Population Size Estimation From Capture-Recapture Studies Using shinyrecap: Design and Implementation of a Web-Based Graphical User Interface

BackgroundPopulation size estimates (PSE) provide critical information in determining resource allocation for HIV services geared toward those at high risk of HIV, including female sex workers, men who have sex with men, and people who inject drugs. Capture-recapture (CRC) is often used to estimate the size of these often-hidden populations. Compared with the commonly used 2-source CRC, CRC relying on 3 (or more) samples (3S-CRC) can provide more robust PSE but involve far more complex statistical analysis.ObjectiveThis study aims to design and describe the Shiny application (shinyrecap), a user-friendly interface that can be used by field epidemiologists to produce PSE.Methodsshinyrecap is built on the Shiny web application framework for R. This allows it to seamlessly integrate with the sophisticated CRC statistical packages (eg, Rcapture, dga, LCMCR). Additionally, the application may be accessed online or run locally on the user’s machine.ResultsThe application enables users to engage in sample size calculation based on a simulation framework. It assists in the proper formatting of collected data by providing a tool to convert commonly used formats to that used by the analysis software. A wide variety of methodologies are supported by the analysis tool, including log-linear, Bayesian model averaging, and Bayesian latent class models. For each methodology, diagnostics and model checking interfaces are provided.ConclusionsThrough a use case, we demonstrated the broad utility of this powerful tool with 3S-CRC data to produce PSE for female sex workers in a subnational unit of a country in sub-Saharan Africa.     

Association of interleukin-6 -174G/C promoter polymorphism with hypertension and left ventricular hypertrophy in dialysis patients

BACKGROUND: Gene polymorphisms of proinflammatory cytokines, such as interleukin-6 (IL-6) and the chemokine receptor CX3CR1, have been found in association with cardiovascular disease in the general population. In dialysis patients, in whom the prevalence of cardiovascular comorbidity is strikingly high, these polymorphisms have not been investigated. METHODS: The -174G/C polymorphism of the IL-6 gene and the chemokine receptor CX3CR1 polymorphisms 249V/I and 280T/M were examined for their association with cardiovascular abnormalities in a cohort of 161 patients with end-stage renal disease (ESRD) treated by hemodialysis. Arterial blood pressure, electrocardiogram (ECG) ischemic changes, and left ventricular mass index (LVMI) were the parameters examined for the association study. The control group was made up of 169 healthy subjects. RESULTS: We found that for both IL-6 and chemokine receptor, genotype frequency and allelic distribution in both ESRD patients and controls were comparable. The genetic association study showed that in the whole group of dialysis patients, individuals with GC + CC genotype for the -174G/C polymorphism had a higher diastolic blood pressure (P = 0.008) and LVMI (P = 0.026) than GG homozygotes. The prevalence of left ventricular hypertrophy (LVH) in the former group was 58.6% vs. 39.2% in the latter (P = 0.02). The same analysis limited to diabetic patients in dialysis, showed that the prevalence of LVH in those with CG + CC genotype was 87.5% vs. 36.3% in those with GG genotype (P = 0.02). In diabetic patients, lower levels of serum albumin was found in the GC + CC genotypic group than in GG subjects; 34.63 +/- 5.18 g/L vs. 41.75 +/- 4.79 g/L (P = 0.003). CONCLUSION: These data demonstrate an association between the IL-6 promoter polymorphism -174G/C and high blood pressure and LVH in hemodialysis patients, especially those with diabetes. The results strengthen the hypothesis that chronic inflammation is a mechanism of cardiovascular damage in dialysis patients and the role played by the IL-6 system in this mechanism.     

Five cases of orbital extramedullary plasmacytoma: diagnosis and management of an aggressive malignancy

Purpose: Multiple myeloma is an insidious haematological malignancy characterised by monoclonal proliferation of plasma cells in the bone marrow. Extramedullary plasmacytoma is a rare manifestation of multiple myeloma and usually occurs in the upper respiratory tract. Orbital involvement is particularly uncommon, but may be associated with devastating visual impairment and poor clinical outcomes. Therefore, this article aims to highlight the need for multidisciplinary management of orbital extramedullary plasmacytoma.

Methods: This is a retrospective observational case series of five patients. All presented to the authors for management of orbital extramedullary plasmacytomas from 2004 to 2015 at Prince of Wales and Mater Hospitals in Sydney, Australia. Medical records were reviewed for pertinent information including demographics, disease features, management strategy, and clinical progress. The study met Medical Ethics Board standards and is in accordance with the Helsinki Agreements.

Results: This case series of five patients underscores the poor prognosis of orbital extramedullary plasmacytoma. Despite aggressive multidisciplinary management, four of these five patients succumbed to their illness during the study period. However, multidisciplinary management did manage to minimise symptoms and preserve quality of life.

Conclusions: On a case-by-case basis, patients may derive palliative benefit from orbital surgery in conjunction with radiotherapy and chemotherapy. Orbital surgeons are encouraged to work within a multidisciplinary framework of medical specialists, including haematologists and radiation oncologists, when determining the optimal management plan in cases of orbital extramedullary plasmacytoma.     

Discovery of an Anion-Dependent Farnesyltransferase Inhibitor from a Phenotypic Screen

By employing a phenotypic screen, a set of compounds, exemplified by 1, were identified which potentiate the ability of histone deacetylase inhibitor vorinostat to reverse HIV latency. Proteome enrichment followed by quantitative mass spectrometric analysis employing a modified analogue of 1 as affinity bait identified farnesyl transferase (FTase) as the primary interacting protein in cell lysates. This ligand-FTase binding interaction was confirmed via X-ray crystallography and temperature dependent fluorescence studies, despite 1 lacking structural and binding similarity to known FTase inhibitors. Although multiple lines of evidence established the binding interaction, these ligands exhibited minimal inhibitory activity in a cell-free biochemical FTase inhibition assay. Subsequent modification of the biochemical assay by increasing anion concentration demonstrated FTase inhibitory activity in this novel class. We propose 1 binds together with the anion in the active site to inhibit farnesyl transferase. Implications for phenotypic screening deconvolution and HIV reactivation are discussed.     

Colorectal Stenting for Malignant and Benign Disease: Outcomes in Colorectal Stenting

INTRODUCTION: Self-expanding metal stents are now an established treatment for malignant colonic obstruction. Favorable outcomes have been reported both for cancer palliation and treatment of acute obstruction as a bridge to surgery. However, little data exists regarding the use of stents for benign colonic obstruction.METHODS: All cases of colonic stent insertion occurring between December 1996 to October 2002 were reviewed. During the study period, 36 patients with malignant obstruction and 6 patients with benign obstructive disease underwent placement of self-expandable stents using a combined endoscopic and fluoroscopic technique.RESULTS: Stent placement was successful in 36 of 42 patients (86 percent). Complications occurred in 16 of 36 patients (44 percent): migration (n = 7), reobstruction (n = 5), perforation (n = 2), fistula formation (n = 1), and stent fracture (n = 1). Stent placement was successful in 100 percent of patients with benign strictures but poststent migration was frequent (2/6).CONCLUSIONS: Stent insertion provided an effective outcome in patients with malignant colonic obstruction as a palliative and preoperative therapy. Although a relatively high migration rate was observed in patients with benign strictures, stenting was still effective in providing luminal patency (median follow-up, 7.5 months). Stenting should be considered as a first-line treatment for malignant strictures and as a potential therapy for selected benign strictures.     

Activity of telithromycin against key pathogens associated with community-acquired respiratory tract infections

OBJECTIVES: To investigate the correlation between in vitro susceptibility of isolates and clinical outcomes with telithromycin in respiratory tract infections. METHODS: The activity of telithromycin was determined by in vitro susceptibility testing of key respiratory tract pathogens isolated from patients with community-acquired pneumonia, acute exacerbations of chronic bronchitis or acute maxillary sinusitis enrolled in 14 Phase III/IV clinical trials evaluating the clinical efficacy of telithromycin. RESULTS: In this pooled analysis, telithromycin mode minimum inhibitory concentration (MIC) and MIC90, respectively, were: 0.016 and 0.03 mg/l against Streptococcus pneumoniae (n=626); 0.03 and 0.5 mg/l for penicillin-resistant S. pneumoniae (n=56); 0.03 and 1 mg/l for erythromycin-resistant S. pneumoniae (n=81); 2 and 4 mg/l against Haemophilus influenzae (including beta-lactamase producers; n=627); both 0.12 mg/l for Moraxella catarrhalis (n=159) and both 0.25 mg/l for Staphylococcus aureus (n=124). Telithromycin (5 or 7-10 days) resulted in overall clinical and bacteriologic success rates of 88.1% (1593/1808) and 89% (1593/1789), respectively. CONCLUSIONS: High levels of in vitro susceptibility to telithromycin are paralleled by high rates of clinical cure and bacteriologic eradication.