Multiple rim-enhancing brain lesions and pulmonary cavitary nodules as the presentation of Nocardia cyriacigeorgica in a patient with non-small cell lung cancer.

Nocardiosis is caused by various strains of the genus Nocardia, a gram-positive, acid-fast bacillus found in organic matter. Disseminated nocardiosis with central nervous system involvement is a rare infection that is most commonly seen in immunocompromised patients. We present a case of a 67-year-old veteran with stage IV adenocarcinoma of the lung undergoing chemotherapy who presented with new cavitary pulmonary lesions. Three weeks into his hospitalization, a sputum culture with acid-fast staining returned positive for Nocardia cyriacigeorgica. A subsequent computed tomography scan of the head demonstrated numerous rim-enhancing lesions presumed to be due to disseminated nocardiosis with central nervous system involvement. Disseminated nocardiosis has a high mortality rate, making prompt detection and treatment paramount for these patients. Our case highlights the importance of considering central nervous system involvement in the evaluation of a patient with nocardiosis.

Assessing Patient Preferences in Rare Diseases: Direct Preference Elicitation in the Rare Chronic Kidney Disease, Immunoglobulin A Nephropathy.

BACKGROUND: Patient preference information is increasingly being used to inform decision making; however, further work is required to support the collection of preference information in rare diseases. This study illustrates the use of direct preference elicitation methods to collect preference data from small samples in the context of early decision making to inform the development of a product for the treatment of immunoglobulin A nephropathy. METHOD: An interview-based swing weighting approach was used to elicit preferences from 40 patients in the US and China. Attributes were identified through a background review, expert engagement and patient focus groups. Participants completed a series of tasks that involved ranking, rating and scoring improvements in the attributes to obtain attribute swing weights and partial value functions. The preference results were then incorporated into a benefit-risk assessment simulation tool. RESULTS: Participants placed the greatest value on avoiding end-stage renal/kidney disease. Similar weight was given to short-term quality-of-life improvements and avoiding infections. Treatment burden (number of vaccinations) received the least weight. Heterogeneity in preferences was also observed. Consistency tests did not identify statistically significant variation in preferences, and qualitative data suggested that the elicitation exercise was sensitive to participants' interpretation of attributes and that participants were able to express their preferences. CONCLUSION: Direct preference elicitation methods can be used to collect preference data from small samples. Further work should continue to test the validity of the estimate generated by such methods.

Systematic literature review of efficacy/effectiveness and safety of current therapies for the treatment of cryopyrin-associated periodic syndrome, hyperimmunoglobulin D syndrome and tumour necrosis factor receptor-associated periodic syndrome.

OBJECTIVES: Several therapies are used for the treatment of rareautoinflammatory conditions like cryopyrin-associated periodic fever syndromes (CAPS), hyperimmunoglobulin Dsyndrome (HIDS)/mevalonate kinase deficiency (MKD) and tumour necrosis factor receptor-associated periodic syndrome (TRAPS). However, reviews reporting on treatment outcomes of these therapies are lacking. METHODS: A systematic literature review was conducted using Embase, MEDLINE, MEDLINE-In Process and Cochrane databases to identify the randomised/non-randomised controlled trials (RCTs/non-RCTs) and real-world observational studies of CAPS, HIDS/MKD and TRAPS published as full-texts (January 2000-September 2017) or conference abstracts (January 2014-September 2017). Studies with data for ≥1 biologic were included. Studies with <5 patients were excluded. RESULTS: Of the 3 342 retrieved publications, 72 studies were included (CAPS, n=43; HIDS/MKD, n=9; TRAPS, n=7; studies with ≥2 cohorts, n=13). Most studies were full-text (n=56), published after 2010 (n=56) and real-world observational studies (n=58). Among included studies, four were RCTs (canakinumab, n=2 (CAPS, n=1; HIDS/MKD and TRAPS, n=1); rilonacept, n=1 (in CAPS); simvastatin, n=1 (in HIDS/MKD)). Canakinumab and anakinra were the most commonly used therapies for CAPS and HIDS/MKD, whereas etanercept, canakinumab and anakinra were the most common for TRAPS. The available evidence suggested the efficacy or effectiveness of canakinumab and anakinra in CAPS, HIDS/MKD and TRAPS, and of etanercept in TRAPS; asingle RCT demonstrated the efficacy of rilonacept in CAPS. CONCLUSIONS: Canakinumab, anakinra, etanercept and rilonacept were reported to be well tolerated; however, injection-site reactions were observed frequently with anakinra, rilonacept and etanercept. Data on the use of tocilizumab, infliximab and adalimumab in these conditions were limited; thus, further research is warranted.

A systematic literature review of efficacy, effectiveness and safety of biologic therapies for treatment of familial Mediterranean fever.

OBJECTIVES: To identify and summarize the existing evidence on the efficacy, effectiveness and safety of biologic therapies used, either as indicated or off-label, in the treatment of FMF. METHODS: A systematic literature review was conducted using Embase®, MEDLINE®, MEDLINE®-In Process, and Cochrane databases to identify randomized/non-randomized controlled trials (RCTs/non-RCTs) and real-world observational studies of FMF published as full-text articles (2000-September 2017) or conference abstracts (2014-September 2017). Studies with data for ≥1 biologic were included. Studies with <5 patients were excluded. RESULTS: Of the 3342 retrieved records, 67 publications, yielding 38 unique studies, were included. All studies were published after the year 2010, and the majority (21) were full-text articles. Most studies (33/38) were prospective/retrospective observational; three were double-blind, placebo-controlled RCTs (one each of anakinra, canakinumab and rilonacept); and two were non-RCTs (both canakinumab). Anakinra (26), canakinumab (21) and etanercept (6) were the most frequently used biologics across studies, whereas use of adalimumab, tocilizumab, rilonacept and infliximab was limited (1-2 studies). The available evidence suggested benefits of anakinra and canakinumab in FMF. CONCLUSION: Anti-IL-1 therapies (i.e. anakinra and canakinumab) appear to be effective and safe options in the treatment of overall FMF, including patients with colchicine resistance and FMF-related amyloidosis. There is a need for properly designed prospective or controlled studies to conclude the superiority of one anti-IL-1 therapy over another. Evidence on the use of TNF-α and IL-6 inhibitors is limited, and further research is suggested.

Clinical, Economic, and Humanistic Burden Associated With Delayed Diagnosis of Axial Spondyloarthritis: A Systematic Review.

INTRODUCTION: Few studies have evaluated the impact of delayed diagnosis of axial spondyloarthritis (axSpA) on the overall burden of disease. The objective of this review was to evaluate the available literature on the clinical, economic, and humanistic burden of delayed diagnosis in patients with axSpA. METHODS: This systematic literature review was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the MEDLINE and Embase databases for English-language publications of original research articles (up to July 12, 2018) and conference abstracts (January 1, 2014, to July 12, 2018) reporting studies of adult patients with delayed diagnosis of axSpA associated with clinical, economic, or humanistic burden. Retrieved publications were screened for eligibility by two independent reviewers; discrepancies were resolved by a third independent reviewer. Data were extracted by one reviewer and validated by a second independent reviewer. RESULTS: A total of 1391 publications were retrieved, of which 21 met the inclusion criteria and were included in the analysis. Of these, 15 reported data on clinical burden, nine on economic burden, and six on humanistic burden, with eight studies reporting a combination of clinical, economic, and/or humanistic burden. Patients with a delayed diagnosis of axSpA generally had higher disease activity, worse physical function, and more structural damage than those who received an earlier diagnosis. Patients with a delayed diagnosis also had a greater likelihood of work disability and higher direct and indirect healthcare costs than those who received an earlier diagnosis. Delayed diagnosis was associated with a greater likelihood for depression, negative psychological impacts, and worse quality of life. CONCLUSIONS: Delayed axSpA diagnosis was associated with more functional impairment, higher healthcare costs, and worse quality of life, highlighting the importance of early recognition of axSpA to reduce extensive burden on patients and society. Plain language summary available for this article.

Patient Needs, Perceptions, and Attitudinal Drivers Associated with Obesity: A Qualitative Online Bulletin Board Study.

INTRODUCTION: To gain insights into the needs, attitudes, perceptions, and preferences of people living with obesity using an online bulletin board (OBB) study. METHODS: The OBB is a moderated asynchronous online qualitative market research method that allows interactive discussion among participants. Participants were recruited via physician referral followed by screening questions to ensure eligibility and willingness to participate. The discussions in the OBB were moderated and allowed anonymized open answers and responses. Analysis was performed using various qualitative analytical tools. RESULTS: This OBB study included 23 participants (n = 11, UK; n = 12, USA). Participants expressed negative emotions associated with obesity. Obesity impacted various aspects of their life, and the feeling of loneliness caused food indulgence, especially during the evenings. Their appearance was their primary cause of anxiety, whilst health considerations were secondary. The participants felt trapped in a cycle where food was (ab)used to overcome problems associated with being obese. Participants were pessimistic about weight management measures as a result of unsuccessful past attempts, with little/no support from healthcare providers, friends, and family for weight management. They preferred medications that would allow them to maintain their current lifestyle yet cause visible weight reduction. Along with medications, they expressed a strong preference for an online support group with similar peers for motivation, support, and sustained outcomes. CONCLUSIONS: As losing excess weight is a challenge for most overweight individuals, the qualitative insights from this OBB can inform the planning and successful execution of various weight management and drug development programs. FUNDING: Novartis Pharma AG, Basel Switzerland.

Systematic literature review on the economic, humanistic, and societal burden of heart failure in children and adolescents.

INTRODUCTION: Unlike the adult heart failure (HF) patient population, there is scarce information on the overall burden of HF in the pediatric population across geographies and within different age groups. AREAS COVERED: A systematic review aims to describe and quantify the economic, humanistic, and societal burden of pediatric (age <18 years) HF on patients and caregivers. Eighteen published studies over a period of 10 years (1 January 2006-20 May 2016) were identified through Embase, Medline, Cochrane Library and selected congresses. Studies from the US reported higher HF-related hospitalization-rates in infants aged <1 year (49.3%-63.9%) versus children aged 1-12 years (18.7%-30.9%) in HF diagnosed patients. Across the studies, the average length of hospital stay was 15 days, increasing to 26 days for infants. Average annual hospital charges were higher for infants (US$176,000) versus children aged 1-10 years (US$132,000) in the US. In Germany, diagnosis-related group (DRG)-based hospital-allowances per HF-case increased from €3,498 in 1995 to €4,250 in 2009. EXPERT OPINION: To our knowledge, this is the first systematic review, which provides valuable insights into the burden of HF in children and adolescents, and strengthens current knowledge of pediatric HF. However, there is a need for larger population-based studies with wider geographical coverage.

Interventions for preventing upper gastrointestinal bleeding in people admitted to intensive care units.

BACKGROUND: Upper gastrointestinal (GI) bleeding due to stress ulcers contributes to increased morbidity and mortality in people admitted to intensive care units (ICUs). Stress ulceration refers to GI mucosal injury related to the stress of being critically ill. ICU patients with major bleeding as a result of stress ulceration might have mortality rates approaching 48.5% to 65%. However, the incidence of stress-induced GI bleeding in ICUs has decreased, and not all critically ill patients need prophylaxis. Stress ulcer prophylaxis can result in adverse events such as ventilator-associated pneumonia; therefore, it is necessary to evaluate strategies that safely decrease the incidence of GI bleeding. OBJECTIVES: To assess the effect and risk-benefit profile of interventions for preventing upper GI bleeding in people admitted to ICUs. SEARCH METHODS: We searched the following databases up to 23 August 2017, using relevant search terms: MEDLINE; Embase; the Cochrane Central Register of Controlled Trials; Latin American Caribbean Health Sciences Literature; and the Cochrane Upper Gastrointestinal and Pancreatic Disease Group Specialised Register, as published in the Cochrane Library (2017, Issue 8). We searched the reference lists of all included studies and those from relevant systematic reviews and meta-analyses to identify additional studies. We also searched the World Health Organization International Clinical Trials Registry Platform search portal and contacted individual researchers working in this field, as well as organisations and pharmaceutical companies, to identify unpublished and ongoing studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs with participants of any age and gender admitted to ICUs for longer than 48 hours. We excluded studies in which participants were admitted to ICUs primarily for the management of GI bleeding and studies that compared different doses, routes, and regimens of one drug in the same class because we were not interested in intraclass effects of drugs. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as recommended by Cochrane. MAIN RESULTS: We identified 2292 unique records.We included 129 records reporting on 121 studies, including 12 ongoing studies and two studies awaiting classification.We judged the overall risk of bias of two studies as low. Selection bias was the most relevant risk of bias domain across the included studies, with 78 studies not clearly reporting the method used for random sequence generation. Reporting bias was the domain with least risk of bias, with 12 studies not reporting all outcomes that researchers intended to investigate.Any intervention versus placebo or no prophylaxisIn comparison with placebo, any intervention seems to have a beneficial effect on the occurrence of upper GI bleeding (risk ratio (RR) 0.47, 95% confidence interval (CI) 0.39 to 0.57; moderate certainty of evidence). The use of any intervention reduced the risk of upper GI bleeding by 10% (95% CI -12.0% to -7%). The effect estimate of any intervention versus placebo or no prophylaxis with respect to the occurrence of nosocomial pneumonia, all-cause mortality in the ICU, duration of ICU stay, duration of intubation (all with low certainty of evidence), the number of participants requiring blood transfusions (moderate certainty of evidence), and the units of blood transfused was consistent with benefits and harms. None of the included studies explicitly reported on serious adverse events.Individual interventions versus placebo or no prophylaxisIn comparison with placebo or no prophylaxis, antacids, H2 receptor antagonists, and sucralfate were effective in preventing upper GI bleeding in ICU patients. Researchers found that with H2 receptor antagonists compared with placebo or no prophylaxis, 11% less developed upper GI bleeding (95% CI -0.16 to -0.06; RR 0.50, 95% CI 0.36 to 0.70; 24 studies; 2149 participants; moderate certainty of evidence). Of ICU patients taking antacids versus placebo or no prophylaxis, 9% less developed upper GI bleeding (95% CI -0.17 to -0.00; RR 0.49, 95% CI 0.25 to 0.99; eight studies; 774 participants; low certainty of evidence). Among ICU patients taking sucralfate versus placebo or no prophylaxis, 5% less had upper GI bleeding (95% CI -0.10 to -0.01; RR 0.53, 95% CI 0.32 to 0.88; seven studies; 598 participants; moderate certainty of evidence). The remaining interventions including proton pump inhibitors did not show a significant effect in preventing upper GI bleeding in ICU patients when compared with placebo or no prophylaxis.Regarding the occurrence of nosocomial pneumonia, the effects of H2 receptor antagonists (RR 1.12, 95% CI 0.85 to 1.48; eight studies; 945 participants; low certainty of evidence) and of sucralfate (RR 1.33, 95% CI 0.86 to 2.04; four studies; 450 participants; low certainty of evidence) were consistent with benefits and harms when compared with placebo or no prophylaxis. None of the studies comparing antacids versus placebo or no prophylaxis provided data regarding nosocomial pneumonia.H2 receptor antagonists versus proton pump inhibitorsH2 receptor antagonists and proton pump inhibitors are most commonly used in practice to prevent upper GI bleeding in ICU patients. Proton pump inhibitors significantly more often prevented upper GI bleeding in ICU patients compared with H2 receptor antagonists (RR 2.90, 95% CI 1.83 to 4.58; 18 studies; 1636 participants; low certainty of evidence). When taking H2 receptor antagonists, 4.8% more patients might experience upper GI bleeding (95% CI 2.1% to 9%). Nosocomial pneumonia occurred in similar proportions of participants taking H2 receptor antagonists and participants taking proton pump inhibitors (RR 1.02, 95% CI 0.77 to 1.35; 10 studies; 1256 participants; low certainty of evidence). AUTHORS' CONCLUSIONS: This review shows that antacids, sucralfate, and H2 receptor antagonists might be more effective in preventing upper GI bleeding in ICU patients compared with placebo or no prophylaxis. The effect estimates of any treatment versus no prophylaxis on nosocomial pneumonia were consistent with benefits and harms. Evidence of low certainty suggests that proton pump inhibitors might be more effective than H2 receptor antagonists. Therefore, patient-relevant benefits and especially harms of H2 receptor antagonists compared with proton pump inhibitors need to be assessed by larger, high-quality RCTs to confirm the results of previously conducted, smaller, and older studies.

Systematic Literature Review on the Incidence and Prevalence of Heart Failure in Children and Adolescents.

While the epidemiology of adult heart failure has been extensively researched, this systematic review addresses the less well characterized incidence and prevalence of pediatric HF. The search strategy used Cochrane methodology and identified 83 unique studies for inclusion. Studies were categorized according to whether the HF diagnosis was reported as primary (n = 10); associated with other cardiovascular diseases (CVDs) (n = 49); or associated with non-CVDs (n = 24). A narrative synthesis of the evidence is presented. For primary HF, the incidence ranged from 0.87/100,000 (UK and Ireland) to 7.4/100,000 (Taiwan). A prevalence of 83.3/100,000 was reported in one large population-based study from Spain. HF etiology varied across regions with lower respiratory tract infections and severe anemia predominating in lower income countries, and cardiomyopathies and congenital heart disease major causes in higher income countries. Key findings for the other categories included a prevalence of HF associated with cardiomyopathies ranging from 36.1% (Japan) to 79% (US); associated with congenital heart disease from 8% (Norway) to 82.2% (Nigeria); associated with rheumatic heart diseases from 1.5% (Turkey) to 74% (Zimbabwe); associated with renal disorders from 3.8% (India) to 24.1% (Nigeria); and associated with HIV from 1% (US) to 29.3% (Brazil). To our knowledge, this is the first systematic review of the topic and strengthens current knowledge of pediatric HF epidemiology. Although a large body of research was identified, heterogeneity in study design and diagnostic criteria limited the ability to compare regional data. Standardized definitions of pediatric HF are required to facilitate cross-regional comparisons of epidemiological data.

The Effect of Formulary Restrictions on Patient and Payer Outcomes: A Systematic Literature Review.

BACKGROUND: Formulary restrictions are implemented to reduce pharmacy costs and ensure appropriate use of pharmaceutical products. As adoption of formulary restrictions increases with rising pharmacy costs, there is a need to better understand the potential effect of formulary restrictions on patient and payer outcomes. OBJECTIVE: To conduct a systematic literature review that assesses the effect of formulary restrictions on the following outcomes: medication adherence, clinical outcomes, treatment satisfaction, drug utilization, health care resource utilization, and economic outcomes. METHODS: Studies published in 2005 or later were identified from the MEDLINE, Embase, and Cochrane databases and the National Health Service Economic Evaluation Database, using 2 sets of search terms. A total of 17 formulary restriction terms (e.g., step therapy [ST] and prior authorization [PA]) and 55 outcome terms were included, resulting in 935 unique search term combinations. Two reviewers independently conducted analyses of the titles, abstracts, and full-text articles. The search was limited to English-language articles that evaluated the effect of ST and/or PA placed by U.S. third-party payers on the following outcomes: patient outcomes (medication adherence, clinical outcomes, and treatment satisfaction) and payer outcomes (drug utilization, health care resource utilization, and economic outcomes). RESULTS: Of 2,321 reviewed articles, 59 articles met the study inclusion criteria. The included studies assessed the effect of ST (n = 18), PA (n = 35), or both (n = 6) on medication adherence (n = 14), clinical outcomes (n = 12), treatment satisfaction (n = 2), drug utilization (n = 39), health care resource utilization (n = 18), and economic outcomes (n = 42). The 59 articles measured 164 outcomes across the patient, health care resource utilization, and economic outcome categories of interest. Of the total number of outcomes, 50.6% (n = 83) were negative in direction or were unfavorable, whereas 40.2% (n = 66) were positive in direction or were favorable, when the perspectives of patients and payers were considered. Of the total number of drug utilization outcomes reported (n = 46), the majority showed lower drug utilization (> 90%). However, in some of the articles, pharmacy cost savings resulting from lower drug utilization appeared to be offset by increased medical costs. CONCLUSIONS: Formulary coverage decisions may have unintended consequences on patient and payer outcomes despite lower drug utilization and pharmacy cost savings; therefore, careful evaluation of restrictions before policy implementation and continued reevaluation after implementation is warranted. DISCLOSURES: This study was funded by Novartis Pharmaceuticals. Park and Ko are employed by Novartis Pharmaceuticals in East Hanover, New Jersey, and Ko holds stock in Novartis. Raza, George, and Agrawal are employed by Novartis Healthcare in Hyderabad, India. Study concept and design were contributed primarily by Park and Ko, along with the other authors. Raza, George, and Agrawal collected the data, along with Park and Ko. Data interpretation was performed by Agrawal, Raza, George, Park, and Ko. The manuscript was written and revised by Raza, George, and Park, along with Ko and Agrawal. Results from this systematic literature review were presented at the AMCP Annual Meeting 2016; San Francisco, California; April 19-22, 2016.

Reporting of methods was better in the Clinical Trials Registry-India than in Indian journal publications.

OBJECTIVE: We sought to evaluate if editorial policies and the reporting quality of randomized controlled trials (RCTs) had improved since our 2004-05 survey of 151 RCTs in 65 Indian journals, and to compare reporting quality of protocols in the Clinical Trials Registry-India (CTRI). STUDY DESIGN AND SETTING: An observational study of endorsement of Consolidated Standards for the Reporting of Trials (CONSORT) and International Committee of Medical Journal Editors (ICMJE) requirements in the instructions to authors in Indian journals, and compliance with selected requirements in all RCTs published during 2007-08 vs. our previous survey and between all RCT protocols in the CTRI on August 31, 2010 and published RCTs from both surveys. RESULTS: Journal policies endorsing the CONSORT statement (22/67, 33%) and ICMJE requirements (35/67, 52%) remained suboptimal, and only 4 of 13 CONSORT items were reported in more than 50% of the 145 RCTs assessed. Reporting of ethical issues had improved significantly, and that of methods addressing internal validity had not improved. Adequate methods were reported significantly more frequently in 768 protocols in the CTRI, than in the 296 published trials. CONCLUSION: The CTRI template facilitates the reporting of valid methods in registered trial protocols. The suboptimal compliance with CONSORT and ICMJE requirements in RCTs published in Indian journals reduces credibility in the reliability of their results.

Interventions for prevention and treatment of vulvovaginal candidiasis in women with HIV infection.

BACKGROUND: Vulvovaginal candidiasis (VVC) is one of the most common fungal infections that recur frequently in HIV infected women. Symptoms of VVC are pruritis, discomfort, dyspareunia, and dysuria. Vulval infection presents as a morbiliform rash that may extend to the thighs. Vaginal infection is associated with white discharge, and plaques are seen on erythematous vaginal walls.Even though rarely or never resulting in systemic fungal infection or mortality, left untreated these lesions contribute considerably to the morbidity associated with HIV infection. Prevention and treatment of this condition is an essential part of maintaining the quality of life for these individuals. OBJECTIVES: -To compare the efficacy of various antifungals given vaginally or orally for the treatment and prophylaxis of VVC in HIV-infected women and to evaluate the risks of the same. SEARCH STRATEGY: The search strategy was comprehensive, iterative and based on that of the HIV/AIDS Cochrane Review Group. The aim was to locate all relevant trials, irrespective of publication status or language. Electronic databases :CENTRAL,Medline, EMBASE, LILACS and CINAHL were searched for randomised controlled trials for the years 1980 to 1st October 2010. WHO ICTRP site and other relevant web sites were also searched for conference abstracts. SELECTION CRITERIA: Randomised controlled trials (RCTs) of palliative, preventative or curative therapy were considered. Participants were HIV positive women receiving one or more of the following:treatment / prophylaxis for VVC or HAART(Highly Active Antiretroviral Therapy). DATA COLLECTION AND ANALYSIS: Three authors independently assessed the methodological quality of the trials and extracted data. The quality of the evidence generated was graded using the GRADE PRO approach. MAIN RESULTS: Our search did not yield any trial investigating treatment of VVC in HIV positive women.Two trials dealing with prophylaxis were eligible for inclusion.One trial (n= 323) favoured the use of weekly Fluconazole as compared to placebo (RR 0.68; 95% CI 0.47 to 0.97).The second trial with three arms of comparison;Clotrimazole,Lactobacillus and Placebo gave no definitive results in preventing an episode of VVC. Clotrimazole against placebo (RR 0.49; 95% CI 0.22 to 1.09), Clotrimazole against lactobacillus (RR 1.11; 95% CI 0.45 to 2.76) and lactobacillus against placebo (RR 0.54 ;95% CI 0.26 to 1.13). AUTHORS' CONCLUSIONS: Implications for practiceNo trials were found addressing treatment of VVC in HIV positive women.In comparison to placebo,Fluconazole was found to be an effective preventative intervention. However, the potential for resistant Candida organisms to develop might impact the feasibility of implementation.Direction of findings suggests that Clotrimazole and Lactobacillus improved the prophylactic outcomes when compared to placebo.Implications for research There is a need to evaluate drugs and drug regimens for VVC treatment and prophylaxis in HIV positive women through randomised clinical trials. Development of resistance to azoles remains under-studied and more work must be done in this area, so as to determine whether routine prophylaxis for VVC is at all needed or whether adequate ART would be sufficient to prevent recurrent VVC. The viral load in vaginal secretions with or without treatment or prophylaxis has not been studied, this is very relevant to the spread of HIV.

Postmortem diagnosis of acute haemorrhagic pancreatitis.

Forensic pathologists can help in the investigation of sudden unexpected deaths in co-operation with the officials responsible for the maintenance of law and order to administer justice. Sudden unexpected deaths form the subject of medicolegal investigation if they occur in apparently healthy individuals, wherein an autopsy would shed light regarding the cause of death. A 4 year retrospective review of autopsy files at the Department of Forensic Medicine, Kasturba Medical College, Mangalore, South India was undertaken for cases of sudden unexpected deaths due to acute haemorrhagic pancreatitis occurring between May 2004 and April 2008. A total of seven cases of acute haemorrhagic pancreatitis diagnosed at autopsy as the cause of sudden unexpected death during the study period are discussed herein.