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Nevin Manimala Statistics

Causal effect of severe and non-severe malaria on dyslipidemia in African Ancestry individuals: A Mendelian randomization study

Ann Hum Genet. 2024 Mar 15. doi: 10.1111/ahg.12555. Online ahead of print.

ABSTRACT

BACKGROUND: Dyslipidemia is becoming prevalent in Africa, where malaria is endemic. Observational studies have documented the long-term protective effect of malaria on dyslipidemia; however, these study designs are prone to confounding. Therefore, we used Mendelian randomization (MR, a method robust to confounders and reverse causation) to determine the causal effect of severe malaria (SM) and the recurrence of non-severe malaria (RNM) on lipid traits.

METHOD: We performed two-sample MR using genome wide association study (GWAS) summary statistics for recurrent non-severe malaria (RNM) from a Benin cohort (N = 775) and severe malaria from the MalariaGEN dataset (N = 17,000) and lipid traits from summary-level data of a meta-analyzed African lipid GWAS (MALG, N = 24,215) from the African Partnership for Chronic Disease Research (APCDR) (N = 13,612) and the Africa Wits-IN-DEPTH partnership for genomics studies (AWI-Gen) dataset (N = 10,603).

RESULT: No evidence of significant causal association was obtained between RNM and high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol and triglycerides. However, a notable association emerged between severe malarial anaemia (SMA) which is a subtype of severe malaria and reduced HDL-C levels, suggesting a potential subtype-specific effect. Nonetheless, we strongly believe that the small sample size likely affects our estimates, warranting cautious interpretation of these results.

CONCLUSION: Our findings challenge the hypothesis of a broad causal relationship between malaria (both severe and recurrent non-severe forms) and dyslipidemia. The isolated association with SMA highlights an intriguing area for future research. However, we believe that conducting larger studies to investigate the connection between malaria and dyslipidemia in Africa will enhance our ability to better address the burden posed by both diseases.

PMID:38488696 | DOI:10.1111/ahg.12555

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Nevin Manimala Statistics

Serum Prestin Level May Increase Following Music Exposure That Induces Temporary Threshold Shifts: A Pilot Study

Ear Hear. 2024 Mar 15. doi: 10.1097/AUD.0000000000001499. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine if blood prestin level changes after exposure to music at high sound pressure levels, and if this change is associated with temporary threshold shift (TTS) and/or changes in distortion product (DP) amplitude.

DESIGN: Participants were exposed to pop-rock music at 100 dBA for 15 min monaurally through headphones. Pure-tone audiometry, DP amplitude, and blood prestin level were measured before and after exposure.

RESULTS: Fourteen adults (9 women; age range: 20 to 54 years, median age = 31 [Interquartile ratio = 6.75]) with normal hearing were included in the study. Mean prestin level increased shortly after exposure to music, then returned to baseline within 1 week, although this trend was not observed in all participants. All participants presented TTS or a decrease in DP amplitude in at least one frequency after music exposure. There was a statistically significant average threshold elevation at 4 min postexposure. Statistically significant DP amplitude shifts were observed at 4 and 6 kHz, 2 min following exposure. Mean baseline serum prestin level (mean: 140.00 pg/mL, 95% confidence interval (CI): 125.92 to 154.07) progressively increased following music exposure, reaching a maximum at 2 hr (mean: 158.29 pg/mL, 95% CI: 130.42 to 186.66) and returned to preexposure level at 1 week (mean: 139.18 pg/mL, 95% CI: 114.69 to 163.68). However, after correction for multiple comparisons, mean prestin level showed no statistically significant increase from baseline at any timepoint. No correlation between maximum blood prestin level change and average TTS or distortion product otoacoustic emission amplitude shift was found. However, in an exploratory analysis, TTS at 6 kHz (the frequency at which maximum TTS occurred) decreased significantly as baseline blood prestin level increased.

CONCLUSIONS: The results suggest that blood prestin level may change after exposure to music at high sound pressure levels, although statistical significance was not reached in this relatively small sample after correction. Baseline serum prestin level may also predict the degree of TTS. These findings thus suggest that the role of baseline serum prestin level as a proxy marker of cochlear susceptibility to intense music exposure should be further explored.

PMID:38488693 | DOI:10.1097/AUD.0000000000001499

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Nevin Manimala Statistics

Immediate Impact on Tear Osmolarity Following the Application of Different Ocular Lubricants in Patients Experiencing Moderate Dry Eye Symptoms

Cornea. 2024 Mar 15. doi: 10.1097/ICO.0000000000003493. Online ahead of print.

ABSTRACT

PURPOSE: This study addresses the growing concern of Dry Eye Disease (DED), which has become increasingly prevalent due to modern lifestyles characterized by prolonged screen usage, global warming, polypharmacy, and extended life expectancy.

METHODS: Grounded in the Dry Eye Workshop II (DEWSII) diagnosis framework, the study focuses on DED as a multifactorial condition affecting the ocular surface’s tear film homeostasis. The study evaluates the short-term impact of 5 commercially available ocular lubricants on disrupting the hyperosmolar environment and determine whether these lubricants can offer potential treatment benefits for DED.

RESULTS: Conducted on 300 eyes (from 150 patients) with 5 preservative-free lubricants compared to a control group, the study reveals that all lubricants effectively reduced tear film osmolarity within 15 minutes of application. Notably, the control group exhibited an increase in average osmolarity (+0.98 mOsm/L) without lubricant use. Siccafluid demonstrated the most substantial osmolarity reduction after 15 minutes, with an average decrease of 11.54 mOsm/L. Statistical significance was observed for Siccafluid, Optive Fusion unique dose (UD), and Systane Ultra UD, while Hyabak and Freegen preservative free (PF) showed lower significance.

CONCLUSIONS: Emphasizing the importance of disrupting the hyperosmolar environment to break the cycle of inflammation, the study concludes that ocular lubricants, at least as an immediate post-application effect, can interrupt this cycle and improve the hyperosmolar environment of the ocular surface.

PMID:38488642 | DOI:10.1097/ICO.0000000000003493

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Electronic Medical Record Data Missingness and Interruption in Antiretroviral Therapy Among Adults and Children Living With HIV in Haiti: Retrospective Longitudinal Study

JMIR Pediatr Parent. 2024 Mar 6;7:e51574. doi: 10.2196/51574.

ABSTRACT

BACKGROUND: Children (aged 0-14 years) living with HIV often experience lower rates of HIV diagnosis, treatment, and viral load suppression. In Haiti, only 63% of children living with HIV know their HIV status (compared to 85% overall), 63% are on treatment (compared to 85% overall), and 48% are virally suppressed (compared to 73% overall). Electronic medical records (EMRs) can improve HIV care and patient outcomes, but these benefits are largely dependent on providers having access to quality and nonmissing data.

OBJECTIVE: We sought to understand the associations between EMR data missingness and interruption in antiretroviral therapy treatment by age group (pediatric vs adult).

METHODS: We assessed associations between patient intake record data missingness and interruption in treatment (IIT) status at 6 and 12 months post antiretroviral therapy initiation using patient-level data drawn from iSanté, the most widely used EMR in Haiti. Missingness was assessed for tuberculosis diagnosis, World Health Organization HIV stage, and weight using a composite score indicator (ie, the number of indicators of interest missing). Risk ratios were estimated using marginal parameters from multilevel modified Poisson models with robust error variances and random intercepts for the facility to account for clustering.

RESULTS: Data were drawn from 50 facilities and comprised 31,457 patient records from people living with HIV, of which 1306 (4.2%) were pediatric cases. Pediatric patients were more likely than adult patients to experience IIT (n=431, 33% vs n=7477, 23.4% at 6 months; P<.001). Additionally, pediatric patient records had higher data missingness, with 581 (44.5%) pediatric records missing at least 1 indicator of interest, compared to 7812 (25.9%) adult records (P<.001). Among pediatric patients, each additional indicator missing was associated with a 1.34 times greater likelihood of experiencing IIT at 6 months (95% CI 1.08-1.66; P=.008) and 1.24 times greater likelihood of experiencing IIT at 12 months (95% CI 1.05-1.46; P=.01). These relationships were not statistically significant for adult patients. Compared to pediatric patients with 0 missing indicators, pediatric patients with 1, 2, or 3 missing indicators were 1.59 (95% CI 1.26-2.01; P<.001), 1.74 (95% CI 1.02-2.97; P=.04), and 2.25 (95% CI 1.43-3.56; P=.001) times more likely to experience IIT at 6 months, respectively. Among adult patients, compared to patients with 0 indicators missing, having all 3 indicators missing was associated with being 1.32 times more likely to experience IIT at 6 months (95% CI 1.03-1.70; P=.03), while there was no association with IIT status for other levels of missingness.

CONCLUSIONS: These findings suggest that both EMR data quality and quality of care are lower for children living with HIV in Haiti. This underscores the need for further research into the mechanisms by which EMR data quality impacts the quality of care and patient outcomes among this population. Efforts to improve both EMR data quality and quality of care should consider prioritizing pediatric patients.

PMID:38488632 | DOI:10.2196/51574

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Anti-hypertensive therapy for preeclampsia: a network meta-analysis and systematic review

Hypertens Pregnancy. 2024 Dec;43(1):2329068. doi: 10.1080/10641955.2024.2329068. Epub 2024 Mar 15.

ABSTRACT

BACKGROUND: Preeclampsia (PE) is a pregnancy disorder that represents a major cause of maternal and perinatal morbidity and mortality.

METHODS: This network meta-analysis was registered with PROSPERO. We searched the PubMed, ClinicalTrials.gov. and Embase databases for studies published from inception to the 31st of March 2023. RevMan5.3 software provided by the Cochrane Collaboration was used for direct meta-analysis (DMA) statistical analysis. Funnel maps, network meta-analysis (NMA), the surface under the cumulative ranking curve (SUCRA) to rank the different interventions and publication bias were generated by STATA 17.0 software.

RESULTS: We included eight randomized controlled trials (RCTs) involving a total of 1192 women with PE; two studies were of high quality and six were of moderate quality. Eight interventions were addressed in the NMA. In the DMA, we found that blood pressure in the Ketanserin group were significantly higher than those in the Nicardipine group. NMA showed that blood pressure in the Dihydralazine group was significantly higher than that in the Methyldopa, Labetalol, Nicardipine and Diltiazem groups. And the blood pressure in the Labetalol group was significantly lower than that in the Nicardipine group. SUCRA values showed that Diltiazem was more effective in lowering blood pressure than other drugs looked at in this study.

CONCLUSION: According to the eight RCTs included in this study, Diltiazem was the most effective in reducing blood pressure in PE patients; Labetalol and Nicardipine also had good effects. Diltiazem is preferred for the treatment of patients with severe PE and high blood pressure.

PMID:38488570 | DOI:10.1080/10641955.2024.2329068

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Mortality in patients with Dupuytren’s disease in the first 5 years after diagnosis: a population-based survival analysis

J Hand Surg Eur Vol. 2024 Mar 15:17531934241235546. doi: 10.1177/17531934241235546. Online ahead of print.

ABSTRACT

Previous studies suggest that Dupuytren’s disease is associated with increased mortality, but most studies failed to account for important confounders. In this population-based cohort study, general practitioners’ (GP) data were linked to Statistics Netherlands to register all-cause and disease-specific mortality. Patients with Dupuytren’s disease were identified using the corresponding diagnosis code and assessing free-text fields from GP consultations. Multiple imputations were performed to estimate missing values of covariates, followed by 1:7 propensity score matching to balance cases with controls on confounding factors. A frailty proportional hazard model was used to compare mortality between both groups. Out of 209,966 individuals, 2561 patients with Dupuytren’s disease were identified and matched to at least four controls. After a median follow-up of 5 years, mortality was found to be actually reduced in patients with Dupuytren’s disease. There was no difference in mortality secondary to cancer or cardiovascular disease. Future studies with longer average follow-up using longitudinal data should clarify these associations in the longer term.Level of evidence: III.

PMID:38488516 | DOI:10.1177/17531934241235546

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The Real-World Impact of App-Based Mindfulness on Headspace Members With Moderate and Severe Perceived Stress: Observational Study

JMIR Mhealth Uhealth. 2024 Mar 4;12:e52968. doi: 10.2196/52968.

ABSTRACT

BACKGROUND: Perceived stress in the United States has drastically increased since the COVID-19 pandemic and is associated with negative mental health outcomes such as depression and anxiety. Digital mental health (DMH) interventions are efficacious tools to address negative mental health outcomes and have helped reduce the severity of psychological symptoms, such as anxiety, depression, and perceived stress, compared to waitlist controls. Although DMH tools have been studied in controlled settings, less is known about the real-world evidence of such interventions.

OBJECTIVE: This study aimed to (1) characterize patterns in baseline perceived stress and changes in perceived stress among Headspace members with moderate and severe baseline perceived stress and (2) examine associations between engagement with Headspace content and changes in perceived stress (ie, evaluate whether there is a dose-response relationship).

METHODS: We evaluated real-world perceived stress and engagement data at 2 time points among Headspace app members with baseline moderate and severe perceived stress. Perceived stress was measured using the Perceived Stress Scale (PSS-10) and engagement using active days and active minutes engaged with Headspace as well as the number of user sessions. Descriptive statistics were computed for all variables. Correlations between baseline and follow-up scores, percent change in PSS-10 scores, days between PSS-10 use, active days, active days per week, active minutes, active minutes per day, sessions, and sessions per week were evaluated. We used t tests to investigate differences in the abovementioned parameters between (1) participants who did and those who did not see improvements in PSS-10 scores (yes vs no improvement) and (2) participants who saw ≥30% improvement versus those who saw a <30% improvement in PSS-10 scores.

RESULTS: Overall, 21,088 Headspace members were included in these analyses. On average, members saw a 23.52% decrease in PSS-10 scores from baseline to follow-up. On average, members had 2.42 (SD 1.76) active days per week and 25.89 (SD 33.40) active minutes per day, and completed 7.11 (SD 8.34) sessions per week. t tests suggest that members who saw improvements in PSS-10 scores from baseline to follow-up had significantly higher baseline PSS-10 scores (Cohen d=0.56), more active days per week (Cohen d=0.33), and more sessions per week (Cohen d=0.27) than those who did not see improvements in PSS-10 scores (all P<.001). Additional t tests suggest that members with ≥30% improvement in PSS-10 scores had significantly higher baseline PSS-10 scores (Cohen d=0.35), more active days per week (Cohen d=0.36), and more sessions per week (Cohen d=0.31) than those with a >30% improvement (all P<.001).

CONCLUSIONS: Real-world use of Headspace is associated with decreased perceived stress. Furthermore, data suggest that more engagement, specifically weekly active days and sessions, is associated with a greater likelihood of stress reduction.

PMID:38488513 | DOI:10.2196/52968

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Correlation between morphological parameters and dosimetric parameters of the heart and spinal cord in the intermediate- and advanced-stage esophageal cancer

Cancer Rep (Hoboken). 2024 Mar;7(3):e2015. doi: 10.1002/cnr2.2015.

ABSTRACT

BACKGROUND: Radiation therapy plays a pivotal role as the primary adjuvant treatment for esophageal cancer (EPC), emphasizing the critical importance of carefully balancing radiation doses to the target area and organs at risk in the radiotherapeutic management of esophageal cancer.

AIMS: This study aimed to explore the correlation between morphological parameters and dosimetric parameters of the heart and spinal cord in intermediate- and advanced-stage esophagus cancer to provide a reference for clinical treatment.

METHODS AND RESULTS: A total of 105 patients with intermediate- and advanced-stage EPC, who received treatment in our hospital from 2019 to 2021, were included. The morphological parameters were calculated by imaging. Intensity-modulated radiation therapy plan was executed at Raystation4.7. The PTV-G stood for the externally expanded planning target volume (PTV) of the gross tumor volume (GTV) and PTV-C for the externally expanded volume of the clinical target volume (CTV). The prescription dose of PTV-G and PTV-C was set as 60Gy/30F and 54Gy/30F, respectively. The linear regression model was used to analyze the correlation between morphologic parameters of EPC and dosimetric parameters of the heart and spinal cord. In 105 cases, the total lung length was correlated with the spinal cord maximum dose (D2 ). The heart mean doses (Dmean ) and heart V40 (the relative volume that receives 40 Gy or more) was correlated with PTV-G volume, PTV-G length; In middle- and upper-segment EPC cases, only the total lung volume was correlated with the spinal cord Dmean , spinal cord D2 , heart Dmean , and heart V40 ; In middle-stage EPC cases, the heart Dmean was correlated with the PTV-G volume, PTV-G length. The total lung length was correlated with the spinal cord D2 ; In middle- and lower-segment EPC, only the PTV-G volume and PTV-G length were correlated with the heart Dmean . All the aforementioned values were statistically significant.

CONCLUSIONS: Combined with the unsegmented tumor and different locations, the organ at risk dose was comprehensively considered.

PMID:38488482 | DOI:10.1002/cnr2.2015

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Carbon monoxide affects early cardiac development in an avian model

Birth Defects Res. 2024 Mar;116(3):e2330. doi: 10.1002/bdr2.2330.

ABSTRACT

INTRODUCTION: Carbon monoxide (CO) is a toxic gas that can be lethal in large doses and may also cause physiological damage in lower doses. Epidemiological studies suggest that CO in lower doses over time may impact on embryo development, in particular cardiac development, however other studies have not observed this association.

METHODS: Here, we exposed chick embryos in ovo to CO at three different concentrations (3, 9, 18 ppm) plus air control (4 protocols in total) for the first 9 days of development, at which point we assessed egg and embryo weight, ankle length, developmental stage, heart weight, ventricular wall thickness, ventricular-septal thickness and atrial wall thickness.

RESULTS: We found that heart weight was reduced for the low and moderate exposures compared to air, that atrial wall and ventricular wall thickness was increased for the moderate and high exposures compared to air and that ventricular septal thickness was increased for low, moderate and high exposures compared to air. Ventricular wall thickness was also significantly positively correlated with absolute CO exposures across all protocols.

CONCLUSIONS: This intervention study thus suggests that CO even at very low levels may have a significant impact on cardiac development.

PMID:38488476 | DOI:10.1002/bdr2.2330

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Evaluation of behavioral variance/covariance explained by the neuroimaging data through a pattern-based regression

Hum Brain Mapp. 2024 Mar;45(4):e26601. doi: 10.1002/hbm.26601.

ABSTRACT

Neuroimaging data have been widely used to understand the neural bases of human behaviors. However, most studies were either based on a few predefined regions of interest or only able to reveal limited vital regions, hence not providing an overarching description of the relationship between neuroimaging and behaviors. Here, we proposed a voxel-based pattern regression that not only could investigate the overall brain-associated variance (BAV) for a given behavioral measure but could also evaluate the shared neural bases between different behaviors across multiple neuroimaging data. The proposed method demonstrated consistently high reliability and accuracy through comprehensive simulations. We further implemented this approach on real data of adolescents (IMAGEN project, n = 2089) and adults (HCP project, n = 808) to investigate brain-based variances of multiple behavioral measures, for instance, cognitive behaviors, substance use, and psychiatric disorders. Notably, intelligence-related scores showed similar high BAVs with the gray matter volume across both datasets. Further, our approach allows us to reveal the latent brain-based correlation across multiple behavioral measures, which are challenging to obtain otherwise. For instance, we observed a shared brain architecture underlying depression and externalizing problems in adolescents, while the symptom comorbidity may only emerge later in adults. Overall, our approach will provide an important statistical tool for understanding human behaviors using neuroimaging data.

PMID:38488475 | DOI:10.1002/hbm.26601