Pre-extensively drug-resistant and extensively drug-resistant tuberculosis in Latin America and the Caribbean: A systematic review and meta-analysis.

BACKGROUND: The growing threat from pre-extensively drug-resistant tuberculosis (pre-XDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) poses a major public health concern in Latin America and the Caribbean (LAC). Therefore, this study aimed to summarize the available evidence on the prevalence of pre-XDR-TB and XDR-TB among patients with multidrug-resistant tuberculosis in LAC. METHODS: A systematic review was conducted in the following databases on June 3, 2023: PubMed, Scopus, Ovid Medline, Web of Science, Scielo and LILACS. We estimated pooled proportions using a random effects model (Dersimonian and Laird). The 95% confidence intervals (95% CI) were calculated using the binomial exact method (Clopper-Pearson Method). Subgroup (by time period and country) and sensitivity analyses were performed. RESULTS: Twenty-nine studies were eligible for qualitative synthesis and 27 for meta-analysis (n = 15,565). The pooled prevalence of XDR-TB in the study participants was 5% (95% CI: 3%-6%), while that of pre-XDR-TB was 10% (95% CI 7%-14%). Cuba (6%, 95% CI 0%-17%) and Peru (6%, 95% CI 5%-7%) had the highest pooled prevalence of XDR-TB. Regarding pre-XDR-TB, Brazil (16%, 95% CI 11%-22%) and Peru (13%, 95% CI: 9%-16%) showed the highest prevalence. CONCLUSIONS: The pooled prevalence of pre-XDR-TB and XDR-TB in LAC was 10% and 5%, respectively. Governments should strengthen drug-resistance surveillance and TB programs.

Systemic Immune-Inflammation Index and Mortality in Testicular Cancer: A Systematic Review and Meta-Analysis.

The systemic immune-inflammation index (SIII) is a marker studied in multiple types of urologic cancer. This systematic review evaluates the association between SIII values with overall survival (OS) and progression-free survival (PFS) in testicular cancer. We searched observational studies in five databases. The quantitative synthesis was performed using a random-effects model. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). The only measure of the effect was the hazard ratio (HR). A sensitivity analysis was performed according to the risk of bias in the studies. There were 833 participants in a total of 6 cohorts. We found that high SIII values were associated with worse OS (HR = 3.28; 95% CI 1.3-8.9; p < 0.001; I2 = 78) and PFS (HR = 3.9; 95% CI 2.53-6.02; p < 0.001; I2 = 0). No indication of small study effects was found in the association between SIII values and OS (p = 0.5301). High SIII values were associated with worse OS and PFS. However, further primary studies are suggested to enhance the effect of this marker in different outcomes of testicular cancer patients.

Atherogenic index of plasma and coronary artery disease: A systematic review.

Various studies suggest that the atherogenic index of plasma (AIP) is associated with the risk of coronary artery disease (CAD) in different clinical scenarios. This review aimed to synthesize evidence of the association between AIP values and CAD. A literature search was carried out on four databases, namely, PubMed, Scopus, Web of Science, and Ovid-Medline. A handsearch was performed on preprint repositories (MedRxiv and Research Square). The effect measurements were expressed as odds ratios (OR) with their corresponding 95% confidence intervals (CI). For the quantitative synthesis, we employed a random-effects model. We analyzed 14 articles (with 40,902 participants) from seven different countries. The quantitative analysis revealed that an increase in one unit of AIP was associated with higher odds of developing CAD (OR 2.11; 95% CI 1.65-2.69; P < 0.001; I 2 = 98%). We conducted subgroup analyses of Chinese (OR 1.89; 95% CI 1.40-2.56; P < 0.001) and non-Chinese studies (OR 2.51; 95% CI 1.42-4.42; P < 0.001). The sensitivity analysis by risk of bias continued to demonstrate an association, and the heterogeneity remained unchanged (OR 1.75; 95% CI 1.33-2.31; P < 0.001; I 2 = 98%). Higher AIP values were associated with higher odds of developing CAD.

Acceptance towards COVID-19 vaccination in Latin America and the Caribbean: A systematic review and meta-analysis.

INTRODUCTION: Vaccination represents an important strategy to mitigate COVID-19 related morbidity and mortality by protecting against severe forms of the disease and reducing hospitalization and death rates. In this sense, the objective of this study is to estimate the prevalence of Vaccination Intention (VI) against COVID-19 in Latin America and Caribbean (LAC). METHODS: We conducted a systematic review with a comprehensive search strategy for the following databases: PubMed, Scopus and Web of Science. A random-effect model meta-analysis was carried out using observational studies assessing the intention to vaccines against COVID-19 in LAC countries. The Clopper-Pearson method was used to estimate 95% Confidence Intervals. The quality assessment was developed using the Newcastle-Ottawa Scale adapted for cross-sectional studies. A subgroup analysis by study location and a sensitivity analysis were developed. RESULTS: Nineteen cross-sectional studies were included. Five meta-analyzes were performed according to the target population of the included studies. The VI in the general population of LAC was 78.0% (95%CI: 74.0%-82.0%). The VI for non-pregnant women was 78.0% (95%CI: 58.0%-99.0%), for elderly population was 63.0% (95%CI: 59.0%-69.0%), for pregnant women was 69.0% (95%CI: 61.0%-76.0%) and for health-personnel was 83.0% (95% CI: 71.0%-96.0%). The sensitivity analysis for general population meta-analysis that included only low risk of bias studies showed a 77.0% VI (95%CI: 73.0%-82.0%) and for non-pregnant women, 85.0% VI (95%CI: 79.0%-90.0%). CONCLUSION: Despite the high prevalence of VI in general population found in our study, VI prevalence from elderly people and pregnant women are lower than other population groups and overall population.

Antibiotic use and resistance: Knowledge, attitudes and perceptions among primary care prescribers in South Africa.

BACKGROUND: Antibiotic resistance (ABR) is a major threat to global health, driven in part by inappropriate prescription of antibiotics in primary care. OBJECTIVES: To describe South African (SA) prescribers' knowledge of, attitudes to and perceptions of ABR. METHODS: We conducted a cross-sectional survey of knowledge of, attitudes to and perceptions of ABR among a convenience sample of primary healthcare providers in SA, the majority from the private sector. We used logistic regression to examine associations between knowledge and prescribing behaviours. RESULTS: Of 264 prescriber respondents, 95.8% (230/240) believed that ABR is a significant problem in SA and 66.5% (157/236) felt pressure from patients to prescribe antibiotics. The median knowledge score was 5/7, and scores were highest in respondents aged <55 years (p=0.0001). Prescribers with higher knowledge scores were more likely than those with lower scores to believe that to decrease ABR, narrow-spectrum antibiotics should be used (adjusted odds ratio (aOR) 1.29, 95% confidence interval (CI) 1 - 1.65) and more likely to report that explaining disease features that should prompt follow-up was a useful alternative to prescribing (aOR 1.47, 95% CI 1.058 - 2.04), and were less likely to report that antibiotics cannot harm the patient if they are not needed, so they prescribe when not necessary (aOR 0.57, 95% CI 0.38 - 0.84). CONCLUSIONS: Prescribers of antibiotics in the private sector in SA were aware of the problem of ABR, but felt pressure from patients to prescribe. Those with higher knowledge scores reported positive prescribing behaviours, suggesting that more education is needed to tackle the problem of ABR.

A Systematic Review of the Current Status of Safer Conception Strategies for HIV Affected Heterosexual Couples in Sub-Saharan Africa.

We conducted a systematic review of safer conception strategies (SCS) for HIV-affected couples in sub-Saharan Africa to inform evidence-based safer conception interventions. Following PRISMA guidelines, we searched fifteen electronic databases using the following inclusion criteria: SCS research in HIV-affected couples; published after 2007; in sub-Saharan Africa; primary research; peer-reviewed; and addressed a primary topic of interest (SCS availability, feasibility, and acceptability, and/or education and promotion). Researchers independently reviewed each study for eligibility using a standardized tool. We categorize studies by their topic area. We identified 41 studies (26 qualitative and 15 quantitative) that met inclusion criteria. Reviewed SCSs included: antiretroviral therapy (ART), pre-exposure prophylaxis, timed unprotected intercourse, manual/self-insemination, sperm washing, and voluntary male medical circumcision (VMMC). SCS were largely unavailable outside of research settings, except for general availability (i.e., not specifically for safer conception) of ART and VMMC. SCS acceptability was impacted by low client and provider knowledge about safer conception services, stigma around HIV-affected couples wanting children, and difficulty with HIV disclosure in HIV-affected couples. Couples expressed desire to learn more about SCS; however, provider training, patient education, SCS promotions, and integration of reproductive health and HIV services remain limited. Studies of provider training and couple-based education showed improvements in communication around fertility intentions and SCS knowledge. SCS are not yet widely available to HIV-affected African couples. Successful implementation of SCS requires that providers receive training on effective SCS and provide couple-based safer conception counseling to improve disclosure and communication around fertility intentions and reproductive health.

Return of warm conditions in the southeastern Bering Sea: Physics to fluorescence.

From 2007 to 2013, the southeastern Bering Sea was dominated by extensive sea ice and below-average ocean temperatures. In 2014 there was a shift to reduced sea ice on the southern shelf and above-average ocean temperatures. These conditions continued in 2015 and 2016. During these three years, the spring bloom at mooring site M4 (57.9°N, 168.9°W) occurred primarily in May, which is typical of years without sea ice. At mooring site M2 (56.9°N, 164.1°W) the spring bloom occurred earlier especially in 2016. Higher chlorophyll fluorescence was observed at M4 than at M2. In addition, these three warm years continued the pattern near St. Matthew Island of high concentrations (>1 µM) of nitrite occurring during summer in warm years. Historically, the dominant parameters controlling sea-ice extent are winds and air temperature, with the persistence of frigid, northerly winds in winter and spring resulting in extensive ice. After mid-March 2014 and 2016 there were no cold northerly or northeasterly winds. Cold northerly winds persisted into mid-April in 2015, but did not result in extensive sea ice south of 58°N. The apparent mechanism that helped limit ice on the southeastern shelf was the strong advection of warm water from the Gulf of Alaska through Unimak Pass. This pattern has been uncommon, occurring in only one other year (2003) in a 37-year record of estimated transport through Unimak Pass. During years with no sea ice on the southern shelf (e.g. 2001-2005, 2014-2016), the depth-averaged temperature there was correlated to the previous summers ocean temperature.

Psoriasis: comorbidities and associations.

Psoriasis is a chronic, genetic, inflammatory skin disease affecting approximately 2% of the population worldwide. Over the past decade, multiple studies have shown that not only is there an association between psoriasis and psoriatic arthritis, depression, and substance abuse, but psoriasis patients also have a higher incidence of obesity, diabetes, heart disease and stroke. In addition, and more concerning, young psoriatic patients particularly those with more severe disease are at an increased mortality risk even when controlling for these factors. The systemic inflammation in psoriasis generates elevation of C-reactive protein, homocysteine, and inflammatory cytokines such as TNF-a, IL-6, IL-17, IL-20, IL-22, and IL-23, which may contribute to the overall morbidity and mortality in these patients. Within this article we will discuss the associations between psoriasis and multiple systemic health problems.

Evidence that mechanosensors with distinct biomechanical properties allow for specificity in mechanotransduction.

Various cell types can sense and convert mechanical forces into biochemical signaling events through a process called mechanotransduction, and this process is often highly specific to the types of mechanical forces applied. However, the mechanism(s) that allow for specificity in mechanotransduction remain undefined. Thus, the goal of this study was to gain insight into how cells distinguish among specific types of mechanical information. To accomplish this goal, we determined if skeletal myoblasts can distinguish among differences in strain, strain rate, and strain-time integral (STI). Our results demonstrate that mechanically induced signaling through the c-jun N-terminal kinase 2 [JNK2] is elicited via a mechanism that depends on an interaction between the magnitude of strain and strain rate and is independent of STI. In contrast to JNK2, mechanically induced signaling through the ribosomal S6 kinase [p70(389)] is not strain rate sensitive, but instead involves a magnitude of strain and STI dependent mechanisms. Mathematical modeling also indicated that mechanically induced signaling through JNK2 and p70(389) can be isolated to separate viscous and elastic mechanosensory elements, respectively. Based on these results, we propose that skeletal myoblasts contain multiple mechanosensory elements with distinct biomechanical properties and that these distinct biomechanical properties provide a mechanism for specificity in mechanotransduction.

Structure activity studies on group C meningococcal polysaccharide-protein conjugate vaccines: effect of O-acetylation on the nature of the protective epitope.

A series of group C meningococcal polysaccharide-tetanus toxoid (GCMP-TT) conjugates were prepared as vaccines with varying percentages of O-acetylation at the C-7 and C-8 positions of sialic acid residues in the polysaccharide (PS). The immune response in mice was highly dependent on the degree of O-acetylation. Less O-acetylation resulted in higher serum bactericidal activity (SBA) towards the O-acetylated (OA) meningococcal strain, C11. In addition, since an unconjugated de-O-acetylated (dOA) GCMP vaccine was previously shown to be highly immunogenic in humans, we had chosen this dOA form to couple with TT by reductive amination for clinical evaluation. This conjugate vaccine was shown to be well-tolerated and highly immunogenic in adults, children, and infants in the UK. To understand the nature of the GCMP protective epitope, a series of spectroscopic and serological studies were conducted, using high resolution H-NMR spectroscopy at 500 MHz and competitive inhibition SBA assays. The dOA GCMP was 10-1000 times better at inhibiting the SBA for an OA strain than the OA GCMP, suggesting that the GCMP-based protective epitope on the bacterium exists in a dOA form. In addition, SBA for an OA strain is highly correlated with dOA GCMP-specific IgG. NMR data on freshly isolated GCMP indicated that, on the surface of the organism, most of the O-acetylation exists at position C-8, with some regions containing dOA or OA C-7 sialic acid. After extraction of PS and storage in solution, most of the O-acetyl groups migrate to C-7, leaving an epitope that is conformationally related, but not quite identical (due to the presence of the O-acetyl group), to the one contained in the dOA PS. We speculate that the role of the O-acetyl group at the C-8 position of the PS on the organism is to form less immunogenic epitopes, or mask the protective epitope, and thus escape immune surveillance. The dOA form of the vaccine may therefore provide better protection against group C meningococcal disease than the OA form by eliciting a greater proportion of functional antibodies that are directly aimed at the protective epitope.

Voices from family medicine: Eugene Farley. Interview by William B. Ventres and John J. Frey.

This transcript is an abridged and edited version of interviews conducted with Eugene Farley, MD, MPH, in May 1991. It is the second in a series that looks into both the founding history of family medicine and the lives of those people who helped create the discipline. Dr. Farley is professor and chair of the Department of Family Medicine and Practice at the University of Wisconsin. In 1989, he received the STFM Recognition Award.

High-dose intensity systemic therapy of metastatic bladder cancer.

Forty-three consecutively diagnosed patients with widely metastatic transitional cell carcinoma of the bladder (TCCB) were treated with a high-dose intensity, chronobiologically timed combination of doxorubicin and cisplatin, followed by Cytoxan (Mead Johnson Pharmaceuticals, Evansville, IN), 5-fluorouracil (5-FU), and cisplatin maintenance for up to 2 years. Fifty-seven percent of the 35 evaluable patients with widespread metastatic cancer responded objectively. Twenty-three percent had complete disappearance of all cancer. Median survival from first treatment for complete responders (CRs) was more than 2 years, and 1 year for partial responders (PRs). Three of the CRs were alive without evidence of cancer more than 2 years after stopping all therapy. High-dose intensity combination chemotherapy can induce durable CRs of widespread bladder cancer.