Diabetic patients show an increased prevalence of non-dipping arterial pressure pattern, target organ damage and elevated arterial stiffness. These alterations are associated with increased cardiovascular risk.The objectives of this study are the following: to evaluate the prognostic value of central arterial pressure and pulse wave velocity in relation to the incidence and outcome of target organ damage and the appearance of cardiovascular episodes  in patients with type 2 diabetes mellitus or metabolic syndrome.Design: This is an observational prospective study with 5 years duration, of which the first year corresponds to patient inclusion and initial evaluation, and the remaining four years to follow-up.Setting: The study will be carried out in the urban primary care setting.Study population: Consecutive sampling will be used to include patients diagnosed with type 2 diabetes between 20-80 years of age. A total of 110 patients meeting all the inclusion criteria and none of the exclusion criteria will be included.Measurements: Patient age and sex, family and personal history of cardiovascular disease, and cardiovascular risk factors. Height, weight, heart rate and abdominal circumference. Laboratory tests: hemoglobin, lipid profile, creatinine, microalbuminuria, glomerular filtration rate, blood glucose, glycosylated hemoglobin, blood insulin, fibrinogen and high sensitivity C-reactive protein. Clinical and 24-hour ambulatory (home) blood pressure monitoring and self-measured blood pressure. Common carotid artery ultrasound for the determination of mean carotid intima-media thickness. Electrocardiogram for assessing left ventricular hypertrophy. Ankle-brachial index. Retinal vascular study based on funduscopy with non-mydriatic retinography and evaluation of pulse wave morphology and pulse wave velocity using the SphygmoCor system. The medication used for diabetes, arterial hypertension and hyperlipidemia will be registered, together with antiplatelet drugs.The results of this study will help to know and quantify the prognostic value of central arterial pressure and pulse wave velocity in relation to the evolution of the subclinical target organ damage markers and the possible incidence of cardiovascular events in patients with type 2 diabetes mellitus.ClinicalTrials.gov Identifier: NCT01065155 The estimated prevalence of type 2 diabetes mellitus (DM2) in the industrialized world is 6-8% . The preClinical blood pressure (CBP) measurement remains the standard of reference, and has been a key element in predicting cardiovascular disease, but there is increasing evidence that home blood pressure (HBP) measurement by the patient, and particularly ambulatory blood pressure monitoring (ABPM), shows a stronger correlation to target organ damage and cardiovascular events -20. The The presence of target organ damage increases the risk of clinical cardiovascular complications in DM2. In this context, left ventricular hypertrophy (LVH), assessed according to electrocardiographic criteria, increases the risk of coronary complications and stroke . Silent On the other hand, the evaluation of major artery stiffness is gaining importance as an indicator, since it is one of the main determining factors of the general condition of blood circulation ,30. ArteConsidering the need in diabetic patients to better establish the prognostic value of central arterial pressure and pulse wave velocity in relation to the evolution of the target organ damage markers , retinal damage and vascular markers (IMT of the carotid artery and ABI)) and the possible incidence of cardiovascular events in DM2 patients, an observational prospective study involving annual follow-up over at least four years is contemplated.To evaluate the prognostic value of central arterial pressure and pulse wave velocity in relation to the incidence and outcome of renal , cardiac (LVH) and vascular damage (IMT and ABI), retinal vascular impairment, and the appearance of cardiovascular episodes  in patients with DM2.An observational prospective study with a duration of 5 years, of which the first year corresponds to patient inclusion, and the remaining four years to follow-up. A minimum of 5 visits are contemplated, comprising a baseline visit at the time of patient inclusion in the study, and annual follow-up visits.The study was approved by an independent ethics committee from the University Hospital of Salamanca (Spain), and all participants signed an informed consent document.The study will be carried out in the rural primary care setting, in the research unit of La Alamedilla primary care center, to which the general practitioners from two primary care centers serving a population of 46,000 inhabitants send patients for the evaluation of possible target organ damage and vascular risk.Consecutive inclusion will be made of the patients referred to the research unit and who meet the corresponding inclusion criteria, i.e., patients diagnosed with DM2 and aged 20-80 years, with none of the following exclusion criteria: patients unable to comply with the protocol requirements , patients participating or who will participate in a clinical trial during the study, and patients with serious comorbidities representing a threat to life over the subsequent 12 months.The sample size has been calculated to determine the time the patients take in suffering an event - the latter being interpreted as morbidity-mortality or the appearance of new target organ damage. To this effect, two groups will be considered, classified according to the median central arterial pressure value. The study accepts an alpha risk of 0.05 and a beta risk of 0.30 in two-sided contrasting for the detection of a minimum difference in relative risk between the two groups of ≥ 2.5 points, and considering an events rate within the high central arterial pressure group  of 35% at the end of the study period. A total of 52 patients are required in each group, estimating a loss to follow-up of 10%. A final total of 110 patients therefore will be included.Patient age, sex, race, educational level and occupational status. Hypertension, dyslipidemia, alcohol consumption, smoking, physical activity and a history of premature cardiovascular disease  in first-degree relatives.Coronary events: Myocardial infarction, unstable angina, stable angina, coronary revascularization. Cerebrovascular events: Ischemic stroke, intracranial hemorrhage, transient brain ischemia. Hospital admissions due to heart failure. Symptomatic peripheral arterial disease: Claudication over a distance of less than 100 m, resting pain, amputation. Heart failure. Atrial fibrillation.Treatment for diabetes. Antihypertensive treatment. Lipid-lowering treatment. Antiplatelet treatment.2) will be calculated. Waist circumference will be measured using a flexible graduated measuring tape with the patient in the standing position without clothing. The upper border of the iliac crests are located, and the tape is wrapped around above this point, parallel to the floor, ensuring that it is adjusted without compressing the skin. The reading is taken at the end of a normal breath according to the recommendations of the 2007 SEEDO Conference [Body weight is to be determined on two occasions using a homologated electronic scale (Seca 770) following due calibration (precision ± 0.1 kg), with the patient wearing light clothing and no shoes. These readings will be rounded to 100 g. Height in turn will be measured with a portable system (Seca 222), recording the average of two readings, and with the patient shoeless in the standing position. The values will be rounded to the closest centimeter. Body mass index (BMI), fibrinogen and glycosylated hemoglobin (HbA1c) in blood and microalbuminuria. The parameters will be measured on a blind basis in the reference laboratory after patient fasting for at least 8 hours.Office blood pressure measurement involves three measurements of systolic (SBP) and diastolic blood pressure (DBP), using the average of the last two, with a validated OMRON model M7 sphygmomanometer , by following the recommendations of the European Society of Hypertension . Pulse pThis parameter will be measured using an OMROM model M7 sphygmomanometer . Three measurements will be made in the morning (between 6:00 and 9:00 a.m.), and three in the afternoon/evening (between 18:00 and 21:00 p.m.), over a period of 7 days, with a minimum interval of one minute between measurements, and excluding the first measurement in each case and the values corresponding to the first day of measurement . The invThe ABPM was performed on a day of standard activity, with an adequate cuff for the size of the patient's arm. A control system, SpaceLabs 90207 model , validated according to the protocol of the British Hypertension Society, was used . The recCarotid ultrasonography to assess IMT was performed by two investigators specifically trained for this before starting the study. A Sonosite Micromax ultrasound  device paired with a 5-10 Mhz multifrequency high-resolution linear transducer with Sonocal software was used for performing automatic measurements of IMT for optimising reproducibility. Measurements were made of the primitive carotid after the examination of a longitudinal section of 10 mm at a distance of 1 cm from the bifurcation, performing measurements in the anterior or proximal wall, and in the posterior or distal wall in the lateral, anterior and posterior projections, following an axis perpendicular to the artery to discriminate two lines, one for the intima-blood interface and the other to the media-adventitious interface. A total of 6 measurements were obtained of the right carotid and other 6 of the left carotid, using average values (average IMT) and maximum values (maximum IMT) calculated by the software automatically. The measurements were obtained with the subject lying down, with the head extended and slightly turned opposite to the carotid examined, following the recommendations of the Manheim Carotid Intima-Media Thickness Consensus . FinallyThis was evaluated using the ankle-brachial index (ABI), performed in the morning without having consumed coffee or tobacco for at least 8 hours prior to measuring and an ambient temperature of 22-24°C. With the feet uncovered, in a supine decubitus position after 20 minutes of rest, the pressure in the lower extremities was measured using a portable Doppler system Minidop Es-100Vx  applying the probe at the anterior or posterior tibial artery at an angle of approximately 60° to the direction of blood flow. The transducer's cuff was quickly inflated in each ankle about 30 mmHg above the systolic pressure and the pressure was allowed to descend (by about 2 mmHg per second) until the first sound corresponding to the systolic pressure was heard. The blood pressure was also measured in both arms . The ABI was calculated separately for each foot by dividing the higher of the two systolic pressures in the ankle by the highest of the two systolic pressures in the arm . It is cThe electrocardiographic examination was performed with a General Electric MAC 3.500 ECG System , that measures automatically the voltage and duration of waves and estimates the criteria of the Cornell voltage-duration product (Cornell VDP)  to assesThe kidney damage was assessed by measuring creatinine plasma concentration, the glomerular filtration rate was estimated by CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration)  and the Retinography was performed with a Topcon TRC NW 200 non-mydriatic retinal camera (Topcon Europe B.C. Capelle a/d IJssel The Netherlands), obtaining images centered on the papilla. Once the images were captured, two independent observers classified them according to the Keith-Wagener classification for hypertensive retinopathy , with a The pulse wave velocity (PWV) was calculated using the SphygmoCor System (Vx Pulse Wave Velocity),  with the patient in the supine decubitus position. The carotid and femoral pulse wave was analyzed, estimating the delay in the electrocardiograma (ECG) wave and calculating the PWV. The space measurements were taken with a measuring tape from the suprasternal notch to the carotid and femoral arteries at the sensor location. A measurement of greater than 12 m/s is considered subclinical organ damage .Using the SphygmoCor system , with the patient in the sitting position and resting the arm on a rigid surface, pulse wave analysis will be made with a sensor in the radial artery - using mathematical transformation to estimate the aortic pulse wave. From the aortic wave morphology, central (aortic) arterial pressure will be estimated, along with central ventricular load, diastolic perfusion pressure, the subendocardial viability index, the pressure increment, central pulse pressure and the augmentation index (PWA), defined as the percentage increase in central pulse pressure: AIx = pressure increase/pulse pressure * 100 .All explorations will be carried out on a yearly basis, and due registry will be made of any changes in the sociodemographic variables or cardiovascular risk factors, and of the appearance of events.The patients referred to the research unit of La Alamedilla primary care center will be interviewed by a contracted nurse specifically trained for the project. A history will be compiled and a basic exploration will be carried out. A 24-hour ambulatory blood pressure monitoring (ABPM) device will be fitted, and the patients will receive an OMRON M7 sphygmomanometer for self-measurement of blood pressure at home. Vascular exploration will be made , and an appointment will be made for blood sampling. Posteriorly, carotid artery ultrasound will be performed by two specifically trained members of the research team. Data input will be made using the Teleform system , with a questionnaire previously designed for the project, and exporting the data to the SPSS version 15.0 statistical package  for posterior analysis.A first descriptive analysis will be made of the sociodemographic and clinical characteristics of the study groups. The data will be presented with the mean and 95% confidence interval in the case of quantitative variables, and as frequency distributions for qualitative variables. The Pearson chi-squared test will be used to analyze associations between qualitative variables. The Student t-test for independent samples will be used to compare the means for the two arterial pressure groups. In turn, the analysis of repeated measures will be based on the McNemar test for qualitative data and the Student t-test for paired data in application to quantitative data.Survival will be analyzed with the Kaplan-Meier and actuarial methods on each visit and at the end of follow-up. The log-rank test will be used for comparing survival in the two groups. Lastly, a Cox regression model will be developed to estimate the event risk between the groups, adjusting for the possible confounding variables analyzed in the study.Hypothesis contrasting will establish an alpha risk factor of 0.05 as the limit of statistical significance. The SPSS/PC+ version 15.0 statistical package will be used .Different processes will be carried out to guarantee study data quality and thus maximize the validity and reliability of the measurements of the results. To this effect, field work operative manuals have been developed, specifying the correct technique for performing each of the tests. Educative leaflets have also been developed to ensure that the patients correctly perform pressure measurement in the home - all these measures confirming the correct practical application of each technique. Meetings will be held on a weekly basis with the principal investigator of the study in order to analyze the entire process, and an annual report on the course of the study will be prepared.In order to guarantee data confidentiality, all the electronic and paper copies of the protocol, signed informed consent documents and results of the tests made in each of the patients will be kept locked in a safe place, and only the study investigators will have access to the data on the subjects who agree to participate in the study.The study has been approved by the ethics committee and complies with Spanish data protection law 15/1999 and its recently developed specifications  1720/2007). Knowledge and agreement to cooperate has been established with the implicated services, signed by the legal representative of the center.The results of this study will be of great scientific relevance, since they will allow us to quantify the degree to which central arterial pressure and pulse wave velocity are related to the different target organ lesions , and to analyze their course over time. To our knowledge, this is the first study to assess target organ damage in diabetic patients and its relationship to central arterial pressure and pulse wave velocity over a follow-up period of at least four years.Pulse wave velocity is the gold standard for assessing the stiffness of the large arteries, and is an important predictor of cardiovascular events . A recenAs regards the relationship between these arterial stiffness measures and target organ lesions and their course over time in diabetic individuals, the existing evidence is scarce and inconclusive. With the present study we hope to contribute evidence to clarify some of these issues.The main limitation of this study is its small sample size for assessing end events. However, this is remedied by the fact that the analysis will be made with the data of a multicenter study in which 800 patients will be included.DM2: Diabetes mellitus 2; AH: Arterial hypertension; BMI: Body mass index; CBP: Clinical blood pressure; BP: Blood pressure; SBP: Systolic blood pressure; DPB: Diastolic blood pressure; HBP: Home blood pressure; ABPM: Ambulatory blood pressure monitoring; ABI: Ankle-brachial index; IMT: Intima-media thickness; HbA1c: Glycated hemoglobin; LVH: Left ventricular hypertrophy; PWV: Pulse wave velocity; ECG: Electrocardiographic; MDRD: Modification of Diet in Renal Disease.The authors declare that they have no competing interests.Conception of the idea for the study: MAGM and LGO. Development of the protocol, organization and funding: MAGM, LGO, ERS, JIRR, YCS, AdCL, BSS, CRM, CCS and LGS. Writing of the manuscript: MAGM. All the authors have read the draft critically, to make contributions, and have approved the final text.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/10/143/prepub


It has recently been hypothesised that acute dehydration in early childhood may “programme” increased blood pressure via salt retention. We examined whether there was an association between episodes of diarrhoea (a proxy for acute dehydration) and later measured blood pressure.In the 1982 Pelotas birth cohort study (Brazil), parents/carers reported hospital admissions for diarrhoea in the first 12 and 20 months of study members’ lives. Blood pressure was subsequently measured directly in adolescence  and early adulthood (aged 23 years).We found no evidence of an association between diarrhoea in the first 12 months of life and blood pressure measured at any point in adolescence or early adulthood. These findings were unchanged after adjustment for a range of covariates. Equally null results were apparent when diarrhoea admissions in the first 20 months of life, access to home sanitation and use of piped water were the exposures of interest.Early life proxies for dehydration and diarrhoea were unrelated to later blood pressure in this examination, the most comprehensive to date, of the potential association. It has recently been suggested that dehydration in infancy, most likely resulting from an episode of diarrhoea, will subsequently lead to a permanent elevation in blood pressure in humans.–The few empirical tests of this hypothesis have been inconclusive. UK children who had a hospital record of dehydration in the first 6 months of life had raised diastolic but not systolic blood pressure.4Several of these studies are characterised by a low number of cases of dehydration or diarrhoea, which hampers data interpretation. The Pelotas study,The 1982 Pelotas birth cohort study has been described in detail elsewhere.8Blood pressure measurement, together with height and weight, was taken in 1997 when the cohort members were aged approximately 15 years ; in 2000 when aged approximately 18 years ; in 2001 when aged approximately 19 years ; and, finally, 2004/5 when aged approximately 23 years . In the earlier home visits, blood pressure was measured twice, at the beginning and at the end of the interview, in the sitting position with a calibrated aneroid sphygmomanometer with appropriate cuff size. In the 2004/5 visit, blood pressure was again recorded twice but using an Omron digital portable wrist monitor . The mean of the two readings were used in the present analyses.Using multiple linear regression we compared the blood pressure of study members who had experienced diarrhoea in the first 12 months of life with those who had not . The perIn the largest analytical sample based on a re-survey of study members with data on diarrhoea status at 20 months and measured blood pressure at age 23 years , the was again no evidence of a diarrhoea–blood pressure relationship. Thus, in 344 diarrhoea cases (8.7%) among 3944 study participants, there was no difference  in systolic  or diastolic  blood pressure according to diarrhoea status in multiply adjusted analyses. All other diarrhoea–blood pressure associations were similarly null.Finally, there was no suggestion that either type of water supply or sanitation facilities in early life, themselves related to diarrhoea occurrence in this cohort, was associated with later blood pressure at any point in follow-up (results not shown).In the present dataset we found little support for any link between diarrhoea in the first 12 or 20 months of life and later blood pressure. The very few results that attained statistical significance at conventional levels are likely to be chance findings given the large number of tests necessarily conducted in the course of these analyses. These findings accord with those from pooled analyses of cohorts from Hertfordshire (UK) where no relation was seen for nurse-recorded diarrhoea up to 5 years of age and blood pressure in old age.In the present study, hospital admissions for diarrhoea may be due to dehydration but also persistent diarrhoea and dysentery. It is not possible to know what proportion of study members were admitted for the former, which is of particular relevance to our programming hypothesis. Further investigation of its association, if any, with blood pressure is therefore required. As outlined elsewhere,In conclusion, in the most comprehensive examination to date of the association between childhood diarrhoea and later blood pressure, we found no support for a relationship.Studies exploring the association between dehydration in early life and later blood pressure reveal equivocal findings and have low statistical power. We attempted to contribute to this evidence base, which is of particular importance in low- and middle-income countries, by examining the association in a cohort which offers both a higher prevalence of diarrhoea (a proxy for dehydration) and a greater number of serial blood pressure measurements than has previously been the case.In the most comprehensive examination to date of the association between childhood diarrhoea and later blood pressure, we found no support for a relationship.


An investigation of emergency department (ED) poisonings was conducted to characterize poisoning demographics and evaluate correlations with select co-morbidities.The study population evaluated consisted of 649 poisoning cases admitted between 2004 and 2007 to an inner-city, level 1 emergency department.P = 0.0001), cocaine poisoning and hypertension , and cocaine poisoning and cardiovascular disease . A change in the pattern of illicit drug use from injection to inhalation was detected and the resulting increase of inhalation and insufflation of illicit substances may partially explain the correlation found between heroin use and asthma.Ethnicity, age, and gender had a substantial impact on the population distribution as poisoning cases were predominantly African Americans (79.9%) between 36 and 45 years old with a 1:3 male to female ratio. Intentional illicit drug overdose was the most prevalent cause of poisoning, heroin being the most frequent substance found in 35.4% (n = 230) of cases, followed by cocaine overdose at 31.7% (n = 206), concomitant heroin and cocaine overdose at 4.3% (n = 28), multiple drug poisoning at 5.5% (n = 36), and antidepressant/antipsychotic poisoning at 6% (n = 39). Significant correlations were found between heroin poisoning and asthma (F = 20.29, DF = 1, These results provide supporting evidence that deliberate poisoning with illicit drugs remains a serious healthcare issue that significantly aggravates co-morbidities and raises treatment costs by increasing both the rate of hospitalization and hospital length of stay. Poisonings from substance abuse and accidental toxic exposure remain a significant concern for hospital emergency departments (ED), with more than four million incidents of poisoning occurring in the United States each year. The Institute of Medicine has recently identified poisoning as the second leading cause of injury-related mortality, with an estimated health care cost of over $12.6 billion annually.2Substance abusers are frequently seen in the ED and the predominating substances being abused generally reflect regional and local trends for illicit drug use. Trends in the United States for illicit drug use indicate that cocaine abuse decreased between 1992 and 2002, though patterns of abuse were not consistent throughout the country as cocaine use actually increased 100% or more in four states during this same time period. Among peHeroin use remains a serious problem in some regions of the United States. A recent change in the route of heroin use has been observed, from a decrease in intravenous injection to the practice of heating heroin in aluminum foil for inhalation. There has also been an increasing trend for mixing heroin with cocaine to be smoked in this manner.Although heroin and cocaine remain the most frequently abused drugs leading to ED visits, ED visits involving prescription narcotic analgesics increased 153% from 1995 to 2002. Concomitant use of drugs were involved in 75% of the drug abuse–related ED visits, and dependence was an underlying factor in these cases. Substance abusers are more likely to be hospitalized for acute intoxication, and 2.3 times more likely to use an emergency room than non-abusers.7et al. 1993 reported a relationship between heroin abuse and pulmonary edema, which was supported by Marby et al. 2004 who found a pattern of heroin overdose-induced pulmonary edema.[9et al. 2005 found that cocaine and heroin abuse increased the rate of intubations and hospital utilization in patients with acute asthma exacerbation.[The association of drug abuse and respiratory co-morbidities, particularly between cocaine and asthma, has been reported sporadically in the scientific literature. In an investigation conducted in Bronx, NY, a correlation between cocaine use and new onset asthma was reported amongst substance abusers. Steenseny edema.9 Levine eerbation.Knowledge of condition-specific morbidity and mortality for patients with asthma as well as other aggravating factors is essential for making critical decisions in emergency care. Some evidence exists indicating that drug abuse may be increased among asthma patients and that drug use may exacerbate their condition, though the etiology and mechanism of action for this pathology has not been explained. There is a need, especially for emergency care providers in underserved minority communities with high frequencies of poisonings and substance abuse, to understand the demographic factors involved in poisoning and related co-morbidities.The study population consists of Chicago city residents visiting the ED of the Sinai Hospital between December 2004 and May 2007. The Sinai Health System provides virtually all-medical and surgical care in the area, including a children's hospital and a rehabilitation center. The ED serves residents up to 5 miles west of the downtown area.Data collection was performed according to HIPAA regulations after approval by the hospital's Institutional Review Board (IRB) committee. The setting was the ED of an inner city level one trauma center with approximately 45,000 visits per year. Patients between 1 and 89 years old and exposed to poisons counting chemical, recreational, and/or pharmaceutical agents were selected. The study population consisted of 649 poisoning cases admitted between 2004 and 2007 to a level 1 ED. Cases were identified using the International Classification of Disease Ninth Revision, (ICD-9-CM). Demographic health data abstracted from patients' medical records included age, gender, race, date and time of the visit, marital status, employment, insurance coverage, chief complaint, and vitals on admission. Data on personal medical history of diabetes mellitus, hypertension, cardio-vascular diseases, asthma, arthritis, HIV status, hepatitis, and seizure disorder was collected. The poisoning data collected referred to the type of poison, the poisoning exposure route, and the circumstances of intoxication . The initial management of the event was also determined in an attempt to correlate it to the final disposition of the cases. Smoking, alcohol use, illicit drug use, insurance coverage, hospital charges, length of stay for those hospitalized, and any history of mental illness such as depression, psychosis, and anxiety disorder was collected from all case records.Poisoning exposure was grouped into fifteen toxic substances or drugs in four separate categories: Pharmaceutical or medicinal drug use, recreational drug use, chemical exposure, and industrial exposure. Circumstances of the exposure were also captured and categorized into intent groups that included: Suicidal, abuse, misuse, unintentional exposure, therapeutic use, and adverse drug events (ADE). The route of exposure was recorded as: Inhalation, ingestion, injection, dermal, and rectal/vaginal. To assess poisoning burden inpatient length of stay (LOS) and health care expenditures on asthmatic patients with a history of drug addiction and poisoning were compared to those with asthma and addiction but with no history of poisoning.t-test or one-way analysis of variance (ANOVA) between groups. The categorical data between groups was analyzed with Chi square tests and full factorial univariate analyses by stepwise multiple logistic regression. Correlation analysis was conducted using the Pearson r correlation coefficient. A P value of less than 0.05 is considered statistically significant. The data was analyzed using SPSS 16.0 statistical package.Continuous variables such as age, length of hospital stay, and duration of time between poisoning and hospital arrival was analyzed using student's n = 277) female and 55.9% (n = 363) male. Poisoning cases were predominantly African Americans (79.9%) followed by Hispanics (11.9%), and Whites (6.6%). Over 69.3% of the total cases were single in comparison to 12.3% who were married. Most patients were uninsured (45.8%), while 35.1% were covered by the Illinois Department of Public Aid (IDPA), Medicare and Medicaid covered 8.2%, and only 5.9% of patients had private coverage.Between December 2004 and May 2007 a total of 649 ED poisonings were identified. The majority of poisoning cases were between 36 and 45 years old. Pediatric cases younger than 15 years old represented only 4.6% of cases and the most frequently affected age was 48. Of the total of 649 poisoning cases there were more male, than female, with 42.7% (n = 230), cocaine 31.7% (n = 206), heroin and cocaine concomitantly taken 4.3% (n = 28), alcohol 2.2% (n = 14), multiple drugs 5.5% (n = 36), antidepressant/antipsychotic 6% (n = 39), ASA 3.4% (n = 22), cardio vascular drugs 2% (n = 13), anti-cold medications 1.1% (n = 2.2), methadone 0.6% (n = 4), CNS stimulants 0.8% (n = 5), Analgesics 1.5% (n = 10), Marijuana 0.5% (n = 3), unknown pills 1.7% (n = 11), and “other” substances 2.9% (n = 19). The routes of poisoning exposure included inhalation 61.5% (n = 400), ingestion 21.1% (n = 137), rectal/vaginal 10.6% (n = 69), and injection at 5.2% (n = 34.). The exposure circumstances included: Abuse 76% (n = 498), suicidal 13.4% (n = 87), misuse 2.2% (n = 14), unintentional 3.2% (n = 21), therapeutic 2.5% (n = 16), and ADE 0.6% (n = 4).The exposure substances identified as most commonly encountered in ED included: Heroin 35.4% (P = 0.0001), as well as between history of cardio-vascular disease and exposure to cocaine . Another significant relationship was detected for the use of cocaine and a history of preexisting hypertension . Depression and psychosis were significantly associated with overall poisonings .A significant relationship was found between asthma and the exposure to heroin . Another significant relationship  was detected between those with a history of alcohol use and poisoning. History of recreational drug use was also found to be significantly related  to poisoning.A statistically significant relationship was found between poisoning exposure and the history of smoking  of cases were diagnosed with a prior history of hypertension.Over 31% (n = 54) used heroin and 47.2% (n = 94) used cocaine, 4% (n = 8) had used a combination of both heroin and cocaine, and 5.5% (n = 11) who used anti-depressants/anti-psychotics. Sixty percent (n = 121) reported they had taken other prescription medications on the day of their poisoning. Over 71.9% (n = 143) of patients with hypertension were hospitalized and only 26% were discharged from ED. Hypertension was not correlated to poisoning overall, however, it was correlated specifically to cocaine poisoning (P = 0.0001).Among these, 27.1% (n = 23) were diagnosed and treated for a psychotic disorder. Most asthma patients had a history of recreational drug use 86.1% (n = 229). Therapeutic adverse events were also reported among asthma patients at a rate of 2.2% (n = 6) and misuse of drugs at a rate of 1.1% (n = 2).Depression among asthma patients was prevalent at 18.2%, and 8.6% (n = 146) of asthmatics. Inhalation was the most commonly reported mode of exposure of asthmatics at 75.5% (n = 203), ingestion was seen in 11.5% (n = 31), then injection 6.3% (n = 17), rectal or vaginal at 4.5% (n = 12), and dermatological 1.1% (n = 3). Smoking was prevalent among asthmatics at 65.1% (n = 175) and regular alcohol intake was seen in 54.6% (n = 147) of asthmatics. At the time of the exposure, 67.7% of asthma patients reported that they were taking their asthma routine maintenance medication and 53.2% of the total asthma groups were under albuterol treatment.A history of prior poisoning that led to an ED visit or hospitalization for similar events was present in 54.3% (P = 0.0001). Asthma was not correlated to any of the other substances of exposure including cocaine, alcohol, or concomitant use of heroin and cocaine. ANOVA resulted in a statistically significant relationship between asthma and depression (P = 0.044) and to psychosis (P = 0.028), however smoking was not statistically significantly associated with asthma with a P value slightly greater than 0.05 (P = 0.066).A significant relationship between exposure to heroin and history of Asthma was found (P = 0.001). Heroin was also found to be correlated to many other variables in our population, such as depression, psychosis, and cardio-vascular diseases [The Pearson correlation test displayed a statistically significant relationship between asthma and heroin use  and to cardiovascular diseases . Cocaine was also significantly correlated to heroin, to heroin and cocaine combined use, to multiple drug use, smoking, and to regular alcohol intake [Cocaine was found to be significantly correlated to chronic hypertension , as was hospital cost (P < 0.0001.).Poisoning and drug addiction remain a significant burden on the healthcare system. The mean LOS for asthmatics without drug abuse was 1.21 days. For asthmatic patients with a history of illicit drug poisoning the mean LOS was 7.07 days. The hospital charges ranged between $99.00 and $18,096.00 with a mean of $2,941 for asthmatics without abuse and between $52.00 and $695,874.00 with a mean of $28,028.00 for the group of asthmatics with illicit drug poisoning. The difference between the LOS for patients with asthma who abused heroin and/or cocaine compared to LOS of asthmatics without abuse was statistically significant .–15 One s16Whereas the mechanism of action for heroin use on asthma remains poorly characterized, the correlation between cocaine use and cardiovascular disease might be more readily explained due to the effect of cocaine on the heart and blood vessels. Cocaine has also been shown to have numerous other effects on cell signaling systems and the vascular bed by modifying peripheral resistance and inducing a potent vasospasm that raises the blood pressure and increases the cardiac output. By the sThere are several potential limitations to this study. The study is retrospective and the information was collected from the patients' charts, which varied in accuracy and availability between cases. Due to the high rates of drug abuse history, it does not seem that this study underestimated the abuse; however, it might have underestimated some co-morbidity such as arthritis, and particularly depression, which is still not screened systematically for every patient visiting ED, especially in a setting of drug overdose emergencies. Another potential limitation of this study was that there was no way for the study to follow up on specific cases and screen patients for suicidal ideation to find out if they have had any intent for self-harm. Future studies might be designed to avoid these limitations by systematically screening of suicidal intent in these poisoning cases as well as assessing undiagnosed depression and other preexisting mental disorders.The results of this study provides supporting evidence that deliberate poisoning with illicit drugs remains a serious healthcare issue that significantly aggravates co-morbidities and raises treatment costs by increasing both the rate of hospitalization and hospital length of stay. Heroin abuse is a burden on asthma patients in terms of both their health and hospital costs, particularly for those that are not covered by insurance. Asthma education and self-management techniques that acknowledge the impact of the use of recreational drugs, specifically heroin or cocaine by insufflations, needs to be provided and patients must be educated on how to prevent significant asthma exacerbation by avoiding common triggers, drug use, and other additional stressors.


Liposuction is a surgical technique to remove excess fat deposits from specific areas of the body. Purpose of this study is to determine how far large volume liposuction is safe and effective.From July 2003 to December 2005, 60 female patients had liposuction of different areas of the body as waist, hips, buttocks, thighs, and knees. Their mean age was 30.6 ± 15.4 years old. A standard liposuction technique was done by using a tumescent infiltration formula. The average amount of infusate was 3000 cc, with an average aspirate amount of 6000 cc. Pre-operative anthropometric measurements as weight, height, body mass index, areas to be liposuctioned in addition to pre-operative hematological investigations as complete blood picture, blood sugar, liver function tests, blood urea, serum creatinine, and serum cholesterol were done.th week, and 4th month after surgery. The rate of complications was low and relatively minor in nature. No major complications were presented. Minor complications have occurred as skin irregularities (20%), Seroma (15%), Garment pressure sore (10%), Cutaneous hyper-pigmentation (5%).The results were evaluated with preoperative and postoperative photographs. Postoperative anthropometric measurements and hematological investigations were done at 6Large-volume liposuction can be performed safely and it can produce desirable morphological and hematological changes. Obesity is a growing health problem. Excess weight and obesity increase morbidity and mortality associated with numerous complications, including type 2 diabetes mellitus, hyperlipidemia, hypertension and atherosclerosis . LiposucIt removes excess fat deposits from specific areas of the body, including chin, neck, cheeks, and upper arms, above the breasts, abdomen, buttocks, hips, thighs, knees, calves and ankles . The besThere are different techniques of liposuction such as dry, wet, super wet and tumescent techniques. Tumescent technique is considered a significant improvement in liposuction surgery. It uses large volumes of a dilute solution of lidocaine, a local anesthetic, in combination with epinephrine. This technique dramatically reduces both the bleeding during surgery and the post-operative bruising and swelling .The most common definitions of large volume liposuction refer to either total fat removal during the procedure  or total volume removed during the procedure  [As with any surgical procedure, liposuction is associated with certain expected side effects such as bruising, swelling and temporary numbness. Although irregularities of the skin are possible following liposuction, this is minimized by the tumescent technique . Major cAs judged by current worldwide experience, liposuction is amazingly safe. Serious complications as infections and allergic reactions are extremely rare.• This study aimed at evaluating the degree of morphological improvement as well as hematological changes in patients undergoing large volume liposuction.st, 2003 and December 31st 2005 with obesity as defined by the WHO (BMI > 30 kg/m2) [• Inclusion criteria, all females admitted to our plastic surgery department between July 10 kg/m2) , request• They were presented by varying degrees of lipodystrophy in different body regions including .• Exclusion criteria, the presence of significant medical diseases such as diabetes (n = 7), cardiac (n = 5), renal (n = 4), hepatic (n = 2), gastrointestinal (n = 2), endocrinal diseases (n = 2) or body dysmorphic disorders (n = 3). These cases were excluded in order to avoid the potential confounding effects that these diseases might introduce.• Each patient was subjected to full history, systematic examination.• Pre-operative anthropometric measurements were taken for every patient including weight, height, body mass index, circumference of the areas to be lipsuctioned as waist, hips, buttocks, thighs, and knees.• Pre-operative hematological investigations in the form of complete blood count, Blood sugar level, Blood urea and serum creatinine, Liver function tests , and Serum cholesterol.• Hemoglobin level and hematocrit value were measured using Celldyne automated cell counter, while blood glucose, urea, serum creatinine, total proteins, albumin, uric acid, total cholesterol were measured using Cobus Integra automated chemistry analyzer (Roche diagnostics kits). The same methods and kits were used for all patients and in all follow up measurements.• Intra-operative local examination of the suctioned part was done by the use of the following tests: static pinching test, dynamic pinching test and the speed of retraction test.• Our cases undergone Tumescent liposuction in which the surgeon injects a solution containing a local anesthetic and vasoconstrictor directly into the subcutaneous fat to be removed. The volume of fluid creates a space between the muscle and the fatty tissue allowing more room for the cannula.• Spinal anesthesia was the rule in all cases.• Intra-operative monitoring of the patients for oxygen and carbon dioxide tension, blood gases, electrocardiography, and urine output through insertion of urinary catheter.• Tumescent formula (Modified Klein's solution) was used which consists of, 20 ml of 2% lidocaine, 1 ml adrenaline (1:1000), 5 ml of sodium bicarbonate solution (8.4%) and Mixed in 500 ml of lactated Ringer's solution.• The injection was continued until the skin became firm and turge.• Marking, positioning, and small stab incision.• Pre-tunneling.• Cross tunneling.• Complete suction indicated when, pinch test less than 1 inch and/or change of feeling from soft to gritty sensation and/or aspirate mixed with blood.• Pressure garment applied for 6 weeks .rd week, soothing corticosteroid creams for 6 weeks and strict diet regimen starting at the end of the 6th week.Broad spectrum antibiotics, non-steroidal anti-inflammatory analgesics twice daily for 2 days, multi-vitamins and iron supplements were routinely given to every patient for one month postoperatively, early ambulation from the second day after surgery, pressure garments for 6 weeks, post-operative massage and ultrasonic wave therapy starting at the 3th week and at the end of the 4th month.Repetition of the anthropometric and hematological measures at 6SPSS version 13 was used for analysis of data which included descriptive analysis and paired t-test for comparison between measurements before the operation and 6 weeks after the operation and also comparison between measurements before the operation and 4 months after the operation.This study included 60 females; their mean age was 30.6 ± 15.4 years old. Overall, patients' weight and body mass index decreased significantly both at 6-weeks post-operative period and at 4-months post-operative period (P < 0.001), table The average amount of liposuction infusate was 2755 cc, with a mean aspirate amount of 6395 cc. Local examination and pre-operative evaluation of the areas of bulge of the patients was done to assess the areas in need for liposuction. We found that all the patients were in need for hip and thigh liposuction and fourteen patients were in need for waist liposuction, twelve patients for knee and four patients for buttocks liposuction in addition to hip and thigh suction, figures , 5. TherThe pulse rate was not decreased significantly at 6-weeks post-operatively but it showed a significant decrease at 4 months postoperatively. There was a significant decrease in systolic blood pressure both at 6 weeks and 4 months post-operatively while there was non-significant decrease in diastolic blood pressure both at 6-weeks and 4 months post-operatively, table Blood glucose level decreased non-significantly 6 weeks after surgery but it started to decrease significantly at 4 months post-operatively. Blood urea and serum creatinine levels decreased significantly both at 6 weeks and 4 months post-operatively.There was a significant decrease in the total protein level, total cholesterol level and serum albumin level 6 weeks after surgery but gradually returned to near the pre-operative levels 4 months post-operatively. There was a significant decrease in the serum uric acid both at 6 weeks and 4 months post-operatively, table Cases did not present with any major complications but only some of them presented with minor complications as skin irregularities in 20% of the patients, seroma in 15%, garment pressure sore in 10% and cutaneous hyperpigmentation in 5%.Since liposuction was initially introduced to the surgical community, its applications have progressively broadened from its use in small regional operations to total body contouring. The tumescent technique uses a large volume of vasoconstrictive subcutaneous infiltration and produces the greatest degree of hemostasis. Approximately 1% of the aspirate is blood . In our No blood transfusion was needed postoperatively for any of our cases. Paul et al  who perfLarge-volume liposuction caused significant decreases in pulse rate and systolic blood pressure over the 4-month post-operative period. The same was found by many authors -15 who rOur results showed significant decrease in the blood glucose level after 4 months postoperatively and this agrees with Gonzalez et al  who showOur results showed significant decrease in blood urea, serum creatinine and uric acid, many authors reported the same effects -20. ConcThe lipid profile showed a significant decrease of the serum total cholesterol level 6 weeks after surgery but returned gradually to near the pre-operative levels at 4-months postoperative period and these results are nearly the same as other investigators ,21 this Overall complication rates were low and relatively minor in nature. There were no major complications even with suctions of larger volumes of fat. These rates were also reported by nearly all authors especially among those who perform large-volume liposuction ,11.Large-volume liposuction can be performed safely and it can produce desirable morphological and hematological changes.The authors declare that they have no competing interests.YS & ME & AA & AT carried out the patient selection, investigation, follow up and management.AT & AAA-E carried out patient management, investigations, follow up, drafting of the manuscript, writing the final manuscript and provided important suggestions.All authors read and approved the final manuscript.Written informed consent was obtained from all patients for publication of this manuscript and any accompanying images. A copy of the written consents is available for review by the Editor-in-Chief of this journal.


Prevention of pre-hypertension is an important goal for primary care patients. Obesity is a risk factor for hypertension, but has not been addressed for pre-hypertension in primary care populations. The objective of this study was to assess the degree to which obesity independently is associated with risk for pre-hypertension in family medicine patients.This study was a retrospective analysis of information abstracted from medical records of 707 adult patients. Multivariable logistic regression was used to test the relationship between body mass index (BMI) and pre-hypertension, after adjustment for comorbidity and demographic characteristics. Pre-hypertension was defined as systolic pressure between 120 and 139 mm Hg or diastolic pressure between 80 and 89 mm Hg.In our sample, 42.9% of patients were pre-hypertensive. Logistic regression analysis revealed that, in comparison to patients with normal body mass, patients with BMI > 35 had higher adjusted odds of being pre-hypertensive . BMI between 30 and 35 also was significant  as was overweight .In our sample of family medicine patients, elevated BMI is a risk factor for pre-hypertension, especially BMI > 35. This relationship appears to be independent of age, gender, marital status and comorbidity. Weight loss intervention for obese patients, including patient education or referral to weight loss programs, might be effective for prevention of pre-hypertension and thus should be considered as a potential quality indicator. Obesity is an independent risk factor for a number of chronic diseases, including hypertension, diabetes, knee replacement, pancreatitis, insomnia, chronic fatigue, and early death. It alsoWeight loss might aid in prevention of pre-hypertension. However, the relevance of weight loss interventions as quality indicators has not been explored. This is an interesting omission, since action to encourage another type of behavior change, smoking cessation, is regarded as good medical care.The objective of this study was to assess the degree to which obesity independently is associated with risk for pre-hypertension in family medicine patients. If obesity increases risk to a clinically relevant extent even after adjustment for age, comorbidity and gender, then in-clinic counseling or referral to weight management programs might be indicated. We use these findings as a starting point to discuss obesity as a quality indicator and potential barriers and strategies for effecting weight loss in primary care clinics.A random sample of adult patients treated in our clinics  and referred for specialist consultations was obtained to evaluate specialty referrals in our department. The data were reanalyzed for the present study. The sample was drawn during the period January through June of 2006. During the period June 2006 through March 2007, patients for whom virtual specialist visits were ordered were added to the data base. An index visit was defined as the visit in which a specialist consultation was ordered. Medical records were the sole source of information used in this study.Blood pressure was recorded for 989 adult patients at the index visit. BMI was missing for 147 patients. Patients whose blood pressure exceeded 140/90 mm Hg were excluded since the research question concerned pre-hypertension. Our final sample included 707 subjects for whom systolic and diastolic pressures, severity, body mass index, age, gender and marital status information was available within six months before or after the index date. Data collection was approved by the local Institutional Review Board as a component of an evaluation of specialty consultation visits. The requirement for obtaining patient consent was waived by the IRB since this was a retrospective review of medical records limited to patients who had granted blanket approval for such studies.The dependent variable in this study was pre-hypertension (yes or no), defined as systolic pressure between 120 and 139 mm Hg or diastolic pressure between 80 and 89 mm Hg. Single blood pressure measurements were used in order to minimize missing data.Independent variables included body mass index (BMI), age, gender, marital status, and severity of illness. Nurses measured weight and height as a routine component of clinic visits and our electronic medical record automatically computed body mass index (BMI). BMI was categorized as "normal" if below 25, "overweight" if between 25 and 30, "Obese I" if between 30 and 35, and "Obese II" if over 35.Age was broken into categories: 18–35, 36–45, 46–55, 56–65, and 66–100. Marital status was coded as married or not married.The Charlson index was used to score co-morbidity. Two traReliability checks were performed to assure coding was being performed in the same way by both raters. Blinded agreement between raters on the total severity score was 80 percent.p < 0.05. We then performed multivariable logistic regression analyses to identify independent associations between the various independent variables and the odds of being pre-hypertensive. All demographic and clinically relevant variables were forced into the model. These included BMI, Charlson score, age, gender, and marital status. Statistical analysis was performed using EpiInfo version 3.3.2.Independent variables, including BMI categories, were compared to hypertensive status in univariate tests using chi-square. A difference between categories was considered statistically significant if Table Multivariable logistic regression analysis was performed to determine the independent effects of BMI category on pressure  BMIs should be recorded in the medical record at least biannually for all patients who visit their providers biannually; and 2) for morbidly obese patients, documentation should be found in the record indicating that some action was taken, such as patient education or referral to a weight loss program. At a minimum, educational materials should be offered that will allow patients to pursue self-help strategies. The purpose of this second recommendation is to prevent pre-hypertension and other medical consequences of obesity.Routine recording of BMI in the electronic record is an important prerequisite to increasing referrals to weight management programs . ConsensAdditional research is needed to test the relative effectiveness of different approaches to weight loss. Variables include the number and length of visits required to help patients lose weight, the types of providers who can most cost-effectively provide the service , and the best modalities . Since we lack firm evidence on the merits of different approaches, the decision about what type of service should be recommended can be left to patient preferences.The author(s) declare that they have no competing interests.JER designed the study, analyzed the data and wrote the first draft. GA and JF wrote additional material. All authors have read and approved the final version of the manuscript.The pre-publication history for this paper can be accessed here:


P for linear trend, 0.11). In men, there was no association with blood pressure.In a prospective study of 36 728 women and 35 688 men during 18 years of follow-up, compared to systolic pressure <130 mm Hg, levels of 130–149, 150–169 and ⩾170 mm Hg in women were associated with relative risks of renal cell cancer of 1.7, 2.0 and 2.0, respectively ( The association of blood pressure with risk of renal cell cancer has been investigated in a number of cohort  in Norway, and 75 058 (88.2 percent) accepted the invitation, filled in a self-administered questionnaire, and attended a clinical examination  divided by the squared value of height (in metres), and grouped into four categories: <18.5, 18.5–24.9, 25–29.9 and ⩾30. Information on smoking was categorised as never, former or currently smoking. Education was divided into three categories, depending on duration .www.kreftregisteret.no) provides information on incident cases of renal cell cancer that occurred during follow-up. Person-years were calculated from the clinical examination until the diagnosis of renal cell cancer or other cancers , death from other causes, or the end of follow-up, 31 December 2002, whichever came first. The relative risk was calculated as the rate of renal cell cancer within a given blood pressure category compared with that in the reference category. We used Cox regression analysis to adjust for potential confounding by body mass index, smoking, use of blood pressure medication and education level. The statistical analyses were conducted using STATA, version 9.0 .The mandatory reporting of cancer by physicians and hospitals to the Cancer Registry of Norway ; diastolic pressure among never users of blood pressure medication, however, showed similar associations to the overall results.In a separate analysis restricted to people who reported never-use of blood pressure medication at baseline, there was a strong and positive association between systolic pressure and risk among women . Thus, tUse of antihypertensive medication, as reported by women at baseline, showed a weak positive association  was associated with consistently lower risk for renal cell cancer than higher levels. No previous study of women has assessed the effect of measured blood pressure on this risk, but a positive association with recorded blood pressure has been found among men (Correspondingly, studies of antihypertensive medication, or history of hypertension, have not shown consistent results. In two prospective studies, antihypertensive treatment was associated with higher risk of renal cell cancer (Contrary to previous evidence, we found that measured blood pressure, or use of blood pressure medication, was not associated with risk for renal cell cancer among men. The reason for this discrepancy is not obvious, but may be the play of chance.In our study, systolic and diastolic blood pressures were measured according to standardised procedures by a team of trained nurses. The cohort consists of the majority of adults in a stable, homogeneous population in Norway, well suited for cancer follow-up, because of the national mandatory reporting system, and the unique identification number allocated to each citizen.Angiogenic and other growth factors are associated with blood pressure increase, and may also be involved in the development of renal cell cancer (


Most patients with sepsis develop potentially irreversible cerebral dysfunctions. It is yet not clear whether cerebral haemodynamics are altered in these sepsis patients at all, and to what extent. We hypothesized that cerebral haemodynamics and carbon dioxide reactivity would be impaired in patients with sepsis syndrome and pathological electroencephalogram patterns.t test for matched pairs was used for statistical analysis (P < 0.05).After approval of the institutional ethics committee, 10 mechanically ventilated patients with sepsis syndrome and pathological electroencephalogram patterns underwent measurements of cerebral blood flow and jugular venous oxygen saturation before and after reduction of the arterial carbon dioxide partial pressure by 0.93 ± 0.7 kPa iu by ypervent ilation. The cerebral capillary closing pressure was determined from transcranial Doppler measurements of the arterial blood flow of the middle cerebral artery and the arterial pressure curve. A P < 0.001), with a consecutive decrease of blood flow velocity in the middle cerebral artery of 21.8 ± 4.8%/kPa (P < 0.001), of cerebral blood flow from 64 ± 29 ml/100 g/min to 39 ± 15 ml/100 g/min (P < 0.001) and of jugular venous oxygen saturation from 75 ± 8% to 67 ± 14% (P < 0.01).During stable mean arterial pressure and cardiac index, reduction of the arterial carbon dioxide partial pressure led to a significant increase of the capillary closing pressure from 25 ± 11 mmHg to 39 ± 15 mmHg (In contrast to other experimental and clinical data, we observed no pathological findings in the investigated parameters of cerebral perfusion and oxygenation. Up to 71% of patients with sepsis develop potentially irreversible cerebral dysfunctions . This seSepsis, the inflammatory response to infection, in critically ill patients provokes severe systemic haemodynamic disturbance, characterized by a high cardiac output despite evidence of myocardial dysfunction, low systemic vascular resistance, hypotension and regional blood flow redistribution resulting in tissue hypoperfusion. Scarce clinical data ,6 and exIn most of the former studies concerning cerebral haemodynamics during sepsis syndrome, only a few aspects of cerebral circulation had been investigated. We therefore tried to investigate simultaneously various parameters to obtain a more broad survey of cerebral perfusion and oxygenation in patients with sepsis syndrome showing abnormal EEG patterns.In accordance with the Helsinki Declaration and after approval by the Bonn University ethics committee, 10 mechanically ventilated patients were studied in whom sepsis had been established for >48 hours. Informed consent was obtained from the patients or from their next of kin. The 1992 criteria of the American College of Chest Physicians and the Society of Critical Care Medicine Consensus Conference Committee were used to define sepsis [The heart rate was obtained from the electrocardiogram. The systemic mean blood pressure (MAP), the central venous pressure and the pulmonary artery pressure were transduced  and recorded . The cardiac output was continuously estimated with the thermal dilution technique . Standard formulae were used to calculate the cardiac index (CI) and the systemic vascular resistance index.MCA) was measured by means of a 2 MHz transcranial Doppler probe . The Doppler probe was fixed to the patient's head using a specially designed holder apparatus (DWL) to ensure a constant angle of insonation during the study period. Transcranial Doppler adjustments of the depth, sample volume, gain, and power were kept constant during the investigation. Data for the arterial pressure and for the VMCA were stored simultaneously via analogue/digital converters with a sample rate of 114 Hz using the integrated hard disk of the transcranial Doppler device. Digital signals were then processed offline using a self-developed software (author MS). The cerebral capillary closing pressure (CCP) was calculated by heart-beat-to-heart-beat analysis from the zero-flow velocity pressure as extrapolated by regression analysis of arterial pressure/VMCA plots [MCA are dynamic values that fluctuate from beat to beat , CCP calculations had been averaged over a period of two respiratory cycles.The blood flow velocity in the middle cerebral artery , cardiac output and intrathoracic blood volume as described previously ,13. BrieThe cerebral metabolic rate of oxygen was calculated as the CBF multiplied by the arterial concentration of oxygen value minus the jugular venous concentration of oxygen valueAn EEG was recorded from each patient before the measurements. EEG recordings followed a standardized protocol on an analogue eight-channel recorder  system with silver/silver chloride bridge electrodes placed according to the international 10–20 system. Examination was composed of recordings with two unipolar montages with the ipsilateral ear or the vertex electrode as reference, with two bipolar montages , and with a unipolar topo-selective and a unipolar Goldmann common reference montage. All EEG reports were analysed by a blinded EEG board-certified physician. EEG reporting was based on the EEG classification by Lüders and Noachter .2) was continuously measured .Arterial and jugular venous bulb blood gases and the pH were determined immediately after sampling with standard blood gas electrodes . The oxygen saturation and haemoglobin in each sample were analysed using spectrophotometry . The end-tidal expired carbon dioxide  between 900 and 1,000 ml/maCO2) between 5.3 and 6.6 kPa, and the inspiratory oxygen fraction was set to maintain an arterial oxygen partial pressure above 12 kPa. After baseline measurements were performed under normoventilation, the ventilatory rate was increased to result in a decrease in ETCO2 of 1.33 kPa (according to 10 mmHg). Changes of the blood gas status were controlled simultaneously by arterial blood gas analysis. Measurements and data collection were performed during stable steady-state conditions confirmed by constancy (± 5%) of the expiratory minute ventilation, the arterial oxygen saturation, the ETCO2, the MAP, and the CI for at least 40 minutes.Pressure-limited ventilatory support was provided with a standard ventilator . The positive end-expiratory pressure and the pressure levels were adjusted to a tidal volume of 6 ml/kg and maximum lung compliance. The ventilator rate was set to maintain an arterial carbon dioxide partial pressure  and the age of the patients, the Acute Physiologic and Chronic Health Evaluation II score, the Multiple Organ Dysfunction Score, the body temperature, the arterial blood gas pH, the MAP, the CI, the systemic vascular resistance index and the ITBVI.Results are expressed as the mean ± standard deviation. Differences between measurements were analysed by t test. Differences were considered statistically significant if P < 0.05.Between-group differences of pathology grades of the EEG recordings following the classification of Lüders and Noachter  were anaStatistical analysis was performed using STATISTICA 6.0 software .The patients' demographic and clinical data are summarized in Table 2 of 1.33 kPa, the expiratory minute ventilation increased (P < 0.05) and the PaCO2 decreased from 5.85 ± 1.06 kPa to 4.92 ± 1.06 kPa (P < 0.01). The MAP, positive end-expiratory pressure, and tidal volume remained essentially constant throughout the intervention.Ventilatory variables and ventilator settings are presented in Table 2 and a MAP of 89 ± 15 mmHg. Hyperventilation did not affect cardiovascular function.Changes in cardiovascular variables are presented in Table aCO2 of 0.93 ± 0.7 kPa  resulted in a decrease in the VMCA from 72 ± 25 cm/s to 59 ± 22 cm/s (P < 0.001). The mean decrease in the VMCA was 21.8 ± 4.8%/kPa, with a range from 17 to 32%/kPa. While the CCP increased from 25 ± 11 mmHg to 39 ± 15 mmHg (P < 0.001), the CBF decreased from 64 ± 29 ml/100 g/min to 39 ± 15 ml/100 g/min (P < 0.001) and the mean SjO2 from 75 ± 8% to 67 ± 14% (P < 0.01). The cerebral metabolic rate of oxygen was 1.9 ± 0.8 ml/100 g/min and did not change significantly during hyperventilation.Changes in cerebral circulatory variables are shown in Table None of the studied factors  had any significant association with cerebrovascular carbon dioxide reactivity.During the stay on the intensive care unit, cerebral computer tomography scans had been carried out in seven of the 10 patients after our measurements (Table P < 0.01). Figure The EEG recordings in the septic patients showed slowing of the background rhythm, as well as intermittent or continuous regional slowing and epileptiform potentials, indicating a severe brain dysfunction during sepsis. The control patients showed no or only mild EEG abnormalities. The average EEG pathology grade  was 1.9 Nine of the 10 patients came to our intensive care unit in deep anaesthesia after surgical intervention. No neurological conspicuousness had been found for the patients in the initial exploration by the anaesthesiologist or surgeon, except for a slight drowsiness in three cases according to Glasgow Coma Scale 14. Eight of the 10 patients survived. Two patients died due to multiple organ failure. All surviving patients showed pathological findings on clinical neurological exploration during the first 5 days after extubation: 3 days after cessation of continuous analgesia, sedation and extubation, their consciousness was severely reduced  without application of sedation. While none of the patients were oriented in regard to time and location, five were disoriented in regard to person. Four of the patients suffered from psychotic symptoms.aCO2 led to a significant increase in the CCP with a consecutive decrease in the VMCA, CBF and SjO2. Despite neurological disorder and pathological EEG patterns, none of the recorded variables of cerebral circulation was pathological in the 10 investigated patients.In the present investigation a reduction of the PaCO2. The authors concluded that endotoxinaemia does not alter cerebral perfusion, and they explained the reduced CBF by acute hypocapnia caused by hyperventilation of their spontaneous breathing patients, indicating intact cerebral carbon dioxide reactivity. Conversely, in clinical trials using transcranial Doppler, Terborg and colleagues [MCA during sepsis syndrome.Experimental and clinical investigations demonstrated disturbed cerebral perfusion during sepsis or septic shock. The question of whether the cerebral carbon dioxide vasomotor reactivity is concomitantly impaired remained unclear. In a previous animal experimental study , cerebralleagues  and Bowilleagues  observedaCO2.The intention of the present investigation was to gain a broader overview of the cerebral haemodynamics during sepsis syndrome by recording simultaneously different parameters of the cerebral circulation and oxygenation before and after reduction of PaCO2 reduction. This would have caused a more modest increase in the CCP, and therefore an underestimation of cerebral vasomotor reactivity.In agreement with Panerai , who empaCO2 by 0.93 kPa led to a mean increase in the CCP of 14 mmHg. In patients recovering from head injury, Weyland and colleagues [aCO2 by about 1.06 kPa. This difference in CCP after varying the PaCO2 was in a distinctly smaller range than that observed in our septic patients. Of course, a comparison with these results is rather difficult because it is not improbable that, during recovery after brain injury, the cerebral perfusion is still disturbed. Nevertheless, cerebral carbon dioxide reactivity in our investigation seems to be normal rather than reduced. This conclusion is supported by the simultaneous recorded VMCA and CBF values.A control of our measurements in the same patients after recovery from sepsis was not feasible because of different difficulties: the lack of cooperation of the surviving patients suffering from psychotic symptoms, the difficulty of proper CBF measurements caused by artefacts during spontaneous breathing, and the lack of clinical indication of jugular bulb oxymetry after recovery from septic shock. We therefore had to compare our results with investigations focusing on the same parameters of the cerebral circulation in patients without severe inflammatory response syndrome or sepsis. In our patients, the mean decrease in the Plleagues  recordedMCA. In contrast to the observations of two previous investigations [MCA (21.8 ± 4.8%/kPa) was in a normal range [As expected, the increase in the CCP, and thus cerebral vasomotor tone, was accompanied by a decreased CBF, which is reflected in a reduced Vigations ,6, the dal range . Terborgal range . The patal range . Neverth2 oriented. An end-tidal partial pressure reduction of 1.33 kPa resulted in a deviant mean decrease in the PaCO2 of 0.93 ± 0.7 kPa, with a wide range of 0.5–2.7 kPa reflecting the disturbance of pulmonary function and perfusion in the septic patients. The calculation of cerebral carbon dioxide reactivity by Bowie and colleagues based on the ETCO2 may also contribute to the different results [The hyperventilation of the patients in our study was ETCO results .Global CBF was measured using a transcerebral double-indicator dilution technique. The few validation studies have shown sufficient agreement with an inert-gas technique using argon in patients with normal cerebrovascular function , whereasaCO2 in patients scheduled for coronary bypass surgery. They recorded the CBF by the same transcerebral double-indicator dilution technique used in our investigation. In both studies, during normocapnia the CBF  was lower than in the septic patients of our investigation (64 ± 29 ml/100 g/min). Variations of the PaCO2 by 1.46 kPa led to changes in the CBF to about 22 and 24 ml/100 g/min, respectively. Compared with these non-septic patients, the CBF decrease in our group of patients was in the same range – although the mean reduction of the PaCO2 was only 0.93 kPa. Investigations on the regional CBF using 133Xe methods [aCO2 . The effects of cerebral carbon dioxide reactivity on global cerebral perfusion are therefore rather more distinct in our investigation despite the fact that the patients suffered from sepsis syndrome. A consecutive decrease in the SjO2 from 75% to 67% reflects this reduction of the cerebral perfusion.Wietasch and colleagues  and Miel methods  also shoWe found pathological activity in the EEG for all septic patients, with significant difference from the nonseptic control patients that cannot be explained by sedation. Both patient groups had comparable sedation as clinically required to achieve a Ramsay sedation score of 3, sufficient for toleration of airway pressure release ventilation respirator therapy including spontaneous breathing. Although the EEG changes are not specific for septic encephalopathy, at least an influence of sepsis must be postulated. Also nonspecific were the pathological findings in clinical neurological exploration of the eight surviving septic patients. Effects of sedation are conceivable. Three days after the cessation of sedation, however, this seems unlikely because sedation had been performed as Ramsay score oriented to avoid accumulation using the short-reacting propofol.In contrast to the experimental and clinical data of Rudinsky and colleagues , of Terb• Cerebral haemodynamics and carbon dioxide reagibility were investigated in 10 mechanically ventilated patients with sepsis syndrome.aCO2 caused a significant increase in the cerebral capillary closing pressure, with a consecutive decrease in the blood flow velocity of the middle cerebral artery, the global cerebral blood flow and the jugular venous oxygen saturation.• Reduction of P• No pathological findings have been observed.2 = end-tidal carbon dioxide partial pressure; ITBVI = intrathoracic blood volume index; MAP = mean arterial pressure; PaCO2 = arterial carbon dioxide partial pressure; SjO2 = jugular venous oxygen saturation; VMCA = blood flow velocity in the middle cerebral artery.CBF = cerebral blood flow; CCP = capillary closing pressure; CI = cardiac index; EEG = electroencephalogram; ETCOThe authors declare that they have no competing interests.CT made substantial contributions to the conception and design of the study and to acquisition, analysis and interpretation of the data, and prepared the manuscript. MK made substantial contributions to the acquisition, analysis and interpretation of data and participated in the preparation of the manuscript. MS made substantial contributions to the analysis and interpretation of data, especially development of the software for measurement of the cerebral capillary closing pressure. AS made substantial contributions to the acquisition, analysis and interpretation of data, especially the EEG recordings, performed the statistical analysis and participated in the preparation of the manuscript. MTH made substantial contributions to the conception and design of the study, and to analysis and interpretation of the data, especially the EEG recordings. GB made substantial contributions to the acquisition and analysis of data. AH made substantial contributions to the conception and design of the study and has revised the manuscript for important intellectual content. CP made substantial contributions to the conception and design of the study, was involved in the preparation of the manuscript, revising it for important intellectual content, and has given final approval of the version published.


Medicine Self-Management Intervention (MESMI), designed to improve blood pressure control and medication adherence in consumers with diabetes and chronic kidney disease recruited from specialist outpatients' clinics.About 30-60% of individuals are non-adherent to their prescribed medications and this risk increases as the number of prescribed medications increases. This paper outlines the development of a consumer-centred We developed a multifactorial intervention consisting of Self Blood Pressure Monitoring (SBPM), medication review, a twenty-minute interactive Digital Versatile Disc (DVD), and follow-up support telephone calls to help consumers improve their blood pressure control and take their medications as prescribed. The intervention is novel in that it has been developed from analysis of consumer and health professional views, and includes consumer video exemplars in the DVD. The primary outcome measure was a drop of 3-6 mmHg systolic blood pressure at three months after completion of the intervention. Secondary outcome measures included: assessment of medication adherence, medication self-efficacy and general wellbeing. Consumers' adherence to their prescribed medications was measured by manual pill count, self-report of medication adherence, and surrogate biochemical markers of disease control.The management of complex health problems is an increasing component of health care practice, and requires interventions that improve patient outcomes. We describe the preparatory work and baseline data of a single blind, randomized controlled trial involving consumers requiring cross-specialty care with a follow-up period extending to 12 months post-baseline.The trial was registered with the Australian and New Zealand Clinical Trials Register (ACTRN12607000044426). The prevalence of chronic diseases continues to increase, necessitating sustained self-management of medications by consumers in the community and long term monitoring by health professionals. Diabetes and chronic kidney disease are two such rapidly escalating global health problems , and diaThe complexity of the treatment for co-existing diabetes and chronic kidney disease involves comorbidity management, in particular hypertension, to improve disease control and health outcomes. Accordingly, the consumer is required to consult with numerous health professionals in primary and specialist settings who prescribe multiple medications for consumers to manage their health. Taking medications as prescribed is a principal requirement for well-managed chronic diseases. When multiple treatments are required for different health problems, medication-related concerns such as adherence, drug interactions and side effects, can be perceived as more troublesome to consumers than the treatments themselves ,5.Adherence can be defined as the extent to which consumers follow the instructions they are given for prescribed treatments . ApproxiWhile medical interventions are very important to manage and prevent further health problems in people with co-existing diabetes and chronic kidney disease, long-term health outcomes depend on the effectiveness of the choices that consumers make for themselves on a daily basis . The quaThe conceptual framework underpinning this project is the modified Health Belief Model (HBM) ,14. The This trial was designed to improve medication self-management in consumers with co-existing diabetes and chronic kidney disease by testing a multifactorial, consumer-centred intervention to improve systolic blood pressure control and medication adherence in a randomized controlled trial (RCT). Consumer-centred interactive interventions to aid decision-making are an effective way of helping consumers with diverse backgrounds to understand their chronic diseases and complex medication regimens .The study is a single-site, single-blind, longitudinal RCT. Participants have been allocated to one of two groups: the intervention group receives a multifactorial intervention designed to improve blood pressure control and medication adherence, and the control group receives standard care offered by the treating hospital's outpatient clinics and primary care provided by the participants' general practitioner. Data are collected at four time points: enrolment baseline data collection (T1), immediately following delivery of the intervention (T2), three months post-intervention (T3) and 9-months post-intervention (T4).The primary aim of the study were to evaluate the effectiveness of a multifactorial intervention in terms of improved systolic blood pressure control in participants with co-existing diabetes and chronic kidney disease. Secondary aims were to determine the effectiveness of the intervention on medication adherence, medication self-efficacy and general wellbeing in consumers with co-existing diabetes and chronic kidney disease. The extent of the relationship between pill counts, self-report of medication adherence and self-efficacy, and other clinical and surrogate biochemical markers of disease control will also be evaluated.1. Compared to participants receiving standard care, participants with diabetes and chronic kidney disease who receive the intervention will show greater reduction in blood pressure at three months post-intervention (T3).2. Compared to participants receiving standard care, participants with diabetes and chronic kidney disease who receive the intervention will show a greater adherence to their prescribed medication regimen at three months post-intervention (T3).3. Improved medication adherence will be associated with increased systolic blood pressure control at three months post-intervention (T3).Medicine Self-Management Intervention (MESMI) to improve blood pressure control and medication adherence. The MESMI consisted of self-monitoring of blood pressure, an individualised medication review, a twenty-minute Digital Versatile Disc (DVD), and fortnightly follow-up telephone contact for 12 weeks to support blood pressure control and optimal medication self-management. All components of the intervention were delivered by a renal specialist nurse with doctoral qualifications trained in motivational interviewing using a checklist and standing script for fidelity purposes.Information derived from the literature and other components of the study were used to develop a multifactorial intervention, the The intervention nurse taught participants in the intervention group to take their own blood pressure using the self blood pressure measurement (SBPM) guidelines of O'Brien et al.  and a cl1C < 7%, and low density lipoprotein (LDL) cholesterol < 2.5 mmol/L as recommended by Harris [The individualised medication review involved the intervention nurse drawing up a chart of the participant's prescribed medications as documented by the research assistant at the enrolment visit (T1), which included the generic and brand name of the medication, what the medication was for, the dose and when to take it, and targets for which to aim. Targets included a blood pressure ≤130 mmHg, blood glucose of < 7 mmol/L, Hb Ay Harris . PrescriThe DVD involved an interactive, psychosocial approach to motivating people to take their medications, appealing to knowledge, thoughts and feelings, underpinned by the modified Health Belief Model . By focuThe content of the DVD was drawn from analysis of medication adherence from the perspectives of consumers with co-existing diabetes and chronic kidney disease and health professionals likely to care for this group . KnowledThe content of the DVD was checked against information in the public arena to ensure a consistent message was being conveyed. We also made sure that the text could easily be read by consumers with visual impairment  and understood at a Year 8 level. The DVD was developed under guidance of the project team and a reference group drawn from the key stakeholders of participants and health professionals engaged in the research.The DVD underwent formative evaluation for internal validity by nine health professionals, one educational expert, and one consumer who provided video footage. Content, readability , and appropriateness of information to meet the learning objectives and desired outcomes were critically evaluated using the Content Validity indices , which wFortnightly telephone calls were planned after the intervention home visit until follow-up at 3-months post-baseline (T2). Each call was conducted using the principles of motivational interviewing by the intervention nurse to promote medication adherence, adapted from the guidelines of Dilorio et al. . The telThe participants' motivation and confidence in taking their medications was then assessed out of a score of 1 to 10, using this information to elicit barriers, concerns and positive self-motivational statements. A summary of these comments was presented back to the participant, inviting any further comments using reflective and normalising statements where appropriate to elicit problem-solving. The participants was then asked to identify three goals they would like to achieve in the next five years to help link their medication adherence to their life. They were also asked to briefly explore connections between their current medication-taking behaviour and their ability to achieve these goals. A summary was presented back to the participants, incorporating suggestions to overcome identified difficulties and affirming desired behaviour. The participants were asked if they had any queries which were addressed, and the call was concluded after thanking the participants for their time and interest. The remaining motivational interviewing calls followed a similar format that incorporated follow-up of suggestions or queries made in previous calls.Participants randomized to the usual care control group received standard care offered to patients with co-existing diabetes and chronic kidney disease attending the diabetes and nephrology outpatients' clinics at the hospital and primary care offered by their general practitioners. Our definition of standard care is the ongoing medical care provided to a patient with co-existing diabetes and chronic kidney disease attending routine outpatient clinic follow up, which has been reported elsewhere . Data weIn the planning stages of the study in 2006, we found that more than 1,400 patients with diabetes at the hospital where recruitment was to take place had urine microalbumin/creatinine ratios ranging from 2 to an extreme of 6020 mg/mmol, with an average microalbumin/creatinine ratio of 97 mg/mmol suitable for our recruitment purposes. Additionally, the renal department at the hospital is one of the largest renal services in Australia treating in excess of 2,300 patients annually with chronic kidney disease. The base rate of systolic blood pressure control > 130 mmHg in the nephrology outpatient clinic population was estimated to be about 50%.A research assistant who was a qualified registered nurse recruited from the diabetes and nephrology outpatient clinics of a metropolitan hospital in Melbourne commencing in August 2008. This research assistant conducted all data collection for the study and was a different person to the intervention nurse. There were two diabetes clinics per week for patients requiring ongoing review with approximately 50 patients booked in per clinic. If the patient did not have hypertension, they were immediately deemed ineligible irrespective of the presence of renal disease. There was one renal clinic per week with approximately 50 patients booked in of whom about 15 had either type 1 or type 2 diabetes. Participants were also recruited from a combined diabetes and nephrology clinic (NephDiab clinic) established to incorporate both diabetes and nephrology specialist review within the same appointment where approximately 20 patients were booked in every month. Patients who met the inclusion criteria were approached by the research assistant and asked if they wanted to participate in a study designed to help them understand and manage their complex medical conditions and prescribed medications better.The inclusion criteria for the MESMI study are listed in Table The participant's blood pressure was taken by the research assistant five times at recruitment, commencing with once on either arm in the sitting position. The blood pressure measurement was then repeated twice on the arm with the lower systolic blood pressure at one minute intervals. These two blood pressure readings were then averaged, and the mean measure was used to check the presence of hypertension. Finally, the standing blood pressure was then taken on the same arm within three minutes to detect the presence of orthostatic hypotension, a common side effect of antihypertensive medications in the older population .Consumers who were not mentally competent  , had an Prior to commencing the study, ethics approval was sought and granted from the Human Research Ethics Committees of the participating hospital (HREC Project No: 2006.239) and university (Ethics ID: 0713622). The trial was prospectively registered with the Australian and New Zealand Clinical Trials Register (ANZCTR) before recruitment of the first participant (Registration number ACTRN12607000044426). Written informed consent was obtained from participants prior to enrolment. The study was conducted according to the protocol and under ethical guidelines of the National Health and Medical Research Council of Australia [Participants who expressed an interest in participating and who met the inclusion criteria were contacted by the research assistant by telephone to organize a home visit. At the home visit, formal informed consent was obtained prior to collecting demographic, social and medical data, sitting blood pressure according to accepted guidelines  taken t. The bas1C, CaP04 and low-density lipids are collected at these four time points from the participant's medical records. Follow-up is projected to continue until July 2010.All participants have data collected at four points in time Table : baselinThe Morisky Medication Adherence Scale  was usedPill counts were conducted at T1, T2, T3 and T4 time points according to the process outlined by Haynes et al. . At enroPill counts were estimated by dividing the number of pills missing from the containers by the number of pills which should be missing if the participant had taken all medications as prescribed . This fi1C and evidence of hypoglycaemic and hyperglycaemic episodes requiring hospitalization as evidence of medication nonadherence.Medication adherence was set at ≥80% as the minimum acceptable level for each prescribed medication, a commonly accepted cut-off point for defining a therapeutic level of medication adherence . InsulinFollowing the baseline visit, a statistician off-site conducted the centralized, stratified block randomization of participants according to age, gender and baseline systolic blood pressure to maintain allocation concealment and to prevent selection bias. The identity of all participants who were randomized to receive the intervention was kept in a locked cabinet in the leading researcher's locked office according to university and hospital ethics approval. Data collection conducted by the research assistant was blinded to the intervention group. At the 9-month visit (T4), participants will be asked if they think they received standard care or the intervention or were unsure and why . HoweverWe based our sample size on Gerin et al.'s  medicatith June 2009. A total of 111 participants were recruited and baseline data taken. The enrolment baseline visits commenced on the 8th September 2008 and ceased on 22nd June 2009. Participant flow is shown in Figure Recruitment commenced on the 27th August 2008 and ceased on 17The analysis will be performed on an intent-to-treat basis. All data will be entered into an ACCESS database by a second research assistant who is blinded to the intervention group. An experienced biostatistician will check the integrity of the database and conduct statistical analyses. Descriptive statistics will be used to summarise demographic, social and medical data between the intervention and usual care groups and any effect of these variables on primary and secondary outcomes. Baseline characteristics of the intervention and usual care groups will be compared. Blood pressure, medication adherence, medication self-efficacy, and general wellbeing between the usual care and intervention groups will be compared to assess the effects of the intervention between groups and within participants at T2, 3 and 4 using t-tests as appropriate. The various measures of medication adherence will be examined for correlations. Continuous variables that are not normally distributed will be examined using equivalent non-parametric tests. Differences in change in binary categorical variables within each group will be analysed using McNemar's test and the changes between the two groups will be assessed by chi-squared tests for trends. Potential confounders may include comorbidities and number of prescribed medications. Statistical significance will be determined with p values of < 0.05.This trial involves an evaluation of the effectiveness of a multifactorial intervention developed from analysis of medication adherence from the perspectives of consumers with co-existing diabetes and chronic kidney disease and multidisciplinary health professionals likely to be involved in their management. This approach was chosen to foster effective communication and partnerships with health professionals necessary for improved medication adherence and patient health outcomes. The major strength of this trial is that it is one of the first published studies to tackle the problem of competing comorbidity management where consumers are required to consult with multiple health practitioners and take multiple prescribed medications.2). The development, dissemination and implementation of chronic kidney disease clinical practice guidelines that harmonize with other specialties are needed to improve patient outcomes of chronic kidney disease [The inclusion criteria presented difficulties, particularly in relation to pathology results recorded in the patient's electronic or hard copy of their medical record to determine eligibility. Although patients had diabetes and evidence of chronic kidney disease, patients did not routinely have microalbumin/creatinine ratios or less commonly, 24 hour urine albumins taken. Additionally, some estimated glomerular filtration rates were recorded as '≥ 60' or '< 90' depending on the point-of-care, and if patients did not have a microalbumin/creatinine ratio recorded in their history, they were excluded. Therefore, we have recruited participants with co-existing diabetes (Type 1 or 2) and microalbumin/creatinine ratios > 2.0 mg/mmol for men, > 3.5 mg/mmol for women or co-existing diabetes (Type 1 or 2) and chronic kidney disease , effectively reducing the pool of patients from which to recruit.At recruitment, we found a significant number of participants spoke a language other than English, most commonly Greek and Italian, who were excluded from the trial because they did not speak English. The latest Australian census shows that one quarter of Australians are born overseas , and conAnother problem was objective evaluation of medication adherence. The cost of electronic pill monitoring for multiple medications was prohibitive. Difficulties with manual pill counts included the sheer number of medications that the participants had on hand. Very few participants could recall when they started their new prescriptions. Some participants were found to have six boxes of the same medications, all of which had been partially used. In another case, a husband and wife shared their prescribed medications, upsetting the count. Many had different storage areas for medications that were not currently prescribed, in addition to complementary medications. There were discrepancies between what participants said verbally and what was being counted by the research assistant. For example, participants stated that they had not missed any pills but their scripts had ran out, and they were found to have missed at least one or two pills or there were more medications counted that should have been taken. One participant admitted to fiddling with her medications, and took gliclazide 80 mg and gliclazide MR 30 mg on alternate days as she was not sure 'which one was better'. Participants also decanted from one container into another. In one instance, there were 65 pills in a container that should have had 50 pills in it. Our research has emphasized the need for an objective, affordable method to monitor adherence to multiple prescribed medications.Despite these issues, the management of comorbidities is an increasing component of health care practice, and as such, is in need of interventions that improve patient outcomes. This research has highlighted the need for quality medical record documentation and a systematic, evidence-based approach to patient care that overrides the needs of specialties in the patient with competing diagnoses.The authors declare that they have no competing interests in the conduct of this research. The funding source had no involvement in the study design and methods.AW, EM & RW: (a) conception and design, or acquisition of data, or analysis and interpretation of data; and (b) the drafting of the article or critical revision for important intellectual content and c) final approval for the version to be published.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2296/11/3/prepub