The role of the multidisciplinary team in surgical management of intractable tubo-ovarian abscess as a late sequelae of challenging Crohn's disease in the modern era: A case report and review of current literature.

Chronic, severe Crohn's disease in a young female patient can result in surgical complexity. The rarity of the presentation of intractable pelvic abscesses within this etiology with additional considerations given to fertility concerns and hence requirement for input from a multi-disciplinary team makes this a vital case in building a consensus for evidence-based surgical management. A 29-year-old nulliparous woman was referred to our tertiary centre for surgical management of Crohn's disease with known tubo-ovarian abscess and abdominoperineal and abdominal wall sinuses. Her previous surgical history included 4 midline laparotomies, subtotal colectomy and proctectomy with stoma formation. The patient underwent egg collection to preserve fertility. This was followed by midline laparotomy and abdominoperineal resection, which involved a retrograde radical modified hysterectomy using the Hudson technique, alongside excision of the perineal sinus, with reconstruction of the perineal defect using an internal pudendal artery perforator gluteal fold flap, and in addition to excision and drainage of the abdominal wall abscess. Involvement was sought from gynecological oncology, colorectal, urology, plastics, stoma, fertility, microbiology, and gastroenterology teams, which enabled successful preservation of end organ function and improvement in patient psychological well-being. This case is a paradigm of surgical challenge, requiring expert gynecological oncology techniques including a retroperitoneal approach, nerve and vessel sparing considerations alongside colorectal and urological procedures. Moreover, we believe that our blueprint for effective multi-disciplinary practice will inform the future management of gynecological surgery. Therefore this report aims to contribute towards the optimum management of the gynecological sequelae of Crohn's disease.

Diagnostic accuracy of the WHO clinical definitions for dengue and implications for surveillance: A systematic review and meta-analysis.

BACKGROUND: Dengue is the world's most common mosquito-borne virus but remains diagnostically challenging due to its nonspecific presentation. Access to laboratory confirmation is limited and thus most reported figures are based on clinical diagnosis alone, the accuracy of which is uncertain. This systematic review assesses the diagnostic accuracy of the traditional (1997) and revised (2009) WHO clinical case definitions for dengue fever, the basis for most national guidelines. METHODOLOGY/PRINCIPAL FINDINGS: PubMed, EMBASE, Scopus, OpenGrey, and the annual Dengue Bulletin were searched for studies assessing the diagnostic accuracy of the unmodified clinical criteria. Two reviewers (NR/SL) independently assessed eligibility, extracted data, and evaluated risk of bias using a modified QUADAS-2. Additional records were found by citation network analysis. A meta-analysis was done using a bivariate mixed-effects regression model. Studies that modified criteria were analysed separately. This systematic review protocol was registered on PROSPERO (CRD42020165998). We identified 11 and 12 datasets assessing the 1997 and 2009 definition, respectively, and 6 using modified criteria. Sensitivity was 93% (95% CI: 77-98) and 93% (95% CI: 86-96) for the 1997 and 2009 definitions, respectively. Specificity was 29% (95% CI: 8-65) and 31% (95% CI: 18-48) for the 1997 and 2009 definitions, respectively. Diagnostic performance suffered at the extremes of age. No modification significantly improved accuracy. CONCLUSIONS/SIGNIFICANCE: Diagnostic accuracy of clinical criteria is poor, with significant implications for surveillance and public health responses for dengue control. As the basis for most reported figures, this has relevance to policymakers planning resource allocation and researchers modelling transmission, particularly during COVID-19.

Country Level Diversity of the HIV-1 Pandemic between 1990 and 2015.

The global diversity of HIV forms a major challenge to the development of an HIV vaccine, as well as diagnostic, drug resistance, and viral load assays, which are essential to reaching the UNAIDS 90:90:90 targets. We sought to determine country level HIV-1 diversity globally between 1990 and 2015. We assembled a global HIV-1 molecular epidemiology database through a systematic literature search and a global survey. We searched PubMed, EMBASE (Ovid), CINAHL (Ebscohost), and Global Health (Ovid) for HIV-1 subtyping studies published from 1 January 1990 to 31 December 2015. We collected additional unpublished data through a global survey of experts. Prevalence studies with original HIV-1 subtyping data collected between 1990 and 2015 were included. This resulted in a database with 383,519 subtyped HIV-1 samples from 116 countries over four time periods (1990 to 1999, 2000 to 2004, 2005 to 2009, and 2010 to 2015). We analyzed country-specific numbers of distinct HIV-1 subtypes, circulating recombinant forms (CRFs), and unique recombinant forms (URFs) in each time period. We also analyzed country-specific proportions of infections due to HIV-1 recombinants, CRFs, and URFs and calculated the Shannon diversity index for each country. Finally, we analyzed global temporal trends in each of these measures of HIV-1 diversity. We found extremely wide variation in complexity of country level HIV diversity around the world. Central African countries such as Chad, Democratic Republic of the Congo, Angola, and Republic of the Congo have the most diverse HIV epidemics. The number of distinct HIV-1 subtypes and recombinants was greatest in Western Europe (Spain and France) and North America (United States) (up to 39 distinct HIV-1 variants in Spain). The proportion of HIV-1 infections due to recombinants was highest in Southeast Asia (>95% of infections in Viet Nam, Cambodia, and Thailand), China, and West and Central Africa, mainly due to high proportions of CRF01_AE and CRF02_AG. Other CRFs played major roles (>75% of HIV-1 infections) in Estonia (CRF06_cpx), Iran (CRF35_AD), and Algeria (CRF06_cpx). The highest proportions of URFs (>30%) were found in Myanmar, Republic of the Congo, and Argentina. Global temporal analysis showed consistent increases over time in country level numbers of distinct HIV-1 variants and proportions of CRFs and URFs, leading to increases in country level HIV-1 diversity. Our study provides epidemiological evidence that the HIV pandemic is diversifying at country level and highlights the increasing challenge to prevention and treatment efforts. HIV-1 molecular epidemiological surveillance needs to be continued and improved.IMPORTANCE This is the first study to analyze global country level HIV-1 diversity from 1990 to 2015. We found extremely wide variation in complexity of country level HIV diversity around the world. Central African countries have the most diverse HIV epidemics. The number of distinct HIV-1 subtypes and recombinants was greatest in Western Europe and North America. The proportion of HIV-1 infections due to recombinants was highest in South-East Asia, China, and West and Central Africa. The highest proportions of URFs were found in Myanmar, Republic of the Congo, and Argentina. Our study provides epidemiological evidence that the HIV pandemic is diversifying at country level and highlights the increasing challenge to HIV vaccine development and diagnostic, drug resistance, and viral load assays.

Factors affecting the electrocardiographic QT interval in malaria: A systematic review and meta-analysis of individual patient data.

BACKGROUND: Electrocardiographic QT interval prolongation is the most widely used risk marker for ventricular arrhythmia potential and thus an important component of drug cardiotoxicity assessments. Several antimalarial medicines are associated with QT interval prolongation. However, interpretation of electrocardiographic changes is confounded by the coincidence of peak antimalarial drug concentrations with recovery from malaria. We therefore reviewed all available data to characterise the effects of malaria disease and demographic factors on the QT interval in order to improve assessment of electrocardiographic changes in the treatment and prevention of malaria. METHODS AND FINDINGS: We conducted a systematic review and meta-analysis of individual patient data. We searched clinical bibliographic databases (last on August 21, 2017) for studies of the quinoline and structurally related antimalarials for malaria-related indications in human participants in which electrocardiograms were systematically recorded. Unpublished studies were identified by the World Health Organization (WHO) Evidence Review Group (ERG) on the Cardiotoxicity of Antimalarials. Risk of bias was assessed using the Pharmacoepidemiological Research on Outcomes of Therapeutics by a European Consortium (PROTECT) checklist for adverse drug events. Bayesian hierarchical multivariable regression with generalised additive models was used to investigate the effects of malaria and demographic factors on the pretreatment QT interval. The meta-analysis included 10,452 individuals (9,778 malaria patients, including 343 with severe disease, and 674 healthy participants) from 43 studies. 7,170 (68.6%) had fever (body temperature ≥ 37.5°C), and none developed ventricular arrhythmia after antimalarial treatment. Compared to healthy participants, patients with uncomplicated falciparum malaria had shorter QT intervals (-61.77 milliseconds; 95% credible interval [CI]: -80.71 to -42.83) and increased sensitivity of the QT interval to heart rate changes. These effects were greater in severe malaria (-110.89 milliseconds; 95% CI: -140.38 to -81.25). Body temperature was associated independently with clinically significant QT shortening of 2.80 milliseconds (95% CI: -3.17 to -2.42) per 1°C increase. Study limitations include that it was not possible to assess the effect of other factors that may affect the QT interval but are not consistently collected in malaria clinical trials. CONCLUSIONS: Adjustment for malaria and fever-recovery-related QT lengthening is necessary to avoid misattributing malaria-disease-related QT changes to antimalarial drug effects. This would improve risk assessments of antimalarial-related cardiotoxicity in clinical research and practice. Similar adjustments may be indicated for other febrile illnesses for which QT-interval-prolonging medications are important therapeutic options.