L-ornithine L-aspartate for people with cirrhosis and hepatic encephalopathy

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the beneficial and harmful effects of L-ornithine L-aspartate versus placebo, no intervention, or other active interventions for people with cirrhosis and hepatic encephalopathy

Prevalence and awareness of lower urinary tract symptoms among males in the Outpatient Clinics of Universiti Kebangsaan Malaysia Medical Centre.

This study aims to determine the prevalence of lower urinary tract symptoms (LUTS) and level of awareness among male outpatients in Universiti Kebangsaan Malaysia Medical Centre (UKMMC). A questionnaire consisting of demographic data, questions related to knowledge, attitude and practice on BPH and the International Prostate Symptom Score (IPSS) was used for this study. Uroflowmetry and bladder scan were used to evaluate the function of the urinary tract and severity of BPH. Urine dipstick was done for glycosuria, proteinuria and haematuria. A total of 220 respondents were surveyed. The prevalence of moderately and severely symptomatic LUTS was 42.7%. The most commonly reported LUTS were nocturia (78.2%), frequency (58.2%) and incomplete emptying (44.6%). The prevalence of glycosuria, proteinuria and haematuria were 23.6%, 11.4% and 1.8% respectively. There was a significant association between increasing age with the severity of LUTS (p=0.005). Out of 102 respondents with voided urine volume greater than 150 mL, there was a significant decrease in maximum (Qmax) (p=0.039) and average (Qave) urine flow rates with every 10 years increase of age (p=0.001). The majority of respondents (59.5%) have heard of BPH before. Over 78.2% of the respondents would seek medical attention if they have LUTS with 15.9% saying they would seek traditional treatment. In conclusion, the prevalence of LUTS was high and the level of awareness was satisfactory

Flumazenil versus placebo or no intervention for people with cirrhosis and hepatic encephalopathy

BACKGROUND: Hepatic encephalopathy is a common complication of cirrhosis which results in poor brain functioning. The spectrum of changes associated with hepatic encephalopathy ranges from the clinically 'indiscernible' or minimal hepatic encephalopathy to the clinically 'obvious' or overt hepatic encephalopathy. Flumazenil is a synthetic benzodiazepine antagonist with high affinity for the central benzodiazepine recognition site. Flumazenil may benefit people with hepatic encephalopathy through an indirect negative allosteric modulatory effect on gamma-aminobutyric acid receptor function. The previous version of this review, which included 13 randomised clinical trials, found no effect of flumazenil on all-cause mortality, based on an analysis of 10 randomised clinical trials, but found a beneficial effect on hepatic encephalopathy, based on an analysis of eight randomised clinical trials. OBJECTIVES: To evaluate the beneficial and harmful effects of flumazenil versus placebo or no intervention for people with cirrhosis and hepatic encephalopathy. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, and LILACS; meeting and conference proceedings; and bibliographies in May 2017. SELECTION CRITERIA: We included randomised clinical trials regardless of publication status, blinding, or language in the analyses of benefits and harms, and observational studies in the assessment of harms. DATA COLLECTION AND ANALYSIS: Two review authors extracted data independently. We undertook meta-analyses and presented results using risk ratios (RR) with 95% confidence intervals (CI) and I(2) values as a marker of heterogeneity. We assessed bias control using the Cochrane Hepato-Biliary Group domains; determined the quality of the evidence using GRADE; evaluated the risk of small-study effects in regression analyses; and conducted trial sequential, subgroup, and sensitivity analyses. MAIN RESULTS: We identified 14 eligible randomised clinical trials with 867 participants, the majority of whom had an acute episode of overt hepatic encephalopathy. In addition, we identified one ongoing randomised clinical trial. We were unable to gather outcome data from two randomised clinical trials with 25 participants. Thus, our analyses include 842 participants from 12 randomised clinical trials comparing flumazenil versus placebo. We classified one randomised clinical trial at low risk of bias in the overall assessment and the remaining randomised clinical trials at high risk of bias. The duration of follow-up ranged from a few minutes to two weeks, but it was less than one day in the majority of the trials.In total, 32/433 (7.4%) participants allocated to flumazenil versus 38/409 (9.3%) participants allocated to placebo died (RR 0.75, 95% CI 0.48 to 1.16; 11 randomised clinical trials; low quality evidence). The Trial Sequential Analysis and the one randomised clinical trial assessed as low risk of bias (RR 0.76, 95% CI 0.37 to 1.53) found no beneficial or harmful effects of flumazenil on all-cause mortality. The methods used to evaluate hepatic encephalopathy included several different clinical scales, electrophysiological variables, and psychometric tests. Flumazenil was associated with a beneficial effect on hepatic encephalopathy when including all randomised clinical trials (RR 0.75, 95% CI 0.71 to 0.80; 824 participants; nine randomised clinical trials; low quality evidence), or just the trial at low risk of bias (RR 0.78, 95% CI 0.72 to 0.84; 527 participants). The Trial Sequential Analysis supported a beneficial effect of flumazenil on hepatic encephalopathy. The randomised clinical trials included little information about causes of death and little information on non-fatal serious adverse events. AUTHORS' CONCLUSIONS: We found low quality evidence suggesting a short-term beneficial effect of flumazenil on hepatic encephalopathy in people with cirrhosis, but no evidence of an effect on all-cause mortality. Additional evidence from large, high quality randomised clinical trials is needed to evaluate the potential benefits and harms of flumazenil in people with cirrhosis and hepatic encephalopathy

Why do women invest in pre-pregnancy health and care? A qualitative investigation with women attending maternity services

Background Despite the importance attributed to good pre-pregnancy care and its potential to improve pregnancy and child health outcomes, relatively little is known about why women invest in pre-pregnancy health and care. We sought to gain insight into why women invested in pre-pregnancy health and care. Methods We carried out 20 qualitative in-depth interviews with pregnant or recently pregnant women who were drawn from a survey of antenatal clinic attendees in London, UK. Interviewees were purposively sampled to include high and low investors in pre-pregnancy health and care, with variation in age, partnership status, ethnicity and pre-existing medical conditions. Data analysis was conducted using the Framework method. Results We identified three groups in relation to pre-pregnancy health and care: 1) The “prepared” group, who had high levels of pregnancy planning and mostly positive attitudes to micronutrient supplementation outside of pregnancy, carried out pre-pregnancy activities such as taking folic acid and making changes to diet and lifestyle. 2) The “poor knowledge” group, who also had high levels of pregnancy planning, did not carry out pre-pregnancy activities and described themselves as having poor knowledge. Elsewhere in their interviews they expressed a strong dislike of micronutrient supplementation. 3) The “absent pre-pregnancy period” group, had the lowest levels of pregnancy planning and also expressed anti-supplement views. Even discussing the pre-pregnancy period with this group was difficult as responses to questions quickly shifted to focus on pregnancy itself. Knowledge of folic acid was poor in all groups. Conclusion Different pre-pregnancy care approaches are likely to be needed for each of the groups. Among the “prepared” group, who were proactive and receptive to health messages, greater availability of information and better response from health professionals could improve the range of pre-pregnancy activities carried out. Among the “poor knowledge” group, better response from health professionals might yield greater uptake of pre-pregnancy information. A different, general health strategy might be more appropriate for the “absent pre-pregnancy period” group. The fact that general attitudes to micronutrient supplementation were closely related to whether or not women invested in pre-pregnancy health and care was an unanticipated finding and warrants further investigation.This report is independent research commissioned and funded by the Department of Health Policy Research Programme Pre-Pregnancy Health and Care in England: Exploring Implementation and Public Health Impact, 006/0068

Hierarchical information clustering by means of topologically embedded graphs

We introduce a graph-theoretic approach to extract clusters and hierarchies in complex data-sets in an unsupervised and deterministic manner, without the use of any prior information. This is achieved by building topologically embedded networks containing the subset of most significant links and analyzing the network structure. For a planar embedding, this method provides both the intra-cluster hierarchy, which describes the way clusters are composed, and the inter-cluster hierarchy which describes how clusters gather together. We discuss performance, robustness and reliability of this method by first investigating several artificial data-sets, finding that it can outperform significantly other established approaches. Then we show that our method can successfully differentiate meaningful clusters and hierarchies in a variety of real data-sets. In particular, we find that the application to gene expression patterns of lymphoma samples uncovers biologically significant groups of genes which play key-roles in diagnosis, prognosis and treatment of some of the most relevant human lymphoid malignancies.Comment: 33 Pages, 18 Figures, 5 Table

Obstetric fistula in Burundi: a comprehensive approach to managing women with this neglected disease.

BACKGROUND: In Burundi, the annual incidence of obstetric fistula is estimated to be 0.2-0.5% of all deliveries, with 1000-2000 new cases per year. Despite this relatively high incidence, national capacity for identifying and managing obstetric fistula is very limited. Thus, in July 2010, Medecins Sans Frontieres (MSF) set up a specialised Obstetric Fistula Centre in Gitega (Gitega Fistula Centre, GFC), the only permanent referral centre for obstetric fistula in Burundi. A comprehensive model of care is offered including psychosocial support, conservative and surgical management, post-operative care and follow-up. We describe this model of care, patient outcomes and the operational challenges. METHODS: Descriptive study using routine programme data. RESULTS: Between July 2010 and December 2011, 470 women with obstetric fistula presented for the first time at GFC, of whom 458 (98%) received treatment. Early urinary catheterization (conservative management) was successful in four out of 35 (11%) women. Of 454 (99%) women requiring surgical management, 394 (87%) were discharged with a closed fistula, of whom 301 (76%) were continent of urine and/or faeces, while 93 (24%) remained incontinent of urine and/or faeces. In 59 (13%) cases, the fistula was complex and could not be closed. Outcome status was unknown for one woman. Median duration of stay at GFC was 39 days (Interquartile range IQR, 31-51 days). CONCLUSION: In a rural African setting, it is feasible to implement a comprehensive package of fistula care using a dedicated fistula facility, and satisfactory surgical repair outcomes can be achieved. Several operational challenges are discussed

Estimating the prevalence of obstetric fistula: a systematic review and meta-analysis.

BACKGROUND: Obstetric fistula is a severe condition which has devastating consequences for a woman's life. The estimation of the burden of fistula at the population level has been impaired by the rarity of diagnosis and the lack of rigorous studies. This study was conducted to determine the prevalence and incidence of fistula in low and middle income countries. METHODS: Six databases were searched, involving two separate searches: one on fistula specifically and one on broader maternal and reproductive morbidities. Studies including estimates of incidence and prevalence of fistula at the population level were included. We conducted meta-analyses of prevalence of fistula among women of reproductive age and the incidence of fistula among recently pregnant women. RESULTS: Nineteen studies were included in this review. The pooled prevalence in population-based studies was 0.29 (95% CI 0.00, 1.07) fistula per 1000 women of reproductive age in all regions. Separated by region we found 1.57 (95% CI 1.16, 2.06) in sub Saharan Africa and South Asia, 1.60 (95% CI 1.16, 2.10) per 1000 women of reproductive age in sub Saharan Africa and 1.20 (95% CI 0.10, 3.54) per 1000 in South Asia. The pooled incidence was 0.09 (95% CI 0.01, 0.25) per 1000 recently pregnant women. CONCLUSIONS: Our study is the most comprehensive study of the burden of fistula to date. Our findings suggest that the prevalence of fistula is lower than previously reported. The low burden of fistula should not detract from their public health importance, however, given the preventability of the condition, and the devastating consequences of fistula

Epidemiological and Clinical Characteristics of Melioidosis Caused by Gentamicin-Susceptible Burkholderia pseudomallei in Sarawak, Malaysia

Burkholderia pseudomallei, the causative agent of melioidosis, is intrinsically resistant to a broad range of antibiotics, including aminoglycosides. In Sarawak, Malaysia, a high proportion of melioidosis cases are caused by gentamicin-susceptible isolates. There are limited epidemiological and clinical data on these infections. Methods. We conducted a retrospective study of culture-confirmed melioidosis among adults admitted to Bintulu Hospital in Sarawak, Malaysia, from January 2011 until December 2016. One hundred forty-eight adults with culture-confirmed melioidosis were identified. Of 129 (87%) tested, 84 (65%) had gentamicin-susceptible B pseudomallei. The average annual incidence of melioidosis was 12.3 per 100 000 population, with marked variation between districts ranging from 5.8 to 29.3 per 100 000 population. Rural districts had higher incidences of melioidosis and overwhelmingly larger proportions of gentamicin-susceptible B pseudomallei infection. Significantly more patients with gentamicin-susceptible infection had no identified risk factors, with diabetes less frequently present in this group. Ninety-eight percent had acute presentations. Pneumonia, reported in 71%, was the most common presentation. Splenic abscesses were found in 54% of those imaged. Bacteremia was present in 88%; septic shock occurred in 47%. Forty-five (35%) patients died. No differences in clinical, laboratory, or outcome characteristics were noted between gentamicin-susceptible and gentamicin-resistant infections. Gentamicin-susceptible B pseudomallei infections are common in Sarawak and dominate in the high-incidence rural interior regions. Clinical manifestations and outcomes are the same as for gentamicin-resistant B pseudomallei infections. Further studies are required to determine if all gentamicin-susceptible B pseudomallei infections in Sarawak are clonal and to ascertain their environmental drivers and niches

Predictors and outcome of surgical repair of obstetric fistula at a regional referral hospital, Mbarara, western Uganda

<p>Abstract</p> <p>Background</p> <p>Obstetric fistula although virtually eliminated in high income countries, still remains a prevalent and debilitating condition in many parts of the developing world. It occurs in areas where access to care at childbirth is limited, or of poor quality and where few hospitals offer the necessary corrective surgery.</p> <p>Methods</p> <p>This was a prospective observational study where all women who attended Mbarara Regional Referral Hospital in western Uganda with obstetric fistula during the study period were assessed pre-operatively for social demographics, fistula characteristics, classification and outcomes after surgery. Assessment for fistula closure and stress incontinence after surgery was done using a dye test before discharge</p> <p>Results</p> <p>Of the 77 women who were recruited in this study, 60 (77.9%) had successful closure of their fistulae. Unsuccessful fistula closure was significantly associated with large fistula size (Odds Ratio 6 95% Confidential interval 1.46-24.63), circumferential fistulae (Odds ratio 9.33 95% Confidential interval 2.23-39.12) and moderate to severe vaginal scarring (Odds ratio 12.24 95% Confidential interval 1.52-98.30). Vaginal scarring was the only factor independently associated with unsuccessful fistula repair (Odds ratio 10 95% confidential interval 1.12-100.57). Residual stress incontinence after successful fistula closure was associated with type IIb fistulae (Odds ratio 5.56 95% Confidential interval 1.34-23.02), circumferential fistulae (Odds ratio 10.5 95% Confidential interval 1.39-79.13) and previous unsuccessful fistula repair (Odds ratio 4.8 95% Confidential interval 1.27-18.11). Independent predictors for residual stress incontinence after successful fistula closure were urethral involvement (Odds Ratio 4.024 95% Confidential interval 2.77-5.83) and previous unsuccessful fistula repair (Odds ratio 38.69 95% Confidential interval 2.13-703.88).</p> <p>Conclusions</p> <p>This study demonstrated that large fistula size, circumferential fistulae and marked vaginal scarring are predictors for unsuccessful fistula repair while predictors for residual stress incontinence after successful fistula closure were urethral involvement, circumferential fistulae and previous unsuccessful fistula repair.</p