Bilingualism is common in South Africa, with many children acquiring isiXhosa as a home language and learning English from a young age in nursery or crèche. IsiXhosa is a local language, part of the Bantu language family, widely spoken in the country.To describe changes in a bilingual child’s speech following intervention based on a theoretically motivated and tailored intervention plan.This study describes a female isiXhosa–English bilingual child, named Gcobisa (pseudonym)  with a speech sound disorder. Gcobisa’s speech was assessed and her difficulties categorised according to Dodd’s  diagnostGcobisa’s speech was categorised as a consistent phonological delay as she presented with gliding of/l/in both English and isiXhosa, cluster reduction in English and several other age appropriate phonological processes. She was provided with 16 sessions of intervention using a minimal pairs approach, targeting the phonological process of gliding of/l/, which was not considered age appropriate for Gcobisa in isiXhosa when compared to the small set of normative data regarding monolingual isiXhosa development. As a result, the targets and stimuli were in isiXhosa while the main language of instruction was English. This reflects the language mismatch often faced by speech language therapists in South Africa. Gcobisa showed evidence of generalising the target phoneme to English words.The data have theoretical implications regarding bilingual development of isiXhosa–English, as it highlights the ways bilingual development may differ from the monolingual development of this language pair. It adds to the small set of intervention studies investigating the changes in the speech of bilingual children following intervention. In addition, it contributes to the small amount of data gathered regarding typical bilingual acquisition of this language pair. As throughout the world, multilingualism is typical in South Africa owing to a culturally and linguistically diverse population, as well as the mobility of the population and the country’s historical and political background. Many people speak two or more languages in their day-to-day life  of isiXhosa–English bilingual speakers and provides some data regarding the English phonology of isiXhosa–English bilingual 3-year olds. Findings suggested that the isiXhosa bilingual children in their sample had the most complete consonant inventories in English when compared with monolingual English speakers, bilingual English–Afrikaans speakers and trilingual English–Afrikaans–isiXhosa speakers in the study. However, the isiXhosa–English children also had the lowest mean percentage of correct vowels. The researchers questioned the validity of this score, suggesting it may have been caused by typical vowel substitutions used by isiXhosa–English bilingual speakers, given the complexity of the English vowel system in comparison to the five vowels of isiXhosa. The study also determined that the phonological processes of cluster reduction and stopping were more prevalent in the English speech of the isiXhosa–English children than in the other groups, as well as the processes of backing and devoicing   (PPVT-4) in initial position, for example, in verbs that, when produced as a command, start with consonants such as ilanga (sun)and medial position, for example, after the prefix of nouns, such as in words and in phrases in isiXhosa.The language of instruction throughout all intervention sessions was English. This was because of a variety of reasons: Gcobisa showed evidence of understanding English to the same degree or more than isiXhosa; in addition, as a language mismatch is common between SLTs and clients in South Africa, this reflected the realities of most SLTs currently providing intervention in South Africa. However, the language of the intervention stimuli was considered further. Although the process of gliding was present in both English and isiXhosa, gliding was still considered to be an age-appropriate process for Gcobisa in English. As such, all targets chosen were in isiXhosa, as the process of gliding is not age appropriate for Gcobisa in isiXhosa.Gcobisa attended 16 sessions of intervention over 8 weeks, attending sessions lasting 30 min, twice a week. Intervention took place in a quiet room at her crèche. She received approximately 8 h of intervention. Each session was guided by a fidelity checklist to ensure sessions adhered to the intervention developed for Gcobisa’s speech sound disorder. Gcobisa was initially shy but soon began participating more in sessions.The following steps, based on those outlined by Baker , were fofamiliarise Gcobisa with the minimal pair pictures and wordstrain Gcobisa to perceive the difference between the minimal pairsimitation of target wordsproduction of minimal pairs, highlighting communication breakdown where appropriategeneralisation activities.Following intervention, Gcobisa’s speech was reassessed. Results are summarised in Following intervention, Gcobisa’s phonetic inventory was age-appropriate with the fricatives [θ] and [ð] present. Gcobisa still used many developmental phonological processes and a few non-developmental processes, but most of them were isolated occurrences, suggesting that she is in the process of eliminating many of these phonological processes. In the phonology subtest, Gcobisa’s PCC improved from 75% to 79%. Her use of gliding reduced from 13 to five instances and her overall inaccuracies from 34 to 24 instances. Gcobisa still made use of the two consistent phonological processes: gliding and cluster reduction. However, gliding of [l] only accounted for two of the five instances of gliding, the remaining three being instances of gliding [ɹ]. The process of gliding is still age-appropriate as it should be eliminated by the age of 5 years and 11 months  and provided some information regarding their English speech development ; mamela (listen); ewe (yes)]. This was a situation not well-documented in the literature, where the targets were in isiXhosa while the instructions and other interactions with the researcher took place in English. This may have had an impact on the generalisation from the treated isiXhosa to the untreated English.Many previous studies considering intervention for bilingual children provided intervention in only one of the multilingual child’s languages (Holm & Dodd, Holm et al. , Holm anThis case study considered the changes in the speech of a bilingual child following intervention. Intervention sessions were conducted predominantly in English, while targets and stimuli chosen were in isiXhosa. These unique conditions appear to have resulted in change to the phonology of both languages. The language mismatch between the researcher and the child mirrors the situation often experienced by South African SLTs, who are not always able to speak all of the languages spoken by their clients. Although providing intervention in both languages is considered ideal (Gildersleeve-Neumann & Goldstein,


Despite free TB services available in public health facilities, TB patients often face severe financial burden due to TB. WHO set a new global target that no TB-affected families experience catastrophic costs due to TB. To monitor the progress and strategize the optimal approach to achieve the target, there is a great need to assess baseline cost data, explore potential proxy indicators for catastrophic costs, and understand what intervention mitigates financial burden. In Cambodia, nationwide active case finding (ACF) targeting household and neighbourhood contacts was implemented alongside routine passive case finding (PCF). We analyzed household cost data from ACF and PCF to determine the financial benefit of ACF, update the baseline cost data, and explore whether any dissaving patterns can be a proxy for catastrophic costs in Cambodia.In this cross-sectional comparative study, structured interviews were carried out with 108 ACF patients and 100 PCF patients. Direct and indirect costs, costs before and during treatment, costs as percentage of annual household income and dissaving patterns were compared between the two groups.The median total costs were lower by 17% in ACF than in PCF . The median costs before treatment were significantly lower in ACF than in PCF . Indirect costs constituted the largest portion of total costs (72.3% in ACF and 61.5% in PCF). Total costs were equivalent to 11.3% and 18.6% of annual household income in ACF and PCF, respectively. ACF patients were less likely to dissave to afford TB-related expenses. Costs as percentage of annual household income were significantly associated with an occurrence of selling property .TB-affected households face severe financial hardship in Cambodia. ACF has the great potential to mitigate the costs incurred particularly before treatment. Social protection schemes that can replace lost income are critically needed to compensate for the most devastating costs in TB. An occurrence of selling household property can be a useful proxy for catastrophic cost in Cambodia. Tuberculosis (TB) is predominantly a disease of the poor . For theThe WHO End TB Strategy highlighted the need for accelerated progress toward universal access and social protection . The StrTo mitigate financial hardship of TB patients and overcome access barriers, various interventions have been implemented in many parts of the world , 4, 17. Cambodia is a low-income country and one of 22 countries with a high burden of TB . The CamTo date, there was only one study that surveyed TB-affected household costs in Cambodia . The surAgainst this background, we aim to examine whether or to what extent the Cambodia’s ACF among household and neighbourhood contacts reduces financial burden of TB-affected household by comparing costs due to TB between actively- and passively-detected patients. The study further aims to examine the association of catastrophic cost with different dissaving patterns using different thresholds as well as to provide a baseline indicator to monitor and evaluate the progress towards eliminating financial hardship due to TB in the context of Cambodia.The intervention was conducted in socio-economically disadvantaged and underserved areas with a relatively high burden of TB. In the selected health centres, community volunteers and health workers conducted house-to-house visits of all smear-positive TB patients who had been registered for treatment during the preceding two years. All of their household contacts regardless of TB symptoms and symptomatic neighbourhood contacts with cough, fever, weight loss, and/or night sweats of more than two weeks were invited to the prescheduled ACF session on a specific date in their nearest health centres. Neighbourhood contacts were included in screening efforts as they are likely exposed to infectious index cases through close community interaction that is typical in rural areas. Two weeks prior to ACF session dates, CENAT-ACF team visited intervention sites to train existing health facility staff and selected community volunteers on the project initiative including screening, diagnosis and care procedures. During the two-week preparation period, the trained staff conducted house-to-house visits for pre-screening and inviting eligible participants to ACF. On the day of ACF session, all participants were re-screened for TB symptoms and a history of contact at ACF sites by clinicians of the CENAT team to verify the eligibility of the participants. They then underwent chest X-ray (CXR) examinations. CXR films were developed immediately and evaluated by a radiologist of the team by classifying either normal or abnormal. Abnormal CXR findings were further classified as active TB, suspected TB, healed TB, or other abnormalities to facilitate clinical diagnosis. Individuals who had abnormal CXR findings and/or TB symptoms were asked to provide a sputum specimen for Xpert MTB/RIF testing. Those with MTB-positive results were reported as bacteriologically-confirmed TB. Diagnosis of bacteriologically-negative TB and extra-pulmonary TB was made onsite by the clinicians in the CENAT-ACF team based on all available evidence, in principle, on the same day of the ACF session. Treatment of the detected patients was managed by routine health services.This is a cross-sectional comparative study involving a questionnaire survey that explores costs associated with TB diagnosis and treatment among actively- and passively-detected TB patients. The intervention group consisted of patients diagnosed through ACF sessions organized at health centres. The control group was taken from patients who were diagnosed and registered in the same health centres within four months prior to the respective ACF sessions. All participants were new pulmonary TB patients with treatment outcome of either “completed” or “cured”. For the simplicity of interpretation of results, patients with unfavourable treatment outcomes and retreatment and extra-pulmonary patients were not included in the study.We employed a combination of purposive sampling  and systematic sampling (for patient selection). Of 30 operational districts (ODs) with intervention in 2012 and 2013, four ODs  were selected based on the implementation timing (ODs with ACF patients who had most recently completed treatment at the time of data collection) and geographical distribution . Within these ODs, we further targeted health centres with relatively high TB case notifications both in ACF and PCF to ensure the adequate number of eligible patients. Then we systematically approached the eligible participants in order from the top of the eligible subject list in each health centre. The difference in the sample size between ACF and PCF in each health centre was set at no more than five patients to avoid a biased representation of the two groups from each health centre. We used a prevalence of catastrophic costs as the outcome variable to guide sample size estimation with the formula described by Pocock [The interviews were conducted by three local research assistants either at the health centre or participants’ house in a private manner. The tool to estimate patients’ costs , a strucDemographic and clinical information were sourced from project database, TB registers, laboratory registers, and individual treatment card. The questionnaire included various questions on health-seeking behaviour, costs associated with TB diagnosis and treatment, and socio-economic information including household income and spending. We collected and calculated a wide range of cost data including direct medical cost, direct non-medical cost, indirect cost, reimbursement and coping costs. Direct medical cost included OOP expenses for facility administration/consultation, laboratory test, X-ray, drug, and hospitalization. Direct non-medical cost included OOP expenses for food, transportation, guardian and caregiver , accommodation, supplemental foods given to patients during treatment, and interest for borrowed money. Indirect cost included patient’s lost income, guardian/caregiver’s lost income and value lost due to sold property. We also collected insurance reimbursement. Many of these costs were, where appropriate, collected separately for two different time periods, “before treatment initiation” and “during 6-months treatment period”.To estimate direct costs before treatment, we obtained the data of actual OOP expenses for each different health-seeking visit related to the single episode of TB before treatment. To estimate direct costs during treatment, we obtained the data on the average costs per visit for the different items and they were multiplied by the number of visits to health facilities during treatment. Our questionnaire captured costs for three types of visits including daily DOT, picking-up drugs, and follow-up examinations. A visit with multiple purposes was counted as one visit.For all health-seeking visits of all participants before treatment, we obtained the total health-seeking time in minutes including time spent for travel, waiting, consultation and hospitalization. For patients who had any income before TB illness, the total health-seeking time per patient was then multiplied by their income per minute before TB illness to estimate lost income due to health-seeking, assuming that a patient worked for 8 hours per day for 5 days per week. For ACF patients, health-seeking time during ACF session was included in the total health-seeking time. For 69 participants (40 ACF and 29 PCF patients), only travel time was available and other components of their health-seeking time were extrapolated using the data from the rest of the samples by types of health facilities visited. For participants who reported sick leave before treatment, we estimated lost income due to sick leave using their income per day before TB illness multiplied by the duration of sick leave in days before treatment.Lost income during treatment was calculated for patients experiencing a change in the average weekly household income due to TB, using the reduced weekly income multiplied by patient’s actual treatment period in weeks. If patients who engaged in housework stopped their work due to TB and their labour force was replaced by someone else, we estimated cost of reduced household activity of patient using self-reported estimated value of the work per day multiplied by the duration of treatment.If the patient was accompanied by a guardian on health facility visits during treatment, their lost income was estimated using the reported income per day multiplied by the number of accompanied visits. If caregivers of the patient quitted their jobs to specifically take care of the patient, their lost income due to caregiving was estimated using the reported lost income per week multiplied by duration of caregiving during treatment. Lost income of guardians and caregivers were combined and reported together. Value lost due to sold property was not an actual selling price but defined as the difference between an actual selling price and self-estimated market value of a sold property that was also asked in the interview.To examine the changes in the proportion of catastrophic costs, costs as percentage of reported annual household income were calculated. The proportion of patients who spent total expenses ≥10%, ≥20%, ≥30% and ≥40% of annual household income were compared between ACF and PCF. The prevalence of dissaving was further explored by stratifying patients into four cost-income bands that were <10%, 10–20%, 20–30% and >30%.https://cran.r-project.org/). All cost data were obtained in local currency (Cambodian Riel) and then were converted into USD for analysis at the rate of 4000 Riel per dollar.For categorical data, distribution and frequency were presented, and a Pearson’s chi-square test was used to examine associations. For numerical data, we presented median, mean, inter-quartile range (IQR), standard deviation (SD) and range in tables. For most of the cost data that were skewed, the median was mainly reported in the text while the mean was also used when describing the proportion of sub-categorized costs among total costs as well as describing the cost data with an extremely skewed distribution where median and IQRs were all zero both in ACF and PCF. The Welch T-test was used for age comparison. A two-sample Wilcoxon rank-sum test was applied to examine the difference in various costs and costs as percentage of annual household income between ACF and PCF. A Fisher’s exact test was employed to assess the association between costs as percentage of annual household income and the prevalence of different dissaving patterns. Statistical significance is defined as p<0.05. All statistical analyses were performed using the statistical software package R 3.2.1 , more children with ≤14 years of age (2.8% vs 0%), and more elderly with ≥65 years of age (30.6% vs 23.0%) although these are not statistically significant differences. Median age was slightly higher in ACF than in PCF . The proportion of participants who were jobless or were only doing housework was higher in ACF than in PCF (41.7% vs 28.0%). Distance from home to nearest health centre was significantly longer in ACF than in PCF . The ACF group had more clinically-diagnosed patients compared to the PCF group .The total cost incurred during an episode of TB showed a considerable variation in both groups, ranging from $6.5 to $1649 in ACF and from $10.8 to $4251 in PCF. The median total costs were lower by 17% in ACF than in PCF  . CompareBefore treatment, drug cost accounted for around 80% of the direct medical costs in both groups; the ACF group reported the significantly higher median cost on drug . The medians of administrative cost, test cost, X-ray cost and hospitalization cost were zero in both groups and could be considered minor expenses. Yet the highest points of the range in administrative and hospitalization costs exceeded $100 in PCF. During treatment, hospitalization costs were incurred in only two patients in PCF and none in ACF, and no other costs were incurred under direct medical costs in both groups.Before treatment, the ACF group reported significantly lower median costs for transportation  and guardian . During treatment, the highest median cost was reported for supplemental food costs in both groups, with a significantly lower cost in ACF . The frequently-bought supplemental foods included fruits, drinks, fish, and dessert in both groups. The medians and IQRs for transportation costs for DOT were zero in both ACF and PCF (p = 0.192), while those for picking-up drugs at health centres were $15 (IQR 0–26.2) in ACF and $12 (IQR 0–30) in PCF (p = 0.747), being substantial expenses under direct non-medical costs during treatment.No insurance reimbursement was reported in the ACF group before and during treatment while 6 PCF patients (6%) before treatment and one PCF patient (1%) during treatment received a reimbursement or subsidy for their OOP expenses  mainly through a donor-funded programme. 12 ACF patients (11.1%) and 17 PCF patients (17.0%) were registered in the non-insurance Cambodian Health Equity Funds (HEFs) and Subsidy Scheme that provides poor people with transportation and food costs associated with their health-seeking to public health facilities in addition to granting a user fee waiver at government health facilities . Of 29 pIndirect costs accounted for 72.3% of total costs in ACF and 61.5% in PCF. In both groups, indirect costs during treatment made up larger proportions than indirect costs before treatment . Before treatment, the ACF group incurred, on average, lower income loss due to health-seeking ($1.6 vs $20.6) and lower income loss due to sick leave ($17 and $38.5), compared to PCF. In particular, lost income due to health-seeking was not a main cost contributor in ACF as it accounted for 5% of total costs before treatment whereas it was 17.7% in PCF.During treatment, lost income of patients  and reduced household activity of patients  represented substantial expenses, which are followed by lost income of guardian/caregivers . There was only one PCF patient that was affected by the value lost due to sold property ($325 lost by selling livestock property).In both groups, the highest mean costs incurred before treatment were lost income due to sick leave and drug cost; these costs accounted for more than 60% of costs before treatment. Likewise, in both group, the highest mean costs incurred during treatment were supplemental food cost, lost income of patients, and reduced household activity of patients; these represented around 80% of costs during treatment.Most of the mean costs were found to be lower in ACF than in PCF, however reduced household activity of patients was more than doubled in ACF than in PCF. Many of the median costs and IQRs were zero, showing that these mean costs were mainly driven by some of the patients spending extremely high costs.Costs as percentage of reported annual household income were consistently lower in ACF than in PCF . The totThe proportion of patients who spent >10% of annual household income on total costs was lower in ACF than in PCF  . The samThe prevalence of dissaving to finance TB-related expenses was found to be low in ACF than in PCF . The larThe prevalence of dissaving was investigated by stratifying patients into four categories according to costs as percentage of annual household income of <10%, 10–20%, 20–30% and >30% . Cost asMedian costs as percentage of annual household income were consistently higher in the group with dissaving as compared to the group without dissaving . They weOur study results quantitatively demonstrated lower household costs incurred in ACF patients as compared to PCF patients. In particular, costs before treatment were significantly lower in ACF than in PCF. Similarly, costs as percentage of household income were consistently lower in ACF with significant differences found in direct costs and costs before treatment. Indirect costs constituted the largest portion of total cost. ACF patients were less likely to dissave to afford TB-related costs. Only a limited number of patients received insurance reimbursement.Why ACF patients incurred lower costs? First, in the Cambodia’s ACF strategy, CENAT actively offered a one-stop shop TB screening service which does not require further repeated visits for patients. Such proactive and tailored approach might reduce diagnostic delays and avoid unnecessary OOP expenditures. For example, in Russia, actively detected patients had the first interaction with a medical health provider one week earlier than passively detected patients , showingSecond, introduction of a rapid sensitive test in ACF, namely Xpert MTB/RIF, in combination with mobile chest X-ray and an onsite clinical assessment greatly increased the diagnostic capacity to detect patients at the early stage of the disease. These patients may typically be asymptomatic or have milder and more chronic symptoms. They therefore might incur lower direct costs due to less-frequent health-seeking visits as well as lower indirect costs due to less sick-leave. In this study, ACF patients were more likely to be bacteriologically-negative  TB, which could partly explain a less severe disease presentation in ACF patients. This has some similarity with the results from our previous study that Cambodia’s ACF detected more patients with lower smear grade and smear-negative TB . Lower cA concern may be raised about the high proportion of clinically-diagnosed patients in ACF. In Cambodia, the national TB prevalence surveys (conducted in 2002 and 2012) revealed that smear-negative and/or asymptomatic patients were significantly under-diagnosed in the routine case finding . This coThird, demographic differences between ACF and PCF patients could have resulted in the cost difference. In this study, the ACF group had more female, more children and elderly, and more patients who were house-worker/jobless. Most of them have less or no regular income and more household work, as compared to an economically active population. This most likely caused lower income loss as well as higher cost of reduced household activity in ACF, which could consequently lowered the overall indirect costs in ACF.The above factors could collectively explain lower costs incurred in ACF. It is often anticipated that ACF detects patients earlier in terms of time therefore reduces only costs before treatment. However, less severity of the disease in ACF may bring prolonged financial benefits for ACF patients over the course of treatment and possibly after treatment completion. Such benefits were more evident in direct costs than in indirect costs perhaps due to the difference in the nature of the two costs that OOP direct expenditure is more responsive to severe patient’s conditions while indirect costs can be triggered even by mild conditions.In this study, the proportion of patients facing total costs corresponding to >10% of annual household income was 63% in PCF. This was similar to the percentage reported in other countries; 65% in Peru , 66–75% Can dissaving be a proxy for catastrophic costs? Madan et al found a significant positive association between the occurrence of dissaving and total costs incurred, and highlighted the potential of using dissaving as a proxy for catastrophic costs . In our In this study, the proportions of TB-affected household experiencing “Sale” were 13.9% in ACF, 21% in PCF and 17.3% for both groups. Previous studies from other countries reported a wide range of proportions; 37% in Ghana , 19% in This study has several limitations. First, patient recall bias may be present as we selected all PCF patients who were registered before the ACF session date in each health centre. We tried to minimize the bias by limiting the sampling timeframe to “within four months prior to ACF”, however PCF patients might have more difficulty to recall the details of their expenses and care seeking as compared to ACF patients, which might have influenced the results. Second, we did not sample patients with unfavourable treatment outcomes, drug-resistant TB and/or human immunodeficiency virus infection. Given that they are more likely to experience catastrophic costs due to TB , 15, theOur study provided an important policy implication. In this study, only a small number of patients in PCF received reimbursement that covered a part of direct costs. This clearly illustrated the current situation of health financing mechanisms in Cambodia that costs incurred due to TB are predominantly derived from OOP spending by individual care seekers. In our study setting, the HEFs scheme has been playing a certain role in removing financial barriers at the point of care for the poor. However this pro-poor financial protection mechanism has been under-utilized for many eligible patients who seek care in private facilities. Continued efforts are required for increasing the quality and credibility of government health services to maximize its utilization, as well as for expanding sustainable public-private mix approach in TB control, which helps avoid unnecessary OOP spending. In this study, the HEFs scheme was not used for reimbursement of non-medical costs. This could be attributable to the difference in benefit packages or its criteria across different ODs, which needs verification in the field. Given that inadequacies of the HEFs scheme have been pointed out also in the context of non-communicable diseases , 45, widIn this manner, strengthening traditional approaches to improve the diagnostic pathway and pursuing the best use of existing schemes are indispensable to minimize OOP spending. However, as is found in other countries , the larAt the same time, programmatic efforts are also required to tailor and package pro-poor and proactive case finding intervention strategies in order to detect vulnerable patients as early as possible before considerable costs occur. The Cambodia’s ACF strategy could be the first evidence-based ACF that can help mitigate both direct and indirect costs.Our study quantitatively demonstrated the financial hardship of TB-affected household in the routine PCF setting in Cambodia and highlighted the great potential of ACF in mitigating the costs incurred particularly before treatment. Future health policy dialogue should consider how best to design and expand the social protection scheme that can replace lost income for TB-affected households. This will compensate for the most devastating costs in TB, help achieve better health outcomes, and eventually prevent further impoverishment in rural poor communities. Measuring their financial risk using an appropriate and practical indicator is the key for future planning and implementation of the WHO End TB Strategy. An occurrence of selling household property to finance TB-related expenses can be a useful proxy for catastrophic cost in Cambodia.S1 File(PDF)Click here for additional data file.S2 File(PDF)Click here for additional data file.


Self-harm is an extremely common reason for hospital presentation. However, few estimates have been made of the hospital costs of assessing and treating self-harm. Such information is essential for planning services and to help strengthen the case for investment in actions to reduce the frequency and effects of self-harm. In this study, we aimed to calculate the costs of hospital medical care associated with a self-harm episode and the costs of psychosocial assessment, together with identification of the key drivers of these costs.In a retrospective analysis, we estimated hospital resource use and care costs for all presentations for self-harm to the John Radcliffe Hospital , between April 1, 2013, and March 31, 2014. Episode-related data were provided by the Oxford Monitoring System for Self-harm and we linked these with financial hospital records to quantify costs. We assessed time and resources allocated to psychosocial assessments through discussion with clinical and managerial staff. We then used generalised linear models to investigate the associations between hospital costs and methods of self-harm.Between April 1, 2013, and March 31, 2014, 1647 self-harm presentations by 1153 patients were recorded. Of these, 1623 (99%) presentations by 1140 patients could be linked with hospital finance records. 179 (16%) patients were younger than 18 years. 1150 (70%) presentations were for self-poisoning alone, 367 (22%) for self-injury alone, and 130 (8%) for a combination of methods. Psychosocial assessments were made in 75% (1234) of all episodes. The overall mean hospital cost per episode of self-harm was £809. Costs differed significantly between different types of self-harm: self-injury alone £753 (SD 2061), self-poisoning alone £806 (SD 1568), self-poisoning and self-injury £987 . Costs were mainly associated with the type of health-care service contact such as inpatient stay, intensive care, and psychosocial assessment. Mean costs of psychosocial assessments were £228 for adults and £392 for individuals younger than 18 years.If our findings are extrapolated to England, the estimated overall annual cost of general hospital management of self-harm is £162 million per year. More use of psychosocial assessment and other preventive measures, especially for young people and against self-poisoning, could potentially lower future costs at a time of major cost pressures in the NHS.National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research, Care Oxford at Oxford Health NHS Foundation Trust, and Department of Health. Self-harm is a major public health challenge in many countries worldwide. In a 2016 reportOnly a small number of studies in England have attempted to cost self-harm events and most of these have focused on the costs of self-poisoning aloneEvidence before this studyWe searched PubMed, PsycINFO, CINAHL, and EconLit for articles published in any language between Jan 1, 1988, and Jan 31, 2017, that provide evidence for the immediate costs to health-care systems of intentional self-harm, as well as the costs of psychosocial assessment. The terms “suicide” and “self-harm” were combined with “costs” and “economic evaluation” in the search process, resulting in 5354 hits and 131 articles examining cost. UK studies focused mainly on costs of self-poisoning with little focus on the costs of self-injury, similar to studies done in Belgium, Ireland, Spain, and the USA. Detailed immediate health-care costs for all methods of self-harm are rare; examples include evaluation in England  and Switzerland. Furthermore, limited information exists about the costs of initial psychosocial assessment in these studies. In England, NICE previously relied on NHS Reference Costs for psychiatric consultations as an indicator of the costs of psychosocial assessments after self-harm.Added value of this studyTo our knowledge, this is the most detailed analysis of the immediate general hospital costs of self-harm in an English hospital to date, taking account and estimating the costs of psychosocial assessment and providing different estimates of cost for different types of self-harm. Our findings show that the mean hospital cost per episode of self-harm was £809. Treatment of combined self-poisoning and self-injury is the most complex. Hospital management of children and adolescents who self-harm is more costly than that for adults. Psychosocial assessment costs a mean of £254; £392 per assessment for patients younger than 18 years and £228 for assessments for adults.Implications of all available evidenceExtrapolating our findings to the whole of England would mean that the overall costs for self-harm management  in general hospitals are substantial. Using our costings, if psychosocial assessment were done for every self-harm presentation, as suggested in NICE guidelines, this would cost around £51 million per year. The study provides fundamental information that can be used to inform economic modelling analyses to better assess the potential costs and benefits of policies to address self-harm.Robust evidence about these costs is necessary to plan service provision and assess the effect of interventions targeting self-harm. Such an intervention is the psychosocial assessment to help determine subsequent care for patients who have self-harmed.We did a year-long retrospective longitudinal study to estimate the hospital care costs associated with self-harm in a single major general hospital, the John Radcliffe Hospital . All patients attending the hospital after self-harm between April 1, 2013, and March 31, 2014, were identified through the Oxford Monitoring System (OMS) for Self-harm. Self-harm is defined as intentional self-poisoning or self-injury, irrespective of the degree of suicidal intention or other types of motives.The Oxford Monitoring System for Self-harm has ethical approval from the NHS Health Research Authority . The OMS also has approval from the Health Research Authority Confidentiality Advisory Group under Section 251 of the NHS Act 2006 to collect non-anonymised patient details without patient consent.We obtained costs for 1623 self-harm presentations by 1140 patients . These costs included emergency department attendances, treatments received in the emergency department and hospital wards, and hospital ward and critical care unit stays. The perspective of this study is that of the hospital provider: the costs represent financial costs to the hospital rather than reimbursement values or the average costs to the NHS.Psychosocial assessment by trained mental health professionals is recommended in the NICE guidelines for self-harm and includes the assessment of patients' needs and risks with the aim of determining appropriate aftercare.We estimated the costs of time spent by different health-care professionals in developing, delivering, and managing psychosocial assessments for patients who self-harmed during the financial year 2013–14. The costs of the OUH liaison psychiatry service, for which it was not possible to separate psychosocial assessment costs from general hospital costs, were already included in the general hospital costs. In addition to those who delivered the assessment , these assessment costs included psychiatrists' time as well as supervision and administrative support provided by administration officers. We used information from a finance manager in the Oxford Health NHS Foundation Trust, as well as extensive discussions with clinical staff, to determine the proportion of full time equivalents (FTE) devoted by each of these professionals to psychosocial assessments.We valued time using gross mid-band salary rates . We inflated salary costs by a factor of 20% to account for overhead costs, such as for accommodation, equipment, utility bills, and cleaning. This factor is usually used by financial administrators in NHS for overhead costs. We separately calculated the cost of psychosocial assessment for patients younger than 18 years and for those 18 years and older. We did this by proportionally allocating the FTEs of each clinician relative to the number of assessments that they delivered to each age group. We then calculated the costs per assessment by dividing total costs by the number of assessments delivered in 2013–14 for the two age groups separately. The costs of psychosocial assessments were added to all other hospital medical costs to determine total hospital costs.We report descriptive statistics  about the study population, methods of self-harm, related services, and costs. Non-parametric tests were used to test differences in costs between two (Mann-Whitney test) or more  independent samples. The approach we used to prepare and do the regression analysis included the specification of model structure and improvement of model fit to the data.To specify the structure of the model , we designed an association pathway between self-harm and costs of self-harm on the basis of available data.We used generalised linear models using gamma distribution in the analysis to deal with potentially highly skewed costs resulting from many low cost episodes and a few episodes with extremely high costs. The link function of the generalised linear models was chosen based on the Akaike information criterion (AIC), the Bayesian information criterion (BIC), and the log-likelihood of the Pregibon link-test. The full regression models  were reduced based on Likelihood-Ratio tests to specify the structure of the model that best fitted the data. Given the low proportion of individuals with more than one repeated self-harm episode, our main analysis concerned a non-hierarchical model structure with standard errors allowing for intragroup correlation. For sensitivity analysis, we reproduced the best fitting generalised linear models using a two-level approach . Details on model specification are provided in the The funder of the study reviewed the study proposal, awarded funding, and monitored the conduct of the study. The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.Between April 1, 2013, and March 31, 2014, 1647 self-harm presentations by 1153 patients were recorded. Of these, 1623 (99%) presentations by 1140 patients could be linked with hospital finance records. 179 (16%) of 1153 patients were younger than 18 years and 69 (6%) were older than 60 years . Most weOf 1647 episodes of self-harm, self-poisoning alone was the most frequently used method (1150 [70%]), followed by self-injury alone (367 [22%]) and combined self-poisoning and self-injury (130 [8%]) . Self-cuPsychosocial assessment was estimated to cost an average of £254 for all patients, including £392 per assessment for patients younger than 18 years and £228 for adults . Mean hoThe generalised linear models with γ distribution and identity link function had the best fit to the data for each of the three regression models , and self-injury and self-poisoning combined .Although for patients admitted to a hospital bed, self-poisoning was associated with a shorter inpatient stay than self-injury, we have shown that the treatment of patients who self-poisoned was more complex and more costly per hospital day than the treatment of patients who self-injured. However, we found no significant differences in costs within the specific types of self-injury methods and self-poisoning methods.We also estimated the mean cost of psychosocial assessment to be £254 but found a difference of £164 between psychosocial assessment for patients younger than 18 years (£392) and the mean cost for adults (£228). This reflects the fact that children and adolescents often have complex needs that require more time for assessment compared with adult patients. This is likely to be determined by greater need to interview other informants, especially parents, and to address safeguarding issues. Furthermore, the incidence of self-harm in people younger than 18 years is particularly high.This study is to our knowledge the most detailed analysis of the immediate general hospital costs of self-harm in England to date, taking account of the use of psychosocial assessment and providing different estimates of cost for different types of self-harm. Previous analysesOutside of the UK, few detailed studies on the costs of all-causes of self-harm are available. In Switzerland, the 1-year costs of all self-harm events at two hospitals in Basel in 2003vs £356) and £2 lower for adults (£228 vs £226) than the costs provided by NICE after inflating to 2013–14 values using the Inflation Hospital Community Health Services Index.To our knowledge, our calculation of the psychosocial assessment costs is the first detailed estimate of assessment costs in England. NICE guidelines on self-harm management included a cost calculation of psychosocial assessment based on reference costs (2009–10) of first time face-to-face consultations with mental health consultants in a community setting.Although the rate of self-harm in Oxford is somewhat lower than in some other centres,Psychosocial assessment, followed by appropriate treatment and care, potentially provides a way of reducing the risk of future self-harmOur estimate of the costs of hospital management of self-harm provides fundamental information for future economic modelling analyses to evaluate the potential costs and benefits of policies for self-harm. These include psychosocial assessment, aftercare interventions, and prevention initiatives. Evidence from such analyses could support policy makers in trying to achieve reduction in suicide.The strengths of this study include use of a large dataset of good data quality, the advanced regression modelling approach, and the precision of the reported costs of psychosocial assessment. The limitations of this study include the lack of a breakdown by mental health conditions, the single hospital setting and the limitation of its scope to the hospital costs after self-harm. Future research might explore the medical costs throughout the care pathways by including ambulance costs, costs borne by the patient and their families, and after-care costs in several settings across England. It will also be important to use follow-up data for patients with self-harm to explore their subsequent use of health and social care services, as well as broader outcomes such as the effect on their quality of life.Hospital management of self-harm involves substantial costs. According to our findings the mean cost is £809 per self-harm episode, including the costs of psychosocial assessment. Given the size of the problem of self-harm nationally in England this translates into approximately £162 million per year from the NHS budget to treat people with self-harm presentations to general hospitals. This highlights the need for effective methods of preventing of self-harm and reducing the extent to which it is repeated.


Toscana and sandfly fever Sicilian viruses , both transmitted by sand flies, are prominent human pathogens in the Old World. Of 1,086 serum samples collected from cattle and sheep during 2013 in various regions of Kosovo , 4.7% and 53.4% had neutralizing antibodies against TOSV and SFSV, respectively. Bunyaviridae, genus Phlebovirus) are negative-sense tri-segmented RNA viruses for which mosquitoes, ticks, and sand flies are vectors. In the Old World, phleboviruses transmitted by sand flies (phlebotomines) are expanding in the Mediterranean basin, where an increasing number of new viruses have been identified  and Salehabad virus . The third group comprises 2 viruses classified as tentative species: Sandfly fever Sicilian virus (SFSV) and Corfou virus  were recorded. Ten milliliters of blood was taken from jugular venipuncture, and serum was separated by centrifugation. All samples were stored at −20°C.5 Vero cells/mL was added and incubated at 37°C in the presence of 5% CO2. The microplates were read under an inverted microscope after 5 days for TOSV and 6 days for SFSV, and the presence  or absence  of cytopathic effect was noted. Cutoff value for positivity was set at titer >20 , and a new phlebovirus was described in Albania, Croatia, and Bosnia-Herzegovina  and sheep (1.96%) in Kosovo ; Figure.Rates of SFSV neutralizing antibodies were much higher than those for TOSV. Results for cattle ranged from 24.0% to 78.2% (mean 58.5%); results for sheep were lower, ranging from 2.7% to 56.7% (mean 22.2%). For sheep, 4 of the 5 regions had rates of 14.0%–56.7%; the rate was much lower (2.7%) in Gjakovë.Few data are available for comparison; 9.6% of tested human serum contained SFSV neutralizing antibodies in the 1970s . Our results are congruent with data from continental Greece, with rates in the same order of magnitude  , followed by P. tobbi (11.2%), P. simici (3.7%), P. papatasi (1%), and other species (3.1%).Published data about the distribution of sand flies and species identification are old and scarce; SFSV positivity varied among the regions for cattle and sheep. The regional prevalence differences might have resulted from geographic and climatic characteristics of the region that could affect the vector sand fly species distribution and population size.Our results confirm that TOSV and SFSV, or an SFSV-like virus, are circulating in several regions of Kosovo, which indicates that humans are exposed to these viruses. This finding merits confirmation through seroprevalence studies and initiation of systematic testing for TOSV and SFSV real-time reverse transcription PCR for febrile illness and central nervous system infections during the warm season.


Cryptococcus species complexes, adding greatly to the ongoing discussion of speciation between these complexes . It is likely that with hundreds of thousands of single nucleotide polymorphism (SNP) mutations separating the major C. gattii molecular types  and Douglas fir (Pseudotsuga menziesii)  , 10.C. gattii isolates are predominantly VGI, with a low-level VGII presence in most Asian countries . It is possible that a common ancestor to VGIV was endemic to such a region prior to the break off of the Indian Subcontinent. Other interesting phylogeographic features include African VGII being found only in Senegal, a previous land partner with Brazil (C. gattii primarily only on the Iberian Peninsula, Europe’s Pangea connection to Africa (R. A. Krulwich; http://www.npr.org/blogs/krulwich/2013/09/12/221874851/a-most-delightful-map.Of interest are possible remnant populations from prior contiguous Pangea regions. For example, India was a contiguous landmass with southern Africa (R. W. Schlische; h Brazil , and theC. gattii around the world. It is however an additional viewpoint in favor of the continental drift dispersal hypothesis.This is not to suggest that the above endemic foci are all due to separation of contiguous endemic populations during the breakup of Pangea, nor does this represent an exhaustive listing of all isolations of


Remote monitoring in obstetrics is relatively new; some studies have shown its effectiveness for both mother and child. However, few studies have evaluated the economic impact compared to conventional care, and no cost analysis of a remote monitoring prenatal follow-up program for women diagnosed with gestational hypertensive diseases (GHD) has been published.The aim of this study was to assess the costs of remote monitoring versus conventional care relative to reported benefits.Patient data from the Pregnancy Remote Monitoring (PREMOM) study were used. Health care costs were calculated from patient-specific hospital bills of Ziekenhuis Oost-Limburg  in 2015. Cost comparison was made from three perspectives: the Belgian national health care system (HCS), the National Institution for Insurance of Disease and Disability (RIZIV), and costs for individual patients. The calculations were made for four major domains: prenatal follow-up, prenatal admission to the hospital, maternal and neonatal care at and after delivery, and total amount of costs. A simulation exercise was made in which it was calculated how much could be demanded of RIZIV for funding the remote monitoring service.P<.001; RIZIV: mean €21.09 [SD €27.94] vs mean €36.19 [SD €41.36], P<.001) and a reduction of 47.16% in HCS and 48.19% in RIZIV costs for neonatal care . HCS costs for medication were 1.92% lower in remote monitoring than conventional care , but were 0.69% higher for RIZIV . Overall HCS costs for remote monitoring were mean €4233.31 (SD €3463.31) per person and mean €4973.69 (SD €5219.00) per person for conventional care (P=.82), a reduction of €740.38 (14.89%) per person, with savings mainly for RIZIV of €848.97 per person . When an additional fee of €525.07 per month per pregnant woman for funding remote monitoring costs is demanded, remote monitoring is acceptable in their costs for HCS, RIZIV, and individual patients.A total of 140 pregnancies were included, of which 43 received remote monitoring (30.7%) and 97 received conventional care (69.2%). From the three perspectives, there were no differences in costs for prenatal follow-up. Compared to conventional care, remote monitoring patients had 34.51% less HCS and 41.72% less RIZIV costs for laboratory test results (HCS: mean €0.00 [SD €55.34] vs mean €38.28 [SD € 44.08], In the current organization of Belgian health care, a remote monitoring prenatal follow-up of women with GHD is cost saving for the global health care system, mainly via savings for the insurance institution RIZIV. Remote monitoring in obstetrics is a relatively new field of research; only a few trials have shown the effectiveness of remote monitoring in obstetrical care for both mother and child. When uterine activity is transmitted by telecommunication, significant prolonged pregnancy survivals are observed ,2. HigheRijksinstituut voor Ziekte- en Invaliditeitsverzekering; RIZIV) and costs for individual patients [The Pregnancy Remote Monitoring (PREMOM) study was designed for women diagnosed with GHD who had their prenatal follow-up in Ziekenhuis Oost-Limburg . According to the Flanders’ register of perinatal outcomes, the prevalence of hypertensive disorders in pregnancy is 4.6%: 0.3% deliver before 34 weeks, 0.6% deliver between 34 and 37 weeks, and 3.7% deliver after 37 weeks . As a copatients . The calData collected from the PREMOM study was used for this cost analysis. The PREMOM study design and data collection method are described in detail elsewhere . Briefly2 . Pregnant women participating in the prenatal remote follow-up program were asked to perform one blood pressure measurement in the morning and one in the evening, one weight measurement a day, and to wear an activity tracker day and night until delivery or hospital admission. The data from the monitor devices were transmitted to a Web-based dashboard developed by the mobile health unit of Hasselt University. Predetermined alarm signals were set and alarm events were communicated with the obstetrician in charge to discuss management options before contacting and instructing patients at home. Therapeutic interventions were according to local management. The clinical goal of routine prenatal outpatient care is to timely detect an abnormal course of maternal and/or fetal health. The study protocol was approved by the local ethics committees responsible for the site. The investigation conformed to the principles outlined in the Declaration of Helsinki. All patients gave written informed consent, and data were treated confidentially.Women consenting for remote monitoring received obstetric surveillance using a Withings Wireless Blood Pressure Monitor, Withings Smart Body Analyzer, and a Withings Pulse OThe objective of the study was to quantify the costs of remote monitoring versus conventional care from the perspectives of the HCS, the RIZIV, and the patients. The costs of the HCS are the total amount of costs that have to be paid to cover the care that has been provided. These HCS costs can be divided into two subgroups who have to pay their part of the costs: (1) RIZIV, the national institutional social security in Belgium, which ensures every insured individual, regardless of financial situation, has access to necessary qualitative medical care in accordance with the tariff agreements between caregivers and government  and (2) All costs related to urgent and nonurgent in-office visits were used in the prenatal follow-up cost analysis: (1) costs of prenatal consultations, (2) costs of ultrasounds, and (3) costs of cardiotocographics.To evaluate the economic impact of remote monitoring on the three major stakeholders, the following data points were collected when the pregnant women were admitted to the prenatal ward: (1) costs related to the laboratory test results of the mother, (2) costs of the medicines, and (3) costs related to the admission.For both groups, the following costs were included for this topic: (1) costs of the delivery, (2) costs necessary for the care of the neonate, and (3) other costs.After analyzing the previously mentioned data, a cost analysis of the total amount of costs was made. This included (1) costs of the prenatal follow-up, (2) costs of the prenatal admission to the prenatal ward, and (3) costs of the maternal and neonatal care at and after delivery.A simulation exercise was made in which the amount that could be demanded by RIZIV for funding of the remote monitoring service was calculated. This charge was calculated by dividing the cost savings in RIZIV  by the mean time of prenatal remote monitoring follow-up per pregnant woman. This charge could be used to finance the costs which were needed to perform remote monitoring in the prenatal follow-up of women at risk for GHD, such as the need of midwives to accompany the pregnant women to their remote monitoring follow-up and to interpret the  signals, the need of obstetrics to refer and supervise the pregnant women at risk, and the need of technical staff to maintain the platform, to give technical support, etc.U test was used to compare costs across groups. Both univariate and multivariate analyses were performed for analyzing the costs for the three domains.The baseline characteristics are continuous data summarized as mean and standard deviation. Categorical data are summarized as count and percentage and were compared using the chi-square test or Fisher exact test, when appropriate. Costs were reported as means, standard deviations, medians, and interquartile ranges. Cost data are typically highly skewed  because The nominal level alpha<.05 was considered significant. All statistical analyses were performed with SPSS release 24.0.P=.02) and smoking  in the remote monitoring group versus 10%, (10/97) in the conventional care group (P=.03).The baseline characteristics of the patients are summarized in The health care costs are presented in To investigate the influence of the maternal demographics and characteristics on the health care costs, a multiple linear regression analysis and a multivariate logistic regression analysis was performed. A detailed overview of these data are provided in No differences were found in costs for prenatal follow-up : not in the costs for the HCS, the RIZIV, or the patients.P<.001; RIZIV: remote monitoring mean €21.09, SD €27.94 vs conventional care mean €36.19, SD €41.36, P<.001). Also, the HCS cost for the medicaments were 1.92% lower in the remote monitoring group compared to the conventional care group , but the RIZIV costs were 0.69% higher in the remote monitoring group compared to the conventional care group .Patients admitted to the remote monitoring group did have 34.51% less HCS and 41.72% less RIZIV costs for laboratory test results compared to conventional care group . Other costs were for the HCS 57.86% and RIZIV 58.63% lower in remote monitoring versus conventional care , but 0.77% higher for the patients in remote monitoring versus conventional care .No differences were found in costs for delivery in the remote monitoring group versus the conventional care group. A reduction of 47.16% in HCS cost and 48.19% in RIZIV costs for neonatal care was found in the remote monitoring group compared to the conventional care group , the RIZIV , or the patients . But, a cost reduction of €740.38 per person (14.89%) was made for HCS and a cost reduction of €848.97 (23.18%) was made for RIZIV in remote monitoring compared to conventional care. Patient’s costs were slightly higher  for remote monitoring than for conventional care.An overview of the total amount of costs is presented in P=.01) and in RIZIV costs by also having a reduction of €110.70 per person in remote monitoring versus conventional care . The patient still does not have to pay more for their prenatal care . An overview of the costs is shown in A simulation exercise was made in which it was calculated how much could be demanded of RIZIV for funding the remote monitoring service. For this study, 43 pregnant women were included in the analysis with a range of 1 day of participation to 145 days of participation in the PREMOM project. The mean time of participation in this project was 44.42 days or 1.41 months . By diviThe main finding of this study is that a remote monitoring prenatal follow-up for pregnant women at risk for GHD reduces the total amount of costs for national health care in comparison to a standard follow-up strategy. This cost reduction is due to a marked reduction in the consumption of health care services, including laboratory test results taken, medication use, and maternal and neonatal admissions. When an additional fee of €525.07 per month per pregnant woman for funding remote monitoring costs is asked, remote monitoring is still acceptable in their costs for HCS, RIZIV, and individual patients.The use of “real-life” data from the hospital bills is the main strength of this study. By using these data, the actual situation of pregnancies complicated with GHD is simulated and these results are generalizable for settings with similar economics and social characteristics. Also, the requested fee of €525.07 per month per pregnant woman is a strength of this study because of the applicability and thoughtfulness of this item. It is very likely that this price will actually cover the costs of a remote monitoring prenatal follow-up program. Finally, by adding this supplement to the RIZIV costs, there will be no increase in costs between the remote monitoring group and conventional care group in the three domains, but the prenatal follow-up and gestational outcomes will be improved for the remote monitoring group as we reported previously .The main limitation of this study is its retrospective structure and the fact that the patients from the PREMOM study were not randomized. Nevertheless, the populations in the two arms were almost homogeneous regarding the baseline clinical characteristics. Second, the PREMOM study and this financial analysis provides a picture of real-life practice in Belgium; we did receive the data from the patient files and the hospital bills, but we do not have information of the patients’ hospital and medical consumption, or the patients’ social costs . Our results could also differ in different HCSs and different economic and social settings, such as in other countries. Additionally, this study is limited to 6 weeks after delivery. It is generally known that neonates that need intensive care at the time of their delivery will have a higher impact on health care costs then neonates who do not need this care. These costs are mostly due to rehospitalizations, acute care visits, or further intensive care for the rest of the infant’s life -19. FurtOnly two studies are known to have performed a cost analysis of a remote monitoring follow-up program in women with high-risk pregnancies. Morrison et al  performeThe main objective of our study was to compare direct costs of a prenatal follow-up program for women diagnosed with GHD between remote monitoring and conventional care in hospital visits for a single-center population based on the initial assumption that remote monitoring technologies were provided with no additional costs. Early detection of clinical and device-related critical events provided by remote monitoring may have a positive impact on complication rates such as the development of severe hypertension, the need of inductions, prenatal hospitalizations, and neonatal hospitalizations. In our previously mentioned study, we reported a reduction in the prevalence of preeclampsia, hospitalization of the mother and the neonate, and inductions of labor . In summThe suggested €525.07 per month per pregnant woman fee for funding remote monitoring allows for HCS to not be elevated. By showing that there is no significant difference in costs between the remote monitoring group and conventional care group, a door is opened for policy makers charged with deciding how limited health care resources should be allocated in the era of exploding needs. This study, together with our previous report, states that better prenatal follow-up and gestational outcomes for the same cost as conventional care are possible by adding remote monitoring to the care of pregnant women with GHD.Firstly, it would also be useful to investigate the QALYs for both the mother and the neonate who received remote monitoring to make further recommendations about this topic. This study is also shortened to postnatal follow-up until 6 weeks after delivery. It would be interesting to monitor the neonates in both groups—remote monitoring and conventional care groups—for longer than 6 weeks postpartum to get insights into the long-term cost benefits. Lastly, because the social costs  are not taken into account, it would be interesting to make additional analyses with these type of costs included. It is plausible that the differences in costs will be even greater when the previously mentioned items are taken into account.The results of this study show that a remote monitoring prenatal follow-up of women with GHD will not increase the costs for the HCS, RIZIV, or patient in comparison with conventional care. Furthermore, a RIZIV fee of €525.07 per month per pregnant woman allows the implementation of remote monitoring without increasing the health care costs for the remote monitoring group. These results are useful for policy makers charged with deciding how limited health care resources should be allocated in the era of exploding need. Further research of the long-term cost-effectiveness of remote monitoring, the QALYs, and social costs is recommended.


Zika virus has recently been introduced to the Americas and is spreading rapidly. We evaluated the characteristics of US travelers to Zika virus–affected countries who were seen at Global TravEpiNet sites during March 2015–October 2016. Nearly three quarters of travelers were men or women of reproductive age. In 2014, a total of 30.8 million US residents traveled internationally, and 39% of trips were to the Caribbean, Central America, and South America (the Americas) , supported by the Centers for Disease Control and Prevention (CDC), is a consortium of US clinical practices providing pretravel healthcare to international travelers. GTEN sites include academic practices, healthcare consortia, health maintenance organizations, pharmacy-based clinics, private practices, and public health clinics , followed by Brazil (12%). Of the 6,440 travelers to Zika virus–affected countries, 4,819 (75%) were persons of reproductive age.A total of 22,736 travelers were seen for a pretravel consultation during March 2015–October 2016. Of these, 6,440 (28%) planned trips to More than half (59%) of travelers to Zika virus–affected countries were women; nearly two thirds (63%) of these women were of reproductive age . OverallLess than 1% of women of reproductive age traveling to Zika virus–affected countries reported being pregnant (n = 7) or breastfeeding (n = 9) at the pretravel consultation . OverallZika virus transmission has increased in the Americas. Providing pretravel counseling on mosquito bite prevention and risk for sexual transmission of Zika virus and recommending that pregnant women not travel to areas with Zika virus transmission are public health priorities. We describe the characteristics of US travelers seeking health advice before travel to Zika virus–affected countries in the Americas. Our findings suggest areas for intervention.http://www.cdc.gov/zika/pregnancy/thinking-about-pregnancy.html). Healthcare providers should stay abreast of these recommendations to counsel travelers to the Americas appropriately.First, we found that three quarters of travelers seen at GTEN sites before visiting countries with Zika virus transmission in the Americas were of reproductive age. Nearly two thirds of women traveling to Zika virus–affected countries were of reproductive age, and only approximately one-third reported using prescription birth control. Five percent of women ages 30–39 years reported planning pregnancy; not all might have disclosed their plans  (Second, we found that one quarter of women of reproductive age traveling to Zika virus–affected countries in the Americas were traveling for mission or nonmedical service trips; another 15% were traveling for research or education. Previous studies show that volunteer travelers are likely to pursue health information but might not adhere to mosquito avoidance measures (,We previously reported that ≈11% of all travelers seen at GTEN sites were VFR travelers (>6 months after their last possible exposure to Zika virus. Last, we did not correlate dates of travel with the time that Zika virus transmission was identified in each country.Our analysis has limitations. Travelers at GTEN sites might not represent all US international travelers, and clinical practice at GTEN sites might differ from other settings where pretravel health care is provided. Also, we did not collect data on contraceptive practices in male travelers; this information would be of interest given the current recommendation for men to use condoms for In conclusion, our findings show that many persons of reproductive age are traveling to Zika virus–affected countries in the Americas. We observed that VFR travelers represent an unexpectedly small proportion of those seeking health advice before travel to these Zika virus–affected countries; outreach efforts to increase the frequency of pretravel health encounters for these travelers are warranted. Clinicians should provide education on mosquito bite prevention for all travelers to Zika virus–affected countries and should discuss use of condoms or abstinence to reduce the risk for sexual transmission during and after travel. In addition, clinicians should assess reproductive plans, review use of effective birth control, and discuss waiting for conception when returning from areas with Zika virus.


The IFNλ family of interferons controls the spread of viruses in the upper respiratory tract and transmission between mice. Related research article Klinkhammer J, Schnepf D, Ye L, Schwaderlapp M, Gad HH, Hartmann R, Garcin D, Mahlakõiv T, Staeheli P. 2018. IFN-λ prevents influenza virus spread from the upper airways to the lungs and limits virus transmission. eLife7:e33354. doi: 10.7554/eLife.33354The evolutionary arms race between viruses and their vertebrate hosts is biased by the different rates at which each can adapt. Slowly evolving vertebrate genomes cannot keep up with the rapid mutations employed by viral genomes to avoid the host’s defenses. One strategy that vertebrates use to counter this apparent disadvantage involves a group of proteins called interferons that infected cells produce when they sense a virus. Named for their ability to ‘interfere’ with influenza virus replication , interfeInterferons can be classed into different families, each of which interacts with a different receptor. The most widely studied family is the IFNαβ family, which interacts with the IFNαβ receptor . The IFNIFNαβ and IFNλ activate largely the same genes, but their receptors are not found on all cell types. Therefore, the distribution of IFNαβ and IFNλ receptors could be behind the different biological effects of each interferon family. Epithelia are thought to express both receptors, and therefore the two interferon families should both have the same effects in the epithelial cells that line the surfaces of organs, including the airways. A number of findings support this. First, the influenza virus triggers the airway epithelia of mice lacking one type of receptor to transcribe practically the same sets of genes as those transcribed in the epithelia of normal mice: however, epithelia that lack both interferon receptors have large 'holes' in their transcriptional profile and allow the virus to replicate extensively . Second,To show that IFNλ has unique roles in epithelial cells Klinkhammer et al. – who are based at Freiburg, Aarhus University and the University of Geneva – infected mice with a strain of influenza virus in a small volume of fluid. This mimics the ways that infections spread between humans better than the larger volumes of fluid used in most studies. Using this technique, infection was initially limited to the epithelia lining the nasopharyngeal cavities.IFNλ receptor-deficient mice infected in this way had a far greater number of virus particles in their upper airways than mice that were deficient in the IFNαβ receptor. This suggests that nasopharyngeal epithelia may be more responsive as a whole to IFNλ than to IFNαβ, or that some cells in these epithelia express only the IFNλ receptor. However, IFNαβ receptors become increasingly important when mice are infected with larger droplets, which brings the virus further down into the lungs, or during an ongoing infection if the virus succeeds in spreading further down along the airways into the lung.The efficiency with which viruses are transmitted from infected to uninfected individuals makes the difference between minor outbreaks (such as sporadic cases of H5N1) and pandemics (such as the H1N1 pandemic of 2009). A lack of a genetically versatile animal model had made it difficult to study how the genome of the host affects transmission frequency, but this changed when it was shown that H3N2 influenza viruses transmit efficiently between mice .Using this model Klinkhammer et al. show that IFNλ determines transmission efficiency by controlling the number of virus particles at the uppermost end of the respiratory tract: the higher the number of viruses in the nasopharyngeal space, the higher the likelihood that they would be shed out of the nose and thus be able to infect a new host. In line with its role further down the respiratory tract, IFNαβ has much less influence on how well the virus spreads between individuals.The results also have clinical relevance. Klinkhammer et al. demonstrate here that IFNλ acts more strongly than IFNαβ and has longer-lasting effects on virus transmission, while others have shown that it also produces comparably minor inflammatory side effects . TreatmeThere had been previous indications that IFNλ has a unique role in controlling infections. Last year it was reported that IFNλ appeared to be the first interferon, and sometimes the only interferon, required to control the influenza virus early in infections and when using low doses of the virus . There a


Focal cartilage defects in the knee may have devastating effect on the knee joint, where two of the main surgical treatment options are microfracture and autologous chondrocyte implantation. Comparative studies have failed to establish which method yields the best clinical results. A cost-effectiveness analysis of microfracture and autologous chondrocyte implantation would contribute to the clinical decision process.A PubMed search identifying level I and level II studies with 5 year follow-up was performed. With the data from these studies, decision trees with associated service provision and costs connected to the two different techniques were designed. In addition to hospital costs, we included costs connected to physiotherapy following surgery. To paint a broader cost picture, we also included indirect costs to the society due to productivity loss caused by work absence.Four high-quality studies, with a follow-up of 5 years, met the inclusion criteria. A total of 319 patients were included, 170 undergoing microfracture and 149 autologous chondrocyte implantation. The re-operation rate was 23 (13.5%) following microfracture, and 18 (12.1%) for autologous chondrocyte implantation. Both groups achieved substantially better clinical scores at 5 years compared to baseline. Microfracture was more cost-effective when comparing all clinical scores.Microfracture is associated with both lower costs and lower cost per point increase in patient reported outcome measures. There is a need of well-designed, high-quality randomized controlled trials before reliable conclusions regarding cost-effectiveness in the long run is possible.III. The articular cartilage in joints is composed of hyaline cartilage, with optimum load bearing and friction properties. Due to limited self-repair ability, an injury to the articular cartilage will lead to permanent damage. Focal cartilage defects (FCDs) of the knee joint may lead to severe morbidity and osteoarthritis , and areThere are numerous treatment options available, where all aim to reduce pain, restore function, and minimize secondary osteoarthritis. Treatments can broadly be divided into bone-morrow stimulation techniques (microfracture), osteochondral autograft or allograft transplantation and cell-based techniques (autologous chondrocyte implantation) , 5. MicrShort- and long-term studies have reported better function and less pain following knee cartilage surgery than prior to surgery , 11–13, Given the increased focus on health care efficiency and the high prevalence of FCDs on the distal femur, one should try to identify the most cost-effective treatment option to contribute to the clinical decision process for these troublesome injuries.Previous published cost-effectiveness analysis is based on short term follow-up only. The purpose of the current study is to compare costs after 5 years between MF and ACI, based on pre-existing level 1 and level 2 studies.Miller et al. performed a cost-effectiveness analysis of cartilage injuries comparing microfracture and osteochondral autograft transplantation . In the According to the standard methods for economic evaluation of health care programs, decision trees following MF and ACI as previously described by Drummond et al. were constructed . TerminaThe costs of revision surgery were calculated for the specific procedures , and included costs of a magnetic resonance imaging and a return visit. For the costs of one overnight stay in an orthopedic ward, a Norwegian estimate is €620 . The lenIn regard to postoperative physiotherapy, there is no consensus regarding frequency or duration. Our assumptions are based on clinical experience and personal communications. After ACI, Brittberg recommends physiotherapy twice weekly for 24 weeks , while Robert LaPrade at Steadman’s clinic recommends physiotherapy twice weekly for 12 weeks following MF . When estimating the costs of physiotherapy following revision surgery, we assumed physiotherapy twice weekly for 12 weeks after diagnostic arthroscopy, MF and mosaicplasty, and twice weekly for 24 weeks for ACI, high tibial osteotomy and total knee arthroplasty. The unit cost of one session physiotherapy is €30 (The Norwegian Physiotherapist Association). No brace was included in the costs.A human capital approach (HCA) was employed to calculate indirect costs (productivity loss). In HCA, the loss to the society is estimated from the income normally earned by the patients . The ideTotal costs at 5 years are calculated by summing primary costs and costs for revision surgery.By comparing total costs and the weighted average of the reported outcome measures, we calculated the costs related to a 1-point increase in each of the reported PROM values following MF and ACI. All costs were converted to 2017 Euros based on the Norwegian consumer price index.A sensitivity analysis was performed to calculate alternative values to see how sensitive the end result is for the choice of value on different variables. Guidelines often discount costs at a 3% annual rate, considered to start at 5 years . Since oSix studies were identified , 32, 33 2 (MF) and 3.2 cm2 (ACI). Based on the decision trees, 147 (86.5%) in the MF group, and 131 (87.9%) in the ACI group achieved success at 5 years  and 33.1 (ACI) years, with lesion sizes 2.5 cmOne study did not specify treatment failure . One stuMF had direct costs of €3254 at baseline Table , rising Different validated patient reported outcome measures (PROMs) were used. The Tegner score was used in three studies , 18, 32,The sensitivity analysis showed that a 66% reduction in the total costs following ACI or a 190% increase in the total costs of MF led to equivalent total costs at 5 years. Comparing only primary direct costs, a reduction in costs of 70% after ACI, or a 239% increase in costs after MF would lead to equivalent costs at baseline. Assuming identical costs for hospital stay, physiotherapy and sick leave after the primary surgery, an increase in costs of 69% following MF and a decrease in costs of 41% after ACI would lead to identical total costs after the primary surgery.The most important finding of the present study was that MF is more cost-effective than ACI for the treatment of FCDs in the distal femur with 5 year follow-up. The main difference in total costs is related to the primary surgery, where MF is less expensive than ACI. Costs following revision surgery are however lower in the ACI group, respectively, €703 (ACI) and €821 (MF) per patient.p value that demonstrates that the difference in cost-effectiveness is statistically significant. However, given the large differences in costs per point improvement between MF and ACI, it is unlikely that our findings are purely coincidental.The included studies have demonstrated that the clinical scores are statistically significantly better at 5 years compared to pre-surgery for both methods. Not all studies reported variances or standard deviations, so we were unable to calculate a precise In a recent study comparing MF, osteochondral autograft transplantation and ACI, Schrock et al. reported that MF was the most cost-effective treatment option for chondral lesions in the knee, confirming our findings . In contThere is a wide variation between surgeons in relation with indication for surgery, preferred surgical technique, postoperative physiotherapy, and outcome assessment . Some ha2 [2 [2 for MF and 3.2 cm2 for ACI), which probably do not affect our result. Recent research on anterior cruciate ligament reconstruction in combination with articular cartilage injury has found the effect of the lesion size to be minor [The effect of the cartilage lesion size on symptoms is poorly investigated. Some authors recommend ACI for cartilage lesions larger than 4 cm2 , 41, but2 [2 . The avebe minor .Kon et al. compared MF with scaffold ACI and found a small clinical benefit in favour of ACI after 5 years . KnutsenThere are technological advances both within MF and ACI. Nanofracture, scaffolds, and autologous matrix-induced chondrogenesis are gaining popularity, and may give a different clinical and cost picture of microfracture derived procedures. Scaffold may induce significantly higher costs when comparing MF with other cartilage procedures. Published papers on ACI are mainly based on first generation procedures, but second and third generation ACI have now been implemented both in clinical trials and practice. However, long-term results are not yet available . BesidesThis study has limitations. Studies with evidence levels 1 and 2 comparing MF and ACI with a minimum follow-up at 5 years are few, leading to relatively small study populations. This may lead to bias and affect the results published in this article. Yet, to this date, these are the only high-quality studies with 5 year follow-up.Another limitation is the fact that the MF group had slightly smaller lesions and, therefore, might represent patients which are more responsive to physiotherapy after surgery. Supervised physiotherapy has also been shown to be effective together with debridement of the lesion , and ourKnutsen et al. published the SF-36 and Tegner score only for the success patients, and not for the failures . This maPhysiotherapy before surgery and costs related to independent training are not included in our calculations because we assume them to be similar for the two groups. A wide range of postoperative physiotherapy protocols after MF and ACI exists. Some permit weight-bearing, while others use continuous passive motion (CPM) , 45–48. Ten patients in the MF group and seven in the ACI group were re-operated, and the procedure was assumed to be diagnostic arthroscopies. If we assumed another re-operation procedure, this would affect the cost estimates. When estimating the costs related to hospital stay, work absence, and physiotherapy after revision surgery, we used the cost estimates from primary surgery, which may be an underestimation.In regard to capital costs, account investments and orthopedic skills were not taken into account, i.e., we have assumed that hospitals can switch between MF and ACI, which in practice is not the case.The unit prices employed in our calculations is extracted from a local orthopedic hospital, and confirmed with other orthopedic hospitals in Norway, which may limit the transferability of the study. An international cost analysis is difficult to perform because different countries face different institutional and financial constraints, including different unit prices. On the other hand, their assumption regarding service provision related to surgery, postoperative physiotherapy and sick leave are comparable to other studies, thereby giving a certain degree of transferability globally , 23, 37.The results are based on 5 year follow-up. In light of cartilage pathologies, this may be sparse. However, failures usually occur within 2–3 years after the initial surgery , 50, so There is evidence for the benefits of cartilage repair surgery using MF and ACI based on the 5 year results published when evaluating health costs related to the procedures. The MF procedure is more cost-effective than ACI based on published 5 year results, but there is a need of well-designed, high-quality randomized controlled trials with long-term results before safe conclusions can be made.


The DTPA-Zn concentration increased with the application of humic acid compared with no humic acid throughout 35 days of the incubation period and the peak value obtained was 3.12 mg/kg in the treatment Zn10 HA2 at 14 days after incubation, showing 50 % increase in Zn content over its corresponding treatment of Zn alone (Zn10HA0). The application of 0.2% humic acid compared with 0.1% resulted in greater increase in DTPA-Zn concentration in soil application. During the 35 days of incubation, highest values of DTPA-Zn were recorded in soil maintained at saturated compared to water logged conditions. However, under alternate wetting and drying condition the DTPA-Zn content gradually decreased up to 21 days and thereafter increased slowly.Lime and humic acid application can play an important role in the availability of zinc in paddy soils. We conducted laboratory incubation experiments on a rice growing soil (Alfisol) to determine the effect of lime, humic acid and different moisture regimes on the availability of Zn. Addition of half doses of liming material (powdered lime stone) recorded highest values of DTPA-Zn followed by no lime and 100% of lime requirement throughout the incubation period. With the progress of incubation, DTPA-Zn increased slightly during the first week and then decreased thereafter. The highest DTPA-extractable Zn content of 2.85 mg/kg was found in the treatment Zn


Dear Editor,in utero, causing microcephaly and growth retardation in neonates.1 AXL receptor tyrosine kinase (AXL) was found to be a key for Zika virus infection in cultured 293T and A549 cells.3 In addition, AXL is highly expressed by human radial glial cells, astrocytes, endothelial cells and microglia in the developing human cortex, and its expression in radial glia is conserved in the developing cortex of mice and ferrets, as well as in human stem cell-derived cerebral organoids.4 Therefore, AXL represents a promising candidate receptor and one of the most promising druggable targets against Zika virus. However, questions remain as to whether AXL is an essential receptor for Zika virus infection in vivo.Zika virus is a global threat to public health, particularly in pregnant women, as the virus can penetrate the placental barrier and infect embryos Axl−/− knockout mice using CRISPR/Cas9 technology  mice with a Zika GZ01 strain isolate (GenBank ID: KU761564.1). Neonatal pups (24–48 h after birth) were infected by intracerebral injection. The mice were killed at day 10 post-infection, and total RNA was extracted from the brains using the RNeasy lipid tissue mini kit . Zika viral titers were measured with RT-PCR using the QuantiTect SYBR Green RT-PCR kit  and Zika virus NS5 primers . Unexpectedly, not only was Zika virus detected in the brains of all Axl−/− mice, but the Zika virus titers showed no significant difference (P>0.05) between BalB/c WT and BalB/c-Axl−/− mice, reaching similar levels at doses of 1200, 120 and 1.2 PFU/mouse (To answer this question, we generated BalB/c-chnology . Success sorting . We thenFU/mouse . These rin vivo using an Axl knockout mouse model. Our results are corroborated by a recent study showing that genetic ablation of Axl does not protect human neural progenitor cells or cerebral organoids from Zika virus infection.5 This provides strong in vivo evidence for drug developers that AXL is not worth further investment as a target against Zika virus infection. Previous studies indicating that AXL might play a major role in Zika virus infection were conducted in cell culture,3 suggesting that AXL might be necessary for infection in some special cell types. The role of AXL in infection with other viruses of the Flaviviridae family, such as the dengue, West Nile, yellow fever and Japanese encephalitis viruses, and the role of AXL in Zika-induced microcephaly need to be further investigated.Our findings confirm that AXL is not the key receptor for Zika virus infection