Overcoming analytical and preanalytical challenges associated with extragenital home collected STI specimens.

Home sample collection for sexually transmitted infection (STI) screening options can improve access to sexual healthcare across communities. For Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG), genital infections have classically been the focus for remote collection options. However, infections may go undiagnosed if sampling is limited to urogenital sites because some individuals only participate in oral and/or anal intercourse. Here we evaluated samples for CT/NG detection after several pre-analytical collection challenges. A paired provider to self-collection validation was performed on rectal [n = 162; 22 + for CT and 9 + for NG by provider-collected (PC)] and throat (N = 158; 2 + for CT and 11 + for NG by provider-collected) swabs. The positive percent agreement for CT and NG ranged from 90.9% to 100%. The discrepancies were more often positive on self-collected (SC) (n = 9 SC+/PC-; n = 1 PC+/SC-; n = 1 PC+/SC Equiv.; n = 2 PC-/SC Equiv.). An empirical limit of detection (LoD) lower than the manufacturer's claim (0.031 vs 2.5 IFU/mL for CT and 0.063 vs 124.8 CFU/ml for NG, respectively) was used to challenge additional variables. Common hand contaminants, including soap, hand sanitizer, lotion, and sunscreen were added to known positive (3× empirical LoD) or negative samples and did not influence detection. Samples at 2× and 10× the empirical LoD were challenged with extreme temperature cycling and extended room temperature storage. Detection was not affected by these conditions. These results indicate that remote self-collection is an appropriate method of sample acquisition for detecting extragenital CT/NG infections. Additionally, they provide a foundation towards meeting the regulatory standards for commercial testing of home collected extragenital samples. IMPORTANCE: There is a clinical need for expanded extragenital bacterial sexually transmitted infection (STI) testing options, but the current regulatory landscape limits the wide-spread promotion and adoption of such services. Improved access, particularly for the LGBTQ+ community, can be achieved by validating testing for specimens that are self-collected at a remote location and arrive at the laboratory via a postal carrier or other intermediary route. Here we provide valuable data showing that self-collected samples for anal and oropharyngeal STI testing are equally or increasingly sensitive compared with those collected by a provider. We systematically consider the effects of storage time, exposure to temperature extremes, and the addition of common toiletries on results.

The cardiovascular disease burden attributable to particulate matter pollution in South America: analysis of the 1990-2019 global burden of disease.

OBJECTIVES: Fine particulate matter <2.5 microns (PM2.5) is the most studied air pollutant. Both short- and long-term exposure to PM2.5 have been linked to cardiovascular disease (CVD). Studies evaluating air pollution in South America are scarce. Therefore, the impact of exposure to PM2.5, household air pollution (HAP), and ambient air pollution (AAP) on CVD mortality and CVD disability-adjusted life years (DALYs) in South American countries from 1990 to 2019 was explored. STUDY DESIGN AND METHODS: The Global Burden of Disease initiative exposure-response function was used to analyze the total PM2.5, ambient PM2.5, and household PM2.5-related CVD deaths and DALYs rates, per 100,000 individuals, in 12 South American countries between 1990 and 2019. The relative change in burden was also assessed by comparing the 1990-1994 to 2015-2019 periods. RESULTS: In 2019, 70,668 deaths and 1,736,414 DALYs due to CVD were attributed to total PM2.5 exposure in South America. Substantial regional heterogeneity was observed concerning the absolute change in PM2.5 concentration levels comparing 1990 to 2019. All South American countries observed a relative decline in CVD deaths and DALYs comparing the 1990-1994 to 2015-2019 periods. No country was able to reach the current World Health Organization 5 µg/m3 recommended limit in 2019. Predominantly, AAP was the greatest contributor to the CVD burden. CONCLUSION: Air pollution substantially impacted CVD in South America; however, this impact was heterogenous, and the relative reduction of HAP and AAP burden was also not uniform. Recognizing PM2.5 importance is key for developing target population and individual-level interventions, which could ultimately alleviate its burden.

Automated computer-based CT stratification as a predictor of outcome in hypersensitivity pneumonitis.

BACKGROUND: Hypersensitivity pneumonitis (HP) has a variable clinical course. Modelling of quantitative CALIPER-derived CT data can identify distinct disease phenotypes. Mortality prediction using CALIPER analysis was compared to the interstitial lung disease gender, age, physiology (ILD-GAP) outcome model. METHODS: CALIPER CT analysis of parenchymal patterns in 98 consecutive HP patients was compared to visual CT scoring by two radiologists. Functional indices including forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLco) in univariate and multivariate Cox mortality models. Automated stratification of CALIPER scores was evaluated against outcome models. RESULTS: Univariate predictors of mortality included visual and CALIPER CT fibrotic patterns, and all functional indices. Multivariate analyses identified only two independent predictors of mortality: CALIPER reticular pattern (p = 0.001) and DLco (p < 0.0001). Automated stratification distinguished three distinct HP groups (log-rank test p < 0.0001). Substitution of automated stratified groups for FVC and DLco in the ILD-GAP model demonstrated no loss of model strength (C-Index = 0.73 for both models). Model strength improved when automated stratified groups were combined with the ILD-GAP model (C-Index = 0.77). CONCLUSIONS: CALIPER-derived variables are the strongest CT predictors of mortality in HP. Automated CT stratification is equivalent to functional indices in the ILD-GAP model for predicting outcome in HP. KEY POINTS: • Computer CT analysis better predicts mortality than visual CT analysis in HP. • Quantitative CT analysis is equivalent to functional indices for prognostication in HP. • Prognostication using the ILD-GAP model improves when combined with quantitative CT analysis.

Development of a panel of recombinase polymerase amplification assays for detection of common bacterial urinary tract infection pathogens.

AIMS: To develop and evaluate the performance of a panel of isothermal real-time recombinase polymerase amplification (RPA) assays for detection of common bacterial urinary tract infection (UTI) pathogens. METHODS AND RESULTS: The panel included RPAs for Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa and Enterococcus faecalis. All five RPAs required reaction times of under 12 min to reach their lower limit of detection of 100 genomes per reaction or less, and did not cross-react with high concentrations of nontarget bacterial genomic DNA. In a 50-sample retrospective clinical study, the five-RPA assay panel was found to have a specificity of 100% (95% CI, 78-100%) and a sensitivity of 89% (95% CI, 75-96%) for UTI detection. CONCLUSIONS: The analytical and clinical validity of RPA for the rapid and sensitive detection of common UTI pathogens was established. SIGNIFICANCE AND IMPACT OF THE STUDY: Rapid identification of the causative pathogens of UTIs can be valuable in preventing serious complications by helping avoid the empirical treatment necessitated by traditional urine culture's 48-72-h turnaround time. The routine and widespread use of RPA to supplement or replace culture-based methods could profoundly impact UTI management and the emergence of multidrug-resistant pathogens.

Successful outpatient management of lymphoedema and lymphorrhoea with wrap around compression: a case study.

Referral to specialist centres for treatment of lymphoedema can often have long waiting times. Management of a patient with massive lymphoedema and lymphorrhoea was provided in a vascular outpatient setting. A new form of compression using a wraparound system was used for the management (Juxta-Fit, Medi UK). Despite having previously been non-concordant with treatment options, the patient was independent with product use. Lymphorrhoea ceased and there was a marked decrease in girth size. The patient's quality of life improved and maintenance treatment was provided. The use of this compression system could be a valuable treatment alternative to compression bandaging for a select patient group for the treatment of lymphoedema.

Retraction notice to "Management of liver hydatid cysts - Current perspectives" [Medical Journal Armed forces India 68 (2012) 304-309].

[This retracts the article DOI: 10.1016/j.mjafi.2012.04.010.].

Abdominal Aortic Aneurysm Diameters: A Study on the Discrepancy between Inner to Inner and Outer to Outer Measurements.

INTRODUCTION: The NHS Abdominal Aortic Aneurysm Screening Programme (NAAASP) uses the maximal anterior to posterior (AP) inner-to-inner (ITI) wall diameter in sizing aortic dimensions when screening with ultrasound. It is recognised that ITI measurements are smaller than outer-to-outer (OTO) measurements, and the primary aim was to calculate the absolute difference in AP ITI and OTO measurements across varying aortic diameters. The secondary aim was to estimate the potential number of patients lost from the screening programme. METHODS: Since April 2012, patients outside the screening programme that undergo ultrasound of abdominal aortas have their ITI and OTO measurements recorded. These measurements were compared retrospectively and analysed for variability at threshold sizes of AAAs. RESULTS: From May 2012 to October 2013, 452 abdominal aortic ultransound scans recorded both ITI and OTO measurements. The majority (81%) were performed on men with the mean age of 78 years. The mean difference between ITI and OTO measurements was 4.21 mm (p < .001). There was no difference between the genders. Thresholds were created for analysis between different ITI and OTO aortic diameters; these were <3 cm, 3.1-4 cm, 4.1-5 cm, and >5 cm. There was no significant difference between the means at each threshold size for ITI diameter (p = .758). In the first 2 years from April 2012, 15,447 men underwent screening.Of these, 177 (1.14%) had sub-threshold ITI aortic diameters between 2.6 cm and 2.9 cm. This would upscale to 5,316 men nationally. CONCLUSION: We have demonstrated a consistent and significant 4mm difference between ITI and OTO diameters in live scanning. Lowering the threshold for entry into a surveillance AAAs to an ITI diameter of 26mm rather than the current 30 mm is advocated. An alternative cost-effective way is to rescreen this small sub-group at 5 or 7 years.

Enzymatic debridement of large burn wounds with papain-urea: Is it safe?

INTRODUCTION: Enzymatic debridement is a method by which burn wounds can be prepared for coverage by skin grafts in patients presenting late. Many agents have been used in the past but none of them have been thoroughly evaluated. The present study was undertaken to assess the efficacy of Debridace, a commonly available debriding agent with papain and urea as its constituents. MATERIAL AND METHODS: A prospective descriptive study design was used to evaluate our experience. Almost symmetrical areas of the burnt surface were assessed and used for comparison. On one half of the wound, Debridace was applied while on the other silver sulphadiazine was used. The primary end point of this study was the extent of the achieved debridement at the end of the study period. Secondary outcomes were the presence of adverse effects such as pain and fever. All patients with sepsis were excluded from the study. RESULTS: The age of the subjects ranged from 9 to 80 years with an SD of 16. Large areas ranging from 5% to 20% body surface area with an SD of 4.27 were debrided by Debridace. Only two patients (3.33%) could complete the study. The rest of the recruited patients either had high fever (63.33%), excruciating pain (13.33%) or both (16.66%), which brought an end to enzymatic debridement. CONCLUSION: Debridace, a papain-urea product, cannot be considered safe as an enzymatic debriding agent in its present form for use in major burn patients who present late with deep burn wounds that are large in size.

Air pollution impairs cognition, provokes depressive-like behaviors and alters hippocampal cytokine expression and morphology.

Particulate matter air pollution is a pervasive global risk factor implicated in the genesis of pulmonary and cardiovascular disease. Although the effects of prolonged exposure to air pollution are well characterized with respect to pulmonary and cardiovascular function, comparatively little is known about the impact of particulate matter on affective and cognitive processes. The central nervous system may be adversely affected by activation of reactive oxygen species and pro-inflammatory pathways that accompany particulate matter pollution. Thus, we investigated whether long-term exposure to ambient fine airborne particulate matter (<2.5 µm (PM(2.5))) affects cognition, affective responses, hippocampal inflammatory cytokines and neuronal morphology. Male mice were exposed to either PM(2.5) or filtered air (FA) for 10 months. PM(2.5) mice displayed more depressive-like responses and impairments in spatial learning and memory as compared with mice exposed to FA. Hippocampal pro-inflammatory cytokine expression was elevated among PM(2.5) mice. Apical dendritic spine density and dendritic branching were decreased in the hippocampal CA1 and CA3 regions, respectively, of PM(2.5) mice. Taken together, these data suggest that long-term exposure to particulate air pollution levels typical of exposure in major cities around the globe can alter affective responses and impair cognition.

Time to treatment initiation with oral antihyperglycaemic therapy in US patients with newly diagnosed type 2 diabetes.

AIM: To compare the time from initial diagnosis to initiation with oral antihyperglycaemic treatment in younger versus older patients with type 2 diabetes, and to evaluate factors associated with initiating treatment. METHODS: This was a retrospective US cohort study with a 2-year follow-up period after diagnosis of type 2 diabetes. Using the General Electric Healthcare's Clinical Data Services electronic medical record database, eligible patients included those aged ≥30 years at initial diagnosis of type 2 diabetes between January 2003 and December 2005. In the 2-year period following diagnosis, the time to the first prescription of an oral antihyperglycaemic agent was compared between younger (30-64 years) and older (≥65 years) patients. Factors associated with time to treatment with an oral antihyperglycaemic agent were examined using Cox proportional hazards regression. RESULTS: Of the 10 743 patients with newly diagnosed type 2 diabetes, 43% were ≥65 years old. The mean age at diagnosis was 73 years for older patients and 52 years for younger patients. Compared to younger patients, a greater proportion of older patients had a baseline haemoglobin A1c (HbA1c) value <7% (38 vs. 32%; p < 0.001). In the 2-year follow-up period, a significantly greater proportion of younger patients (59%) received oral antihyperglycaemic treatment compared to older patients (44%; p < 0.001). The median time between diagnosis and initiating treatment with an oral antihyperglycaemic agent was 350 days for younger patients and >2 years for older patients. After adjusting for covariates, older patients had a greater risk of not receiving treatment with oral antihyperglycaemic therapy than younger patients [adjusted hazard ratio = 0.82 (95% confidence interval: 0.75, 0.90)]. CONCLUSIONS: In patients with newly diagnosed type 2 diabetes, the time to initiation of oral antihyperglycaemic therapy was significantly longer in older patients (≥65 years old) than younger patients (<65 years).

Hepatic abscesses.

Hepatic abscesses are potentially lethal diseases if early diagnosis and treatment are not instituted. They are prevalent all over the globe and pyogenic abscesses are predominant over amoebic. With better control of intra abdominal and systemic infections by a spectrum of antibiotics, aetiology of pyogenic abscesses are secondary to interventions and diseases in the biliary tree to a large extent today. The common organisms isolated are the Gram negative group. Amoebic abscesses continue to plague some regions of the world where hygiene and sanitation are questionable. Over the years, diagnosis, treatment and prognosis have evolved remarkably. Imaging modalities like ultrasonography and CT scan have become the cornerstone of diagnosis. The absence of ionizing radiation makes MRI an attractive alternative in patients who require multiple follow up scans. Serological testing in amoebic abscesses has become more reliable. Though antibiotics have remained the principal modality of management, percutaneous drainage of abscesses have vastly improved the chances of cure and bring down the morbidity drastically in pyogenic abscesses. Amoebic abscesses respond well to medical treatment with nitroimidazoles, and minimally invasive surgical drainage is an option in cases where open surgery is indicated.

Management of liver hydatid cysts - Current perspectives.

Human hydatid disease or cystic echinococcosis (CE), caused by the larval form of cestode Echinococcus granulosus still continues to a common problem in health care environments as different as Europe/North America and resource poor countries of the South America and the East. The Liver is the most frequently parasatized organ in humans. While ultrasonography remains the main diagnostic tool, computed tomography and serology improve the accuracy of diagnosis in Liver hydatid cysts (LHC). Although surgery is the only modality applicable over the entire spectrum of the disease, systemic chemotherapy and percutaneous drainage have evolved as alternative therapies in the last three decades. Various laparoscopic techniques have also been described for safe and optimal management of this entity. In this paper, we review the current management procedures of LHC with particular emphasis on the evidence base and setting specific problems.

The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial.

Prior small studies have shown multiple benefits of frequent nocturnal hemodialysis compared to conventional three times per week treatments. To study this further, we randomized 87 patients to three times per week conventional hemodialysis or to nocturnal hemodialysis six times per week, all with single-use high-flux dialyzers. The 45 patients in the frequent nocturnal arm had a 1.82-fold higher mean weekly stdKt/V(urea), a 1.74-fold higher average number of treatments per week, and a 2.45-fold higher average weekly treatment time than the 42 patients in the conventional arm. We did not find a significant effect of nocturnal hemodialysis for either of the two coprimary outcomes (death or left ventricular mass (measured by MRI) with a hazard ratio of 0.68, or of death or RAND Physical Health Composite with a hazard ratio of 0.91). Possible explanations for the left ventricular mass result include limited sample size and patient characteristics. Secondary outcomes included cognitive performance, self-reported depression, laboratory markers of nutrition, mineral metabolism and anemia, blood pressure and rates of hospitalization, and vascular access interventions. Patients in the nocturnal arm had improved control of hyperphosphatemia and hypertension, but no significant benefit among the other main secondary outcomes. There was a trend for increased vascular access events in the nocturnal arm. Thus, we were unable to demonstrate a definitive benefit of more frequent nocturnal hemodialysis for either coprimary outcome.

N-terminal pro-B-type natriuretic peptide is an independent predictor of all-cause mortality and MACE after major vascular surgery in medium-term follow-up.

OBJECTIVE: Recent interest has focussed on the role of biomarkers to predict outcome in patients undergoing major vascular surgery. We wished to determine if pre- and postoperative N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) levels could predict all-cause mortality (ACM; primary aim) and major adverse cardiac event (MACE) (secondary aim) in the medium-term follow-up in patients who have undergone elective major vascular surgery. METHOD: Patients who underwent major elective vascular surgery (n = 136) were followed up for up to 2 years. ACM and first MACE episode were identified from the case notes and the patient management system database of the hospital intranet. RESULTS: One patient was lost to follow-up. In the mean follow-up of 654 days, 27 (20%) died and 23 (17%) patients suffered a MACE. Receiver operator curve (ROC) analysis showed that a pre-operative NT-pro-BNP level with a cut-off of 359 pg ml(-1) had a sensitivity and specificity of 73% each (area under the curve (AUC) 80%, p < 0.001) in predicting ACM and sensitivity of 74% and specificity of 71% (AUC 75%, p < 0.001) to detect a MACE. The overall 2-year survival rate was 84%, 93% in the <359 pg ml(-1) group and 68% in the ≥359 pg ml(-1) group (p < 0.001). Following multivariate analysis, pre-operative NT-pro-BNP at a value of ≥359 pg ml(-1) remained an independent predictor of ACM (odds ratio 3.6 (confidence interval (CI): 1.6-8.1), p = 0.002) Postoperative NT-pro-BNP was a predictor of mortality but not a MACE. CONCLUSION: This study has shown that pre-operative NT-pro-BNP is an independent predictor of ACM and MACE on medium-term follow-up.

Osteonecrosis of the distal tibia after a pronation external rotation ankle fracture: literature review and management.

Posttraumatic osteonecrosis of the distal tibia is a rare but recognized complication of Weber C ankle fractures. To our knowledge, we report the first documented case managed with early percutaneous drilling of the defect. The patient noticed an improvement in symptoms, and magnetic resonance imaging confirmed resolution of the avascular area. The previously reported complication of secondary periarticular collapse and subsequent osteoarthritis was avoided. We advocate that a high index of suspicion, early detection, and drilling can encourage neovascularisation and prevent secondary joint destruction.