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Nevin Manimala Statistics

A network analysis of mechanisms of change during exposures over the course of intensive OCD treatment

J Affect Disord. 2024 Mar 18:S0165-0327(24)00512-3. doi: 10.1016/j.jad.2024.03.089. Online ahead of print.

ABSTRACT

Exposure and response prevention (ERP) is an evidence-based treatment for obsessive-compulsive disorder (OCD). Theories for how it works vary in their emphasis on active mechanisms of change. The current study aimed to clarify mechanisms of change in ERP for OCD using network analysis, comparing ERP networks at the start and end of intensive treatment (partial hospital and residential). In our sample of 182 patients, the most central node in both networks was engagement with exposure, which was consistently related to greater understanding of ERP rationale, higher willingness, and less ritualization, accounting for all other variables in the network. There were no significant differences in networks between the start and end of treatment. These results suggest that nonspecific parameters like facilitating engagement in exposures without ritualizing and providing a clear rationale to clients may be key to effective treatment. As such, it may be useful for clinicians to spend adequate time underscoring the need to eliminate rituals to fully engage in exposure tasks and explaining the rationale for ERP prior to doing exposures, regardless of theoretical orientation. Nonetheless, findings represent group-level statistics and more fine-grained idiographic analyses may reveal individual-level differences with respect to central mechanisms of change. Other limitations include demographic homogeneity of our sample.

PMID:38508457 | DOI:10.1016/j.jad.2024.03.089

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Inter- and intrapopulation differences in the association between physical multimorbidity and depressive symptoms

J Affect Disord. 2024 Mar 18:S0165-0327(24)00513-5. doi: 10.1016/j.jad.2024.03.090. Online ahead of print.

ABSTRACT

BACKGROUND: The association between physical multimorbidity and depression differs by populations. However, no direct inter- or intrapopulation comparison of the association has been conducted. Thus, this study aims to estimate the association in China and the United States and reveal inter- and intrapopulation differences in the association.

METHODS: Middle-aged and older adults from the China Health and Retirement Longitudinal Study and the Health and Retirement Study were included. Physical multimorbidity was defined as the simultaneous presence of two or more chronic physical conditions and depressive symptoms was measured by the Center for Epidemiologic Studies Depression Scale. Generalized estimating equation model and stratification multilevel method were the main statistical models.

RESULTS: The presence of physical multimorbidity was associated with a higher risk of depression in both China (RR = 1.360 [95 % CI: 1.325-1.395]) and the US (RR = 1.613 [95 % CI: 1.529-1.701]). For individuals at a low risk of multimorbidity, multimorbidity was associated with 47.4 % (95 % CI: 1.377-1.579) and 71.1 % (95 % CI: 1.412-2.074) increases in the likelihood of depression in China and the US. The effect size was smaller for individuals at a moderate or high risk. However, the cross-national differences were greater for those with a high risk of multimorbidity.

LIMITATIONS: The self-report measures, attribution bias.

CONCLUSIONS: Compared to Chinese adults, the presence of physical multimorbidity led to an additional increase in depressive symptoms for American counterparts. The association was stronger for individuals at a low risk of multimorbidity, but cross-national differences were observed mostly among individuals at a high risk.

PMID:38508455 | DOI:10.1016/j.jad.2024.03.090

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Nevin Manimala Statistics

Monthly Analysis of Infant Mortality Rate in Portugal during the COVID-19 Pandemic: Insights from Continuous Monitoring

Acta Med Port. 2024 Mar 20. doi: 10.20344/amp.19642. Online ahead of print.

ABSTRACT

INTRODUCTION: The COVID-19 pandemic significantly impacted global public health. Infant mortality rate (IMR), a vital statistic and key indicator of a population’s overall health, is essential for developing effective health prevention programs. Existing evidence primarily indicates a decrease in IMR during the COVID-19 pandemic. We conducted a national-level analysis to calculate IMR and describe its course over the years (from 2016 until 2022), using a month-by-month analysis.

METHODS: Data on the number of deaths under one year of age was collected from the Portuguese E-Death Certification System (SICO), and data on the number of monthly live births was obtained from Statistics Portugal. The IMR was calculated per month, considering the previous 12 months’ cumulative number of deaths under one year of age and the number of live births.

RESULTS: In Portugal, the IMR decreased before and during the COVID-19 pandemic. The lowest values were observed in September and October 2021 (2.15 and 2.14 per 1000 live births, respectively). The IMR remained below the threshold of three deaths per 1000 live births during the pandemic’s critical period.

CONCLUSION: Portugal has achieved remarkable progress in reducing its IMR over the last 60 years. The country recorded its lowest-ever IMR values during the COVID-19 pandemic. Further studies are needed to fully understand the observed trends.

PMID:38507776 | DOI:10.20344/amp.19642

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Ribociclib plus Endocrine Therapy in Early Breast Cancer

N Engl J Med. 2024 Mar 21;390(12):1080-1091. doi: 10.1056/NEJMoa2305488.

ABSTRACT

BACKGROUND: Ribociclib has been shown to have a significant overall survival benefit in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. Whether this benefit in advanced breast cancer extends to early breast cancer is unclear.

METHODS: In this international, open-label, randomized, phase 3 trial, we randomly assigned patients with HR-positive, HER2-negative early breast cancer in a 1:1 ratio to receive ribociclib (at a dose of 400 mg per day for 3 weeks, followed by 1 week off, for 3 years) plus a nonsteroidal aromatase inhibitor (NSAI; letrozole at a dose of 2.5 mg per day or anastrozole at a dose of 1 mg per day for ≥5 years) or an NSAI alone. Premenopausal women and men also received goserelin every 28 days. Eligible patients had anatomical stage II or III breast cancer. Here we report the results of a prespecified interim analysis of invasive disease-free survival, the primary end point; other efficacy and safety results are also reported. Invasive disease-free survival was evaluated with the use of the Kaplan-Meier method. The statistical comparison was made with the use of a stratified log-rank test, with a protocol-specified stopping boundary of a one-sided P-value threshold of 0.0128 for superior efficacy.

RESULTS: As of the data-cutoff date for this prespecified interim analysis (January 11, 2023), a total of 426 patients had had invasive disease, recurrence, or death. A significant invasive disease-free survival benefit was seen with ribociclib plus an NSAI as compared with an NSAI alone. At 3 years, invasive disease-free survival was 90.4% with ribociclib plus an NSAI and 87.1% with an NSAI alone (hazard ratio for invasive disease, recurrence, or death, 0.75; 95% confidence interval, 0.62 to 0.91; P = 0.003). Secondary end points – distant disease-free survival and recurrence-free survival – also favored ribociclib plus an NSAI. The 3-year regimen of ribociclib at a 400-mg starting dose plus an NSAI was not associated with any new safety signals.

CONCLUSIONS: Ribociclib plus an NSAI significantly improved invasive disease-free survival among patients with HR-positive, HER2-negative stage II or III early breast cancer. (Funded by Novartis; NATALEE ClinicalTrials.gov number, NCT03701334.).

PMID:38507751 | DOI:10.1056/NEJMoa2305488

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Exploring Options for Proximity-Dependent Biotinylation Experiments: Comparative Analysis of Labeling Enzymes and Affinity Purification Resins

J Proteome Res. 2024 Mar 20. doi: 10.1021/acs.jproteome.3c00908. Online ahead of print.

ABSTRACT

Proximity-dependent biotinylation (PDB) techniques provide information about the molecular neighborhood of a protein of interest, yielding insights into its function and localization. Here, we assessed how different labeling enzymes and streptavidin resins influence PDB results. We compared the high-confidence interactors of the DNA/RNA-binding protein transactive response DNA-binding protein 43 kDa (TDP-43) identified using either miniTurbo (biotin ligase) or APEX2 (peroxidase) enzymes. We also evaluated two commercial affinity resins for purification of biotinylated proteins: conventional streptavidin sepharose versus a new trypsin-resistant streptavidin conjugated to magnetic resin, which significantly reduces the level of contamination by streptavidin peptides following on-bead trypsin digestion. Downstream analyses involved liquid chromatography coupled to mass spectrometry in data-dependent acquisition mode, database searching, and statistical analysis of high-confidence interactors using SAINTexpress. The APEX2-TDP-43 experiment identified more interactors than miniTurbo-TDP-43, although miniTurbo provided greater overlap with previously documented TDP-43 interactors. Purifications on sepharose resin yielded more interactors than magnetic resin in small-scale experiments using a range of magnetic resin volumes. We suggest that resin-specific background protein binding profiles and different lysate-to-resin ratios cumulatively affect the distributions of prey protein abundance in experimental and control samples, which impact statistical confidence scores. Overall, we highlight key experimental variables to consider for the empirical optimization of PDB experiments.

PMID:38507741 | DOI:10.1021/acs.jproteome.3c00908

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Differences in socio-demographics status, risk behaviours, healthcare uptake and HIV/ sexually transmitted infections (STIs) between brothel-based and street-based female sex workers in Yunnan, China

Int J STD AIDS. 2024 Mar 20:9564624241239480. doi: 10.1177/09564624241239480. Online ahead of print.

ABSTRACT

BACKGROUND: Heterosexual contact is the primary mode of HIV transmission in China and commercial sex is thought to play a crucial role in China’s epidemic. Female sex workers (FSWs) in China tend to be either brothel-based (BSWs) or street-based (SSWs), but few studies have investigated the differences between these important segments of this difficult-to-reach, high-risk population. Our aim was to explore the differences between SSWs and BSWs in terms of socio-demographic characteristics, sexual and risky practices, HIV/STI-related knowledge, health services, HIV/STI prevalence and other aspects.

METHODS: A cross-sectional survey was conducted in Yunnan Province of China in partnership with a local FSW-friendly non-governmental organization. Face-to-face interviews using a structured questionnaire were conducted to collect data on socio-demographic characteristics, sex work history, sexual behaviours, HIV/STI-related knowledge, HIV testing history, and healthcare services uptake. Blood samples were taken for HIV and syphilis testing, and urine samples for gonorrhea and chlamydia testing. Descriptive statistics were used to evaluate differences between SSWs and BSWs.

RESULTS: A total of 185 BSWs and 129 SSWs were included in the study. SSWs were older and less educated, had more dependents and more clients, lower condom use and accessed fewer healthcare services. Moreover, 37.2% of SSWs and 24.9% of BSWs were found to have HIV/STI infection. Unfortunately, the awareness related to STIs was relatively low in both groups, especially SSWs.

CONCLUSIONS: Our study provides evidence that confirms the disproportionately high vulnerability of SSWs to HIV and other STIs, underscoring the urgent need for the Chinese health and public health sectors to prioritize outreach to SSWs. Awareness and educational programs, condom distribution, testing and health check-ups should be included in a comprehensive strategy for HIV/STI prevention in this high-risk population.

PMID:38507707 | DOI:10.1177/09564624241239480

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Validation of a Method for Surveillance of Nanoparticles in Mussels Using Single Particle Inductively Coupled Plasma Mass Spectrometry

J AOAC Int. 2024 Mar 20:qsae024. doi: 10.1093/jaoacint/qsae024. Online ahead of print.

ABSTRACT

BACKGROUND: Determining the concentration of nanoparticles in marine organisms is important for evaluating their environmental impact and to assess potential food safety risks to human health.

OBJECTIVE: The current work aimed at developing an in-house method based on single particle inductively coupled plasma mass spectrometry suitable for surveillance of nanoparticles in mussels.

METHOD: A new low-cost and simple protease mixture was utilized for sample digestion, and a novel open-source data processing was used, establishing detection limits on a statistical basis using false positive and false negative probabilities. The method was validated for 30 and 60 nm gold nanoparticles spiked to mussels as a proxy for seafood.

RESULTS: Recoveries were 76-77% for particle mass concentration and 94-101% for particle number concentration. Intermediate precision was 8-9% for particle mass concentration and 7-8% for particle number concentration. Detection limits for size was 18 nm and for concentration 1.7 ng/g and 4.2 x 105 particles/g mussel tissue.

CONCLUSION: The performance characteristics of the method were satisfying compared with numeric Codex criteria. Further, the method was applied to titanium-, chromium- and copper-based particles in mussels.

HIGHLIGHTS: The method demonstrates a new practical and cost-effective sample treatment and streamlined, transparent and reproducible data treatment for the routine surveillance of NPs in mussels.

PMID:38507699 | DOI:10.1093/jaoacint/qsae024

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Cardiorespiratory Effects of Yogic Versus Slow Breathing in Individuals with a Spinal Cord Injury: An Exploratory Cohort Study

J Integr Complement Med. 2024 Mar 20. doi: 10.1089/jicm.2023.0641. Online ahead of print.

ABSTRACT

Background: An intricate physiological and pathophysiological connection exists between the heart and lungs, which is especially important in individuals with spinal cord injury (SCI). While an exercise intervention may seem the best approach to leverage this relationship, the prior work has shown that, despite numerous health benefits, regular exercise training does not improve cardiorespiratory control in individuals with SCI. Breath training presents an alternative intervention that is uniquely accessible, with yogic breathing directly engaging linked fluctuations in respiration and cardiovascular control. In addition, there is evidence across a range of populations that regular yogic breathing reduces cardiovascular disease risk. It is possible that the chronic decrease in breathing frequency associated with regular yogic breathing, rather than the specific yogic breathing techniques themselves, is the primary contributor to the observed risk reduction. Methods: Therefore, in 12 individuals with traumatic SCI from C4 to T8, the authors compared Unpaced and conventional 0.083 Hz (Slow) paced breathing with various yogic breathing techniques including: (1) inspiratory-expiratory breath holds (i.e., Kumbhaka or “Box Breathing”), (2) extended exhalation (1:2 duty cycle), and (3) expiratory resistance via throat constriction (i.e., Ujjayi). Beat-to-beat heart rate and blood pressure were measured as well as end-tidal CO2 and O2 saturation were measured. Statistical analysis was performed using a one-way repeated-measures analysis of variance with post hoc pairwise t tests corrected for multiple comparisons. Results: As expected, all slow breathing patterns markedly increased respiratory sinus arrhythmia (RSA) compared with Unpaced in all (n = 12) individuals. More importantly, Ujjayi breathing appeared to improve ventilatory efficiency over Unpaced breathing in individuals with SCI by increasing O2 saturation (97.6% vs. 96.1%; p = 0.042) and tended to decrease end-tidal CO2 (32 mmHg vs. 35 mmHg; p = 0.08). While other slow breathing patterns demonstrated similar effects, only Ujjayi improved RSA while increasing heart rate and improving ventilatory efficiency. Conclusions: Hence, slow breathing per se can result in important cardiorespiratory changes, but the yogic breathing practice of Ujjayi, with glottic throat resistance, may hold the greatest promise for improving cardiorespiratory control in individuals with SCI (CTR ID No. NCT05480618).

PMID:38507692 | DOI:10.1089/jicm.2023.0641

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Association Between Hashimoto’s Thyroiditis and Rheumatoid Arthritis: A Bidirectional Mendelian Randomization Study

Genet Test Mol Biomarkers. 2024 Mar 20. doi: 10.1089/gtmb.2023.0594. Online ahead of print.

ABSTRACT

Background: We aim to investigate the possible causal association between Hashimoto’s thyroiditis (HT) and rheumatoid arthritis (RA) using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted to evaluate the causal association between HT and RA. We obtained summary statistics data from two extensive genome-wide association studies (GWAS) comprising 15,654 cases of HT and 14,361 cases of RA. The primary effect estimate utilized in this study was the inverse-variance weighted (IVW) method. To ensure the reliability and stability of the results, we employed several additional methods for testing, including MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO. Results: Our study revealed compelling evidence of bidirectional causality between HT and RA. When HT was considered as an exposure factor and RA was considered as an outcome factor, this study revealed a positive correlation between HT and RA (IVW: odds ratio [OR] = 2.4546, 95% confidence interval [CI], 1.1473-5.2512; p = 0.0207). Conversely, when we examined RA as the exposure factor and HT as the outcome factor, we still found a positive correlation between them (IVW: OR = 1.2113, 95% CI, 1.1248-1.3044; p = 3.9478 × 10-7). Conclusions: According to our research findings, there exists a bidirectional positive causal relationship between HT and RA among European populations. This implies that individuals with HT have an elevated risk of developing RA, and conversely, individuals with RA have an increased risk of developing HT.

PMID:38507672 | DOI:10.1089/gtmb.2023.0594

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Updated Analysis of Comparative Toxicity of Proton and Photon Radiation for Prostate Cancer

J Clin Oncol. 2024 Mar 20:JCO2301604. doi: 10.1200/JCO.23.01604. Online ahead of print.

ABSTRACT

PURPOSE: Previous comparative effectiveness studies have not demonstrated a benefit of proton beam therapy (PBT) compared with intensity-modulated radiation therapy (IMRT) for prostate cancer. An updated comparison of GI and genitourinary (GU) toxicity is needed.

METHODS: We investigated the SEER-Medicare linked database, identifying patients with localized prostate cancer diagnosed from 2010 to 2017. Procedure and diagnosis codes indicative of treatment-related toxicity were identified. As a sensitivity analysis, we also identified toxicity based only on procedure codes. Patients who underwent IMRT and PBT were matched 2:1 on the basis of clinical and sociodemographic characteristics. We then compared GI and GU toxicity at 6, 12, and 24 months after treatment.

RESULTS: The final sample included 772 PBT patients matched to 1,544 IMRT patients. The frequency of GI toxicity for IMRT versus PBT was 3.5% versus 2.5% at 6 months (P = .18), 9.5% versus 10.2% at 12 months (P = .18), and 20.5% versus 23.4% at 24 months (P = .11). The frequency of only procedure codes indicative of GI toxicity for IMRT versus PBT was too low to be reported and not significantly different. The frequency of GU toxicity for IMRT versus PBT was 6.8% versus 5.7% (P = .30), 14.3% versus 12.2% (P = .13), and 28.2% versus 25.8% (P = .21) at 6, 12, and 24 months, respectively. When looking only at procedure codes, the frequency of GU toxicity for IMRT was 1.0% at 6 months, whereas it was too infrequent to report for PBT (P = .64). GU toxicity for IMRT versus PBT was 3.3% versus 2.1% (P = .10), and 8.7% versus 6.7% (P = .10) at 12 and 24 months, respectively.

CONCLUSION: In this observational study, there were no statistically significant differences between PBT and IMRT in terms of GI or GU toxicity.

PMID:38507655 | DOI:10.1200/JCO.23.01604