Nevin Manimala

Int J STD AIDS. 2023 Nov 15:9564624231214583. doi: 10.1177/09564624231214583. Online ahead of print.

ABSTRACT

INTRODUCTION: We assessed trends in HIV and syphilis prevalence, HIV incidence, related risk factors, and preventive behaviors among men who have sex with men (MSM) in Vietnam from 2015 to 2020.

METHODS: Data originated from the HIV Sentinel Surveillance Plus system, which sampled MSM at venues and hotspots in seven of Vietnam’s 63 provinces in 2015, 2016, 2018, and 2020 (N = 1100-1445 per year; ∼150-300 per province per year).

RESULTS: HIV prevalence estimates increased from 6.6% (95% CI 4.5-9.6) in 2015 to 13.8% (95% CI 10.5-18.2, p = .001 for trend) in 2020 overall, and separately in An Giang, Can Tho, Hai Phong, and Khanh Hoa provinces but not in Ho Chi Minh City, Hanoi, or Kien Giang. Syphilis prevalence increased from 2.7% (95% CI 1.4-5.1) in 2015 to 12.6% (95% CI 8.7-18.0) in 2020 overall (p < .001 for trend), and separately in An Giang, Can Tho, and Hai Phong provinces but not in Ho Chi Minh City or Kien Giang. We calculated time-at-risk from first anal sex to first HIV-positive or last HIV-negative test to estimate HIV incidence. Estimated HIV incidence suggested increasing rates of seroconversion from 1.36 per 100 person-years experienced by participants in 2015 to 2.61 per 100 person-years among participants in 2020 (hazard ratio per year 1.13, 95% CI 1.08-1.18, p < .001). There was a statistically significant increase in HIV testing, STI testing, and receipt of free condoms over the period (p < .05 for trend), and a statistically significant decrease in amphetamine use (p = .043 for trend).

CONCLUSIONS: Despite prevention efforts and improvements in some risk indicators, consecutive cross-sectional sampling results provide evidence of increasing incidence of HIV and syphilis among MSM in Vietnam, especially outside the major cities. Aggressive HIV prevention and treatment services can be expanded while conducting deeper investigations into the causes of these increases.

PMID:37967472 | DOI:10.1177/09564624231214583

J Integr Complement Med. 2023 Nov 15. doi: 10.1089/jicm.2022.0785. Online ahead of print.

ABSTRACT

Introduction: Yoga is a mind-body practice often used to improve health. Systematic reviews (SRs) of randomized controlled trials on yoga for health are foundational to evidence-based yoga interventions and require rigorous and transparent methods, including preparation of a protocol (e.g., PROSPERO) and following SR reporting guidelines (e.g., Preferred Reporting Items for Systematic Reviews and Meta-Analyses [PRISMA]). Objective: To evaluate the availability of protocols and the completeness of reporting for SRs on yoga for health. Methods: We used a previously assembled database of SRs focused on the use of yoga for health. The authors independently extracted data on protocol availability, PROSPERO registration, and reporting for each PRISMA 2009 checklist item. Discrepancies were discussed or referred to a third author. We used Stata 10 software to produce descriptive statistics and tests for relationships between registration, reporting, and publication year, country, and journal type. Results: We included 147 reviews published between 2005 and 2019. The most common first author country was the United States or Germany (total 67/147; 46%), and the most common journal type was specialty journals (71/147; 48%). Most reviews (116/147; 79%) made no mention of a protocol or registration, and only 15/147 (10%) reviews were linked to an accessible protocol or registration. Most SRs published in 2010 or later mentioned or cited PRISMA (97/139; 70%), and individual PRISMA items were addressed between 10% and 100% of the time. PRISMA reporting improved; over time, but there was no relationship with country or journal type. Discussion: This study identifies a need for increased SR registration for yoga research. The assessment of PRISMA reporting did not evaluate the comprehensiveness with which each item was reported, and while trends are encouraging, there is likely room for improvement. We recommend registering all yoga SRs and following updated PRISMA and recent yoga-specific guidelines for reporting. This may increase transparency, minimize bias, and produce high-quality data to inform evidence-based yoga practices.

PMID:37967461 | DOI:10.1089/jicm.2022.0785

Europace. 2023 Nov 15:euad320. doi: 10.1093/europace/euad320. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Atrial fibrillation (AF) is associated with high risk of comorbidities and mortality. Our aim was to examine causal and predictive relationships between 4,137 serum proteins and incident AF in the prospective population-based AGES/Reykjavik study.

METHODS: The study included 4,765 participants, of whom 1,172 developed AF. Cox proportional hazards regression models were fitted for 4,137 baseline protein measurements adjusting for known risk factors. Protein associations were tested for replication in the Cardiovascular Health Study (CHS). Causal relationships were examined in a bidirectional, two-sample Mendelian randomization analysis. The time-dependent AUC-statistic was examined as protein levels and an AF-polygenic risk score (PRS) were added to clinical risk models.

RESULTS: The proteomic signature of incident AF consisted of 76 proteins, of which 63 (83%) were novel and 29 (38%) were replicated in CHS. The signature included both NT-proBNP-dependent (e.g., CHST15, ATP1B1, SVEP1) and independent components (e.g., ASPN, AKR1B, LAMA1/LAMB1/LAMC1). Nine causal candidates were identified (TAGLN, WARS, CHST15, CHMP3, COL15A1, DUSP13, MANBA, QSOX2, SRL). The reverse causal analysis suggested that most AF-associated proteins were affected by the genetic liability to AF. NT-proBNP improved the prediction of incident AF events close to baseline with further improvements gained by the AF-PRS at all timepoints.

CONCLUSION: The AF proteomic signature includes biologically relevant proteins, some of which may be causal. It mainly reflects an NT-proBNP-dependent consequence of the genetic liability to AF. NT-proBNP is a promising marker for incident AF in the short term, but risk assessment incorporating a PRS may improve long-term risk assessment.

PMID:37967346 | DOI:10.1093/europace/euad320

J Clin Oncol. 2023 Nov 15:JCO2301745. doi: 10.1200/JCO.23.01745. Online ahead of print.

ABSTRACT

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The primary analysis of the Early positron emission tomography (ePET) Response-Adapted Treatment in localized Hodgkin Lymphoma H10 Trial demonstrated that in ePET-negative patients, the risk of relapse increased when involved-node radiotherapy (INRT) was omitted and that in ePET-positive patients, switching from doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) to bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPesc) significantly improved 5-year progression-free survival (PFS). Here, we report the final results of a preplanned analysis at a 10-year follow-up. In the favorable (F) ePET-negative group, the 10-year PFS rates were 98.8% versus 85.4% (hazard ratio [HR], 13.2; 95% CI, 3.1 to 55.8; P value for noninferiority = .9735; difference test P < .0001) in favor of ABVD + INRT; in the unfavorable (U) ePET-negative group, the 10-year PFS rates were 91.4% and 86.5% (HR, 1.52; 95% CI, 0.84 to 2.75; P value for noninferiority = .8577; difference test P = .1628). In ePET-positive patients, the difference in terms of PFS between standard ABVD and intensified BEACOPPesc was no longer statistically significant (HR, 0.67; 95% CI, 0.37 to 1.20; P = .1777). In conclusion, the present long-term analysis confirms that in ePET-negative patients, the omission of INRT is associated with lower 10-year PFS. Instead, in ePET-positive patients, no significant difference between standard and experimental arms emerged although intensification with BEACOPPesc was safe, with no increase in late adverse events, namely, second malignancies.

PMID:37967311 | DOI:10.1200/JCO.23.01745

Prehosp Emerg Care. 2023 Nov 15:1-9. doi: 10.1080/10903127.2023.2283079. Online ahead of print.

ABSTRACT

OBJECTIVES: Emergency medical services workers, such as paramedics, provide important emergency care and may be exposed to potential carcinogens while working. Few studies have examined the risk of cancer among paramedics demonstrating an important knowledge gap in existing literature. This study aimed to investigate cancer risks among paramedics in a large cohort of Ontario workers.

METHODS: Paramedics were identified in the Occupational Disease Surveillance System (ODSS) from 1996 to 2019. The ODSS was established by linking lost-time worker’s compensation claimants to administrative health data, including the Ontario Cancer Registry to identify incident cases of cancer. Cox-proportional hazard models were used to calculate age and sex-adjusted hazard ratios and 95% confidence intervals to estimate risk of cancer among paramedics compared to all other workers in the ODSS.

RESULTS: A total of 7,240 paramedics were identified, with just over half of the paramedics identifying as male similar to the overall ODSS cohort. Paramedics had a statistically significant elevated risk of any cancer (HR 1.19, 95% CI 1.06-1.34), and elevated risks for melanoma (HR 2.18, 95% CI 1.46-3.26) and prostate cancer (HR 1.73, 95% CI 1.34-2.22). Paramedics had a statistically significant reduced risk for lung cancer (HR 0.48, 95% CI 0.28-0.83). Findings were similar to cancer risks identified in firefighters and police in the same cohort.

CONCLUSIONS: This study contributes valuable findings to understanding cancer risks among paramedics and further supports the existing evidence on the increased risk of cancer among emergency medical services workers. We have observed some similar results for firefighters and police, which may be explained by similar exposures, including vehicle exhaust, shiftwork, and intermittent solar radiation. This can lead to a better understanding of carcinogens and other exposures among paramedics and inform cancer prevention strategies.

PMID:37967276 | DOI:10.1080/10903127.2023.2283079

J Clin Endocrinol Metab. 2023 Nov 15:dgad670. doi: 10.1210/clinem/dgad670. Online ahead of print.

ABSTRACT

CONTEXT: Few meta-analyses regarding the incidence of endocrine immune related adverse effects (eirAEs) have been published and many trials were published thereafter.

OBJECTIVE: To assess the risk and incidence of eirAEs of any grade and grade 3-5 by immune checkpoint inhibitor (ICI) mono or combination-therapy in solid tumors current literature was updated in this comprehensive meta-analysis.

METHODS: An electronic search using PubMed/Medline, Embase and the Cochrane Library was performed. Randomized controlled studies (RCT) assessing eirAEs under ICI-mono or ICI-combination therapy were selected. Stata software version 17 was used for statistical analyses and risk of bias was evaluated by using Review Manager version 5.3.

RESULTS: 69 RCTs with 80 independent reports, involving 42,886 patients were included in the study. Meta-analysis revealed the following pooled estimates for the risk ratio and the incidence, respectively: for any grade hypothyroidism 7.81 (95% CI, 5.68-10.74, p< 0.0001) and 7.64% (95% CI, 6.23-9.17, p< 0.0001); significantly increased also for hyperthyroidism, hypophysitis/hypopituitarism and adrenal insufficiency; and for insulin-dependent diabetes mellitus 1.52 (95% CI, 1.07-2.18, p= 0.02), and 0.087% (95% CI, 0.019-0.189, p= 0.0006), respectively. Meta-regression showed that combination of ICIs (nivolumab plus ipilimumab and durvalumab plus tremelimumab, respectively) is an independent risk factor for any grade hypophysitis/hypopituitarism, and that ICI agent is an independent factor of risk for adrenal insufficiency, but that cancer type is not an independent risk factor for eirAEs.

CONCLUSION: We showed that risk, independent from cancer type, and incidence of eAEs are substantially increased under ICI therapy. Combination of ICIs is increasing the risk for eirAEs, in particular for hypophysitis/hypopituitarism.

PMID:37967245 | DOI:10.1210/clinem/dgad670

J Clin Endocrinol Metab. 2023 Nov 15:dgad664. doi: 10.1210/clinem/dgad664. Online ahead of print.

ABSTRACT

CONTEXT: Polycystic ovarian syndrome (PCOS) is a heterogeneous disorder, with disease loci identified from genome-wide association studies (GWAS) having largely unknown relationships to disease pathogenesis.

OBJECTIVE: To group PCOS GWAS loci into genetic clusters associated with disease pathophysiology.

DESIGN/SETTING/PATIENTS OR OTHER PARTICIPANTS: Cluster analysis was performed for 60 PCOS-associated genetic variants and 49 traits using GWAS summary statistics. Cluster-specific PCOS partitioned polygenic scores (pPS) were generated and tested for association with clinical phenotypes in the Mass General Brigham Biobank (MGBB, N=62,252). Associations with clinical outcomes (type 2 diabetes/T2D, coronary artery disease/CAD and female reproductive traits) were assessed using both GWAS-based pPS (DIAMANTE, N=898,130, CARDIOGRAM/UKBB, N=547,261) and individual-level pPS in MGBB.

INTERVENTIONS/MAIN OUTCOME MEASURES/RESULTS: Four PCOS genetic clusters were identified with top loci indicated as following: (i) Cluster 1/Obesity/insulin resistance (FTO); (ii) Cluster 2/Hormonal/menstrual cycle changes (FSHB); (iii) Cluster 3/Blood markers/inflammation (ATXN2/SH2B3); (iv) Cluster 4/Metabolic changes (MAF, SLC38A11). Cluster pPS were associated with distinct clinical traits: Cluster 1 with increased body mass index (BMI; p=6.6×10-29); Cluster 2 with increased age of menarche (p= p=1.5×10-4); Cluster 3 with multiple decreased blood markers, including mean platelet volume (MPV; p=3.1 x10-5); and Cluster 4 with increased ALP (p=0.007). PCOS genetic clusters GWAS-pPS’s were also associated with disease outcomes: Cluster 1 pPS with increased T2D (OR 1.07; p=7.3×10-50), with replication in MGBB all participants (OR 1.09, p=2.7×10-7) and females only (OR 1.11, 4.8×10-5).

CONCLUSIONS: Distinct genetic backgrounds in individuals with PCOS may underlie clinical heterogeneity and disease outcomes.

PMID:37967238 | DOI:10.1210/clinem/dgad664

Proc Natl Acad Sci U S A. 2023 Nov 21;120(47):e2317870120. doi: 10.1073/pnas.2317870120. Epub 2023 Nov 15.

NO ABSTRACT

PMID:37967219 | DOI:10.1073/pnas.2317870120

Ann Med. 2023;55(2):2274511. doi: 10.1080/07853890.2023.2274511. Epub 2023 Nov 15.

ABSTRACT

INTRODUCTION: At present, there are some randomized controlled trials (RCTs) of oral small molecule drugs. The purpose of this study was to evaluate the efficacy and safety of oral small molecule drug treatment for COVID-19.

METHODS: RCTs were identified through systematic searches of PubMed, Embase, and Cochrane Central Register of Controlled Trials through 1 April 2023. A total of nine RCTs were included, including 30,970 COVID-19 patients comparing five treatments (azvudine, molnupiravir, paxlovid, VV116, and placebo). The Cochrane risk of bias tool for randomized trials (RoB) was used to assess the bias risk of the included studies. The direct and indirect evidence were combined using a Bayesian network meta-analysis (PROSPERO Code No: CRD42023397837).

RESULTS: Direct analysis showed that paxlovid was associated with a reduced risk of mortality (odds ratio [OR] 0.12, 95% confidence interval [CI] 0.06-0.25) and hospitalization (OR = 0.04, 95% CI: 0.00-0.67) compared with placebo. Network meta-analysis showed that paxlovid had the highest probability of being the best management strategy in patients with COVID-19, reducing mortality (OR = 0.11, 95% CI: 0.01-1.99; surface under the cumulative ranking curve [SUCRA]: 0.77) and hospitalization (OR = 0.06, 95% CI: 0.00-1.03; SUCRA: 0.95). For prespecified safety outcomes, SUCRA values ranked VV116 (OR = 0.09, 95% CI: 0.00-2.07: SUCRA 0.86) as the most beneficial intervention for the prevention of serious adverse events.

CONCLUSIONS: When compared to other antiviral medications, paxlovid can reduce the mortality and hospitalization of COVID-19 patients.

PMID:37967171 | DOI:10.1080/07853890.2023.2274511

PLoS One. 2023 Nov 15;18(11):e0294441. doi: 10.1371/journal.pone.0294441. eCollection 2023.

ABSTRACT

OBJECTIVE: Crohn’s disease (CD) can be associated with a wide range of extraintestinal manifestations (EIMs), including neurological ones. Published studies differ in their conclusions about the epidemiology and etiopathogenesis of neurological EIMs. The aims of this study were to demonstrate the presence and find risk factors of peripheral (somatic and autonomic) neuropathy patients with severe CD on anti-TNFα biological therapy.

MATERIAL AND METHODS: A clinical examination focusing on detection of peripheral sensor-motor nervous dysfunction (including Sudoscan) and examination of autonomic nervous system dysfunction (using Ewing´s battery tests and spectral analysis) together with laboratory tests and collection of demographic data followed by administration of questionnaires were performed on a total of 30 neurologically asymptomatic outpatients with severe CD on anti-TNFα biological therapy.

RESULTS: Peripheral sensor-motor nervous function via clinical neurological examination was pathological in 36.7% and Sudoscan in 33.3% of cases. Statistically significant associations between vibration perception test and age, CD and biological therapy duration, body mass index and Crohn’s Disease Activity Index were proved while statistically significant associations between temperature perception test and age and BMI were proved as well. Additionally, a decrease of total protein in a patient´s serum below the physiological cut-off in the 6 months prior to measurement was associated with a pathological result of a Sudoscan. Cardiovascular autonomic neuropathy based on Ewing´s battery tests was present in 56.7% of patients, no statistically significant risk factors were found. Our peripheral neuropathy questionnaire correlated with the results of the Sudoscan test and some tests of the clinical examination of peripheral sensor-motor nervous function (discriminatory contact perception test, temperature perception test).

CONCLUSIONS: This study demonstrated a relatively high prevalence of peripheral (especially autonomic) neuropathy and verified some risk factors for the development of peripheral somatic neuropathy in asymptomatic patients with severe form of CD on anti-TNFα biological therapy.

PMID:37967139 | DOI:10.1371/journal.pone.0294441