Natural History and Genomic Landscape of Chemotherapy-Resistant Muscle-Invasive Bladder Cancer.

PURPOSE: Patients with residual invasive bladder cancer after neoadjuvant chemotherapy (NAC) and radical cystectomy have a poor prognosis. Data on adjuvant therapy for these patients are conflicting. We sought to evaluate the natural history and genomic landscape of chemotherapy-resistant bladder cancer to inform patient management and clinical trials. METHODS: Data were collected on patients with clinically localized muscle-invasive urothelial bladder cancer treated with NAC and cystectomy at our institution between May 15, 2001, and August 15, 2019, and completed four cycles of gemcitabine and cisplatin NAC, excluding those treated with adjuvant therapies. Survival was estimated using the Kaplan-Meier method, and multivariable Cox proportional hazards models were used to identify predictors of recurrence-free survival (RFS). Genomic alterations were identified in targeted exome sequencing (Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets) data from post-NAC specimens from a subset of patients. RESULTS: Lymphovascular invasion (LVI) was the strongest predictor of RFS (hazard ratio, 2.15 [95% CI, 1.37 to 3.39]) on multivariable analysis. Patients with ypT2N0 disease without LVI had a significantly prolonged RFS compared with those with LVI (70% RFS at 5 years). Lymph node yield did not affect RFS. Among patients with sequencing data (n = 101), chemotherapy-resistant tumors had fewer alterations in DNA damage response genes compared with tumors from a publicly available chemotherapy-naïve cohort (15% v 29%; P = .021). Alterations in CDKN2A/B were associated with shorter RFS. PIK3CA alterations were associated with LVI. Potentially actionable alterations were identified in more than 75% of tumors. CONCLUSION: Although chemotherapy-resistant bladder cancer generally portends a poor prognosis, patients with organ-confined disease without LVI may be candidates for close observation without adjuvant therapy. The genomic landscape of chemotherapy-resistant tumors is similar to chemotherapy-naïve tumors. Therapeutic opportunities exist for targeted therapies as adjuvant treatment in chemotherapy-resistant disease.

Development and validation of a preliminary multivariable diagnostic model for identifying unusual infections in hospitalized patients.

Diagnostic delay leads to poor outcomes in infections, and it occurs more often when the causative agent is unusual. Delays are attributable to failing to consider such diagnoses in a timely fashion. Using routinely collected electronic health record (EHR) data, we built a preliminary multivariable diagnostic model for early identification of unusual fungal infections and tuberculosis in hospitalized patients. We conducted a two-gate case-control study. Cases encompassed adult patients admitted to 19 Mayo Clinic enterprise hospitals between January 2010 and March 2023 diagnosed with blastomycosis, cryptococcosis, histoplasmosis, mucormycosis, pneumocystosis, or tuberculosis. Control groups were drawn from all admitted patients (random controls) and those with community-acquired infections (ID-controls). Development and validation datasets were created using randomization for dividing cases and controls (7:3), with a secondary validation using ID-controls. A logistic regression model was constructed using baseline and laboratory variables, with the unusual infections of interest outcome. The derivation dataset comprised 1043 cases and 7000 random controls, while the 451 cases were compared to 3000 random controls and 1990 ID-controls for validation. Within the derivation dataset, the model achieved an area under the curve (AUC) of 0.88 (95% confidence interval [CI]: 0.87-0.89) with a good calibration accuracy (Hosmer-Lemeshow P = 0.623). Comparable performance was observed in the primary (AUC = 0.88; 95% CI: 0.86-0.9) and secondary validation datasets (AUC = 0.84; 95% CI: 0.82-0.86). In this multicenter study, an EHR-based preliminary diagnostic model accurately identified five unusual fungal infections and tuberculosis in hospitalized patients. With further validation, this model could help decrease time to diagnosis.

Temporal Relationship and Clinical Outcomes of Acute Kidney Injury Following Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis.

OBJECTIVES: Conduct a systematic review and meta-analysis to assess prevalence and timing of acute kidney injury (AKI) development after acute respiratory distress syndrome (ARDS) and its association with mortality. DATA SOURCES: Ovid MEDLINE(R), Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Ovid PsycINFO database, Scopus, and Web of Science thought April 2023. STUDY SELECTION: Titles and abstracts were screened independently and in duplicate to identify eligible studies. Randomized controlled trials and prospective or retrospective cohort studies reporting the development of AKI following ARDS were included. DATA EXTRACTION: Two reviewers independently extracted data using a pre piloted abstraction form. We used Review Manager 5.4 software (Cochrane Library, Oxford, United Kingdom) and Open Meta software (Brown University, Providence, RI) for statistical analyses. DATA SYNTHESIS: Among the 3646 studies identified and screened, 17 studies comprising 9359 ARDS patients met the eligibility criteria and were included in the meta-analysis. AKI developed in 3287 patients (40%) after the diagnosis of ARDS. The incidence of AKI at least 48 hours after ARDS diagnosis was 20% (95% CI, 0.18-0.21%). The pooled risk ratio (RR) for the hospital (or 30-d) mortality among ARDS patients who developed AKI was 1.93 (95% CI, 1.71-2.18). AKI development after ARDS was identified as an independent risk factor for mortality in ARDS patients, with a pooled odds ratio from multivariable analysis of 3.69 (95% CI, 2.24-6.09). Furthermore, two studies comparing mortality between patients with late vs. early AKI initiation after ARDS revealed higher mortality in late AKI patients with RR of 1.46 (95% CI, 1.19-1.8). However, the certainty of evidence for most outcomes was low to very low. CONCLUSIONS: While our findings highlight a significant association between ARDS and subsequent development of AKI, the low to very low certainty of evidence underscores the need for cautious interpretation. This systematic review identified a significant knowledge gap, necessitating further research to establish a more definitive understanding of this relationship and its clinical implications.

Acetazolamide for acute kidney injury in patients undergoing high dose methotrexate therapy: a systematic review and meta-analysis.

BACKGROUND: Urine alkalization is one of the standard treatments to prevent acute kidney injury in patients receiving high-dose methotrexate. Carbonic anhydrase inhibitors are promising adjuvants/substitutes with advantages such as faster urine alkalization time and prevention of fluid overload. However, there is limited and contradictory evidence on its efficacy and safety. We aimed to compare the efficacy and safety of carbonic anhydrase inhibitors to standard treatments in adult patients receiving high-dose methotrexate. METHODS: The protocol was registered at PROSPERO (CRD42022352802) in August 2021. We evaluated the use of carbonic anhydrase inhibitors in combination with standard treatment compared to standard treatment alone. We excluded articles irrelevant to the efficacy and safety of acetazolamide in patients receiving high dose methotrexate and/or did not provide sufficient data regarding doses, recruitment criteria, and follow-up period. Two authors performed the data extraction independently. RESULTS: Among 198 articles retrieved, six observational studies met all eligibility criteria. Four studies with five datasets (totaling 558 patients/cycles) had enough data to be included in the meta-analysis. We independently report the results from the two remaining studies. The results did not show a significant difference between acetazolamide versus standard treatment in acute kidney injury (AKI) rate (OR = 0.79, 95% CI 0.48-1.29, P = 0.34, I2 = 0%). Regarding the time to urine pH goal, there was no significant time difference between the two groups (Mean Difference = 0.07, 95% CI - 1.9 to 2.04, P = 0.95, I2 = 25%). Furthermore, our meta-analysis showed that acetazolamide did not reduce length of stay (Mean Difference = 0.75, 95% CI - 0.8 to 2.31, P = 0.34, I2 = 0%). In one study, the only reported side effect of acetazolamide was hypokalemia (nearly 50% in the acetazolamide group). CONCLUSIONS: This systematic review showed no significant difference between acetazolamide and standard care treatment regarding urine alkalinization time and AKI rate in adult patients receiving high dose methotrexate. We suggest performing a large blinded, randomized, controlled trial to evaluate the potential benefits of this low-cost medication.

Brief Report: HIV Pre-Exposure Prophylaxis Awareness and Use Among Adolescents in Kenya.

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) is an effective prevention tool; however, use among adolescents is thought to be low. To determine the unmet need and opportunity to expand use, we assessed awareness, prior use, and willingness to take PrEP among Kenyan adolescents. METHODS: The Maneno Yetu study recruited a community-based sample of adolescents aged 15-19 years (N = 3061) in Kisumu for a survey using respondent-driven sampling. RESULTS: Overall, 50% of adolescents had heard of PrEP and 2% had used PrEP. Girls were more likely than boys to have heard of PrEP (53.4% vs. 45.1%; P < 0.001) and used PrEP (3.6% vs. 0.3%; P < 0.001). Among participants, 14% engaged in transactional sex and 21% experienced forced sexual contact. PrEP use was higher among adolescents who engaged in transactional sex (4.8% vs. 0.6%; P < 0.001) and experienced forced sexual contact (2.7% vs. 0.7%; P < 0.001) compared with those who did not. Among adolescents with no prior use, 53% were willing to consider using PrEP, although girls were less willing than boys (49.7% vs. 55.9%; P = 0.001). CONCLUSIONS: PrEP is an important prevention tool, especially for adolescents whose circumstances potentially expose them to HIV-positive or unknown status sexual partners, yet remains underused, particularly in resource-limited settings. Although many expressed willingness to use PrEP, low awareness and use highlight the need to expand HIV prevention education and services tailored for adolescents. Our finding that boys were more willing to use PrEP suggests campaigns should also be designed to reach male youth to narrow the gender gap and expand uptake in the adolescent population.

Potential of aerobic granular sludge membrane bioreactor (AGMBR) in wastewater treatment.

This investigation is a review of the potential of aerobic granular sludge membrane bioreactor (AGMBR) in wastewater treatment due to the advantage of combination of membrane and aerobic granules for reducing membrane fouling and enhancing removal performance. The AGMBR is the same as the membrane bioreactor (MBR), but the activated sludge is replaced by aerobic granular sludge. This technology combines the advantages of aerobic granular sludge, such as good settleability, strong ability to withstand shock-loadings and high organic loading rate, and capacity of simultaneous chemical oxygen demand (COD) and nitrogen removal, and advantages of membrane bioreactor (MBR) such as excellent effluent quality, high biomass content, low excess sludge production, and small land requirement. Therefore, it can be considered a promising option for efficient wastewater treatment. Most studies have shown that aerobic granules could control membrane fouling, which often occurs in MBR. The main fouling mechanism was determined to be surface fouling by floccular sludge in MBR but pore fouling by colloids and solutes in AGMBR. Aerobic granular sludge also removed COD and nitrogen simultaneously, with more than 60% total nitrogen removal efficiency. The formation and stability of aerobic granules in AGMBR with various operational modes are discussed in this study.

Dementia care practices among community healthcare workers in Vietnam: a qualitative descriptive study.

BACKGROUND: Vietnam is one of the most rapidly aging countries in the world and the likelihood that someone may have dementia rises dramatically as the population ages. Although caring for persons living with dementia is important, little is known about the circumstances under which community healthcare professionals in Vietnam provide dementia care. This study aimed to describe the practice of caring for persons with dementia among community healthcare professionals in Vietnam. METHODS: This qualitative descriptive study was conducted with 23 community healthcare professionals recruited from 10 primary healthcare centers, representing 10 of 24 districts in Ho Chi Minh City, Vietnam. Participants were physicians (n = 11), physician's assistants (n = 8) and community nurses (n = 4). Data were collected through in-depth face-to-face semi-structured interviews. Interview data were audio recorded, transcribed verbatim, and analyzed using content analysis. RESULTS: The mean age of the 23 participants was 44.6 ± 8.8 years; most were female (n = 16, 69.6%); and the mean time of working in the field of dementia care was 15.9 ± 8.4 years. Analysis of the interview data revealed five categories, which informed how care was provided: 1) Knowledge about dementia and its prevalence among older adults; 2) Identification of dementia in Vietnam; 3) Lack of attention to early diagnosis of dementia and difficulty in providing continuous care; 4) Dependence on family members for prompt and continuous care; and 5) challenges to providing dementia care. Despite having knowledge about dementia, some healthcare professionals incorrectly viewed dementia as an inevitable part of the ageing process. Participants reported that their limited training and practical experience in caring for persons with dementia caused a lack of confidence in dementia care. CONCLUSIONS: The quality of care provided to persons living with dementia was negatively impacted by the limited training of healthcare personnel. The diagnosis, treatment, and provision of supportive services to persons living with dementia and their families are substantial challenges for the Vietnamese healthcare system. It is crucial to initiate and cultivate dementia care education programs aimed at expanding curricula for physicians, physicians' assistants, and nurses.

The Diagnostic Accuracy of Metagenomic Next-Generation Sequencing in Diagnosing Pneumocystis Pneumonia: A Systemic Review and Meta-analysis.

Background: Pneumocystis pneumonia (PCP) is a growing concern as the immunocompromised population expands. Current laboratory approaches are limited. This systematic review aimed to evaluate metagenomic next-generation sequencing (MNGS) tests' performance in detecting PCP. Methods: Five databases were searched through December 19, 2022, to identify original studies comparing MNGS with clinically diagnosed PCP. To assess the accuracy, symmetric hierarchical summary receiver operating characteristic models were used. Results: Eleven observational studies reporting 1442 patients (424 with PCP) were included. Six studies focused exclusively on recipients of biologic immunosuppression (none with HIV-associated immunosuppression). Six were exclusively on bronchoalveolar lavage, while 1 was on blood samples. The sensitivity of MGNS was 0.96 (95% CI, 0.90-0.99), and specificity was 0.96 (95% CI, 0.92-0.98), with negative and positive likelihood ratios of 0.02 (95% CI, 0.01-0.05) and 19.31 (95% CI, 10.26-36.36), respectively. A subgroup analysis of studies exclusively including bronchoalveolar lavage (BAL) and blood samples demonstrated a sensitivity of 0.94 (95% CI, 0.78-0.99) and 0.93 (95% CI, 0.80-0.98) and a specificity of 0.96 (95% CI, 0.88-0.99) and 0.98 (95% CI, 0.76-1.00), respectively. The sensitivity analysis on recipients of biologic immunosuppression showed a sensitivity and specificity of 0.96 (95% CI, 0.90-0.98) and 0.94 (95% CI, 0.84-0.98), respectively. The overall confidence in the estimates was low. Conclusions: Despite the low certainty of evidence, MNGS detects PCP with high sensitivity and specificity. This also applies to recipients of biologic immunosuppression and tests performed exclusively on blood samples without the need for BAL. Further studies are required in individuals with HIV-associated immunosuppression.

Flight Path Setting and Data Quality Assessments for Unmanned-Aerial-Vehicle-Based Photogrammetric Bridge Deck Documentation.

Imagery from Unmanned Aerial Vehicles can be used to generate three-dimensional (3D) point cloud models. However, final data quality is impacted by the flight altitude, camera angle, overlap rate, and data processing strategies. Typically, both overview images and redundant close-range images are collected, which significantly increases the data collection and processing time. To investigate the relationship between input resources and output quality, a suite of seven metrics is proposed including total points, average point density, uniformity, yield rate, coverage, geometry accuracy, and time efficiency. When applied in the field to a full-scale structure, the UAV altitude and camera angle most strongly affected data density and uniformity. A 66% overlapping was needed for successful 3D reconstruction. Conducting multiple flight paths improved local geometric accuracy better than increasing the overlapping rate. The highest coverage was achieved at 77% due to the formation of semi-irregular gridded gaps between point groups as an artefact of the Structure from Motion process. No single set of flight parameters was optimal for every data collection goal. Hence, understanding flight path parameter impacts is crucial to optimal UAV data collection.

HIV Infection Among Adolescents Residing in Urban Informal Settlements of Kenya.

Adolescents comprise approximately 15% of new HIV infections in Kenya. Impoverished living conditions in informal settlements place residents at high risk for HIV infection. We assessed factors associated with HIV infection among adolescents residing in urban informal settlements in Kisumu. We recruited 3,061 adolescent boys and girls aged 15-19. HIV prevalence was 2.5% overall, all newly identified cases were among girls and infection was positively associated with not completing a secondary education (p < .001). Girls who had ever been pregnant (p < .001) or out-of-school without completing a secondary education (p < .001) were more likely to be HIV-positive. Our findings of higher HIV prevalence among adolescent girls who had been pregnant or did not complete secondary school highlight the need to facilitate access to HIV testing, HIV pre-exposure prophylaxis, and sexual and reproductive health services as components of a comprehensive prevention strategy to decrease HIV infections in this priority population.

Adverse pathologic features impact survival outcomes for small renal masses following nephrectomy.

PURPOSE: While most small renal masses (SRM) < 4 cm have an excellent prognosis following resection, the impact of adverse T3a pathologic features on oncologic outcomes of SRMs remains unclear. We sought to compare clinical outcomes for surgically resected pT3a versus pT1a SRMs at our institution. MATERIALS AND METHODS: We retrospectively reviewed records of patients who underwent radical or partial nephrectomy (RN, PN) for renal tumors <4 cm at our institution between 2010 and 2020. We compared features and outcomes of pT3a vs pT1a SRMs. Continuous and categorical variables were compared using Student's t and Pearson's chi-squared tests, respectively. Postoperative outcomes of interest including overall, cancer-specific, and recurrence-free survival (OS, CSS, and RFS) were analyzed using Kaplan-Meier method, Cox proportional hazard regression, and competing risk analysis. Analyses were performed using R statistical package (R Foundation, v4.0). RESULTS: We identified 1,837 patients with malignant SRMs. Predictors of postoperative pT3a upstaging included higher renal score, larger tumor size, and presence of radiologic features concerning for T3a disease (odds ratio [OR] = 5.45, 95% confidence interval [CI] 3.92-7.59, P < 0.001). On univariable modeling, pT3a SRMs had higher positive margin rates (9.6% vs 4.1%, P < 0.001), worse OS (hazard ratio [HR] = 2.9, 95% CI 1.6-5.3, P = 0.002), RFS (HR 9.32, 95% CI 2-40.1, P = 0.003), and CSS (HR = 3.6, 95% CI 1.5-8.2, P = 0.003). On multivariable modeling, pT3a status remained associated with worse RFS (HR = 2.7, 95% CI 1.04-7, P = 0.04), but not OS (HR 1.6, 95% CI = 0.83-3.1, P = 0.2); multivariable modeling was deferred for CSS due to low event rates. CONCLUSIONS: Adverse T3a pathologic features portend worse outcomes for SRMs, highlighting the crucial role of pre-operative planning and case selection. These patients have relatively poor prognosis, and should be monitored more closely and counseled for consideration of adjuvant therapy or clinical trials.

Evaluation of the EsteR Toolkit for COVID-19 Decision Support: Sensitivity Analysis and Usability Study.

BACKGROUND: During the COVID-19 pandemic, local health authorities were responsible for managing and reporting current cases in Germany. Since March 2020, employees had to contain the spread of COVID-19 by monitoring and contacting infected persons as well as tracing their contacts. In the EsteR project, we implemented existing and newly developed statistical models as decision support tools to assist in the work of the local health authorities. OBJECTIVE: The main goal of this study was to validate the EsteR toolkit in two complementary ways: first, investigating the stability of the answers provided by our statistical tools regarding model parameters in the back end and, second, evaluating the usability and applicability of our web application in the front end by test users. METHODS: For model stability assessment, a sensitivity analysis was carried out for all 5 developed statistical models. The default parameters of our models as well as the test ranges of the model parameters were based on a previous literature review on COVID-19 properties. The obtained answers resulting from different parameters were compared using dissimilarity metrics and visualized using contour plots. In addition, the parameter ranges of general model stability were identified. For the usability evaluation of the web application, cognitive walk-throughs and focus group interviews were conducted with 6 containment scouts located at 2 different local health authorities. They were first asked to complete small tasks with the tools and then express their general impressions of the web application. RESULTS: The simulation results showed that some statistical models were more sensitive to changes in their parameters than others. For each of the single-person use cases, we determined an area where the respective model could be rated as stable. In contrast, the results of the group use cases highly depended on the user inputs, and thus, no area of parameters with general model stability could be identified. We have also provided a detailed simulation report of the sensitivity analysis. In the user evaluation, the cognitive walk-throughs and focus group interviews revealed that the user interface needed to be simplified and more information was necessary as guidance. In general, the testers rated the web application as helpful, especially for new employees. CONCLUSIONS: This evaluation study allowed us to refine the EsteR toolkit. Using the sensitivity analysis, we identified suitable model parameters and analyzed how stable the statistical models were in terms of changes in their parameters. Furthermore, the front end of the web application was improved with the results of the conducted cognitive walk-throughs and focus group interviews regarding its user-friendliness.

Prenatal exposure to benzo[a]pyrene depletes ovarian reserve and masculinizes embryonic ovarian germ cell transcriptome transgenerationally.

People are widely exposed to polycyclic aromatic hydrocarbons, like benzo[a]pyrene (BaP). Prior studies showed that prenatal exposure to BaP depletes germ cells in ovaries, causing earlier onset of ovarian senescence post-natally; developing testes were affected at higher doses than ovaries. Our primary objective was to determine if prenatal BaP exposure results in transgenerational effects on ovaries and testes. We orally dosed pregnant germ cell-specific EGFP-expressing mice (F0) with 0.033, 0.2, or 2 mg/kg-day BaP or vehicle from embryonic day (E) 6.5-11.5 (F1 offspring) or E6.5-15.5 (F2 and F3). Ovarian germ cells at E13.5 and follicle numbers at postnatal day 21 were significantly decreased in F3 females at all doses of BaP; testicular germ cell numbers were not affected. E13.5 germ cell RNA-sequencing revealed significantly increased expression of male-specific genes in female germ cells across generations and BaP doses. Next, we compared the ovarian effects of 2 mg/kg-day BaP dosing to wild type C57BL/6J F0 dams from E6.5-11.5 or E12.5-17.5. We observed no effects on F3 ovarian follicle numbers with either of the shorter dosing windows. Our results demonstrate that F0 BaP exposure from E6.5-15.5 decreased the number of and partially disrupted transcriptomic sexual identity of female germ cells transgenerationally.

Uptake and continuation of HIV pre-exposure prophylaxis among women of reproductive age in two health facilities in Kisumu County, Kenya.

INTRODUCTION: In 2020, Kenya had 19,000 new HIV infections among women aged 15+ years. Studies have shown sub-optimal oral pre-exposure prophylaxis (PrEP) use among sub-populations of women. We assessed the uptake and continuation of oral PrEP among women 15-49 years in two health facilities in Kisumu County, Kenya. METHODS: A retrospective cohort of 262 women aged 15-49 years, initiated into oral PrEP between 12 November 2019 and 31 March 2021, was identified from two health facilities in the urban setting of Kisumu County, Kenya. Data on baseline characteristics and oral PrEP continuation at months 1, 3 and 6 were abstracted from patient records and summarized using descriptive statistics. Missing data in the predictor variables were imputed within the joint modelling multiple imputation framework. Using logistic regression, we evaluated factors associated with the discontinuation of oral PrEP at month 1. RESULTS: Of the 66,054 women screened, 320 (0.5%) were eligible and 262 (82%) were initiated on oral PrEP. Uptake was higher among women 25-29 years as compared to those 15-24 years (77% vs. 33%). Oral PrEP continuation declined significantly with increasing duration of follow-up; 37% at month 1, 21% at month 3 and 12% at month 6 (p<0.05). In the adjusted analysis, women 15-24 years had lower adjusted odds of continuing at month 1 than women ≥25 years (adjusted odds ratio [aOR]: 0.41, 95% CI: 0.21-0.82). There was no association between being sero-discordant and continuation of oral PrEP at month 1 (aOR; 1.21, 95% CI 0.59-2.50). Women from the sub-county hospital were more likely to continue at month 1 of follow-up compared to women enrolled in the county referral hospital (aOR 5.11; 95% CI 2.24-11.70). CONCLUSIONS: The low eligibility for oral PrEP observed among women 15-49 years in an urban setting with high HIV prevalence calls for a review of the screening process to validate the sensitivity of the screening tool and its proper application. The low uptake and continuation among adolescent girls and young women underscores the need to identify and address specific patient- and facility-level barriers affecting different sub-populations at risk for HIV acquisition.

Respondent-driven sampling to recruit adolescents in Kenya.

PURPOSE: Respondent-driven sampling (RDS) uses long-chain referral whereby members of the target population recruit other members. We describe the use of RDS for a mixed-methods sexual and reproductive health (SRH) study in Kisumu, Kenya. METHODS: Initial seeds for the cross-sectional surveys were selected from adolescents aged 15-19 residing in urban informal settlements. Participants were provided up to five referral coupons to distribute. RESULTS: Across four communities, 18 seeds were selected, 13,489 coupons distributed, and 3381 adolescents referred, yielding a 25% coupon return rate. We enrolled 3061 participants for a 23% survey rate. Median referral lag time was three days (IQR 1, 7). Demographic characteristics reached equilibrium between recruitment waves 5 to 8 in three communities, and waves 7 to 15 in the fourth. CONCLUSIONS: Our study demonstrated that RDS is a feasible and efficient approach for recruiting a large sample of adolescents. Though our research focused on SRH, many adolescents residing in the impoverished urban environments where our study was implemented also experience food insecurity, housing instability and violence. RDS can therefore be a valuable recruitment approach for future studies to reach vulnerable adolescents and design interventions that address the variety of health-related challenges that affect this underserved population.

Efficacy of Kinesio Taping Compared to Other Treatment Modalities in Musculoskeletal Disorders: A Systematic Review and Meta-Analysis.

Kinesio taping is widely used in musculoskeletal conditions. We performed a systematic review and meta-analysis on the efficacy of kinesio taping in musculoskeletal disorders compared to other interventions. Twelve electronic databases were used for systemic search and data relevant to pain and disability were extracted. The protocol was registered in PROSPERO (CRD42018087606). Meta-analysis was performed to compare the efficacy of kinesio taping to other modalities of musculoskeletal disorders. As a result, 36 studies were included in the quantitative analysis. Kinesio taping was found to provide an improvement of both pain and disability when applied to any region of the body. In the first five days of application, kinesio taping significantly reduced the pain in all body regions (SMD = -0.63, 95%CI: -0.87, -0.39). This was also noted after four-to-six weeks of application (SMD = -0.76, 95%CI: -1.07, -0.45). When kinesio taping was used for disability in low back pain patients, it significantly reduced the disability within five days of application (SMD = -0.70, 95%CI: -1.29, -0.11). Finally, kinesio taping has shown an improvement of the disability in all body regions after four-to-six weeks of application (SMD = -0.59, 95%CI: -0.96, -0.22). Our findings support kinesio taping as an adjuvant to other treatments for musculoskeletal disorders. Abbreviations KT = Kinesio taping; MSK = musculoskeletal; SD = standard deviation; CR = conventional rehabilitation; NDI = Neck Disability Index; NPS = Numerical Pain Scale; CTM = Cervical Thrust Manipulation; PIR = Post-isometric muscle relaxation; NPRS Numerical Pain Rating Scale; OA = osteoarthritis; ROM = Range of motion; VAS = visual analogue scale; VAS-W = visual analogue scale-worst pain; VAS-U = visual analogue scale-usual pain; VAS-R = visual analogue scale-resting pain; VAS-A = visual analogue scale-activity pain; VAS-N = visual analogue scale-night pain; NPDS = Neck Pain Disability Scale; QA = Quality assessment.

Gene-based Confirmatory Germline Testing Following Tumor-only Sequencing of Prostate Cancer.

BACKGROUND: Tumor-only genomic profiling is an important tool in therapeutic management of men with prostate cancer. Since clinically actionable germline variants may be reflected in tumor profiling, it is critical to identify which variants have a higher risk of being germline in origin to better counsel patients and prioritize genetic testing. OBJECTIVE: To determine when variants found on tumor-only sequencing of prostate cancers should prompt confirmatory germline testing. DESIGN, SETTING, AND PARTICIPANTS: Men with prostate cancer who underwent both tumor and germline sequencing at Memorial Sloan Kettering Cancer Center from January 1, 2015 to January 31, 2020 were evaluated. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Tumor and germline profiles were analyzed for pathogenic and likely pathogenic ("pathogenic") variants in 60 moderate- or high-penetrance genes associated with cancer predisposition. The germline probability (germline/germline + somatic) of a variant was calculated for each gene. Clinical and pathologic factors were analyzed as potential modifiers of germline probability. RESULTS AND LIMITATIONS: Of the 1883 patients identified, 1084 (58%) had a somatic or germline pathogenic variant in one of 60 cancer susceptibility genes, and of them, 240 (22%) had at least one germline variant. Overall, the most frequent variants were in TP53, PTEN, APC, BRCA2, RB1, ATM, and CHEK2. Variants in TP53, PTEN, or RB1 were identified in 746 (40%) patients and were exclusively somatic. Variants with the highest germline probabilities were in PALB2 (69%), MITF (62%), HOXB13 (60%), CHEK2 (55%), BRCA1 (55%), and BRCA2 (47%), and the overall germline probability of a variant in any DNA damage repair gene was 40%. Limitations were that most of the men included in the cohort had metastatic disease, and different thresholds for pathogenicity exist for somatic and germline variants. CONCLUSIONS: Of patients with pathogenic variants found on prostate tumor sequencing, 22% had clinically actionable germline variants, for which the germline probabilities varied widely by gene. Our results provide an evidenced-based clinical framework to prioritize referral to genetic counseling following tumor-only sequencing. PATIENT SUMMARY: Patients with advanced prostate cancer are recommended to have germline genetic testing. Genetic sequencing of a patient's prostate tumor may also identify certain gene variants that are inherited. We found that patients who had variants in certain genes, such as ones that function in DNA damage repair, identified in their prostate tumor sequencing, had a high risk for having an inherited cancer syndrome.

Targeted Therapies in Advanced and Metastatic Urothelial Carcinoma.

This review describes the current landscape of targeted therapies in urothelial carcinoma. The standard of care for advanced urothelial carcinoma patients remains platinum-based combination chemotherapy followed by immunotherapy. However, median overall survival for these patients is still <1 year and there is an urgent need for alternative therapies. The advent of next-generation sequencing has allowed widespread comprehensive molecular characterization of urothelial tumors and, subsequently, the development of therapies targeting specific molecular pathways implicated in carcinogenesis such as FGFR inhibition, Nectin-4, Trop-2, and HER2 targeting. As these therapies are demonstrated to be effective in the second-line setting, they will be advanced in the treatment paradigm to localized and even non-muscle invasive disease.

Burden and mortality of sepsis and septic shock at a high-volume, single-center in Vietnam: a retrospective study.

BACKGROUND: Sepsis and septic shock have high mortality rates and often require a prolonged hospital stay. Patient outcomes may vary according to multiple factors. We aim to determine the prevalence of antimicrobial resistance and factors associated with mortality and hospital stay. METHODS: Clinical and microbiological data of patients with sepsis or septic shock were retrospectively collected for 15 months. Patients with negative blood cultures and patients that did not meet the SEPSIS 3 criteria were excluded. RESULTS: We included 48 septic shock and 28 septic patients (mean APACHE II 20.32 ± 5.61 and mean SOFA 9.41 ± 3.17), with a mean age of 60.5 ± 16.8 years and 56.6% males. WBCs, neutrophils, INR, and fibrinogen levels were significantly associated with mortality. 59.5% of the cultured bacteria were gram-negative (most common E. coli) and 27.8% were gram-positive (most common S. aureus), while 7.6% were other types of bacteria and 5.1% were fungi. Resistance patterns to gram-negative were varying, and resistance to piperacillin/tazobactam, carbapenems, and aminoglycosides were from 60% to 100% (A. baumanii), while they were highly sensitive to Colistin. E. coli was also resistant to ceftriaxone (77.8%) and sulbactam/cefoperazone (44.4%). Resistance rates for Gram-positives were high, from 86% to 100% for oxacillin, while for vancomycin, teicoplanin, and linezolid, they were often low but arrived up to 42.8%. According to our logistic regression analysis, patients over 65 year-old and those who received corticosteroids had a significantly increased risk of in-hospital mortality (OR: 4.0; OR: 4.8). CONCLUSION: Sepsis still poses a significant threat to patients' health, even when positive blood culture results allow the administration of specific antibiotic treatment.

The timing setting in kinetic dengue studies: A systematic review.

Dengue is classified as an endemic infectious disease, which is transmitted by Aedes mosquitos. Kinetic studies, which monitor the viral load of the disease, have been the mainstay for several decades in humanity's quest to control this disease. Our study aims to systematically evaluate the usage of different timing systems in dengue kinetic studies. A search in nine electronic databases and manual search of reference and citation lists were conducted to find relevant studies. A quality assessment using the National Institute of Health tools for observational cohort and cross-sectional studies was performed. The protocol was registered in PROSPERO with number CRD42018086435. As results, among included 87 studies, 71 studies (81.6%) use a timing system which is based on the day of illness onset, of which, 11 studies designate the day of illness onset as "day 0″ (type 1A) while 60 studies designate it as "day 1″ (type 1B). Only ten articles (11.5%) designate the day of defervescence as "day 0″, the day before and after defervescence as "day -1″ and "day +1″, respectively. Four articles (4.6%) use a timing system based on the day of hospital admission. Lastly, two studies (2.3%) designate the day of hemorrhagic manifestation as "day 0″ and two studies (2.3%) designate the day of pharmacological treatment as "day 1″. Therefore, the timing system which designates the day of illness onset as "day 1″ (type 1B) was most commonly used. Inconsistent definitions of "day 0″ and "day 1″ may lead to disparities in results across the studies and may have a negative impact on treatment guidelines implementation.