example,\nwhat they thought about MWHS; whether they had\nstayed in a MWH before or not; how they felt about\ntheir stay in a MWH; what they thought about accessi-\nbility to MWHS in their area; whether they would you\nuse it if they were pregnant again and why; what they\nthought about whether mothers' shelters were import-\nant in helping women deliver at a health centre or not;\nand if so to explain why and how. The second theme\nwas on the decision-making process regarding utilisa-\ntion of MWHS and included questions about how the\ndecision is made and who makes it when women want\nto go to the MWHS. The third theme focused on the\nimportant factors which affect women's actual utilisa-\ntion of MWHS.\n",
"Since there were two different settings (with or with-\nout MWHS present) in which the interviews took place,\ntwo interview guides were developed reflecting these dif-\nferent settings. The overall themes were the same for\nboth interview guides, however some questions were dif-\nferent. For example, at the health care facility with a\nMWH, women were asked if and why they did or did\nnot go to stay at the MWH in the last period of their\npregnancy. If they did stay in the MWH, their perspectives\nwere explored. At the health care facility without a MWH,\nwomen were asked to share their view on MWHS. Fur-\nthermore, the women were asked if they would use the\nMWH if available at the health care facility and why.\n",
"Data analysis\n",
"Demographic information was entered into the excel\nsheet and transferred into IBM SPSS Statistics 21 for\nprocessing. Descriptive statistics and frequencies were\nused to summarise the demographics of the respondents\nand respective percentages were computed (see Table 1\nbelow).\n",
"The voice recordings from the interviews were tran-\nscribed and translated into English by the research assis-\ntants. To check for accuracy, a few transcripts (20 %)\nwere back - translated into Tonga. Members of the re-\nsearch team then compared the Tonga and English ver-\nsions for differences and similarities while listening to\nthe original voice recording. After verification of accur-\nacy in translation, each transcript was then thoroughly\nread by one research assistant while the other one was\nlistening to the corresponding voice recording. Each trans-\nlated transcript was compared with the hand-written field.\nnotes that the research assistants had prepared during the\n"
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"Table 1 Background characteristics of the respondents\n",
null,
"Table 1 Background characteristics of the respondents\nContinued)\n",
null,
"interviews. After proof-reading and making corrections,\nthe transcripts were saved on a password-protected com-\nputer. The word documents were then exported into\nNvivo 10 MAC for processing. The exported data were\nthen coded and the categories and key sub-themes were\nidentified. In order to make it easy to compare the per-\nspectives of women from the facilities with a MWH\nand those from health care facilities without a MWH,\nthe data from the two groups of respondents was coded.\nseparately. Data analysis was based on the three prede-\ntermined themes. An inductive approach was used to\nderive the sub-themes from the main themes by content-\nanalysing and groOuping all the similar statements made\nwith respect to particular themes. Several sub-themes\nemerged from the data analysis; all sub-themes are de-\nscribed below in the respective sections for the main re-\nsearch themes.\n",
"Results\n",
"Demographics\n",
"Table 1 summarizes the demographic characteristics of\nthe 32 respondents included in the study. The mean age\nwas 26.8 years old and the majority (84.4 %) of the re-\nspondents were married, and had an average of 3 chil-\ndren. Most of the respondents (68.8 %) were farmers\nand about two in five (38.7 %) had an income of less\nthan 100 ZMW per month. The estimated walking\ntime to the clinic from the place of the respondents'\nresidence was one hour and 40 min and the majority\n(87.5 %) had delivered their youngest child at the\nhealth care facility. Of the 32 respondents, 22 were\ninterviewed at a health care facility with a MWH and\n10 were interviewed at a health care facility without a\nMWH. Only 2 out of 22 (9.1 %) of the respondents\ninterviewed at a health care facility with a MWH had a\nhome delivery compared to 2 out of 10 (20 %) that\nwere interviewed at a health care facility without a\nMWH. Of the 22 respondents interviewed at a health\ncare facility with a MWH, 6 (27.3 %) utilized a MWH\nand 16 (72.7 %) did not. Out of the 32 respondents\ninterviewed, 6 (18.75 %) experienced complications\nduring labour.\n"
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"Theme 1: perspective on maternity waiting homes\n",
"The first theme focused on women's perspectives regard-\ning MWHS as well as accessibility and utilisation of\nMWHS.\n",
"All respondents mentioned that MWHS were import-\nant since they helped pregnant women to overcome the\nproblem of having to travel long distances to healthcare\nfacilities. They explained that during the last month of\ntheir pregnancy, pregnant women could go and stay in\nthe MWHS and wait for their labour near the health care\nfacility. Respondents, especially those from healthcare fa-\ncilities without MWHS, added that, with a MWH at the\nhealth care facility, women could decide themselves\nwhen to leave home to go and stay there instead of hav-\ning to travel to the clinic when they are already in estab-\nlished labour. They stated that women could either walk\nfrom home to the MWHS when they still had the\nstrength to do so or they could use private transport. Re-\nspondents mentioned that women who resided far from\nthe health centres experienced delays in reaching the\nhealth care facility and that MWHS were especially im-\nportant for these women. It was also mentioned that\nMWHS were especially convenient for the women who\nexperienced labour and delivery at night. They explained\nthat MWHS were important for the pregnant women\nwho lived far from the health care facility as it was ex-\ntremely difficult for them to find transport during the\nnight. They explained that while staying at the MWH,\nwomen had immediate access to health care and felt\nprotected against labour complications. Moreover, re-\nspondents explained that women were happy that they\nwere able to rest in the MWH before they went into\nlabour. When labour started, it was easy for them to ac-\ncess facility based delivery.\n",
"\"It's a good idea, You can come here if you don't have\ntransport at your place. You may walk when you still\nhave strength, then you overcome the distance, you\nstay here waiting for the right time to come, rather\nthan being at hone until your time comes and walking\na long distance while something is paining\" (20-year-old\nrespondent)\n",
"In contrast, most respondents who lived close to the\nhealth centres with MWHS believed that they did not\nneed the MWHS because their place was near to the\nhealth care facility. Furthermore, most multigravida\nolder respondents preferred to wait at home as they be-\nlieved they would recognise the labour in time to go to\nthe healthcare facility. They explained that it was only\nnecessary to go to the MWHS if the woman had compli-\ncations during pregnancy. The young respondents ex-\nplained that they didn't have enough knowledge on the\nMWHS as they had just experienced their first pregnancy.\n",
"Therefore, they just decided to stay at home and only went\nto the clinic when they were in established labour.\n",
"When asked whether most women had access to the\nMWHS, all 22 respondents from the health care facilities\nwith a MWH explained that it was easy for women to\ngo and stay there, as there were no rules or regulations\nregarding the use of the service. In contrast, the 10\nwomen from the health care facilities without MWHS\nargued that it was hard for them to reach the centres\nwhich had MWHS.\n",
"Regarding their experience while staying in the MWHS,\nthe 6 respondents who had used the MWHS and most of\nthe older women from the health centres with MWHS\ncomplained that women felt abandoned by the healthcare\nstaff as nurses did not check on them and that it was a\nwaste of time staying at the MWHS as it was possible for\none to reside there for weeks without being attended to by\nnurses or midwives. Moreover, the 13 out of the 22 (60 %)\nrespondents who lived close to health care facilities with a\nMWH but had not used the service were concerned with\npregnant women's inactivity when staying in the MWWHS\nwaiting for labour. They argued that it was not good for\npregnant women to stay in the MWH because the nurses\nadvised them to rest while staying there. Most older\nwomen stated that they preferred to have their labour start\nearlier and felt that staying active would assist pregnant\nwomen have their labour start early. Therefore, respon-\ndents explained that some women preferred to stay at\nhome and keep working until the onset of their labour.\n",
"When asked whether they would use the MWHS if\nthey were available, all 10 respondents from the health\ncentres without MWHS reported that they would like to\nsee MWHS provided at their health care facility, and that\nmost women would utilise it. They explained that that\nmost women would stop worrying about transport if\nMWHS were available at their health care facility.\n",
"If the clinic had the maternal waiting home, the mother\nshelter here, most pregnant women would come here\nand stay to wait for her time\" (44-year-old respondent)\n",
"When asked whether most women used MWHS where\nthey were available, all the respondents from both the fa-\ncilities with MWHS and those without reported that\nmost women did not utilise the service. They mentioned\nthat most women did not go to stay in the MWHS be-\ncause they delayed making the decision to leave home.\nThey explained that although they had planned to stay in\nthe MWH, some women, especially the older ones with\nmany children, went into labour while they were still at\nhome due to lack of transport to take them to the MWHS.\nRespondents explained that especially young women de-\nlayed utilising the MWHS because they had difficulties in\nestimating the right time to go to the MWHS.\n"
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"When you check the top left of this page, can you find any 'Theme 1: perspective on maternity waiting homes'?",
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"Is it correct that there is no 'Theme 1: perspective on maternity waiting homes' on the bottom of this page?",
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"T wanted to stay there but the problem was that it\nvas my first pregnancy so I didn't know when labour\nvould start So I am planning to come there next\nime\" (24-year-old respondent)\n",
"Regarding the reasons for utilising the MWHS all\nreported long distances and lack of transport from\nhome to the health care facility as the main reason\nfor utilising the MWHS. Additionally, fear of compli-\ncations was another important reason for utilising the\nMWHS. They explained that, often, they were advised\nby the nurses during antenatal care (ANC) visits to\nstay in the MWHS. Women who attended ANC at a\nclinic without a MWH were advised to go and wait\nfor delivery at the district hospital or at a health\ncentre with a MWH.\n",
"Thad some complications; I had some problems so\nwas told to stay at the clinic before time of delivery\"\n(25-year-old respondent)\n",
"Theme 2: decision making process and barriers to utilising\na maternity waiting home\n",
"The second theme focused on the decision-making\nprocess regarding whether or not to utilise MWHS as\nwell as the factors that influence the decision-making\nprocess.\n",
"Asked about who makes the decision for pregnant\nwomen to use the service, most young respondents with\nfew (that is one or two) children from both the health\ncare facilities with MWHS and those without mentioned\nthat the husband is the one who decides whether or not\nthe woman should go and stay at the MWH during the\nlast months of pregnancy. They explained that although\nmost women discussed with their husbands the import-\nance of their stay at the MWHS and often persuaded\nthem to allow their wives to use the MWHS, the final\ndecision whether the woman should use the MWH or\nnot was made by the husband. In addition, young re-\nspondents mentioned that the women's mother and\nmothers-in law were also involved in the decision-\nmaking process. Furthermore, all respondents from both.\nthe health care facilities with MWHS and those without\nalso mentioned that nurses at the clinic play an import-\nant role in the decision-making process as they often ad-\nvise women during ANC visits to come and stay at the\nMWH, especially when there were indications of compli-\ncations. However, most older respondents mentioned\nthat they made the decision alone and that they did not\nreceive help from anyone in the decision- making\nprocess.\n",
"\"The kusband is the one who decides\" (23-year-old\nvespondent)\n",
"\"When we are in the month of 8, the nurses at the\nclinic tell us to come and wait for our time here, yes\"\n18-year-old respondent)\n",
"Regarding the factors affecting the decision-making\nprocess, respondents who had used MWHS and those\nwho had experienced complications during previous\npregnancies mentioned the risk of complications as the\nmajor reason to utilise MWHS. Young respondents with\nno experience with childbirth indicated that fear of com-\nplications was the major reason for using MWHS. They\nexplained that as the husband made the final decision,\nhe considered the advice from the nurses at the clinic.\nThey indicated that sometimes during ANC women\nwere told that their baby was not in the right position in\nthe womb, which could cause problems during delivery.\nAdditionally, respondents explained that some women,\nespecially the young ones, were advised by nurses that\nthey would not be able to push the baby out and needed\nmedical help with this process. They also explained that\nsome women, especially the old ones with many children\nwere advised to go and deliver at the clinic because they\nmight bleed a lot after giving birth. If they stay in the\nMWH before giving birth, women who experience these\nkinds of complications receive immediate medical help,\nas they do not experience delays in reaching the clinic.\n",
"Asked about which group of women were more at risk\nof developing complications, respondents mentioned\nthat all women were at risk of developing complications.\nThey explained that especially young women who had\nno experience with childbirth were at greater risk of de-\nveloping complications such as prolonged or obstructed\nlabour than older ones with many children. Furthermore,\nolder women who had complications during their previous\npregnancies and deliveries were believed to be at a higher\nrisk of developing complications in future pregnancies.\nMoreover, respondents explained that women (regardles\nof their age) who were told by nurses during ANC visits\nthat they had pregnancy complications such as the baby\nnot lying well in the uterus, having high blood pressure,\netc, were also believed to be more at risk of developing\ncomplications during labour. Respondents explained that,\ncompared to the older women with many children, young\nmothers were more likely to anticipate complications be-\ncause they were scared of labour complications and be-\nlieved that they had no experience with childbirth. They\nexplained that many multigravida older respondents be-\nlieved that they had enough experience with childbirth\nand that they knew themselves quite well, and that they\nwould know whether they would develop complications\nor not.\n",
"\"Complications, that's what they look at. Maybe when\nvou deliver at homne and you bleed a lot, they won't\n"
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"help you. But here at the hospital they can control the\nbleeding So that is what they consider before deciding\nwith the kusband\" (23-year-old respondent)\n",
"Another important factor that the families considered\nduring the decision making process is distance. Most re-\nspondents interviewed from both the health care facil-\nities with a MWH and those without explained that\nwalking from home to the clinic while in labour pain\nwas difficult when living far from a health centre. Thus,\nit might be safer to stay at the MWHS before delivering.\nAdditionally, respondents mentioned that availability of\ntransport also plays an important role as the couple de-\ncides on whether the woman should go and stay in the\nMWH or not.\n",
"The distance, it's difficult for the woman to walk\nwhen she feels the labour pains from home coming\nhere. It's better for her to come here and stay\"\n(28-year-old respondent)\n",
"Regarding challenges in the decision making process,\nmore than half (18 out of 32) of the respondents inter-\nviewed from both the health care facility with a MWH\nand those without indicated that the lack of a family\nmember to take care of the children and another one to\naccompany the woman to the MWH and help her while\nstaying there usually made it difficult for the pregnant\nwoman to leave home to go and stay at the clinic. They\nexplained that many women had young children who-\ncould not stay by themselves while their mother was\naway at the MWH awaiting labour. Respondents ex-\nplained that often, the husband was not able to stay at\nhome to take care of the children due to various com-\nmitments, including working in the field.\n",
"Another factor that was considered by the wife and\nhusband as they made the decision was the availability\nof funds to buy the requirements for the baby and\nmother to use during labour at the clinic. Respondents\nmentioned that during ANC, nurses advised pregnant\nwomen to prepare for childbirth, and that as they went\nto give birth at the clinic they should carry baby clothes\nand requirements for the mother such as a wrapper and\ncleaning materials like bleach. Respondents explained\nthat the husband was expected to find the money for the\nbaby and mother requirements at the clinic. However,\nrespondents explained that most families did not have\nenough money to buy these items and husbands who-\nfailed to provide these requirements refused to allow\ntheir wives to go and stay at the MWHS.\n",
"Moreover, when making the final decision, husbands\nconsidered the availability of people to work in the field.\nMost respondents who had not used MWHS interviewed\nat a health centre with MWHS mentioned that some\n",
"women had not used MWHS because their husbands re-\nfused to allow them to leave home due to difficulties of\nhaving someone to work in the field, especially during\nharvest time.\n",
"There is a challenge of how, who should take care of\nthe children\" (36-year-old respondent)\nThere is no problem, unless this time when we are\niarvesting, but we have to ask from the husband and\nsay I want to go to the clinic. Husbands will then give\nus permission\" (18-year-old respondent)\n",
"Theme 3: factors affecting staying in maternity walting\nhomes\n",
"Respondents were asked if they faced challenges regard-\ning the utilisation of MWHS. Most respondents from\nboth the health care facilities with MWHS and those with-\nout mentioned that pregnant women faced many chal-\nlenges when using the MWHS. Respondents who had\nused MWHS complained that many MWHS had no beds\nor mattresses and pregnant women had to carry their own\nbeddings from home. They mentioned that those who\nfailed to carry their own beddings and mattresses had to\nsleep on the floor. Respondents explained that this was a\nhuge challenge for pregnant women as they had to walk.\nlong distances and could not carry beddings on their\nheads. Similarly, respondents from the health care facil-\nities without a MWHS stressed the need for pregnant\nwomen to be comfortable during their stay at the MWHS\nand that beds and mattresses should be made available.\n",
"\"As for now we just sleep on the floor. There are no\nmattresses unless you bring them from home\"\n(35-year-old respondent)\n",
"\"If they put beds and mattresses it could help women\nto be delivering at the hospital\" (17-year-old\nrespondent)\n",
"Furthermore, respondents who had used the MWHS\nand most respondents from the healthcare facilities with\nMWHS stated that the available MW'Hs had limited space\nfor sleeping. They explained that some MWHS were very\ncrowded because pregnant women came with an accom-\npanying relative. They explained that sometimes women\nhad to sleep outside because of the lack of space.\n",
"There is no much space in the shelter. Pregnant\nwomen need space as they stay at the mother' shelter.\nBecause of not having enough space women have\nproblems\" (25-year-old respondent, IDI30)\n",
"In contrast, all the 7 respondents from the two mis-\nsion health facilities were happy with the quality of\n"
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"MWHS and the services provided there. They mentioned\nthat the MWHS in the two health facilities had enough\nspace for women and their accompanying relatives and\nthat they had enough beds and mattresses for pregnant\nwomen to use. They also indicated that pregnant women\nstaying in these MWHS were provided with blankets by\nthe healthcare staff.\n",
"Another important challenge was the lack of food for\npregnant women when staying in the MWHS. Respon-\ndents who had used MWHS and those from the health.\ncare facilities with MWHS mentioned that food was not\nprovided to the pregnant women who stayed in the\nMWHS. They stated that women had to carry their own\nfood from home. Respondents explained that it was hard\nfor pregnant women to take their own food to the\nMWHS because they had limited food supplies which\nwere not even enough to share with the other family\nmembers remaining at home. Additionally, respondents\nwho had used MWHS indicated that it was usually un-\nknown how long women would stay at the MWHS, and\nthis made it difficult to estimate how much food they\nneeded to take with them. They explained that often, the\nfood ran out before women gave birth. In order to get\nextra food, women had to travel back home. They ex-\nplained that while walking home, women risked giving\nbirth on the way.\n",
"The issue of carrying their own food is a problem. You\nfind that she just has a small amnount of food then she\nhas to share it with the family, with children and\nkusband. So it's a challenge\" (41-year-old respondent)\n",
"\"It's difficult for a mother if the food finishes. She has\nto go back home. Some women delivered on the way\nwhen they went back home to get food\" (32-year-old\nrespondent, IDI29)\n",
"Another important problem was lack of water at the\nMWHS. Most respondents from health care facilities\nwith MWHS stated that most MWHS had no water and\nwomen had to walk long distances to get it. They ex-\nplained that, although in most cases, the accompanying\nrelatives would draw water for the pregnant women, but\nwhen the pregnant woman was alone, she had to walk\nthe distance herself. In contrast, the respondents from\nthe two mission health facilities were happy with the qual-\nity of the water supply, cooking facilities, and sanitary con-\nditions. They indicated that MWHS in these facilities had\nrunning water and pregnant women did not have to walk\nlong distances to look for water as the case was in the\nother health facilities.\n",
"\"As for me, I can't stay there for one simple reason;\nthere is no water kere, It is far where we get water\n",
"from. They kave to improve on the issue of water...\"\n(35-year-old respondent)\n",
"Furthermore, respondents who had used MWHS and\nthose interviewed at a health care facility with MWHS\nmentioned that the sanitation was poor in the MWHs\nand needed improvement. They mentioned that some\nMWHS had no toilets and bathrooms.\n",
"In addition, respondents who had used MWHS ex-\nplained that nurses and midwives did not visit the\nmothers in the MWHS. They explained that some\nmothers stayed for a long time in the MWHS without\nthe nurses or midwives checking on them to ensure\nwhether they needed help or not. Respondents explained\nthat the non availability of nurses put most women at\nrisk of complications even if they stayed at the MWHS.\nThey stated that it is important that nurses and mid-\nwives make regular visits to the women staying in the\nMWHS so that those who need care are identified and\nassisted on time. On the contrary, the 7 respondents\nfrom the mission facilities said that most women from\nthese facilities were happy with the way nurses treated\nthem when they used the MWHS. They indicated that\nnurses usually visited the pregnant women staying in the\nMWHS and asked those who had problems to go and.\nsee the nurse or midwife at the clinic. Moreover, during\nthese visits, the nurses identified the women who had no\nresources to buy the mother baby requirements and\nassisted them by providing them with these require-\nments from the clinic.\n",
"If nurses are there, there is no problem; even if some\nof the things are missing there is no problem, just\nnurses are important\" (24-year old respondent)\n",
"Discussion\n55\nIS\n",
"The aim of this study was to explore women's experi-\nences and beliefs concerning utilisation of maternity\nwaiting homes in Kalomo, Zambia. Our findings show\nthat that most women appreciate the important role\nMWHS play in improving access to skilled birth attend-\nance and improving maternal health outcomes. However\nseveral individual, family and health system-related fac-\ntors prevent utilisation of these services.\n",
"Consistent with previous studies which highlighted the\nimportance of MWHS in improving access to facility-\nbased skilled birth attendance [14-22), our findings sug-\ngest that most women in rural Zambia have a positive\nattitude towards this service. Their positive attitude\nseems to be based on their beliefs and their outcome ex-\npectations, i.e. what they would gain from the use of the\nservice. For example, respondents believed that MWHS\nwere an important means to overcome physical barriers\nsuch as the long distance to the health care facilities.\n"
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"Furthermore, respondents believed that MWHS were an\nimportant means to improve access to skilled and facility-\nbased birth attendance. Moreover, they saw them as able\nto prevent complications during labour and delivery since\npregnant women could easily get assistance from nurses\nand midwives at the clinic. Moreover, respondents per-\nceived social gains from the use of MWHS. They believed\nthat staying in the MWHS provided pregnant women with\nan opportunity to rest from the strenuous field work\nwhich characterised their livelihood in the rural areas.\nStaying away from strenuous exercise and resting in the\nMWHS as they approached their labour was seen as im-\nportant in improving labour and delivery outcomes for\nboth the mother and the baby. Moreover, these beliefs\nseem to be based on the respondents' past experience and\ninformation provided by nurses during ANC at the clinic.\nThus, MWHS were seen to have many important benefi-\ncial effects, not only to improve access to skilled birth at-\ntendance, but also to improve mother and birth health\noutcomes.\n",
"This finding is important since it is in line with the\noriginal idea of the MWHS which started out as an inter-\nvention to improve maternal health outcomes for the\nwomen with high-risk pregnancies, but later included\npregnant women who had limited access to facility-based.\nskilled birth attendance (15). Our findings are also in line\nwith a study from Liberia (18] which showed the import-\nance of MWHS in improving access to skilled maternity\ncare. Thus, public health programmes focusing on improv-\ning access to skilled birth attendance could benefit from\nintervention promoting increased availability of MWHS.\n",
"Interestingly, although our findings emphasise a posi-\ntive role MWHS can play in improving access to facility-\nbased skilled birth attendance services in rural areas, the\nresults also show that most women who had access to a\nMWH did not utilise them because of various factors\nsuch as women's dependence on their husbands for\ndecision-making, non-availability of funds to buy the re-\nquirements for the baby and mother to use during labour\nat the clinic, concerns about a relative to remain at home\nand take care of the children and concerns about the poor\nstate of the MWHS. This finding is also important as it in\nline with studies from other developing countries, for ex-\nample, Ghana 121), which reported low utilisation of\nMWHS. Further, this finding highlights the complexity of\nwomen' health seeking behaviour and the need for pub-\nlic health interventions to not only focus on the target\npopulations' attitude and intention, but also to ensure\nthat health promotion interventions target factors that\nmight make it difficult to enact the intended behaviour.\nIndeed, many studies investigating the implementation of\nvarious health behaviours ranging from exercise to breast\ncancer screening (28-30] have all reported the challenge\nof \"intention-behaviour gap\". For example, a study by\n",
"Stekelenburg et al in Zambia (14] reported that although\nthe majority of the women (94 %) showed high intentions\nto use MWHS only half of them (54 %) actually did. Simi-\nlarly, one of our recent studies [8] which focused on pre-\ndictors of maternal healthcare service utilisation in rural\nZambia showed that most women who had high inten-\ntions to give birth in a health facility under skilled birth\nattendance actually ended up giving birth at home.\nThese findings highlight the need for health promotion\ninterventions to consider providing the requisite skills and\nresources in order to enable people to implement their\nintended behaviour.\n",
"Regarding the decision to go and stay at the MWHs\nCur findings shed light not only on the decision-making\nprocess, but also on an important interplay of factors\nthat determine the pregnant women's decision to use the\nMWHS. According to the women that were interviewed,\nthey receive adequate information from the nurses about\nthe existence and the importance of the MWHS. This in-\nformation is in turn shared with the husband or with\nparents when the husband is not available. Interestingly\ndespite discussing the issue of childbirth with her hus-\nband, our findings suggest that the pregnant woman does\nnot make the final decision. Rather, the women indicated\nthe husbands play the most important and final role in the\ndecision making process and made the final decision.\nWomen's dependence on their husband for the final deci-\nsion could have been as a result of the socio-cultural be-\nliefs recognising the husband as the head of the household.\nand their need for socioeconomic support from the hus-\nband. From the interviews, it became apparent that the\nhusband was seen as a provider and women looked up to\nhim for the final decision. Moreover, the dependence on\nthe husband and lack of decision-making autonomy was\nalso perceived as a result of respect for the husband who\nis perceived to be the head of the household, and hence\nthe decision-maker in most matters affecting the family.\nThis finding is in line with other studies from developing\ncountries (31, 32] which have identified the importance of\nwomen's low socioeconomic status and dependence on\ntheir husbands as an important factor which negatively af-\nfects women's health seeking behaviour and prevents them.\nfrom accessing skilled birth services, and which often leads\nto adverse maternal health outcomes.\n",
"Interestingly, our findings show that, although the dis-\ntance to the clinic and the woman's risk of developing\ncomplications are the major factors which are consid-\nered by the husband as he makes the final decision, our\nresults also suggest that the husband's final decision is\nnot based solely on the available information from the\nnurses and midwives. Rather, our results suggest that\nseveral other factors such as the availability of funds to\nbuy the requirements for the baby and mother to use\nduring labour at the clinic, the availability of a relative to\n"
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"remain at home and take care of the children, and the\navailability of people to work in the field when the woman\nis away, are major influences on the final decision on\nwhether the woman shoukl leave home or not. Our find-\nings suggest that husbands who fail to raise adequate re-\nsources to provide for their wives either delay making the\ndecision or stop their wives from leaving home to go and\nstay at the MWH. Thus, although women discuss child\npreparedness and matters relating to child birth, the final\ndecision is made by the husband. His decision is based not\non the woman's risk to develop labour and childbirth-\nrelated complications and her access to skilled care in case\nof such complications, but mainly on the availability of\nresources at the family level. These findings thus clearly\nshow the complexity of the decision-making process\nregarding women's utilisation of skilled birth attendance\nservices. The findings are also in line with a study by\nThaddeus and Main [13] as well as studies from Ghana\nand Bangladesh [21, 32] that reported the importance of\nindividual, family and community level factors in delaying\nor preventing access to maternal healthcare services in de-\nveloping countries. Thus, our findings highlight the im-\nportance of the individual level factors, the immediate-\nfamily members such as the husband, mother and other\nrelatives, and the community in which the woman lives as\nimportant targets for intervention [33]. Moreover, these\nfindings suggest that partner involvement and engaging\nthe community in which the woman lives is an import-\nant way to reduce the burden of work on the pregnant\nwomen in their late stages of pregnancy to enable them\nuse MWHS.\n",
"Another striking finding from our study is how women's\nperception of the availability and quality of the basic social\nand healthcare services provided in the MWHS influ-\nences their decision whether to use the service or not.\nAlthough dependence on their husbands to be allowed\nto use MWHS is an important factor limiting pregnant\nwomen's utilisation of MWHS, the results also suggest\nthat before leaving home, women take into consider-\nation other important factors. Among these are the\navailability and quality of sleeping space, beds and mat-\ntresses, water and sanitary facilities, food and the cook-\ning facilities in the MWHS. Our findings suggest that\nmany MWHS did not have these basic facilities and that\nwhere they were available, they were either inadequate\nor not in good quality. These findings are important as\nthey highlight the importance of basic social needs\nsuch as shelter, water and food as determinants of\nskilled birth care utilisation. Before women are ex-\npected to use the available service, healthcare systems\nneed to ensure that basic services are provided and\nbasic needs are met (7). Further, these findings suggest\nthe gains to be made for public health interventions\n(that is, improved access to MWHS and skilled birth\n",
"attendance) that focus on providing such needs in the\nhealthcare facilities.\n",
"Women also consider their medical safety when stay-\ning in the MWHS. For example, most respondents were\nconcerned about the fact that nurses and midwives\nnever visited the pregnant women when they stayed in\nthe MWHS to assess and monitor their conditions. This\nfinding is important as it shows that although the ori-\nginal aim of the MWHS was to increase access to skilled\nbirth attendance; this service may actually not be meet-\ning this aim since women still feel they have no access\nto skilled care despite staying close to the clinic. This\nfinding is also in line with various studies from Zambia\n17-9] which have highlighted the importance of the\navailability of skilled birth attendants in health facilities\nin order to increase access to skilled birth attendance as\nwell as improve labour and childbirth outcomes.\n",
"Potential limitations of our study should be noted. First,\nlike all qualitative studies, our study findings may not be\ngeneralisable to other areas with different socio-cultural,\neconomic and geographical contexts. Furthermore, these\nfindings are only based on the experiences of the few\nwomen who accepted to participate in the IDIS; since the\nrecruitment of the respondents was done at the clinic dur-\ning the routine children's under five clinic at the health\ncentre, we do not have information on the differences be-\ntween the women who accepted to participate in the inter-\nviews and those who did not. Moreover, although the\ndistrict has one of the lowest maternal healthcare service\nutilisation rates (4, 7, 8, 25), most of the respondents inter-\nviewed had given birth at the clinic and at the hospital.\nThe reason for this selection was to have women who had\nexperience with MWHS and clinic delivery. However, the\nselected respondents' experiences may not be representa-\ntive of the views of the other women in the community,\nespecially those who had given birth at home. Moreover,\ninterpretation of the findings may have been influenced.\nby the researchers' individual judgment and experience.\nUnfortunately, we could not conduct focus group dis-\ncussions to compare and confirm the findings due to lo-\ngistical challenges. This could have affected the validity\nof the findings.\n",
"Despite these limitations, we believe our study has\nprovided important insights into the role of MWHS to\nimprove access to skilled facility-based skilled birth at-\ntendance. As far as we know, this is the first qualitative\nstudy conducted on the subject in rural Zambia.\n",
"Conclusion\n",
"In conclusion, our findings suggest that MWHS could be a\nuseful intervention in improving access to, and utilisation\nof facility-based skilled birth attendance services. Mater-\nnity waiting homes are an important means to mitigate\nlong distances to health facilities and to enable women to\n"
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"The authors declare that they have no competing interests\n",
"Authors' contributions\n",
"All outhors designed the study. CS conducted dara collection Under the\nsupervisian of KM, DH and RACR, CS conducted data analysis and wrote the\nfirst draft of the manuscript. KM and RACR revised the manuscript. DH\nadvised on the final mamusorpt All authors read, commenited on and\nppioved the final maruscript.\n",
"Acknowledgements\n",
"Ths work was supported by the Netherlands Organsation for intermational\nCooperation (Mufficl as part of the first author's PhD scholarship, PhDV37.\n",
"Author details\n",
"Mnistry of Health, Morue District Medical Office. PO. Box 600144 Mone,\nZambia \"Departrent of Work and Sodal Psychology. Maastricht Lriversiky.\nPO. Box 616, 620OMD, Maastricht, The Netherlands. Departmert of Global\nHealth, Maastricht University, Facuky of Health, Medicine and Life Science,\nPO. Box Gla 6200MD, Maastricht, The Netheriands. \"Zambia Centre for\nAppiled Heslth Research and Development, PO. Ban 30910, Lusaka, Zarmbia\nCentre for Global Health and Development Boston University, Crosstown\n3nd floor, 201 Massachusetts Avenue, Boston, MA 02118 USA \"Department\nof Internationa Heakth, Bostan University School of Public Health, Crosstown\n3rd floor, 801 Massachusetts Avenue, Bostor, MA 02118 USA\n",
"Receved: 20 January 2015 Accepted 25 Ju\nPublished online: 08 July 2015\n",
"Pablished online: 08 July 2015\n",
"Liganish\nwalable on http://www.nhairtimedacentre/factsheetsfs348len/\nindechtmi, accessed on \" lanuany, 2015.\nWorld Health Orgarisation. 2014. Trends in matemal martalty 1990-2013.\navalable at hepwwwwhontreproductivehealthvoubkationmanitaing\nmateretrortalty 201 1en, accessed on 9th lanuary, 2015\nWorld Health Oiganiation.2005. The World Hicath Repart 2005. make\nesery mather and child count, avalable at htra/fwww.nha int/whư\n2005/enl accessed on, s lanuary, 2015\nCereral Statistics Cfice, Miristry af Heath, Tiopical Disease Research Centre\nUniversity af Zambia and Macio ntemational rc Zambla Demagraphic and\nHealth Survey Preliminary Boport. Maryland, LSA: ICE rtemational Rockile,\n2014. p. 13-4.\nGraham WI, Bell 15, ulough CH Can skiked amendance at delivery reduce\nmatemal mortaly in developing countries Safe Mathehood Strategles a\nHov evid 2001,1797-130.\nGabysch S Couners 5, Cox . Campbell OMR The induence of distance and\nlevel of care on delivery place in Rural Zamkia: a study of inked natioral\ndata in geographic inormaton system PLOS Med 201181), e100394\nSalukarje C, Massar K Hamer CH, Rter RAC. Understanding the\npykhosocial and ervironmental factors and baes afecting utiktion of\nmateinal heathore serices in Kakome, Zambir a quaitative study. Hedih\nEduc Res 201429131521-32\nSanarje C Marsar K, Hamer DH, Ruter RAC. Paychosocial and envionmercal\npredictors of the intention 10 use marernal heakhcre services in Kalomo\nZambia, Heath Educ Res 2014291008-40\nSekelenbug i, Kyanamina 5. Mukelibai M. Wifes ( Roosnaien . Waiting\ntoo long kw use of marenal healn services in Kalabo. Zimbia Trop Med\nIre Health 2004390-398\nO United Nations. 2013. The Mennium Development Goals Report 2013\nAvadbie at: htp://ww.urorgimilerniumgosis/pdfireport-201 3/mdy-\nregort-201 3-erglish pd. acessed on 9\" Jarary, 2015.\n1. Wakaven G Telfer M Rowley I. Ronsmare C Matenal mertalty in rutal\nGambir levels, caaes and contributing factors. Bul World h\n200785|03-13\nHeakh Organ\n2. Lohela TI. Campbel OM, Gabryach S. Distance to care, faclity delvery\nond early neonatal mortality in Malawi and Zambia. PLos One.\n2012112 es21 10.\n1. Thaddes S, Maine D. Toa far to wak matenal mortalty in contest Soc Sa\nMed. 1994:1091-1 10.\n4. Stekelenburg i, Lorkhujpen LN, Spaars W, Hooemalen V. Matemity watng\nhomes in rutal dsricts in Africa A comerstone of safe matherhood?\n",
"have access to life-saving interventions during labour and\nchildbirth. MWHS can also assist women to take rest from\nthe laborious field work, which predisposes them to vari-\nous pregnancy and childbirth related complications [34].\nHowever, currently, these potential benefits are not being\nrealised in rural Zambia due to the various challenges in-\ncluding individual, family, community and health system-\nrelated factors which women face when seeking to use the\nservice. These factors include lack of decision-making au-\ntonomy and dependence on husbands, prevalent gender\ninequalities, low socioeconomic status and socio-cultural\nnorms, and concerns about a relative to remain at home\nand take care of the children, as well as concerns about\nthe poor state and lack of basic social and healthcare\nneeds in the MWHS - such as adequate sleeping space,\nbeddings, water and sanitary services, food and cooking\nfacilities - as well as failure by nurses and midwives to visit\nthe mothers staying in the MWHS to ensure their medical\nsafety all prevent women from using MWHS.\n",
"These findings suggest important targets for interven-\ntions. For example, our findings suggest a need for an\nintegrated community intervention focusing on sup-\nporting families to reduce the burden of work on the\npregnant women during the late stages of pregnancy.\nMoreover, interventions need to focus on recognising\nand improving the low social status of women and\nprovide them with skills and resources to ensure\ndecision-making autonomy with regard to childbirth.\nInterventions should focus on promoting partner in-\nvolvement by providing husbands with knowledge and\nskills to support their pregnant women in their utilisa-\ntion of MWHS and facility delivery services. Moreover,\nalthough, public health interventions should focus on\nincreasing the number of MWHS, there is also an ur-\ngent need to consider the provision of basic needs\nsuch as adequate sleeping space, beddings, water and\nsanitary services, and food and cooking facilities. Fur-\nther, interventions should focus on increasing the\navailability of trained and skilled birth attendants such\nas nurses and midwives to ensure quality of care and\nmedical safety for women both in the MWHS and dur-\ning labour. Finally, further research is needed to meas-\nure and confirm the significance and importance of\nthese findings in determining access to MWHS. Re-\nsearch is also needed to determine whether access to\nand utilisation of MWHS actually ensure access to\nskilled birth attendance and improved mother and\nnewborn health outcomes. Findings from those studies\ncan be the basis for advocacy for a public health policy\non MWHS in developing countries, which is currently\nnon-existent.\n",
"Competing interests\n"
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"publikations/matemal_periratal healthMSM_K_21/env), accessed on 1\"\nAanuory. 2015\nE Kely 1 Kohh E Poovan P. Schiler R Hedto A Winter AH et al. The tole of a\nmaterity waiting area (MWA) in reducing matemal mortalty and stitinhs\nin high nak wamen in rural Ethiopia. BOG An int 1 Obstet Gyraecol.\n1179 20101711377-83\nMlard P, Raley 1, Hanson 1 Ateratal vilage stay and pregnancy outcome\nin nura Zmbabwe Cert At I Med. 1991371-4\n1. Lori JR. Murro M, Rominski S, Wilams G, Dah BT, Boyd Cl, et al Materity\nwaiting homes and tradrional midwives in rural Libera nt J Gyrecol\nObstet. 201 123114-8.\n. Andermrichael G, Hale 8, Kasia A, Mufunda 1. Matemity waiting homes a\npanacea for matermralineorstai conundrums in Enitrea J Ertreon Med Assoc.\n200418-21,\n1 van Lonkhujzen L Stegeman M. Nyrongo R van Roasmalen 1 Use of\nmaterity wating home h nrd Zamba. Ar J Reprod Heath 200371132-6\n1. Wison 1 Colison A Achandson D, Kwote G. Senah KA, Tinkorang EK The\nmaterity wating home concept the Nawam, Ghana experience Int\nGynecol Ctstet. 1997s9516-72\n2. Mamba L. Nasair FA, Ondieki C. Kimanga D Reasons for low utlicatioh af a\nmaterity wating home in nual Kerwa ht 1 Gynecol Obstet.\n201010821 52-1\n1. Certra Statistics Ofice, 2010, Zamba 2010 Census of popubtion and\nhousing - Prelminary repart. Avalatle ort hngu/www.zamstatsgovan\nkomphel, accessed 15 January. 2015.\n4. Certral Statistics Offie: Livng Condrions Poveny in Zambia 1991-2006.\nAvalatie on: httpu//www.zamstatsgov.amvicm phpl, accessed on 11\"\nlanuary, 2015\n. Hamer De, Semrau K. Everet LL, Mazambe A Sedenberg P. Goggin Ce al\nErrergency Obstetrical and Neonatal Capacity and Health Certer Acress in\nKalomo Dnct. Zambla: Paper presented at the Second Global Sympasium\non Heath Systems Reseach 2012\n5 Ary D, Jacobs L, Sorersen C Waker D. introduction to research in\neducaton sth ed Wadsworth, CA: Cengage Leaming 2013\n2 Kng N, Homrocks C rtentews in Qualtative Researth Ist ed USA: SAGE\nPublications Itd: 2010. p. 25-41.\n1 Armitage Cl. Implemertation intentions and eating a low- far det a\nrandomsed controitrial. Heskh Prychol 200421319-23\n3 Sreeran P, Whib TL, Golwitzer PM. The inteplay between goal intention\nand mplementation intertian. Persorlaty Soc Paychal Bul. 200531 87-98\na. Sreeran P, Cebell S. Uung implentation rtenton to ncrease attendance\nfor cevica cancer screering Heath Paychol. 20,19-283-4\n1. Spezer 6, Story WT. Singh K. Factors associated with institutional delvery im\nChana the role of decision-making autonomy and cnmmunity norms, BMC\nPregnancy Chidbrth 2014,1438\n2 Scory WT. Burgard SA. Coupies reports of hourehold deckionmaking and\nthe utikation of materal heath services in ongiadesh Soc Sci Med\n201275243-11\n1. Mayer CA, Muntafa A. Drivers and deterents of facity delvery in sub-Saharan\nAfrica a systematic IEview. Reprod Heath. 2013104\n4 Agbla F, Egin A, Barts NW. Occupational working condtions as sk factors\nfor preterm bith in Benin, West Africa. Bev Enidemigi Sante Publigue\n",
"Submit your next manuscript to BioMed Central\nand take full advantage of:\n",
"* Convenient online submission\n",
"No space constraints or color figure charges\n",
"Immediate publication on acceptanco\n"
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"edible oils and fats, Journal of Hygienic Engineering and Design:\nFood Production and Processing, vol. 4, pp. 112-116, 2013.\n[4] R. Abdulla, E. S. Chan, and P. Ravindra. \"Biodiesel production\nfrom Jatropha curcas: A critical review,\" Critical Reviews in\nBiotechnology, vol. 31, no. 1, pp. 53-64, 2011.\n[5] L. Azócar, G. Ciudad, H. J. Heipieper, and R. Navia, \"Biotech-\nnological processes for biodiesel production using alternative\noils.\" Applied Microbiology and Biotechnology, vol. 88, no. 3. pp.\n621-636, 2010.\n(6] A. J. Komakech, N. E. Banadda, J.R. Kinobe et al., \"Character\nization of municipal waste in Kampala, Uganda.\" Journal of thhe\nAir e Waste Management Association, vol. 64, no. 3, pp. 340-\n348, 2014.\n[7) I R. Tumuhairwe, 1. S. Tenywa, E. Otabbong, and S. Ledin,\n\"Comparison of four low-technology composting methods for\nmarket crop wastes,\" Waste Management, val. 29, no. 8, pp.\n2274-2281, 2009.\n[8] R. Leasing, \"Isolation and cultivation of oleaginous yeast for\nmicrobial od production,\" Asia-Pacific Journal of Science and\nTechnology, vol. 16, no. 2. pp. 112-126, 2017\n[9) A. P. Wacoo, M. Ocheng, D. Wendiro, P. C. Vuzi, and I.F.\nHawumba, \"Development and characterization of an electroless\nplated silver/cysteine sensor platform for the clectrochemical\ndetermination of aflatoxin B1.\" Journal of Sensors, vol. 2016,\nArticle ID 3053019, 2016.\n[10) LE Saeman, J.L Bubl, and E. E. Harris, \"Quantitative sacchari-\nfication of wood and cellulose\" Industrial and Engineering\nChemistry, vol. 17. pp. 35-37, 1945.\n[11) G. L. Miller, \"Use of dinitrosalicylic acid reagent for determina-\ntion of reducing sugar\" Analyrical Chermistry, vol. 31, no. 3, pP.\n426-428, 1959.\n[12] I. Schulze. S. Hansen, S. Großhans et al., \"Characterization of\nnewly isolated oleaginous yeasts-Cryptococcus podzolicus, Tri-\nchosporon porasum and Pichia segobiensis,\" AMB Express, vol. 4.\narticle 24, 2014.\n[13] D. Yang, X. Yang, and J. Chen, \"Design and implementation\nof direct digital frequency synthesis multiple signal generator\nbased on FPGA, Journal of Xian University of Technology, vol.\n4. no. 29, pp. 439-443, 2013.\n[14] K. Forfang, B. Zimmermann, G. Kosa, A. Kohler, and V.\nShapaval, \"FTIR spectroscopy for evaluation and monitoring of\nlipid extraction efficiency for oleaginous fungi, PLoS ONE, vol.\n12, no. 1, Article ID el170611, 2017.\n[15] N. Kiangkitiwan and K. Srikulkit, \"Poly(lactic acid) filled with\ncassava starch-g-soybean oil maleate,\" The Scientifie World\nJournal, vol. 2013, Article ID 860487, 2013.\n[16] Y. B. C. Man, \"Analysis of canola oil in virgin coconut oil using\nFTIR spectroscopy and chemometrics.\" Journal of Food and\nPharmaceutical Sciences, vol. 1, no. 1, 2013.\n[17) P. K. P. Kumar and A. G. G. Krishna, \"Physicochemical charac-\nteristics of commercial coconut oils produced in India.\" Grasas\ny Aceites, vol. 66, no. I. article no. el62, 2015.\n|18] M. Enshaeich, L Nahvi, and M. Madani, \"Improving microbial\noil production with standard and native oleaginous yeasts by\nusing Taguchi design,\" International Journal of Environmental\nScience and Technology, vol. 11, no. 3. pp. 597-604, 2014,\n[19] A. Areesirisuk. T. Yen, C. Chiu, C. Liu, and J. Guo, \"Optimiza-\ntion on Yeast Lipid Production of Psuedozyma sp. with Re-\nsponse Surface Methodology for Biodiesel Manufacturing.\"\nLurnal af d cwenced daricultumal Tecfnolosier vol 2 ng 1 2015\n"
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"Utilization of Solid Waste as a Substrate for Production of\nOil from Oleaginous Microorganisms\n",
"Fortunate Laker,' Arnold Agaba,' Andrew Akatukunda,' Robert Gazet, Joshua Barasa,\nSarah Nanyonga,' Deborah Wendiro , and Alex Paul Wacoo\n1,3,4,5\n",
"Department of Chemistry, Faculty of Science, Kyambogo University, PO, Box 1, Kyambogo, Uganda\nDepartment of Microbiology and Biotechnology Centre, Product Development Directory, Liyanda Industrial Research Institute,\nPO. Box 7086, Kampala, Uganda\nYoba for Life Foundation, Hunzestraat 133-A, 1079 WB Amsterdam, Netherlands\nDepartment of Moleralar Cell Physiology VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, Netherlands\nDepartment of Nursing. Muni University, PO. Box 725, Arua, Ugunda\n",
"Academic Editor: Difeng Gao\n",
"Copyright e 2018 Fortunate Laker et al. This is an open access article distributed under the Creative Commons Attribution Likense,\nwhich permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.\n",
"The overwhelming demand of oil and fats to meet the ever increasing needs for biofuel, cosmetics production, and other industrial\npurposes has enhanced a number of innovations in this industry. One such innovation is the use of microorganisms as alternative\nsources of oll and fats. Organic solid waste that is causing a big challenge of disposal worldwide is biodegradable and can be utilized\nas substrate for alternative oil production. The study evaluated the potential of isolated yeast-like colonies to grow and accumulate\noil by using organic solid waste as substrate. Of the 25 yeast-like colonies isolated from the soil samples collected from three different\nsuburbs in Kampala district, Uganda, 20 were screened positive for accumulation of lipid but only 2 were oleaginous. The NHC\nisolate with the best oil accumulation potential of 48.8% was used in the central composite design (CCD) experiments. The CCD\nexperimental results revealed a maximum oil yield of 61.5% from 1.25 g/l. cell biomass at 10 g/L of solid waste and temperature of\n25°C. The study revealed that organic solid waste could be used as a substrate for microbial oil production.\n",
"1. Background\n",
"Vegetable oils are the most traded, with palm oil being the\nmost preferred due to its wide application in food, cosmetics,\nand biofuel industries. As the high demand of vegetable\noil is being met, on the other hand, there is depletion of\nnatural resources, a rise in poor cultivation practices, and\neventually altered global climatic conditions that pose a threat\nto food security [1]. This therefore calls for exploration into\nother possible sources of oil production. Microorganisms\nsuch as oleaginous yeast have been found to accumulate large\nquantities of oil and can be utilized as alternative sources in oil\nproduction [2]. The composition of oleaginous yeast oil does\nnot greatly differ from that of the vegetable oil, since their\nfatty acid compositions are comparable (3). In addition, the\nmicroorganisms have a high growth rate and require minimal\n",
"land space, and their oil production is not affected by climatic\nchanges; moreover, they do not cause depletion of natural\nresources and hence do not pose a threat to food security [4).\nHowever, the major challenge is the high cost of production\n[5].Solid waste, whose disposal is a global challenge (ref.), can\nbe effectively utilized as a cheaper substrate for alternative oil\nproduction.\n",
"In Kampala, the capital city of Uganda, approximately\n28,000 tons of solid waste are collected monthly, of which\nabout 90% are organic [6]. Management of the waste is con-\ntinuously challenged by the rapidly inereasing population\nof residents, increase in the rate of economic activities, and\nlack of sufficient funding from central government [7]. The\nwaste is characterized by 213.5 g/Kg dry weight of nitrogen,\n22g/Kg dry weight of phosphorus, 26 g/Kg dry weight of\npotassium, and a very high carbon content [6]; it can be\n"
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"efficiently used as a substrate for microbial oil production.\nThere is, therefore, a need to screen for the best functional\noil-producing microorganisms and determine the optimal\nconditions. In this study, possibility of producing microbial\noil from oleaginous yeast using solid organic waste as a sub-\nstrate was investigated.\n",
"2. Materials and Methods\n",
"2.1. Soil Sample Collection. Seven soil samples were collected\nfrom wastes dumping sites in Kyambogo University, Banda,\nand Kireka, suburbs within Kampala District, Uganda. The\nsamples were obtained approximately 2-8 cm below the soil\nsurface and were stored in sterile transparent polythene bags\nat room temperature prior to transfer to the laboratory.\n",
"2.2. Isolation of Yeast Cells. The yeast cells were isolated on\npotato dextrose agar (PDA) (Conda, Madrid, Spain) plates\nwhich contained dextrose 20.0 g/L, infusion from potato\n200,0 g/L, bacteriological agar 15.0 g/L, and 50.0 mg chloram-\nphenicol supplement. The supplement was initially dissolved\nin 3.0 ml. of absolute ethanol prior to being added to the med-\nium base. The soil samples (5.0 g) were suspended in 9.0 ml of\nsterilized deionized water. The suspensions were thoroughly\nmixed for one minute at 2600 rpm using a vortex mixer\n(Stuart, Florida, USA) and subsequently followed by a tenfold\nserial dilution using sterile-buffered peptone water broth\n(Conda, Madrid, Spain). From each sample suspension, a\ndilution from 10* to 10 was chosen and an aliquot of 0.3 ml.\nfrom each was spread onto PDA. The plates were incubated\n(ESCO Isothermal Incubator, Singapore) at 30'C for a period\nof 3 days. Yeast-like colonies were isolated and subsequently\ncross-streaked onto fresh PDA plates.\n",
"2.3. Screening for Oleaginous Yeasts. A loop full of each isolate\nsuspension was inoculated into 100 ml. nitrogen limiting\nmedium contained in 250 Erlenmeyer flask. The medium\ncontained the following in g/L: glucose 70, (NH,),SO, 0.1,\nKH,PO, 0.4, MgSO, 7H,0 1.5, ZnSo, 0.0043, CaCl, 0.003,\nMnCl, 0.0012, CuSO, 0.0005, and yeast extract 0.795. The\nsamples were incubated in an incubator shaker (Excella E25,\nNew Brunswick Scientific, USA) at 150 rpm and 30 C for 4\ndays. The samples were then analyzed for their cell dry weight\nand percentage lipid content as described by Leasing [8). The\nscreening of samples was carried out in triplicate.\n",
"2.4. Characterization of Microbial Oil. The oil was struc-\nturally characterized by a Fourier transform infrared spec-\ntrophotometer (FTIR) (Perkin Elmer, Massachusetts, USA)\nas described by Wacoo et al. [9], with slight modification.\nBriefly, a thin layer of the microbial oil sample was placed in\nbetween the potassium iodide cells and held firmly by the cell-\nholder prior to being placed into the FTIR for read-up. The\nspectrum for the microbial oil was measured from 400 cm\nto 4000 cm at a scan speed of 500 nm/min. The spectrum\nfor the microbial oil was plotted on the same axis as those of\nsunflower, coconut, and palm oil for comparative purpose.\n",
"TABLE I: Levels of independent variables.\n",
null,
"2.5. Solid Waste\n",
"2.5.1. Collection and Treatment. The solid waste for the\nproduction of microbial oil was collected without sorting\nwaste disposal sites of a market, a residential place, and a\nrestaurant. The waste was sorted and the organic solid waste\nwas sun-dried and subsequently ground into a powder prior\nto being used in the production experiment. The powder\nwaste was used as a substitute of glucose in the nitrogen-\nlimiting medium mentioned in Section 2.3.\n",
"2.5.2. Determination of the Glucose Equivalent from the Solid\nWaste. The sorted waste was first hydrolyzed using concen-\ntrated sulphuric acid followed by a method described by\nSaeman et al. [10]. Estimation of glucose from the hydrolyzed\nwaste was done according to Miller [11].\n",
"2.5.3. Central Composite Design Optimization of Cultivwation\n",
"2.5.3. Central Composite Design Optimization of Cultivation\nConditions for Microbial Oil Production. Central composite\ndesign was used to efficiently identify the optimum values\nof the temperature and solid waste which could lead to high\noil accumulation. A two-factor five-level central composite\ndesign was therefore used to study the effect of solid waste\nand temperature on the oil yield of the selected yeast. Thirteen\nexperiments were sufficiently used to estimate the second-\norder regression coefficients for the two variables as shown\nin (1) and the levels of the independent variables as shown\nin Table 1. The predicted values were determined by a model\nfitting technique using the design expert software. Regression\nanalysis was performed on the experimental data and evalu-\nation for significance of fit of the model done as required.\n",
"= a0 + alX, + a2X, + a12X,X, +\nal1x,\n22X\n",
"Equation (1). Second-order polynomial model equation is\nused to express yield as a function of independent variables\nsolid waste composition and temperature, where a0 is the\ninterception coefficient, X, and X, are amount of solid\nwaste and temperature, respectively, al2 is the interaction\ncoefficient, and all and a22 are the quadratic terms.\n",
"3. Results and Discussion\n",
"3.1. Isolation of Oleaginous Yeasts. In the current study, 25\noleaginous microorganisms with yeast-like colonies were\nisolated on PDA containing chloramphenicol antibiotics\n(Table 2). Only three yeast-like colonies were isolated from\nthe soil samples from Banda and Kireka compared to 22 from\nKyambogo University.\n"
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"TABLE 2: Isolation and screening for lipid-producing yeasts.\n",
null,
"All the results are means t tandard deviation of triplicate analysis\n",
"3.2. Screening for the Oleaginous Yeasts. All the isolated yeast-\nlike colonies were screened for accumulation of lipid as\ndescribed in Section 2.3. The results revealed that all the\nisolates could utilize the nitrogen-limiting media for their\ngrowth. The cell biomass varied from 1.27 g/L to 9.49 g/L for\nisolates NHC and GC2N, respectively. The potential of the\nisolated yeasts to accumulate lipid varied greatly. Out of the\n25 isolates, 20 were positive for accumulation of lipid but\nonly 2 isolates (Table 2) were defined as oleaginous yeast with\nlipid accumulation of more than 20% of cellular dry weight\n[12]. Sample NHC with the lowest cell biomass of 1.27 g/L.\naccumulated the highest lipid content of 48.8% and was thus\nselected for further studies.\n",
"3.3. Characterization of the Microbial Oil Using FTIR.\n",
"The microbial oil from NHC isolate was characterized as\ndescribed in Section 24. The spectrum from the microbial oil\nwas plotted on the same axis as those of sunflower, coconut,\nand palm oil as shown in Figure 1. Compared to the three\nvegetable oils named above, the functional group of yeast\noil was identified using the FTIR. The absorption peaks for\nfunctional group (carbonyl ester group) appeared at position\nfrom 1650 to 1850 cm. Many other researchers identified\ncarbonyl ester groups at this position [13-15). The peaks\n",
null,
"FIGURE 1: FTIR spectra of (A) sunflower oil, (B) refine coconut oil,\n(C) crude palm oll, and (D) oil extracted from yeast (current study).\n",
"corresponding to the C-H stretching vibrations appeared\nranging from 2920 cm to 3010 cm\n",
"The microbial oil was quite similar to coconut and sun-\nflower oil at position 1655 cm and this peak was attributed\nto cis -C=C- stretch (16). This therefore indicates that, like\nrefined coconut and sunflower oil, microbial oil contained\nsome unsaturated fatty acids, Previous studies reported\n"
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"TAmLE 3: Central composite design and the corresponding experimental results and predicted values,\n",
null,
"Microbial oil yield\nrature (X,)\n30\n.9289\nActual (%)\nPredicted (%)\n21.15\n21.29\n53.2\n54.38\n30\n21.4\n21.29\n25\n61.5\n62.79\n30\n20.8\n21.29\n35\n283\n29.75\n30\n50.7\n48.43\n30\n21.11\n21.29\n35\n28\n26.24\n30\n22.05\n21.29\n2.0711\n24.6\n25.32\n25\n35.9\n34.3\n30\n23.3\n25.57\n0.6\n0.5\nd\n0.4\n1-\n0.3\n0.2\nMarket\nPrivate\nresidence\nUniversity\nhostel\nRestaurant\nWaste collection point\nWaste glucose equivalent (g/g)\n",
"approximately 91% unsaturated fatty acid in sunflower oil [3].\nAlthough crude coconut oil has been reported to contain\n>91% saturated fatty acid [17], the current study used refined\ncoconut oil and it revealed that it contained fairly high con-\ntent of unsaturated fatty acid as depicted at peak 1655 cm\n(Figure 1 (B)). Microbial oil had approximately equal stretch\nat this position similar to the refined coconut oil. However,\nmicrobial oil was quite different from crude palm oil, which\ndid not have stretch at this position.\n",
"3.4. Solid Waste\n",
"3.4.1. Determination of Glucose Equivalent from the Solid\nWaste. Glucose has been reported as the best substrate for\nmicrobial oil production, since it can be assimilated by most\noleaginous microorganisms to produce oil [18]. Therefore,\nequivalent glucose contents from each collected waste were\ndetermined as described by Saeman et al. [10] and Miller\n(11]. The results of equivalent glucose from the collected solid\nwaste are shown in Figure 2. The equivalent glucose contents\nper gram of waste were 0.5 g. 0.48g. 0.4 g, and 0.3g for\nwastes collected from the university hostel, restaurant, home,\nand market, respectively. The high glucose content in the\nwastes from the university hostel may be attributed to the\nhigh content of digestible food remains and papers, whereas\nthe low glucose content in the market wastes may be due to\ndecomposing food waste and indigestible solid materials.\n",
"3.4.2. Central Composite Design Optimization of Cultivation\nConditions for Microbial Oil Production. The corresponding\nresults and the predicted values from the CCD are shown\nin Table 3. For the optimization purposes, the amount of\nsolid waste and temperature were selected as the independent\nvariables. The generated data from the CCD were analyzed\nby multiple regressions using design expert software to fit the\nquadratic polynomial model.\n",
"As shown in Table 3, the amount of solid waste and\ntemperature had significant effects on the percentage of oil\nyield attained. Considering the results from all the runs, the\n",
"FIGURE 2: Characterization of solid waste collected for microbial oil.\nproduction.\n",
"concentration of microbial biomass stretched from 0,55 g/L.\nto 1.25 g/L (data not shown) and the content of microbial oil\nranged from 21.15% to 615%. However, the trend in yield was\nneither constant nor uniform; that is, increase in temperature\nand/or glucose concentrations did not result in an increase in\nthe yield. This may have been brought about by incomplete\nextraction of cells from the reactor and centrifuge tubes\namong others. Comparative analysis between both actual\nand predicted yields indicated that there was a very high\ncorrelation between them, giving a very small deviation.\nComparative analysis of the microbial biomass to previous\nstudies indicated that the yield was quite low, although the\noil contents were highly similar (19].\n",
"Equation (2). This is the final equation in terms of coded\nfactors.\n",
"Equation (2) shows the values of coefficient and regres-\nsion models which correctly described the experimental data.\n"
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"TABLE 4: ANOVA statistical results for the response surface quadratic model\n",
null,
"Model\n2396.26\n5\n479\nA: temperature\n831.23\n1\n831\nR: solid waste\n522.44\n522\nAB\n160.02\n160\nA\n554.22\n554\n442.52\n442\nResidual\n22.05\n7\n3.\nLack of fit\n21.14\n3\n7.0\nPure error\n0.91\n4\n0.\nCor. total\n2418.32\nOil yield\nI0.00\n8.75\n750\n25.1821\n625\n5.00\n25.00\n27.50\n300\n32.50\n35.00\nasM PIjos\n",
"FIGURE 3: The graph of the predicted respanse developed\nfunction of solid waste concentration and temperature.\nas a\n",
"The regression model indicated correlation between the two\nvariables (amount of solid waste and temperature) that were\nused for microbial oil production with correlation coefficient\n(R*) of 0.98. Therefore, the value of this R' strongly suggested\nthat the experimental models represent the relationship\nbetween the experimental results and the predicated values.\nThe predicted values were sufficiently correlated with the\nactual values as shown in Table 3.\n",
"The correlation obtained from the regression analysis\n(Table 4) was very positive and significant. It could be\nobserved that the fit was almost 100% as lack of fit was almost\nnegligible (<0.0001) and hence statistically significant. The\nanalysis of variance (ANOVA) showed that the model can\npredict the interactions of the independent variable with 95%\nconfidence limit.\n",
"The predictability plot as a function of the amount of\nsolid waste and temperature is shown in Figure 3. The oil\nyield increased quadratically with decrease in both glucose\n",
"concentration and temperature. The best oil percentage yield.\nwas achieved at the lowest temperature of 25 Cand the lowest\namount of solid waste of 5 g/L. The predicted results obtained\nwere very close to the expected values.\n",
"4. Conclusion\n",
"This study has not only demonstrated that oleaginous micro-\norganism can be programmed for maximum cell biomass\ngeneration and oil production but also revealed the ability of\nthe oil-producing microorganism to turn nuisance organic\nsolid waste into valuable oil. Utilization of solid waste as a\nsubstrate for production of oil by oleaginous microorganism\nis a novel process that establishes the economic value of\nwastes besides proving a solution to the waste disposal chal-\nlenge.\n",
"Conflicts of Interest\n",
"The authors declare that there are no conflicts of interest.\n",
"Authors' Contributions\n",
"Fortunate Laker, Arnold Agaba, and Andrew Akatukunda\ncontributed equally to this work and are joint first authors.\n",
"Acknowledgments\n",
"The authors would like to acknowledge Uganda Industrial\nResearch Institute (UIRI) for support in carrying out this\nresearch and would also like to thank Okoth Thomas of\nChemistry Department (UIRI) for his contribution towards\nsample analysis.\n",
"References\n",
"1] C. E. Ludena and C. Mejia, \"Climate Change, Agricultural Pro-\nductivity and Its Impacts on the Food Industry: A General\nEquilibrium Analysis, in presentation at the poster session of the\nInternational Association of Agricultural Economists Trienniai\nConference, Foz do Iguaçu, Brazil, 2012.\n2] T. M. Jiru, D. Abate, N. Kiggundu, C. Pohl, and M. Groenewald,\n\"Oleaginous yeasts from Ethiopia,\" AMB Express, vol 6, na. l,\narticle no. 78, 2016.\n"
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"Phenotypic Profile of Rh and Kell Blood Group Systems among\nBlood Donors in Cote d'Ivoire, West Africa\n",
"National Bload Transfusion Center, 52 baulevard de Marseille, BP 15 Abidjan, Cote d'ivoire\nLaboratory of Imamunology. UFR of Medical Sciences. BP 34 Aridjan 01. Cote d'Ivoire\nLaboratory of Immunology, UFR of Pharmaceutical and Biological Sciences, BP 34 Abidjan 01, Cote d'Ivoire\nHospital and University Centre of Cocody, BP 1843 Abidjan 08, Cote d'Ivoire\n",
"Academic Editor: Silvano Wendel\n",
"Copyright @ 2014 L. Siransy Bogui et al. This is an open access article distributed under the Creative Commons Attribution License.\nwhich permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.\n",
"Few countries in sub-Saharan Africa make systematic searches for antigens C, e, E, and e of the Rh and Kell system antigens in\nthe donor and recipient, thereby exposing transfused patients. Purpose and Objectives. In this paper, we propose to determine the\nred cell Rh and Kell blood groups among blood donors from traditional techniques to improve medical care of transfused patients\nThis study will allow us to assess the frequency of blood group antigens in these systems. Study Design and Methods. We carried out\na study on the red cell typing in the blood donor population of the National Blood Transfusion Center in Abidjan. This study was\nperformed on 651 bloud donors. Reselts. For the Rh system, the antigen frequencies of D, c, e, C, and E are, respectively. 92.93%,\n99.85%, 99.85%, 21.97%, and 13.82%. Kantigen is found in 0,77% of donors. Discussion and Conclusion, Although the frequencies of\nthe most immunogenic antigens are lower than in the white race, lack of preventive measures makes the immunological risk high\nin Africa. Furthermore, Africa is full of specificities that are important to note for a better care of our patients.\n",
"1. Introduction\n",
"In Cote d'Ivoire and in other African countries [1. 2), most\nof transfusions are done only based on ABO and D antigens.\nAlthough blood transfusions can save life, they are not\nwithout risk Blood transfusion can carry immediate or\ndelayed immunological risks; the most common and most\nserious is the hemolytic transfusion reaction by antibody\nincompatibility. Knowledge about the frequency of red cells\nantigens phenotypes in Ivorian population is important for\nthe creation of a donor data bank and to minimize risks\nof alloimmunization. This requires the determination of\nthe immunological characteristics of blood products and\nblood recipients by performing immunohematology analysis\nsuch as phenotyping in Rh and Kell blood group systems.\nCurrently, there are thirty-three major blood group systems\n[3], but analyses recommended in the usual situation are\nABO, Rh, and Kell typing and detecting red cell antibodies.\n",
"Unfortunately, in sub-Saharan countries, few practice this\nsystematic search for antigens C, c, e, E, and K in the donor\n",
"and recipient, thereby exposing the transfused patient to high\nrisk of alloimmunization (4].\n",
"Very few studies are available, reporting antigens frequen-\ncies of Rh and Kell blood groups in sub-Saharan countries.\n",
"This study is the first report on the frequency of blood\ngroups system Rh and Kell in blood donors in Cote d'Ivoire.\nThis work will perform Rh and Kell red cell typing among\nblood donors by traditional techniques to implement this into\nthe routine for blood donors and recipients. It also allows us\nto determine the frequency of the major Rh and Kell blood.\ngroup antigens and phenotypes commonly found among\nblood donors from Cote d'Ivoire to improve transfusion\npractices.\n",
"2. Materials and Methods\n",
"It was a retrospective study conducted at the Laboratory\nof Immunohaematology of the National Blood Transfusion\nCenter of Abidjan, the capital of Cote d'Ivoire.\n"
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"2.1. Blood Donors. We analyzed grouping data in Rh and Kell\nblood group systems from 651 volunteer regular blood donors\ncoming to the national blood on one year. The blood donors\nhave an age range from 18 to 60 years.\n",
"Those excluded from donating blood fell within the\nfollowing categories:\n",
"(i) taking drugs for high blood pressure or heart failure,\n(ii) having Hb below 11 g/dl. (for females) or 12 g/dL. (for\nmales);\nKi) testing positive for HBSAR, HCV, and HIV antibodies\nand syphilis;\n(iv) having had jaundice, liver discase, epilepsy, diabetes,\nduodenal or gastric ulcer, asthma, tuberculosis, or\nother pathology:\n(v) taking self-injected drugs;\n(vi) having sickle cell disease:\nvii) being a prostitute and/or homosexual;\nwiii) having severe weight loss within the last six months.\n",
"2.2. Methods. For optimal results, the determination was\nperformed using a tube freshly drawn into ethylenedi-\naminetetraacetate according to manufacturer's instructions.\nThe techniques are direct agglutination of the antigens\nwith slide technique for Rh system antigens and indirect\nantiglobulin technique by tube technique for Kell system\nantigens. Rh phenotyping was done using five monoclonal.\nmonospecific antisera: anti-D, anti-E, anti-C, anti-c, and\nanti-e while Kell phenotyping was performed with anti-K\naccording to manufacturer's instructions All reagents were\nsupplied by Orgenics PBS, Eurobio.\n",
"Positive and negative control red cells and Coombs\"\ncontrol cells were also performed as controls. Data were\nentered and analyzed with Epi Info version 6.1.\n",
"3. Results\n",
"We determined blood group antigens in 651 donors with sex\nratio 3.6 in favor of men.\n",
"605 blood donors representing 92.93% of the blood\ndonors were found to be RhD positive while 46 blood donors\nrepresenting 7.07 were found to be RhD negative (Figure 1).\n",
"The c and e antigens have the highest frequency with\n99.83%, C and E antigen were less frequent with 21.97% and\n13.82%, respectively (Table 1).\n",
"Seven phenotypes were detected among the blood donors\n(Table 2). The most frequent phenotype among the RhD\npositive was R,r 65.12% followed by R,r 20% and R,r 12.73%.\nAmong the RhD negative, the most frequent was rr (80.43%).\n",
"In the Kell blood group system, 5 blood donors (0.77%)\nwere typed as K antigen positive and 645 (98.08%) as k\nantigen positive antigens. Accordingly, the K-k+ phenotype\nwas the most common in these donors (98.92%).\n",
null,
"FIGURE I: Prevalence of RhD antigen in blood donors.\n",
"4. Discussion\n",
"Our study focused on 651 regular and volunteer blood donors\nwho have made donations at the National Blood Transfusion\nCenter. The techniques used were the traditional techniques\nof agglutination on slide or in tube (indirect antiglobulin).\nAlthough recent years have been marked by the appearance\nof microtechnology, we wanted to show that, even with\ntraditional techniques, such typing can be performed in a\ndepartment with limited resources. The findings in our study\nwill introduce plan for better care of the patients.\n",
"4.1. The Rh System. After ABO blood group, the Rh system is\nthe most important in transfusion medicine. In Cote d'Ivoire,\nthe blood transfusions are done only regarding ABO and\nRhD antigens exposing patients to high alloimmunization.\nAkre [4] found that 62.8% of patients suffering from sickle\ncell disease and transfused were immunized against Rh and\nKell antigens systems. Rh was involved in 44.44% while\nKell was involved in 27.78% in sickle cell patients transfused\nagainst 38% for both in France [12]. The most frequent\nalloantibodies were anti-E, anti-C, and anti-KELI developed\nafter transfusion of standard red cell units.\n",
"In our study, the frequency of D antigen was 92.93%. This\nis comparable with the findings in the north of Cote d'Ivoire\n[3] and in the black population (13). It is higher in other\nsub-Saharan Africa countries [1, 2, 5] and non-sub-Saharan\nAfrica countries [7-10] (Table 3). Frequencies are lower in the\nUS, France, and Nigeria where the authors found respective\nprevalence of 85.4%, 85%, and 81.5% [6, 11, 12].\n",
"The prevalence of the RhD negative is 7.7%. These results\nagree with the work of Seka (14] who found 7.28% and the\nwork of Cabannes (15, 16] that quoted values ranging from\n1.70 to 9.3% in sub-Saharan Africa.\n",
"The frequencies of e and e antigens in our study are\nhigh (99, 85%) (Table 1) while the frequencies of C and E\nantigens are lower, respectively, 21.97% and 13.82%. Among\nwhites, European, and Asian people, e antigen is the most\npopular, and then comes Cantigen (17]. As regards to Cand E\nantigens, frequencies are higher than in our study (C70% and\nE 26%) (5, 9, 12, 171. Among RhD negative donors, E antigen\nis absent.\n"
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"TABLE I: Rh and Kell antigens frequency among 651 Ivorian blood donors.\n",
null,
"TABLE 2: Rh and Kell phenotypes frequencies in Cote d'Ivoire blood danors (n = 651).\n%3D\n",
null,
"TABLE 3: Antigens frequencies of Rh blood group compared with published results.\n",
null
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"In the Rh system, seven phenotypes on eighteen known\n[13] were identified in our population (Table 2). The phe-\nnotype most frequently encountered is the phenotype Rar\n(65.12%) regarding RhD positive blood donors and rr 80.43%\namong RhD negative blood donors. This profile is different\nfrom that observed in the whites where the phenotype R,r\nor R,R, is the most popular [12, 13]. R,R, was found in one\ndonor.\n",
"4.2. The Kell System. The importance of this system is due to\nthe K antigen, which has strong immunogenicity. It is among\nthe most immunogenic system after the Rh system.\n",
"In the Kell system, k antigen was found in 98.92% of blood\ndonors which is comparable with frequency in whites.\n",
"The prevalence of K antigen was found to be 0.92% of\ndonors enrolled in the study, contrary to France where 9%\nof individuals are K+ (12] and to Germany where 4% express\nthe K antigen (18].\n",
"The most common phenotype was K-k+ which is also\ncommon in white people. The antigens Kp' and Kp were\nfound, respectively, at frequencies of 0.61% and 82.80% in our\nsample, against 0.2% and 99.8% in whites (17].\n",
"5. Conclusion\n",
"Immunohematology data on blood donors are very few\nin West Africa. The ABO and D antigens are the main\nexamination; other investigations are not performed.\n",
"Furthermore, Africa is full of its own specificities that are\nimportant to note for better care of patients by improving\nroutine tests like phenotyping red cells, screening, and\nidentifying red cells antibodies.\n",
"Research in that field should benefit from common\nwork from West Africa national blood transfusion centers to\nenhance safety in transfusion medicine.\n",
"Conflict of Interests\n",
"The authors declare that there is no conflict of interests\nregarding the publication of this paper.\n",
"References\n",
"[] C. T. Hamed. M. A. Bollahi, L Abdelhamid et al. \"Frequencies\nand ethnic distribution of Rh(D) blond group in Mauritania,\"\nInternational lournal of Immunogenetics, vol. 39, pp. 151-154,\n2012.\n(2) S. H. Mandengue, G. Lehman Leopold, P. Assomo-Ndemba,\nand M. Mbangue, \"Distribution des antigènes des systèmes\nABO, thésus, Kell, MNSS et Duffy chez des drepanocytaires et\ndonneurs de sang bénévoles à Douala (Cameroun): risques de\nréactions transfusionnelles,\" Médecine d'Afrigue Noire, vol. 50,\nno 1. pp. 22-24, 2003.\n[3] A. Santovito, C. Burgarello, P. Cervella et al. \"Erythrocyte\npolymorphisms in fiveethnic groups of Northern Cote d'Ivoire\"\nInternational Journal of Immanogenetics, vol. 36, na. 3, pp. 189-\n191, 2009.\n",
"nisation anti érythrocytaire post transfusionnelle chez les\ndrépanocytaires au CHU de Cacody Abidjan,\" International\nJournal of Pharma and Bio Sciences, vol. 9, no. 2. pp. 64-70, 2008.\n[5] A. Loua, M. R. Lamah, N. Y. Haba, and M. Camara, \"Frequency\nof blood groups AB0 and rhesus D in the Guinean population.\"\nTransfusion Clinique et Biologique, vol. 14, no. 5, pp. 435-439,\n2007\n|6] A. G. Falusi, O. G. Ademowo, C. A. Latunji et al., \"Distribution\nof ABO and RH genes in Nigeria,\" African Journal of Medicine\nand Medical Schences, vol. 29, no. 1, pp. 23-26, 2000.\n(7] Z A. Randriamanantany, D. H. Rajaonatahina, E E Razafi\nmanantsoa et al, \"Phenotypic and allelic profile of ABO\nand Rhésus D blood graup system among blood danor in\nAntananarivo,\" International Journal of Immunogenetics, vol. 39,\nno. 6, pp. 477-479, 2012.\n[8] A. Benahadi. R. Alami, and S. Boulahdid, \"La distribution\ndes antigènes de groupe sanguins ABO et Rhésus au Maroc,\"\nTransfusion Clinique et Biologigu, vol. 20, no. 3, p. 313, 2013.\n[9) N. Agarwal, R. M. Thapliyal, and K. Chatterjee, \"Blood group\nphenotype frequencies in blood donors from a tertiary care\nbospital in north India, Blood Research, vol. 48, no. 1. pp. 51-\n54, 2013.\n[10] M. R. Keramati, H. Shakibaci, M. L. Kheiyyami et al., \"Blood\ngroup antigens frequencies in the northeast of Iran,\" Transfusion\nand Apheresis Science, vol, 45, no. 2. pp. 133–136, 2011.\n[11] G. Garratty, S. A. Glynn, and R. McEntire, \"ABO and Rh(D)\nphenotype frequencies of different racial/ethnic groups in the\nUnited States,\" Transfusion, vol. 44, no. 5. pp. 703-706, 2004.\n[12] I. Mendel, Bases Immunologiques de la transfusion sanguine,\nhttp://efs-alsace.fr/.\n[13] G.Daniels, Hauman Blood Group, John Willey & Sons, Hoboken.\nNI. USA, Znd edition, 2002.\n14] S. S. Joseph, Contribution à l'étude des groupes sanguins\nérythrocytaires en Cote d'Ivoire. Inventaire et repartition selon les\nethnies (Thése médecinej. Facuhé de Médecine, Abidjan, Cote\ndIvoire, 1985.\n15) R. Cabannes, \"Hématologie des ethnies de Côte d'Ivoire. Son\napport à la connaissance des populations de ce pays\" Médecine\nd'Afrique Noire, vol. 28, pp. 65-72, 1981.\n[16] R.Cabannes, A. Senarail. F. Pene, A. Sangare, F. Sombo Mambo.\nand P. Kple Faget, \"Etude hémotypologique des populations\nde l'afrique de l'Ouest. Référence particulière aux populations\nivairiennes et aux Peulh de l'afrique de lOuest,\" Annales de\nl'Universitë d'Abidjan. Série B, Médecine, vol. 13, pp. 11-16, 1979.\n[17] M. A. Kahar and R. D. Patel, \"Phenotype frequencies of blood\ngroup systems (Rh, Kell, Kidd, Duffy, MNS, P, Lewis, and\nLutheran) in blood donors of south Gujarat, India,\" Asian\nJournal of Transfusion Science, vol. 8, no. 1, pp. 51-55, 2014.\n[18] F. E Wagner, D. Kasulke, M. Kerowgan, and W. A. Flegel,\n\"Frequencies of the blood groups ABO, Rhesus, D category VI,\nKell, and of clinical relevant high-frequency antigens in South-\nWestern Germany\" Infusionstherapie und Transfusionsmedizin,\nvol. 22, no. 5, pp. 285-290, 1995,\n"
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"Open Access\n",
"Evaluating the enhancement\nand improvement of China's technology\nand financial services platform innovation\nstrategy\n",
"Ching-Sung Wu', Kuang-Hua Hu\" and Fu-Hsiang Chen\n",
"Keywords: Innovation, Technology and finance, Investment and finance, Credit rating,\nCredit guarantee, Multiple attribute decision making (MADM)\n",
"Abstract\n",
"The development of high-tech industry has been prosperous around the world in past\ndecades, while technology and finance have already become the most significant\nissues in the information era. While high-tech firms are a major force behind a country's\neconomic development, it requires a lot of money for the development process, as\nwell as the financing difficulties for its potential problems, thus, how to evaluate and\nestablish appropriate technology and financial services platforms innovation strategy\nhas become one of the most critical and difficult issues. Moreover, how the chosen\nintertwined financial environment can be optimized in order that high-tech firms\nfinancing problems can be decided has seldom been addressed Thus, this research\naims to establish a technology and financial services platform innovation strategy\nimprovement model, as based on the hybrid MADM model, which addresses the main\ncausal factors and amended priorities in order to strengthen ongoing planning. A\nDEMATEL technique, as based on Analytic Network Process, as well as modified VIKOR,\nwill be proposed for selecting and re-configuring the aspired technology and financial\nservices platform. An empirical study, as based on China's technology and financial\nservices platform innovation strategy, will be provided for verifying the effectiveness\nof this proposed methodology. Based on expert interviews, technology and financial\nservices platforms innovation strategy improvement should be made in the following\norder: credit guarantee platform (C)_credit rating platform (B)_investment and finance\nplatform (A).\n",
"khh0622gmailcom\nAccounting School\nNanfang Colege of Sun\nYat-sen Universty\nWenquan Town, Conghua\nGuangzhou 510970.China\nFull Iist of author information\nis available at the end of the\narticle\n",
"Background\n",
"Since the implementation of open policy following its reform in 1978, China's remark-\nable economic achievement has attracted world attention, and has continued to develop\nrapidly. In 2010, China became the world's second largest economy. However, though\nthe envy of the world, China's speed of economic development and wealth accumula-\ntion have also exacted a heavy price. Its economic development is locked in a high\nenergy consumption and low efficiency mode, and its persistent low status in the global\n",
"o The Authorsl 2016 This article is dntritted under the terms of the Creative Commons Attrbution 40 International License\nhp//creatvesommarorglicenetyieo, whch permits untesticted use, detribubon, and reproduction in any medium\nvided you give apprapriate credit to the original ashorisộ and the saurce, provide e krik to the Creative Commons liceme and\nndicate fchanges were made\n"
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"industrial chain, excessive resource consumption and severe environmental pollution\nhave become intolerable (Yan and Huang 2013).\n",
"In the mean time, the world's major developed countries have increased their invest-\nment in technological innovation, focused on basic research, and actively developed\nnew energy, new materials, environmental protection and other emerging industries,\nand have seized the pinnacle of international economy and technology. Evidently, tech-\nnological innovation is critical in global competition (Wang and Xu 2012). Therefore\neconomic development must transform and adjust its mode by promoting technologi-\ncal innovation and entrepreneurship to enhance the international competitiveness of\nenterprises and industries. Technological systems and management must be reformed\nand become innovative, and financial innovation must be introduced and encouraged.\nAs such, the integration of technology and finance is a key intervention point for uni-\nfying technology and economy (You and Zhu 2011). With accelerating technological\ninnovation in China, the role of technology and finance is becoming more prominent. In\nrecent years, the government of China has formulated pluralistic technology and finance\npolicies involving many departments such as the Ministry of Science, the People's Bank\nof China, the Ministry of Finance, the China Banking Regulatory Commission, and the\nSecurities Regulatory Commission to promote technological innovation, define the role\nof technology and finance development in providing financial services to technological\ninnovations, and resolve funding needs for transforming and industrializing technologi-\ncal innovations (Wang and Xu 2012).\n",
"Technology and finance is the in-depth integration of technology and financial innova-\ntion activities. It is an overall term for activities that promote technological innovation\nand the development of technological industry where in order to integrate technologi-\ncal innovation and financial capital, governments, financial institutions, investors and\nother financial resources providers offer various capital, innovative financial products,\nfinancial policy and financial service to enterprises or institutions that develop, trans-\nform outcomes and industrialize technology innovation (Xu et al. 2011). Establishing\nan intermediary service system for technology and finance is an important part of inte-\ngrating science and finance. The Chinese government has already established an ini-\ntial technology and financial service platform. For example, with \"surplus power\" as its\ncore, the Chengdu High-tech Zone has created an investment and finance platform for\nSmall and Medium Enterprises (SMES), and the Suzhou Industrial Park has established\nthe first national loan platform for technological SMES. In addition, areas such as the\nZhongguancun Science Park, Pudong New District, Wuxi High-tech Zone have also set\nup technology and finance service groups, technology venture capital groups and tech-\nnology and finance service centers. These platforms are becoming effective technology\nand financial service platforms for connecting technological and financial resources, and\nprovide highly effective and comprehensive investment and finance service for technol-\nogy industry by attracting all kinds of financial and intermediary institutions (Ma 2014).\n",
"Technology and financial service platforms mainly provide investment and finance\nservice, technology innovation guidance, and comprehensive and integrated finan-\ncial service (You and Zhu 2011). In terms of investment and finance, relevant Chinese\ngovernment departments (usually the technology sector, investment sector and finan-\ncial sector) explore the technical standards, profitability, and market prospects and\n"
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"potential of technological industries according to development policies for promoting\ntechnological innovation industries. Promising technology industries and technological\ninnovations are recommended to investment and financial institutions. Through these\ntechnology and financial service platforms, investment and financial institutions provide\nfinancial resources for innovation according to the needs of the technology companies,\nIn terms of technology innovation guidance, the Risk Investment Funds, SME Guaran-\ntee Agency and Petty Loan Institutions of technology and financial service platforms\ngive priority to high-tech new technology enterprises, and high technology growth\nenterprises are supported through \"equity\". \"loans\" and \"guarantee. In particular, policy\nhigh-tech industries are given funding during their \"start-up\" and \"development period\"\nto maximize the effect of financial capital on technological expansion (Perez 2002). In\nterms of providing comprehensive integrated finance services, technology and financial\nservice platforms converges the comprehensive and integrated financial services that\nbanks, securities, insurance and trust funds and other financial institutions provide for\nenterprises, which also enhances cooperation among the financial institutions and unify\ndevelopment.\n",
"The local Chinese governments exert their organizational coordination and supervi-\nsory capacity to establish regional technology and financial service platforms. Through\nthese platforms, new high-tech enterprises can quickly grasp the regulations and poli-\ncies of various government levels, submit their development needs and advantage, and\ncommunicate effectively with financial institutions to obtain financial resources for\nexpanding their operations. Financial institutions can quickly discern the credit infor-\nmation and financial needs of high-tech and new technology industries, and at the same\ntime integrate the results of external credit ratings to more effectively control credit risk\nand reduce credit cost, thereby generating technology innovation profit on the finan-\ncial capital (Perez 2002). Through technology and financial service platforms, the gov-\nernment can also learn more about the development needs of high technology and new\ntechnology enterprises, and further revise relevant government policies and regulations,\nsuch as standardizing guarantee markets and developing credit rating markets to pro-\nvide a better financial environment. In summary, China's regional technology and finan-\ncial service platforms innovation strategy can primarily be categorized into \"Investment\nand Financial Platform, Credit Rating Platform\" and \"Credit Guarantee Platform\" (Ma\n2014; Wang and Xu 2012; Xu et al. 2011; You and Zhu 2011).\n",
"While high-tech firms in developing countries play a significant role in job creation\nand national economic development, it is difficult to obtain financing for them (Xiong\net al. 2010; Huda 2012). In order to assist the growth of high-tech firms, the European\nUnion set up a special financing institution for high-tech firms, including the European\ninvestment bank and the European investment fund. The European investment bank\nprovided concessional loans for entrepreneurial firms or high-tech firms in the expan-\nsion phase; while the European investment fund was the first international high-tech\nfirms' credit guarantee institution, which afforded a guarantee to small businesses, with\nemployees not exceeding 50, in information and communications technology invest-\nment. The China Banking Regulatory Commission (CBRC 2015) also founded the China\nAssociation of Microfinance Companies on January 30, 2015, and one of its main works\nis to promote the exploration of techniques and product innovation related to high-tech\n"
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"firms loans, in order to lower the funding costs of high-tech SMES, improve loan quality\nand efficiency, and increase the innovative development of the microfinance industry.\n",
"Although the design of a comprehensive technology and financial services platform is\nvery important, it is not an easy task. Prior studies of technology and financial service\nplatforms primarily put greater focus on the construction and operation of technology\nand financial service platforms (You and Zhu 2011; Ma 2014); the synergy of technol-\nogy innovation and technology and finance (Wang and Xu 2012), and the coupling coor-\ndinated degree evaluation of regional sci-tech innovation and technology and finance\n(Xu et al. 2011). Fewer studies addressed how microfinance for high-tech enterprises\nshould be designed to fit any finance market, and how high-tech enterprises develop-\nment should be designed by considering factors related to lending channels and credit\nrisks. Reviewing the above technology and financial services platform studies shows that\nthe focus was on unilateral considerations, and while those factors did not exhaustively\nimprove the credit environment, they are based on the assumption of conventional sta-\ntistical techniques (Park and Ren 2001; Xiong et al. 2010; Abroud et al. 2013), with some\nrestrictions, such as linearity, normality, and independence. Given that such assump-\ntions are often inconsistent with the means for improving technology and financial\nservices platform factors, these methods have their intrinsic limitations in terms of effec-\ntiveness and validity. In fact, technology and financial services platform factors are not\nindependent, and among them there exists an influential interrelationship (dependence\nand feedback); meanwhile, Multiple Attribute Decision Making (MADM) approaches\ncan be applied to solve this problem (Lu et al. 2015) While this method has been widely\napplied in various fields, it was seldom used by financial industries, such Hu et al. (2015),\nShen et al. (2014) and Wu et al. (2010). Therefore, in order to improve the technology\nand financial services platform, this paper considered all related variables (called dimen-\nsions/criteria) of microloans and risk precaution, as based on Guangdong's development\nof technology and financial services as the empirical case.\n",
"Thus, this paper proposes a novel hybrid MADM framework for Guangdong's tech-\nnology and financial services platform, which combines the Decision Making Trial and\nEvaluation Laboratory (DEMATEL) technique to determine a total influence matrix of\ndimensions and criteria, and construct an influential network relationship map (INRM)\nto identify the influential levels of different dimensions/criteria. The concept of Analytic\nNetwork Process (ANP) and the total influence matrix of DEMATEL would be applied\nto derive the influencing weights of DANP (DEMATEL-based ANP). Then, the per-\nformance of dimensions and criteria will be evaluated using the modified VIKOR and\nDANP. After the influential factors/criteria are introduced, the aspired technology and\nfinancial services platform of Guangdong will be surveyed again to ensure improvement.\n",
"This novel hybrid MADM proposed for solving real-world technology and financial\nservices platform problems improves upon the previous methods in the following ways:\n(1) providing interdependency model according to DANP concepts to overcome prob-\nlems of dependence and feedback among technology and financial services platform\nfactors; (2) incorporating modified VIKOR approaches to prioritize improvements tech-\nnology and financial services platform factors according to the aspiration levels, allowing\nthe proposed method to avoid selecting the seemingly best solution from among inferior\nchoices, options or alternatives. Instead, all factors were replaced by aspiration levels\n"
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"obtained from modified VIKOR; (3) offering strategy improvement planning models that\ngive decision-makers multiple solutions for technology and financial services platform\nfactors improvement priorities. Hence, the novel hybrid MADM shifts the focus from\nsimple ranking and selection of the most preferable factors or alternatives to perfor-\nmance improvements and methods.\n",
"The remainder of this paper is organized, as follows, In section \"Literature review\", the\nassessed dimensions and criteria are introduced. In section \"Building a novel MADM\nmodel for technology and financial services platform improvement\", a MADM based\nanalytic framework and methods by introducing the DEMATEL technique and modi-\nfied VIKOR are proposed for constructing the technology and financial services plat-\nform. Section \"An empirical case: an improvement plan for Guangdong technology and\nfinancial services platform\" presents an empirical study of Guangdong's finance services\nselection of high-tech enterprises, and its aspired level of technology and financial ser-\nvices achievements will be provided. Section \"Conclusions and remarks\" offers conclu-\nsions with observations and remarks.\n",
"Literature review\n",
"The development of technology and finance is often associated with financial risk. High-\ntech enterprises belong to an unstable, immature, and fast changing industry, in com-\nparison with others. Whether it is the demands of technology financing or the supply\nside, intermediaries and governments are faced with different risks. For long-term stable\ndevelopment of technology and financial services, the demands of high-tech enterprise\ninvestment and financing, as well as the related issues of corporate credit risk, must be\nprudently considered. The investment and financial platform, credit rating platform,\nand credit guarantee platform, are all crucial components of technology and financial\nservices.\n",
"Investment and financial platform\n",
"In the start-up and expansion stages, high-tech enterprises require the support of\nhigh-tech loans and venture capital; therefore, high-tech microfinance institutions are\nan important pillar for the development of science and finance. Relative to large firms,\nstart-up stage high-tech businesses do not have an abundance of assets that can be eval-\nuated and pledged as collateral, and tend to have few transaction records, little credit\nhistory, or information transparency (Berger and Udell 1998). In view of this situation,\nmost high-tech enterprises received their external funding through private equity and\nthe debt market, rather than public markets (Berger and Udell 1998; Kaivanto and Stone-\nman 2007). While African microenterprise credit programs have increased in the last\ndecade, there appears to be little evidence of increased income or levels of employment,\nthus, it is undeniable that in some cases microcredit can stimulate enterprise growth and\nimprove performance (Buckley 1997). For high-tech enterprises and new public firms\nin developing countries, public equity finance is a useful and appropriate loan approach\n(Pretes 2002; Brown and Petersen 2010). Bose (2005) also argued a positive relation-\nship between equity finance and economic growth. Byström (2008) believed that credit\nderivatives (such as collateralized debt obligations) could extend the finance market to\nmicroenterprises/high-tech enterprises, and accelerate loans growth. Cumming (2007)\n"
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"proposed that the Australian governmental innovation investment funds foster the\ndevelopment of start-up and high-tech firms. Due to advances in information technol-\nogy and the development of financial markets, the high-tech enterprise financing net-\nwork is a trend based on professional personnel, which could provide finance related\ninformation, enhance the efficiency of financing, and promote the high-tech industry.\n",
"Credit rating platform\n",
"The databases of banks have accumulated large quantities of information regarding the\nfinances, payment records, and creditworthiness of cdients. Banks can conduct a credit\nrisk assessment, endow different credit terms for individuals, and conduct credit crisis\nprevention dependent on such databases (Oreski et al. 2012; Agier and Szafarz 2013;\nBartoli et al. 2013; Garcia et al. 2013). Huda (2012) indicated that the government should\nconstruct databases of high-tech firms in order to reduce asymmetric information,\nand act as an agency for banks in their financial distributions to high-tech firms that\nlack financing. Avery et al. (2004) showed that credit databases can be used to build a\nconsumer credit model, which should incorporate situational data (such as temporary\neconomic and personal shocks), in order to enhance the potential effectiveness of such\nmodels. Voordeckers and Steijvers (2006) used a database of SMES (high-tech firms\nare included in SMES) credit approval rates from a Belgian bank to show that stronger\ncreditor protection regarding business collateral and personal commitments would be\nconducive to the approval of credit and better loan terms (Berger and Udell 1995). Zhu\nand Zhang (2012) also pointed out that, data preprocessing of customer credit cards can\nimprove the prediction accuracy of risk detection.\n",
"A credit rating database offers assessments regarding borrowers' creditworthiness,\ninvestment risk, and default probability for financial institutions (Chen and Cheng\n2013). Akdemir and Karsli (2012) suggested that, while credit rating agencies play a\npraiseworthy role in Eurozone financial markets, if the reputation of an agency was sus-\npect, and did not provide correct ratings, it may elevate global financial market crisis.\nCredit rating agencies provide rating reviews that are influenced by the informational\ncontent of crediting ratings, which possibly extend their economic function in financial\nmarkets (Bannier and Hirsch 2010). Due to higher uncertainty and lower institutional\nquality in emerging markets, rating effects have stronger effects (Erbas 2005). A regula-\ntor could provide an incentive to deviate from credit rating agencies and offer inflated\nratings, thus, an approval scheme exists to lead to correct ratings (Stolper 2009). There\nexists a financial system with a perfect credit rating that microfinance institutions were\nmore than willing to expand the frontier of finance by providing loans to high-tech\nenterprises (Hartarska and Nadolnyak 2008). Property appraisal estimates from external\nor internal appraisers were different due to information asymmetry; however, external\nappraiser agencies are better able to provide a reasonable assessment of the fair value of\nassets (Muller and Riedl 2002).\n",
"Credit guarantee platform\n",
"While most countries seek to encourage high-tech firms' growth, essentially expansion\ncapital able to support substantive growth have less access to debt financing, as com-\npare with larger firms (Riding et al. 2001; Beck et al. 2005). However, Crowling (2010)\n"
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