Integration of HIV services with primary care in Yangon, Myanmar: a retrospective cohort analysis.

OBJECTIVES: Integration of HIV care with general healthcare may improve patient engagement. We assessed patient outcomes in four clinics offering HIV care integrated into primary care clinics in Yangon, Myanmar. METHODS: We carried out a retrospective cohort analysis of 4551 patients who started antiretroviral therapy between 2009 and 2017. Mortality and disengagement from care were assessed using Cox regression. RESULTS: People living with HIV presented late with low CD4 counts [median (25th , 75th percentile) = 178 (65, 308) from 4216 patients] and advanced HIV (69% with stage 3 or 4). Survival was 0.95 at 1 year and 0.90 at 5 years. Males were at a higher risk of mortality than females [unadjusted hazard ratio (uHR) = 1.6 (95% CI: 1.3-2.0). Patients linked to HIV care via antenatal care or partner/parent notification were at reduced risk of mortality [uHR = 0.4 (95% CI: 0.1-1.0) and uHR = 0.5 (95% CI: 0.3-0.7)] relative to patients who presented for HIV testing. The cumulative incidence of disengagement was 0.06 at 1 year and 0.15 at 5 years. Young adults had a higher risk of disengagement than did children and older patients. Women linked to HIV care via antenatal care services were at increased risk of disengagement relative to patients who came for HIV testing (uHR = 2.4; 95% CI: 1.7-3.4). Mortality and disengagement remained steady over calendar time as the programme scaled up. CONCLUSIONS: HIV care within a primary care model is effective to attain early linkage to care, with high survival. However, close attention should be given to disengagement from care, in particular for pregnant women.

Lung hyperinflation and functional exercise capacity in patients with COPD - a three-year longitudinal study.

BACKGROUND: Lung hyperinflation contributes to dyspnea, morbidity and mortality in chronic obstructive pulmonary disease (COPD). The inspiratory-to-total lung capacity (IC/TLC) ratio is a measure of lung hyperinflation and is associated with exercise intolerance. However, knowledge of its effect on longitudinal change in the 6-min walk distance (6MWD) in patients with COPD is scarce. We aimed to study whether the IC/TLC ratio predicts longitudinal change in 6MWD in patients with COPD. METHODS: This prospective cohort study included 389 patients aged 40-75 years with clinically stable COPD in Global Initiative for Chronic Obstructive Lung Disease stages II-IV. The 6MWD was measured at baseline, and after one and 3 years. We performed generalized estimating equation regression analyses to examine predictors for longitudinal change in 6MWD. Predictors at baseline were: IC/TLC ratio, age, gender, pack years, fat mass index (FMI), fat-free mass index (FFMI), number of exacerbations within 12 months prior to inclusion, Charlson index for comorbidities, forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and light and hard self-reported physical activity. RESULTS: Reduced IC/TLC ratio (p < 0.001) was a statistically significant predictor for decline in 6MWD. With a 0.1-unit decrease in baseline IC/TLC ratio, the annual decline in 6MWD was 12.7 m (p < 0.001). Study participants with an IC/TLC ratio in the upper quartiles maintained their 6MWD from baseline to year 3, while it was significantly reduced for the patients with an IC/TLC ratio in the lower quartiles. Absence of light and hard physical activity, increased age and FMI, decreased FEV1 and FVC, more frequent exacerbations and higher Charlson comorbidity index were also predictors for lower 6MWD at any given time, but did not predict higher rate of decline over the timespan of the study. CONCLUSION: Our findings demonstrated that patients with less lung hyperinflation at baseline maintained their functional exercise capacity during the follow-up period, and that it was significantly reduced for patients with increased lung hyperinflation.

Metabolic syndrome and the seminal cytokine network in morbidly obese males.

Given the increasing prevalence of metabolic syndrome (MetS) in males of reproductive age, the objective of this prospective case-controlled study was to investigate the impact of subacute systemic inflammation associated with MetS on seminal cytokines and standard sperm parameters in comparison with healthy men. Between 2011 and 2014, we recruited 27 patients with MetS out of 41 obese patients screened from an internal outpatient clinic. Twenty-seven age-matched healthy controls were enrolled from 54 men requesting vasectomy in a urological outpatient clinic. A multiplex analysis was performed to quantify simultaneously the level of 30 cytokines (Eotaxin, FGF, Fraktalkine, GCSF, GMCSF, Granzyme A, IFN-γ, IL-1α, IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-17A, IL-21, IP-10, I-TAC, MCP-1, MIG, MIP-1α, MIP-1ß, RANTES, TNF-α, and VEGF) in each 50 µL of blood and seminal plasma during the andrological work-up. Semen analysis was performed according to the WHO (Global status report on noncommunicable diseases, 2010) recommendations, including standard sperm parameters as well as peroxidase-positive leukocytes and polymorphonuclear elastase. Blood levels of C-reactive protein, interleukins 6 and 10 were elevated in MetS (p > 0.001). Two-way hierarchical cluster analysis showed characteristic cytokine networks in semen greatly differing from those in blood, but not between MetS and controls. No deterioration of semen analysis was evident in men diagnosed with MetS. Our results suggest that there is no transmission of the systemic inflammation associated with MetS into semen based on cytokine profiles and that MetS does not impair standard semen parameters to a clinically significant extent.

Validation of the German version of the 'Hypogonadism Related Symptom Scale' (HRS) in andrological patients with infertility, HIV infection and metabolic syndrome.

As commonly used self-reported screening instruments for male hypogonadism demonstrated lack of specificity, a Hypogonadism Related Symptom Scale (HRS) was developed in 2009 as a novel self-rating screening tool. As the questionnaire has not been validated, the purpose of our study was to perform a validation in patients presenting with different disorders (e.g. infertility, HIV infection or metabolic syndrome) and disease-related risk to develop hypogonadism. Two hundred and eighteen patients aged 19-71 years (40.1 ± 9.5) who completed the HRS and other common questionnaires [International Index Of Erectile Function (IIEF), National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), Hospital Anxiety and Depression Scale (HADS), short form (SF)-12] were included. In all patients, blood levels of total testosterone, luteinizing hormone, follicle-stimulating hormone, oestradiol and sex hormone-binding globulin were determined and free testosterone was calculated. Cronbach's α for the scale was 0.896, split-half 0.871 for the 1st half and 0.807 for the 2nd half. Spearman-Brown coefficient was 0.767, and Guttman split-half coefficient was 0.759. Consistent correlations were found between HRS and IIEF5 (ρ = 0.57, P < 0.001), and HADS (ρ = -0.6, P < 0.001). In addition, HRS was significantly correlated with total testosterone (ρ = 0.135, P < 0.05), free testosterone (ρ = 0.148, P < 0.05) and oestradiol (ρ = -0.134, P < 0.05). Our validation study confirms the data from the initial development of the HRS questionnaire. Clinicians might have an additional advantage from the HRS when investigating males with suspected hypogonadism.

Acute epididymitis in ultrasound: results of a prospective study with baseline and follow-up investigations in 134 patients.

OBJECTIVES: To perform a comprehensive follow-up analysis of ultrasonographic scrotal features and associated signs in patients with acute epididymitis. METHODS: Between 2007 and 2012, 134 adults (median age 54 years) with acute epididymitis underwent scrotal ultrasonography and palpation at first presentation and after 2 weeks and 3 months. RESULTS: At first presentation, 61 patients (45.5%) had hydrocele, 63 (47.0%) concomitant orchitis, and 8 (5.9%) epididymal abscess. Epididymitis was predominantly located in 24 cases (17.9%) in the head, 52 cases (38.8%) in the tail, and 58 cases (43.3%) in both. On the affected side, testicular volume was 16.9 ± 6.8 ml and peak systolic velocity of the testicular artery was 23.7 ± 7.5 cm/s, compared to the healthy side with 12.3 ± 4.4 ml and 9.5 ± 3.6 cm/s respectively (P<0.001). Concomitant orchitis was associated with hydrocele, testicular enlargement and pain (P<0.01). Orchiectomy due to secondary testicular infarction was necessary in four cases, while in all other patients ultrasound parameters normalized. Only 16/90 patients (17.8%) showed a persistent epididymal swelling after 3 months. CONCLUSIONS: Common ultrasound features include hydrocele, epididymal enlargement, hyperperfusion, and testicular involvement. Under conservative treatment, ultrasound parameters normalize without evidence of testicular atrophy even in patients with epididymal abscess or concomitant orchitis.

Prostatitis and andrological implications.

AIM: The prostatitis syndrome is a frequent disease affecting men in their reproductive age. The prostatitis syndrome is classified according to the National Institutes of Health (NIH) definition. Andrological implications of the prostatitis syndrome might encompass fertility issues, sexual dysfunctions and endocrinological alterations and influences. METHODS: A medline query using the terms prostatitis AND andrological implication, fertility, sexual dysfunction or endocrinology was performed. RESULTS: Acute bacterial prostatitis and andrological implications have not been adequately addressed. Patients with chronic bacterial prostatitis and chronic pelvic pain syndrome have been investigated evaluating sperm parameters. Some studies showed impaired sperm parameters. In chronic bacterial prostatitis, half of the patients reveal significant bacteriospermia with still debatable deleterious effects on sperm quality. Few interventional studies have addressed fertility issues in those patients. Anti-inflammatory treatment perhaps could have a positive impact on sperm parameters. Sexual dysfunction can be described by different components such as erectile, ejaculatory, orgasmic and sexual desire dysfunctions. Sexual dysfunction in chronic prostatitis adds to the number of positive symptom phenotypes and correlates therefore with increasing symptom scores in patients with chronic prostatitis syndromes. However, prospective interventional studies on the role of sexual dysfunctions are missing. Hormones have been found to modulate the inflammatory response via different receptors, particularly via estrogen receptor alpha. This evidence, however, is mainly limited to pre-clinical studies currently. CONCLUSION: Andrological implications are heterogenous and frequently described in patients with chronic prostatitis syndrome. Nonetheless, andrological factors have not been routinely addressed as primary variables in the different studies, which makes further research necessary.

Exendin-4 protects hypoxic islets from oxidative stress and improves islet transplantation outcome.

Oxidative stress produced during pancreatic islet isolation leads to significant ß-cell damage. Homeostatic cytokines secreted subsequently to islet transplantation damage ß-cells by generating oxygen free radicals. In this study, exendin-4, a glucagon-like peptide-1 analog improved islet transplantation outcome by increasing the survival of diabetic recipient mice from 58% to 100%. We hypothesized that this beneficial effect was due to the ability of exendin-4 to reduce oxidative stress. Further experiments showed that it significantly reduced the apoptotic rate of cultured ß-cells subjected to hypoxia or to IL-1ß. Reduction of apoptotic events was confirmed in pancreatic islet grafts of exendin-4-treated mice. Exendin-4 enhanced Akt phosphorylation of ß-cells and insulin released from them. It even augmented insulin secretion from islets cultivated at hypoxic conditions. Exposure to hypoxia led to a decrease in the activation of Akt, which was reversed when ß-cells were pretreated with exendin-4. Moreover, exendin-4 increased the activity of redox enzymes in a hypoxia-treated ß-cell line and reduced reactive oxygen species production in isolated pancreatic islets. Recovery from diabetes in mice transplanted with hypoxic islets was more efficient when they received exendin-4. In conclusion, exendin-4 rescued islets from oxidative stress caused by hypoxia or due to cytokine exposure. It improved the outcome of syngenic and xenogenic islet transplantation.

The effects of acute tryptophan depletion on impulsivity and mood in adolescents engaging in non-suicidal self-injury.

OBJECTIVE: Non-suicidal self-injury (NSSI) is associated with impaired emotion regulation and impulsivity. Low serotonin (5-hydroxytryptamine) function is associated with NSSI, impaired emotion regulation and impulsivity. We investigated the effects of experimentally lowered 5-hydroxytryptamine activity, via acute tryptophan depletion (ATD), on impulsive action, reflection impulsivity and mood in female adolescents engaging in NSSI. METHODS: Thirty-two female adolescents engaging in NSSI participated in a parallel group ATD study. Following ATD, impulsive action was assessed using the Continuous Performance Test, Identical Pairs Version. Reflection impulsivity was assessed using the Matching Familiar Figures Test. Mood-lowering was examined using the Profile of Mood States. RESULTS: Following ATD, the participants showed an impulsive response style (as reflected in their low ß) and increased attentional capacity (as reflected in their elevated d'). ATD did not affect reflection impulsivity or mood. CONCLUSIONS: Acute tryptophan depletion caused an impulsive response style and increased attentional capacity. Importantly, the findings suggest that low serotonin function is a vulnerability among female adolescents for engaging in NSSI when in emotional distress.

The majority of colorectal resections require an open approach, even in units with a special interest in laparoscopic surgery.

AIM: Proponents suggest that laparoscopic colorectal resection might be achievable in up to 90% of cases, while keeping conversion rates below 10%. This unselected prospective case series reports on the proportion of patients having a completed laparoscopic colorectal resection in two units where laparoscopic colorectal practice is well established and readily available. METHOD: All patients undergoing elective and emergency colorectal resection during a 6-month period were identified. The underlying pathology and the surgical approach (laparoscopic or open) were recorded. The contraindications to laparoscopic resection were also documented. The need and rationale for conversion to an open approach were recorded. RESULTS: In total, 205 consecutive patients (160 elective and 45 emergency procedures) underwent colorectal resection for malignancy [117 (57%) patients] and benign pathology [88 (43%) patients]. Laparoscopic resection was attempted in 127/205 (62%) patients and 31/127 (24%) of these were converted to open surgery. The main reasons for not attempting laparoscopic resection were locally advanced disease and emergency surgery. The commonest reasons for conversion were advanced disease and to allow completion of rectal dissection and/or cross-stapling of the rectum. CONCLUSION: Despite a special interest in laparoscopic colorectal surgery of the two colorectal units who provided the data for this study, fewer than half (96/205; 47%) of the patients in this consecutive unselected series who were undergoing major colorectal resection had the procedure completed laparoscopically.

Influence of urogenital infections and inflammation on semen quality and male fertility.

BACKGROUND: Urogenital infections and inflammation are a significant etiologic factor in male infertility. METHODS: Data for this review were acquired by a systematic search of the medical literature. Relevant cross-references were also taken into account. RESULTS: We address infectious and inflammatory diseases of different compartments of the male genital tract and discuss their andrological sequelae. Chronic urethritis might be responsible for silent genital tract inflammation with negative impact on semen quality. In chronic pelvic pain syndrome, morphological abnormalities of spermatozoa and seminal plasma alterations are detectable. In the majority of men with epididymitis, a transient impairment of semen quality can be found during the acute infection. However, persistent detrimental effects are not uncommon, even after complete bacteriological cure. The relevance of chronic viral infections as an etiologic factor in male infertility is believed to be underestimated. Data concerning the impact of HIV infection on male fertility are of increasing interest as with the improvement in life expectancy, issues of sexuality and procreation gain importance. Moreover, effects of noninfectious systemic inflammation on the male reproductive tract have to be considered in patients with metabolic syndrome, a disorder of growing relevance worldwide. Finally, microbiological and related diagnostic findings in urine and semen samples are reviewed according to their relevance for male infertility. CONCLUSIONS: Available data provide sufficient evidence that in men with alterations of the ejaculate, urogenital infections and inflammation have to be considered.

Improved intraportal islet transplantation outcome by systemic IKK-beta inhibition: NF-κB activity in pancreatic islets depends on oxygen availability.

Intraportal islet transplantation suffers from low efficiency caused by substantial islet mass loss after transplantation. How this process is regulated is still unclear. Here, we show that NF-κB activation was detectable in islet grafts shortly after transplantation of porcine islets to diabetic NMRI nu/nu mice, and systemic NF-κB inhibition in transplanted animals significantly prolonged islet graft survival. Proinflammatory cytokines alone did not cause evident cell death in pancreatic islet within 24 h, while the combination of cytokines with hypoxia resulted in a strong induction of cell death that could be blocked dose-dependently by a selective IKK-ß inhibitor. Under hypoxia, NF-κB activity impaired expression of antiapoptotic gene BCL-xL, c-FLIP and survivin. NF-κB activation in isolated islets was reduced by hypoxia in a time-dependent manner, accordingly, NF-κB activation in transplanted islets diminished by time. Our data indicate that, while NF-κB has an antiapoptotic role under normoxia, low oxygen conditions decrease its activity and transform it to a proapoptotic transcription factor in pancreatic islets. We conclude that NF-κB inhibition represents a potential strategy to improve islet transplantation efficiency.

Fish'n ChIPs: chromatin immunoprecipitation in the zebrafish embryo.

Chromatin immunoprecipitation (ChIP) is arguably the assay of choice to determine the genomic localization of DNA- or chromatin-binding proteins, including post-translationally modified histones, in cells. The increasing importance of the zebrafish, Danio rerio, as a model organism in functional genomics has recently sparked investigations of ChIP-based genome-scale mapping of modified histones on promoters, and studies on the role of specific transcription factors in developmental processes. ChIP assays used in these studies are cumbersome and conventionally require relatively large number of embryos. To simplify the procedure and to be able to apply the ChIP assay to reduced number of embryos, we re-evaluated the protocol for preparation of embryonic chromatin destined to ChIP. We found that manual homogenization of embryos rather than protease treatment to remove the chorion enhances ChIP efficiency and quickens the assay. We also incorporated key steps from a recently published ChIP assay for small cell numbers. We report here a protocol for immunoprecipitation of modified histones from mid-term blastula zebrafish embryos.

Innate immunity and heat shock response in islet transplantation.

Islet transplantation is an extremely effective therapy for patients with type I diabetes, providing tight control of blood glucose and persistent insulin release. Islet grafts struggle with various stress responses and immunity attacks, which contribute to loss of islet grafts in the long term. In this review we focus upon the innate immunity and heat shock responses, which are closely relevant to the outcome of islet grafts. Potential strategies provided by more comprehensive interventions to control innate immunity and by selective induction of heat shock proteins may ameliorate the outcome of islet transplantation.

Staple line haemorrhage following laparoscopic left-sided colorectal resections may be more common when the inferior mesenteric artery is preserved.

BACKGROUND: Anastomotic bleeding following stapled left-sided colorectal resections is uncommon. There have been few reports on the incidence, severity, management and outcome of such stapled line haemorrhage in the literature. Here, we report our experience of anastomotic bleeding from a stapled anastomosis in laparoscopic left-sided colorectal surgery. METHODS: Data were collected prospectively on all patients undergoing laparoscopic colorectal surgery from 2003. Patients who had a left-sided stapled anastomosis requiring intervention for staple line haemorrhage were studied. Patients who underwent laparoscopic surgery for benign colorectal disease were compared with those who underwent laparoscopic surgery for a malignant condition. Risk factors for bleeding, management and outcome are reported. RESULTS: Over a 5-year period, 143 patients underwent laparoscopic left-sided colorectal surgery, 72 for benign disease and 71 for a malignant condition. Postoperative anastomotic bleeding occurred in six patients (4%). All were in the benign pathology group, and all had preservation of the inferior mesenteric artery during surgery. None of the patients required operative intervention for staple line haemorrhage. CONCLUSIONS: Anastomotic bleeding from a stapled anastomosis in laparoscopic left-sided colorectal surgery is an infrequent complication and it may be more common with preservation of the inferior mesenteric artery. In the majority, bleeding is self limiting and will settle with nonoperative means. Endoscopic procedures may be useful for confirmation of bleeding and for therapeutic intervention, and may avoid the need for surgical intervention.

ASAT/ALAT ratio provides prognostic information independently of Child-Pugh class, gender and age in non-alcoholic cirrhosis.

OBJECTIVE: The aspartate amino transferase/alanine amino transferase (ASAT/ALAT) ratio is increased in cirrhosis. Some studies indicate that the ratio may provide prognostic information as well. The purpose of this study was to further elucidate the role of the ASAT/ALAT ratio as a predictor of survival by assessing it together with classical risk factors such as age, gender and Child-Pugh (CP) class in a mixed cohort of patients with cirrhosis. MATERIAL AND METHODS: Eighty-nine patients with alcoholic cirrhosis and 81 patients with non-alcoholic cirrhosis treated at Aker University Hospital between 1999 and 2004 were identified retrospectively. Survival data from these patients per August 2006 were retrieved from the Norwegian Death Registry. Clinical and biochemical data at time of diagnosis were assessed as predictors of survival using the Kaplan-Meier method and Cox regression models. RESULTS: Median ASAT/ALAT ratio was significantly higher in alcoholic cirrhosis (2.42) as compared with non-alcoholic cirrhosis (1.42). In both groups, a ratio above the median was predictive of poor outcome, p=0.024 and p=0.032, respectively. Other significant predictors of death were CP class (p<0.001), clinical decompensation (p<0.001) and age (p=0.001). Cox regression analyses showed that the ASAT/ALAT ratio was a predictor of death independently of CP class, gender and age in non-alcoholic, but not in alcoholic cirrhosis. The estimated increased hazard (risk of dying) in non-alcoholic cirrhosis was 5% (CI: 1-8%) per 0.10 increase in ASAT/ALAT ratio. CONCLUSIONS: A high ASAT/ALAT ratio is associated with increased mortality in cirrhosis. In non-alcoholic patients the ratio may provide prognostic information independently of classical risk factors.

Effect of experimentally induced hypoglycemia and different insulin levels on feelings of hunger in type 1 diabetic patients.

INTRODUCTION: This study investigates the impacts of experimentally induced hypoglycemia and different insulin infusion rates on feelings of hunger. METHODS: Blood glucose and insulin levels were manipulated by hyperinsulinemic glucose clamp technique. Participants were 16 patients with type 1 diabetes (age 36.2+/-11.7 yrs, diabetes duration 9.0+/-6.3 yrs, HbA1c 8.2+/-2.0%). One group (n=8) received moderate, constant insulin infusion (0.8 microU/kg/min), whereas the insulin infusion was doubled in the other group (1.6 microU/kg/min). Blood glucose was lowered stepwise from euglycemia (5.6 mmol/l) to moderate hypoglycemia (2.5 mmol/l). RESULTS: As expected, there was a significant effect of hypoglycemia on feelings of hunger (F (3, 42)=41.7, p<0.01). But during high insulin infusion, feelings of hunger were significantly less intense than during moderate insulin infusion (F (1, 14)=7.2, p=0.02). CONCLUSION: Peripheral insulin levels seem to be associated with the intensity of feelings of hunger.

Ischaemia is linked to inflammation and induction of angiogenesis in pancreatic islets.

Beta-cell replacement is the only way to restore euglycaemia in patients with type-1 diabetes. Pancreatic tissue, processed for subsequent clinical islet transplantation, is exposed to ischaemia causing injury and death in a large number of islets before and after transplantation. In this review we summarize what is known on the sources of environmental stress for pancreatic islets, such as insufficient oxygen supply during pancreas procurement and in culture prior to intraportal transplantation, nutritional and oxygen deprivation during the isolation process, and the consequences of hyperglycaemia. An increasingly recognized role in the modulation of beta-cell function and these environmental stress factors plays the vascular network of the pancreatic islets. Islet revascularization by angiogenesis is relevant for the survival of the graft subsequent to transplantation. Potential strategies offered by therapeutic induction of revascularization to ameliorate the detrimental impact of these factors on the quality of islet transplants are discussed.

Glucose evaluation trial for remission (GETREM) in type 1 diabetes: a European multicentre study.

OBJECTIVE: Strict metabolic control during the 1st year of type 1 diabetes is thought to be a key factor for achieving clinical remission. The aims of this study were two-fold: (i) to evaluate the frequency and duration of spontaneous remission (defined according to the parameters issued by the International Diabetic Immunotherapy Group (IDIG)) in a European population of consecutive recent onset type 1 diabetes patients (aged 5-35 years), followed-up for a period of 36 months with a common protocol of intensive insulin therapy and without adjunct immune-intervention; and (ii) to identify the predictive factors for clinical remission. RESEARCH DESIGN AND METHOD: A total of 189 consecutive patients with newly diagnosed type 1 diabetes according to ADA criteria were recruited in participating centres (Belgium, Czech Republic, Estonia, France, Germany, Hungary, Italy, Poland, Romania, Sweden and Turkey) and followed-up for a period of up to 36 months. In all patients, intensive insulin therapy was implemented consisting of three or four injections of regular insulin daily with NPH insulin at bedtime. Adjustment of insulin dose was made according to a common protocol. Various clinical characteristics (age, gender, severity of presentation, etc.), history (presence of diabetic siblings in the family, etc.) and integrated parameters of metabolic control (HbA(1c), blood glucose, the total insulin dose at hospital discharge adjusted for body weight) were collected. RESULTS: Twenty-two patients (11.6%) experienced remission. The median duration of remission was 9.6 months and the range was 31 months. There was a wide variation among centres. Logistic regression analysis focused on the centre as the main variable in achieving remission. CONCLUSION: Remission was shown to be very heterogeneous between centres depending on 'other factors' such as patient care and family awareness of the disease rather than on 'measurable factors' such as sex, age, HbA(1c) and severity of presentation at diagnosis. Using intensive insulin therapy and optimisation of metabolic control, remission occurred in nearly one out of eight patients.