Nevin Manimala

Acta Otorhinolaryngol Ital. 2023 Jun;43(3):183-188. doi: 10.14639/0392-100X-N2288.

ABSTRACT

OBJECTIVE: With the increased prevalence of incidental thyroid cancer, determining the predictors of thyroid malignancy has become a source of debate. This study aimed to determine the impact of thyroid stimulating hormone (TSH) levels on rates of thyroid cancer in euthyroid patients.

METHODS: A retrospective study included 421 patients who underwent thyroidectomy at a tertiary hospital between 2016 and 2020. Patients’ demographics, history of cancer, pre-operative workup and final histology reports were obtained. The study sample was divided into two groups based on the final histopathology (benign vs malignant). The two groups were compared using the appropriate statistical tests to determine the predictors of thyroid cancer in euthyroid patients.

RESULTS: TSH levels were significantly higher in patients with malignant nodules compared to those with benign nodules (1.94 vs 1.62, p = 0.002). It was 1.54 times more likely for thyroid nodules to be malignant when TSH levels were higher (p = 0.038). Meanwhile, larger nodules (> 4 cm) were significantly more prevalent in benign nodules (43.1%) than in malignant nodules (21.1%). Larger nodules decreased the possibility of thyroid cancer by 24% (OR = 0.760, p-value = 0.004).

CONCLUSIONS: High TSH levels in euthyroid patients were significantly correlated with the risk of thyroid malignancy. In addition, as Bethesda category proceeded toward malignancy, TSH levels increased. High TSH levels and small nodule diameters can be used as additional parameters in predicting thyroid cancer in euthyroid patients.

PMID:37204842 | DOI:10.14639/0392-100X-N2288

J Med Internet Res. 2023 May 19;25:e42729. doi: 10.2196/42729.

ABSTRACT

BACKGROUND: To date, non-occupational postexposure prophylaxis (PEP) has been widely accepted as a safe and effective intervention for HIV in many countries, yet it remains an underutilized prevention strategy in China. Evidence indicated a high demand for PEP among Chinese men who have sex with men, but the uptake and access to PEP service remain limited. In an era of rapid development of web-based technology, online medical platforms in China hold great promise in facilitating PEP provision and delivery by addressing problems such as accessibility, convenience, privacy protection, and antidiscrimination by integrating online and offline resources. However, there is a paucity of data concerning the uptake and outcomes of online PEP in China.

OBJECTIVE: The aim of this study is to explore online PEP service provision and understand PEP uptake and outcome through a web-based cross-sectional study.

METHODS: From January 2020 to June 2021, we conducted a retrospective web-based survey among those seeking online PEP services via the internet medical platform “HeHealth” using a structured questionnaire. Participants were surveyed on sociodemographic characteristics, sexual and drug-related behaviors, history of preexposure prophylaxis (PrEP) usage, and PEP uptake. Statistical analysis included descriptive analysis, chi-square test, and multivariable logistic regression. P values <.05 were deemed statistically significant.

RESULTS: No HIV seroconversions were observed among 539 PEP users. Our sample demonstrated that most participants seeking online PEP services were gay (397/539, 73.7%), single (470/539, 87.2%), having an education of more than 12 years (493/539, 91.5%), and with an average monthly income of 7000 RMB (1 RMB=US $0.14) or more (274/539, 50.8%). Sexual exposures accounted for 86.8% (468/539) of the cases, with anal sex being the most common indication (389/539, 72.2%) for seeking PEP use. Among 539 participants, 60.7% (327/539) sought online PEP for relatively low-risk exposures, whereas 39.3% (212/539) were considered high-risk exposures. Nearly all (537/539, 99.6%) initiated PEP within 72 hours and 68.6% (370/539) within 24 hours of exposure. All users (539/539) were prescribed a 3-drug regimen, with most comprising 3TC/TDF+DTG (lamivudine, tenofovir disoproxil fumarate, and dolutegravir; 293/539, 54.4%), followed by FTC/TDF+DTG (emtricitabine, tenofovir disoproxil fumarate, and dolutegravir; 158/539, 29.3%). The adjusted model showed that greater odds of PrEP usage were associated with an age of 35 years or older versus the age group of 25-34 years (adjusted odds ratio [AOR] 2.04, 95% CI 1.24-3.37), having an education of 17 years or more versus an education of 12 years or less (AOR 3.14, 95% CI 1.29-7.62), average monthly income of 20,000 RMB or more versus less than 3000 RMB (AOR 2.60, 95% CI 1.09-6.23), and having high-risk sexual behavior during PEP treatment (AOR 2.20, 95% CI 1.05, 3.69).

CONCLUSIONS: The 0% infection rate in this study demonstrated that online PEP could be a valuable risk-reduction option to improve HIV prevention service within China. However, further research is needed to better facilitate PrEP transition among online PEP users.

PMID:37204828 | DOI:10.2196/42729

JAMA Netw Open. 2023 May 1;6(5):e2314336. doi: 10.1001/jamanetworkopen.2023.14336.

ABSTRACT

IMPORTANCE: The BCG vaccine-used worldwide to prevent tuberculosis-confers multiple nonspecific beneficial effects, and intravesical BCG vaccine is currently the recommended treatment for non-muscle-invasive bladder cancer (NMIBC). Moreover, BCG vaccine has been hypothesized to reduce the risk of Alzheimer disease and related dementias (ADRD), but previous studies have been limited by sample size, study design, or analyses.

OBJECTIVE: To evaluate whether intravesical BCG vaccine exposure is associated with a decreased incidence of ADRD in a cohort of patients with NMIBC while accounting for death as a competing event.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was performed in patients aged 50 years or older initially diagnosed with NMIBC between May 28, 1987, and May 6, 2021, treated within the Mass General Brigham health care system. The study included a 15-year follow-up of individuals (BCG vaccine treated or controls) whose condition did not clinically progress to muscle-invasive cancer within 8 weeks and did not have an ADRD diagnosis within the first year after the NMIBC diagnosis. Data analysis was conducted from April 18, 2021, to March 28, 2023.

MAIN OUTCOMES AND MEASURES: The main outcome was time to ADRD onset identified using diagnosis codes and medications. Cause-specific hazard ratios (HRs) were estimated using Cox proportional hazards regression after adjusting for confounders (age, sex, and Charlson Comorbidity Index) using inverse probability scores weighting.

RESULTS: In this cohort study including 6467 individuals initially diagnosed with NMIBC between 1987 and 2021, 3388 patients underwent BCG vaccine treatment (mean [SD] age, 69.89 [9.28] years; 2605 [76.9%] men) and 3079 served as controls (mean [SD] age, 70.73 [10.00] years; 2176 [70.7%] men). Treatment with BCG vaccine was associated with a lower rate of ADRD (HR, 0.80; 95% CI, 0.69-0.99), with an even lower rate of ADRD in patients aged 70 years or older at the time of BCG vaccine treatment (HR, 0.74; 95% CI, 0.60-0.91). In competing risks analysis, BCG vaccine was associated with a lower risk of ADRD (5-year risk difference, -0.011; 95% CI, -0.019 to -0.003) and a decreased risk of death in patients without an earlier diagnosis of ADRD (5-year risk difference, -0.056; 95% CI, -0.075 to -0.037).

CONCLUSIONS AND RELEVANCE: In this study, BCG vaccine was associated with a significantly lower rate and risk of ADRD in a cohort of patients with bladder cancer when accounting for death as a competing event. However, the risk differences varied with time.

PMID:37204792 | DOI:10.1001/jamanetworkopen.2023.14336

JAMA Netw Open. 2023 May 1;6(5):e2314443. doi: 10.1001/jamanetworkopen.2023.14443.

ABSTRACT

IMPORTANCE: Intensive vs standard treatment to lower systolic blood pressure (SBP) reduces risk of mild cognitive impairment (MCI) or dementia; however, the magnitude of cognitive benefit likely varies among patients.

OBJECTIVE: To estimate the magnitude of cognitive benefit of intensive vs standard systolic BP (SBP) treatment.

DESIGN, SETTING, AND PARTICIPANTS: In this ad hoc secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), 9361 randomized clinical trial participants 50 years or older with high cardiovascular risk but without a history of diabetes, stroke, or dementia were followed up. The SPRINT trial was conducted between November 1, 2010, and August 31, 2016, and the present analysis was completed on October 31, 2022.

INTERVENTION: Systolic blood pressure treatment to an intensive (<120 mm Hg) vs standard (<140 mm Hg) target.

MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of adjudicated probable dementia or amnestic MCI.

RESULTS: A total of 7918 SPRINT participants were included in the analysis; 3989 were in the intensive treatment group (mean [SD] age, 67.9 [9.2] years; 2570 [64.4%] men; 1212 [30.4%] non-Hispanic Black) and 3929 were in the standard treatment group (mean [SD] age, 67.9 [9.4] years; 2570 [65.4%] men; 1249 [31.8%] non-Hispanic Black). Over a median follow-up of 4.13 (IQR, 3.50-5.88) years, there were 765 and 828 primary outcome events in the intensive treatment group and standard treatment group, respectively. Older age (hazard ratio [HR] per 1 SD, 1.87 [95% CI, 1.78-1.96]), Medicare enrollment (HR per 1 SD, 1.42 [95% CI, 1.35-1.49]), and higher baseline serum creatinine level (HR per 1 SD, 1.24 [95% CI, 1.19-1.29]) were associated with higher risk of the primary outcome, while better baseline cognitive functioning (HR per 1 SD, 0.43 [95% CI, 0.41-0.44]) and active employment status (HR per 1 SD, 0.44 [95% CI, 0.42-0.46]) were associated with lower risk of the primary outcome. Risk of the primary outcome by treatment goal was estimated accurately based on similar projected and observed absolute risk differences (C statistic = 0.79). Higher baseline risk for the primary outcome was associated with greater benefit (ie, larger absolute reduction of probable dementia or amnestic MCI) of intensive vs standard treatment across the full range of estimated baseline risk.

CONCLUSIONS AND RELEVANCE: In this secondary analysis of the SPRINT trial, participants with higher baseline projected risk of probable dementia or amnestic MCI gained greater absolute cognitive benefit from intensive vs standard SBP treatment in a monotonic fashion.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01206062.

PMID:37204788 | DOI:10.1001/jamanetworkopen.2023.14443

Int Health. 2023 May 19:ihad037. doi: 10.1093/inthealth/ihad037. Online ahead of print.

ABSTRACT

Giardia duodenalis is one of the major causes of diarrhea among children. We performed a systematic review and meta-analysis to assess the prevalence of G. duodenalis and associated risk factors among Asian children. We searched online databases (PubMed, Scopus and Web of Science) and Google Scholar search engine for studies published from 1 January 2000 to 15 March 2022 that measured the prevalence of G. duodenalis among Asian children. Accordingly, the pooled prevalence and 95% CIs were estimated using a random-effects meta-analysis model for the included studies. A total of 182 articles from 22 Asian countries met the inclusion criteria. The pooled prevalence of G. duodenalis infection among Asian children was estimated as 15.1% (95% CI 14.1 to 16%). The highest and lowest pooled prevalence values of G. duodenalis infection were estimated for Tajikistan and China as 26.4% (95% CI 22.9 to 30%) and 0.6% (95% CI 0.001 to 1.02%), respectively. The infection had a higher prevalence in males than in females (OR=1.24; 95% CI 1.16 to 1.31; p<0.001), which was statistically significant. Giardiasis is common among Asian children, hence, a prevention and control scheme of this protozoan in children should be considered by health officials and health policymakers, especially in Asian countries where the prevalence is highest.

PMID:37204774 | DOI:10.1093/inthealth/ihad037

Head Neck. 2023 May 19. doi: 10.1002/hed.27404. Online ahead of print.

ABSTRACT

BACKGROUND: A nomogram that incorporates tumor response at mid-radiotherapy (mid-RT) to predict the prognosis of locoregionally advanced nasopharyngeal carcinoma (LA-NPC) has not been established.

METHODS: This study retrospectively reviewed 583 patients with LA-NPC who underwent magnetic resonance imaging scans at mid-RT (the fourth week of RT) between 2015 and 2019.

RESULTS: Primary tumor (PT) response at mid-RT was found to predict disease-free survival (DFS) and overall survival (OS). Independent factors from multivariable analysis to predict DFS and OS were assembled into nomograms with (nomograms A_mid-RT and B_mid-RT ) or without (nomograms A_baseline and B_baseline ) PT response. Internal validation revealed good performance of these nomograms in discrimination: C-statistics = 0.761 for nomogram A_mid-RT and 0.809 for nomogram B_mid-RT , which showed better discrimination performance than (C-statistics: 0.755) nomogram A_baseline and (C-statistics: 0.798) nomogram B_baseline (Z-statistic = 2.476, p < 0.05; Z-statistic = 1.971, p < 0.05).

CONCLUSION: The nomograms based on PT response at mid-RT showed favorable predictive accuracy for DFS and OS in patients with LA-NPC.

PMID:37204765 | DOI:10.1002/hed.27404

J Genet Eng Biotechnol. 2023 May 19;21(1):64. doi: 10.1186/s43141-023-00522-9.

ABSTRACT

BACKGROUND: Arsenic, a ubiquitous toxic metalloid, is a threat to the survival of all living organisms. Bioaccumulation of arsenic interferes with the normal physiological pathway. To overcome arsenic toxicity, organisms have developed arsenite methyltransferase enzyme, which methylates inorganic arsenite to organic arsenic MMA (III) in the presence of S-adenosylmethionine (SAM). Bacteria-derived arsM might be horizontally transported to different domains of life as arsM or as3mt (animal ortholog). A systematic study on the functional diversity of arsenite methyltransferase from various sources will be used in arsenic bioremediation.

RESULTS: Several arsenite methyltransferase protein sequences of bacteria, fungi, fishes, birds, and mammals were retrieved from the UniProt database. In silico physicochemical studies confirmed the acidic, hydrophilic, and thermostable nature of these enzymes. Interkingdom relationships were revealed by performing phylogenetic analysis. Homology modeling was performed by SWISS-MODEL, and that was validated through SAVES-v.6.0. QMEAN values ranged from – 0.93 to – 1.30, ERRAT score (83-96), PROCHECK (88-92%), and other parameters suggested models are statistically significant. MOTIF and PrankWeb discovered several functional motifs and active pockets within the proteins respectively. The STRING database showed protein-protein interaction networks.

CONCLUSION: All of our in silico studies confirmed the fact that arsenite methyltransferase is a cytosolic stable enzyme with conserved sequences over a wide range of organisms. Thus, because of its stable and ubiquitous nature, arsenite methyltransferase could be employed in arsenic bioremediation.

PMID:37204693 | DOI:10.1186/s43141-023-00522-9

Int Urol Nephrol. 2023 May 19. doi: 10.1007/s11255-023-03584-3. Online ahead of print.

ABSTRACT

INTRODUCTION: To decrease complication rate, we developed a novel MG needle for kidney puncture consisting of a pointed cannula, an atraumatic mandrin-bulb and a spring mechanism pushing the mandrin-bulb forward.

AIM OF THE STUDY: To assess efficacy and safety of kidney puncture during percutaneous nephrolithotomy (PCNL) using a novel less-traumatic MG needle within a clinical trial.

MATERIALS AND METHODS: We conducted a prospective randomized single-center study. In the experimental group, kidney puncture was performed with a novel MG needle while in the control group, standard Trocar or Chiba puncture needles were used.

PRIMARY ENDPOINT: hemoglobin drop.

RESULTS: A total of 67 patients were enrolled. Patients who underwent standard puncture (n = 33) had higher hemoglobin drop in the early postoperative period (p = 0.024). Although there was no statistical difference in overall complication rate between the two groups (p = 0.351), two severe Clavien-Dindo IIIa complications with urinoma occurred in patients from the control group.

CONCLUSION: Less-traumatic needle for kidney puncture may reduce hemoglobin drop and prevent the development of severe complications. At the same time, in terms of stone-free rate (SFR), the efficacy of PCNL remains the same regardless of the needle used for renal access.

PMID:37204679 | DOI:10.1007/s11255-023-03584-3

BioDrugs. 2023 May 19. doi: 10.1007/s40259-023-00600-x. Online ahead of print.

ABSTRACT

BACKGROUND: The US Food and Drug Administration (FDA) interchangeability guidelines state that the primary endpoint in a switching study should assess the impact of switching between the proposed interchangeable product and the reference product on clinical pharmacokinetics (PK) and pharmacodynamics (if available), as these assessments are generally sensitive to changes in immunogenicity and/or exposure that may arise due to switching. In addition, interchangeability designation requires no clinically meaningful difference in safety and efficacy of switching between the biosimilar and reference, compared with when using the reference product alone.

OBJECTIVES: The aim of this study was to investigate the PK, immunogenicity, efficacy, and safety in participants undergoing repeated switches between Humira^® and AVT02 as part of a global interchangeable development program.

METHODS: This multicenter, randomized, double-blind, parallel-group study in patients with moderate-to-severe plaque psoriasis comprises three parts: lead-in period (weeks 1-12), switching module (weeks 12-28), and the optional extension phase (weeks 28-52). Following the lead-in period during which all participants received the reference product (80 mg in week 1, followed by 40 mg every other week), participants with a clinical response of ≥ 75% improvement in the Psoriasis Area and Severity Index (PASI75) were randomized 1:1 to receive AVT02 alternating with the reference product (switching arm) or reference product only (non-switching arm). At week 28, participants who were PASI50 responders could opt to take part in an open-label extension phase receiving AVT02 up to week 50, with an end of study visit at week 52. PK, safety, immunogenicity, and efficacy were evaluated at various timepoints throughout the study for both switching and non-switching arms.

RESULTS: In total, 550 participants were randomized to switching (277) and non-switching arms (273). The switching versus non-switching arithmetic least square means ratio [90% confidence intervals (CIs)] was 101.7% (91.4-112.0%) for the area under the concentration-time curve over the dosing interval from weeks 26-28 (AUC_{tau, W26-28}) and 108.1% (98.3-117.9%) for maximum concentration over the dosing interval from weeks 26-28 (C_{max, W26-28}). The 90% CIs for the switching versus non-switching arithmetic means ratio for primary endpoints AUC_{tau, W26-28} and C_{max, W26-28} were within the prespecified limits of 80-125%, demonstrating comparable PK profiles between groups. In addition, the PASI, Dermatology Life Quality Index, and static Physician’s Global Assessment efficacy scores were highly similar for both treatment groups. There were no clinically meaningful differences between the immunogenicity and safety assessments of repeated switching between AVT02 and the reference product, versus the reference product alone.

CONCLUSIONS: This study demonstrated that the risk, in terms of safety or diminished efficacy of switching between the biosimilar and the reference product, is not greater than the risk of using the reference product alone, as required by the FDA for interchangeability designation. Beyond the scope of interchangeability, a consistent long-term safety and immunogenicity profile, with no impact on the trough levels up to 52 weeks, was established.

CLINICAL TRIAL REGISTRATION: NCT04453137; date of registration: 1 July 2020.

PMID:37204631 | DOI:10.1007/s40259-023-00600-x

Sports Med. 2023 May 19. doi: 10.1007/s40279-023-01836-x. Online ahead of print.

ABSTRACT

Blood-based biomarkers can provide an objective individualized measure of training load, recovery, and health status in order to reduce injury risk and maximize performance. Despite enormous potentials, especially owing to currently evolving technology, such as point-of-care testing, and advantages, in terms of objectivity and non-interference with the training process, there are several pitfalls in the use and interpretation of biomarkers. Confounding variables such as preanalytical conditions, inter-individual differences, or an individual chronic workload can lead to variance in resting levels. In addition, statistical considerations such as the detection of meaningful minimal changes are often neglected. The lack of generally applicable and individual reference levels further complicates the interpretation of level changes and thus load management via biomarkers. Here, the potentials and pitfalls of blood-based biomarkers are described, followed by an overview of established biomarkers currently used to support workload management. Creatine kinase is discussed in terms of its evidence for workload management to illustrate the limited applicability of established markers for workload management to date. We conclude with recommendations for best practices in the use and interpretation of biomarkers in a sport-specific context.

PMID:37204619 | DOI:10.1007/s40279-023-01836-x