Nevin Manimala

Alzheimers Dement. 2022 Feb 25. doi: 10.1002/alz.12631. Online ahead of print.

ABSTRACT

INTRODUCTION: We examined baseline differences in depression and antidepressant use among cognitively normal older adults in five ethnoracial groups and assessed whether depression predicted a faster progression to incident cognitive impairment across groups.

METHODS: Data from the National Alzheimer’s Coordinating Center (n = 8168) were used to examine differences between non-Hispanic Whites (nHW), African Americans (AA), Hispanics, Asians, and American Indian and Alaskan Natives in cross-sectional and longitudinal models.

RESULTS: AA had a lower risk of depression compared to nHW at baseline. No statistical interactions were noted between ethnoracial groups and depression. However, depression independently predicted a faster progression to incident cognitive impairment. Hispanics and Asian participants had a higher hazard for progression compared to nHW.

DISCUSSION: Previously established risk factors between depression and dementia were not found among AA and nHW participants. The relationship between depression and ethnoracial groups is complex and suggests differential effects on progression from cognitive normality to impairment.

PMID:35213795 | DOI:10.1002/alz.12631

Radiat Res. 2022 Feb 25. doi: 10.1667/RADE-21-00059.1. Online ahead of print.

ABSTRACT

Recent analysis of all solid cancer incidence (1958-2009) in the Life Span Study (LSS) revealed evidence of upward curvature in the radiation dose response among males but not females. Upward curvature in sex-averaged excess relative risk (ERR) for all solid cancer mortality (1950-2003) was also observed in the 0-2 Gy dose range. As reasons for non-linearity in the LSS are not completely understood, we conducted dose-response analyses for all solid cancer mortality and incidence applying similar methods [1958-2009 follow-up, DS02R1 doses, including subjects not-in-city (NIC) at the time of the bombing] and statistical models. Incident cancers were ascertained from Hiroshima and Nagasaki cancer registries, while cause of death was ascertained from death certificates throughout Japan. The study included 105,444 LSS subjects who were alive and not known to have cancer before January 1, 1958 (80,205 with dose estimates and 25,239 NIC subjects). Between 1958 and 2009, there were 3.1 million person-years (PY) and 22,538 solid cancers for incidence analysis and 3.8 million PY and 15,419 solid cancer deaths for mortality analysis. We fitted sex-specific ERR models adjusted for smoking to both types of data. Over the entire range of doses, solid cancer mortality dose-response exhibited a borderline significant upward curvature among males (P = 0.062) and significant upward curvature among females (P = 0.010); for solid cancer incidence, as before, we found a significant upward curvature among males (P = 0.001) but not among females (P = 0.624). The sex difference in magnitude of dose-response curvature was statistically significant for cancer incidence (P = 0.017) but not for cancer mortality (P = 0.781). The results of analyses in the 0-2 Gy range and restricted lower dose ranges generally supported inferences made about the sex-specific dose-response shape over the entire range of doses for each outcome. Patterns of sex-specific curvature by calendar period (1958-1987 vs. 1988-2009) and age at exposure (0-19 vs. 20-83) varied between mortality and incidence data, particularly among females, although for each outcome there was an indication of curvature among 0-19-year-old male survivors in both calendar periods and among 0-19-year-old female survivors in the recent period. Collectively, our findings indicate that the upward curvature in all solid cancer dose response in the LSS is neither specific to males nor to incidence data; its evidence appears to depend on the composition of sites comprising all solid cancer group and age at exposure or time. Further follow up and site-specific analyses of cancer mortality and incidence will be important to confirm the emerging trend in dose-response curvature among young survivors and unveil the contributing factors and sites.

PMID:35213725 | DOI:10.1667/RADE-21-00059.1

Eur J Cardiothorac Surg. 2022 Feb 25:ezac124. doi: 10.1093/ejcts/ezac124. Online ahead of print.

ABSTRACT

OBJECTIVES: The comparative effectiveness and safety of proton pump inhibitors (PPIs) versus histamine-2 receptor blockers for stress ulcer prophylaxis in the cardiac surgical intensive care unit population is uncertain. Although the Proton Pump Inhibitors versus Histamine-2 Receptor Blockers for Ulcer Prophylaxis Therapy in the Intensive Care Unit (PEPTIC) trial reported a higher risk of mortality in the PPI arm with no difference in gastrointestinal bleeding, detailed information on surgical variables and clinically relevant surgical subgroups was not available.

METHODS: The analysis included all Canadian cardiac surgery patients enrolled in the PEPTIC trial. Data were electronically linked using unique patient identifiers to a clinical information system. Outcomes of interest included in-hospital mortality, gastrointestinal bleeding, Clostridium difficile infections, ventilator-associated conditions and length of stay.

RESULTS: We studied 823 (50.6%) randomized to PPIs and 805 (49.4%) to histamine-2-receptor blockers. In the intention-to-treat analysis, there were no differences in hospital mortality [PPI: 4.3% vs histamine-2 receptor blockers: 4.8%, adjusted odds ratio (aOR) 0.97, 95% confidence interval (CI) 0.55-1.70], gastrointestinal bleeding (3.9% vs 4.8%, aOR 1.09, 95% CI 0.66-1.81), C. difficile infections (0.9% vs 0.1%, aOR 0.18, 95% CI 0.02-1.59), ventilator-associated conditions (1.6% vs 1.7%, aOR 0.92, 95% CI 0.85-1.00) or median length of stay (9.2 vs 9.8 days, adjusted risk ratio 1.06, 85% CI 0.99-1.13). No significant treatment differences were observed among subgroups of interest or per-protocol populations.

CONCLUSIONS: In a secondary analysis of cardiac surgery patients enrolled in the PEPTIC trial in Canada, no differences in effectiveness or safety were observed between use of PPIs and histamine-2 receptor blockers for stress ulcer prophylaxis.

CLINICAL TRIAL REGISTRATION NUMBER: anzctr.org.au identifier: ACTRN12616000481471.

PMID:35213716 | DOI:10.1093/ejcts/ezac124

J Clin Endocrinol Metab. 2022 Feb 25:dgac110. doi: 10.1210/clinem/dgac110. Online ahead of print.

ABSTRACT

OBJECTIVE: Subclinical hypothyroidism is known to increase the risk of cardiovascular diseases and mortality. However, the longitudinal association between subclinical hypothyroidism and incident metabolic syndrome remains unclear yet.

METHODS: A total of 3,615 participants from Beijing Health Management Cohort (BHMC) were enrolled from 2012 to 2014, and followed through 2019. People were grouped into subclinical hypothyroidism and euthyroidism according to serum free thyroxine and thyrotropin (TSH) concentrations. We used Cox proportional hazards regression models to investigate the relationship between TSH level and incident metabolic syndrome considering the modification effect of sex and age.

RESULTS: Of 3,615 participants, 1,929 were men (53.4%); mean (SD) age was 43.51 (11.73) years. Through out follow-up (median [interquartile range], 3.0 [2.8-3.2] years), 738 individuals developed metabolic syndrome. Subclinical hypothyroidism was significantly associated with metabolic syndrome development only in men, and the adjusted hazard ratio was 1.87 (95% CI: 1.21-2.90) compared with euthyroidism group. Of note, there was no increased risk of metabolic syndrome in people aged 50 years or older with subclinical hypothyroidism.

CONCLUSIONS: Subclinical hypothyroidism is associated with incident metabolic syndrome in young men. Further studies are needed to evaluate the targeted threshold and benefit of thyroid hormone replacement therapy for metabolic health.

PMID:35213715 | DOI:10.1210/clinem/dgac110

J Clin Endocrinol Metab. 2022 Feb 25:dgac105. doi: 10.1210/clinem/dgac105. Online ahead of print.

ABSTRACT

CONTEXT: Acylated ghrelin (AG) stimulates appetite and is elevated compared to its unacylated (UAG) counterpart in Prader-Willi syndrome (PWS). GLWL-01 is a selective, reversible inhibitor of ghrelin-O-acyltransferase (GOAT), the enzyme that converts UAG into AG.

OBJECTIVE: Assess the efficacy, pharmacokinetics, pharmacodynamics, and safety of GLWL-01 in the treatment of PWS patients.

DESIGN: Double-blind, placebo-controlled Phase 2 crossover study with two active treatment periods of 28-days in 19 patients (16 to 65 years; body mass index (BMI) ≥28 kg/m 2) with genetically confirmed PWS.

SETTING: Seven hospital-based study centers in the US and Canada.

INTERVENTION: Patients received placebo or GLWL-01 (450 mg twice daily) orally after lead-in placebo and washout periods.

MAIN OUTCOME: The Hyperphagia Questionnaire for Clinical Trials (HQ-CT) and Caregiver Global Impression of Change (CGIC) were used to measure reductions in hyperphagia. Plasma concentrations of AG and UAG were evaluated as correlates.

RESULTS: Treatment resulted in significant differences compared to placebo in plasma AG (p=0.0002), UAG (p=0.0488), and AG/UAG (p=0.0003). GLWL-01 did not significantly reduce hyperphagia-related behavior or bring about changes in global clinical endpoints, as assessed by caregivers. Anthropometric and clinical parameters correlated with obesity did not significantly change in response to treatment. Less than half of patients reported a treatment emergent adverse event (TEAE). No deaths, serious adverse events, or severe TEAEs were reported.

CONCLUSIONS: GLWL-01 was safe and well-tolerated. Pharmacological parameters confirmed the inhibition of GOAT following administration of GLWL-01. Patients’ eating behaviors, BMI, blood glucose, and total cholesterol, among other similar measures, were not modified.

PMID:35213714 | DOI:10.1210/clinem/dgac105

Hum Reprod. 2022 Feb 25:deac038. doi: 10.1093/humrep/deac038. Online ahead of print.

ABSTRACT

STUDY QUESTION: Which success rates do female and male IVF patients expect, what determines their expectations and do patients reconsider their expectations after receiving a personal IVF prognosis at the expense of anxious reactions?

SUMMARY ANSWER: Female and male IVF patients have unrealistic high expectations which are positively associated with their dispositional optimism, and which are only reconsidered by patients receiving a less than average IVF prognosis, which leads to more anxious reactions in females.

WHAT IS KNOWN ALREADY: Female patients undergoing IVF are known to have unrealistic expectations of the success of their own IVF cycle. The available evidence suggests women expect above average performance of their fertility clinic and (family) reproductive systems. The association of gender and personality trait dispositional optimism, with expectations of IVF success and the impact of providing couples with their IVF prognosis have not been studied previously.

STUDY DESIGN, SIZE, DURATION: A total of 148 partnered individuals participated in this prospective survey at two separate points in treatment: following oocyte aspiration (T1) and embryo transfer (T2) (2019-2020, participation rate = 85%). At the time of embryo transfer, gynaecologists provided couples with their IVF prognosis, calculated with the Adapted van Loendersloot model. Women and their male partners completed questionnaires independently and immediately following oocyte aspiration and embryo transfer.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Dispositional optimism (‘LOT-R’ questionnaire) and expectations of IVF success (numerical rating scale) were assessed in eligible couples commencing a 2nd-6th IVF cycle on T1. Expectations of IVF success and anxiety (‘Spielberger State-Anxiety Inventory’) were (re)assessed on T2. The inter-partner correlation of expectations of IVF success was examined. Linear mixed models examined hypothesized determinants of expectations of IVF success (T1) and explored (determinants of) whether participants reconsidered their expectations after receiving their IVF prognosis (T1-T2) and whether couple’s IVF prognosis was associated with anxious reactions (T2).

MAIN RESULTS AND THE ROLE OF CHANCE: The mean of the IVF success rates expected by patients immediately after oocyte aspiration was 59.1% (±20.0), irrespective of gender (P = 0.077). Partners expectations of IVF success were moderately correlated (r = 0.483; P < 0.001). Expectations of IVF success were positively associated with the participant’s dispositional optimism (P < 0.001) but were not associated with their partner’s dispositional optimism, women’s age and their previous (un)successful IVF experiences. Gynaecologists gave couples their calculated IVF prognosis ranging from 4.8% to 69.2% (mean = 30.9%) at the time of embryo transfer. Gender did not influence whether participants reconsidered their expectations after receiving their prognosis. In contrast to the subgroup (n = 78), who received at least an average IVF prognosis and that did not reconsider their expectations of IVF success, the subgroup (n = 70) receiving a below average IVF prognosis lowered their expectations of IVF success (interaction effect: P < 0.001) from 55% to 46%. A below average IVF prognosis was associated with anxious reactions in women but not in men (interaction effect: P = 0.011).

LIMITATIONS, REASONS FOR CAUTION: The study design and sample size were more optimal for examining hypothesized determinants of patient’s expectations of IVF success than for studying the impact of sharing prognoses with patients. Whether (reconsidering) expectations influences IVF discontinuation rates and achieved live birth rates has yet to be followed-up.

WIDER IMPLICATIONS OF THE FINDINGS: Clinics are advised to offer patients the opportunity of receiving their IVF prognosis. Providing prognoses is in line with patient preferences and tempers the unrealistic high expectations of both partners in couples with a less than average prognosis. A sensitive communication style is indicated, as lower prognoses are associated with mild anxious reactions in women.

STUDY FUNDING/COMPETING INTEREST(S): E.A.F.D. holds a postdoctoral fellowship of the Research Foundation-Flanders (12H9819N) and this study was funded by the Research Council of the KU Leuven (C14/18/106; project of J.V., K.P. and E.A.F.D.) and as an investigator sponsored study of K.P. and E.A.F.D. by Merck nv/sa Belgium, an affiliate of Merck KGaA, Darmstadt, Germany. The authors declare no conflict of interest related to this study.

TRIAL REGISTRATION NUMBER: N/A.

PMID:35213695 | DOI:10.1093/humrep/deac038

PLoS One. 2022 Feb 25;17(2):e0264441. doi: 10.1371/journal.pone.0264441. eCollection 2022.

ABSTRACT

INTRODUCTION: In 2014, the Joint United Nations Programme on HIV/AIDS set an ‘ambitious’ 90-90-90 target for 2020. By 2016, there were disparities observed among countries in their progress towards the targets and some believed the targets were not achievable. In this report, we present the results of data from the Ethiopia Population-based HIV Impact Assessment survey analyzed to assess progress with the targets and associated factors.

METHODS: We conducted a nationally representative survey in urban areas of Ethiopia. Socio-demographic and behavioural data were collected from consenting participants using a structured interview. HIV testing was done following the national HIV rapid testing algorithm and seropositivity confirmed using a supplemental laboratory assay. HIV viral suppression was considered if the viral load was <1,000 RNA copies/ml. Screening antiretroviral drugs was done for efavirenz, lopinavir, and tenofovir, which were in use during the survey period. In this analysis, we generated weighted descriptive statistics and used bivariate and logistic regression analysis to examine for associations. The 95% confidence interval was used to measure the precision of estimates and the significance level set at p<0.05.

RESULTS: Of 19,136 eligible participants aged 15-64 years, 614 (3% [95% CI: 0.8-3.3]) were HIV-positive, of which 79.0% (95% CI: 4.7-82.7) were aware of their HIV status, and 97.1% (95% CI: 95.0-98.3 were on antiretroviral therapy, of which 87.6% (95% CI: 83.9-90.5) achieved viral load suppression. Awareness about HIV-positive status was significantly higher among females (aOR = 2.8 [95% CI: 1.38-5.51]), significantly increased with age, the odds being highest for those aged 55-64 years (aOR = 11.4 [95% CI: 2.52-51.79]) compared to those 15-24 years, and was significantly higher among those who used condom at last sex in the past 12 months (aOR = 5.1 [95% CI: 1.68-15.25]). Individuals with secondary education and above were more likely to have achieved viral suppression (aOR = 8.2 [95% CI: 1.82-37.07]) compared with those with no education.

CONCLUSION: Ethiopia made encouraging progress towards the UNAIDS 90-90-90 targets. The country needs to intensify its efforts to achieve the targets. A particular focus is required to fill the gaps in knowledge of HIV-positive status to increase case identification among population groups such as males, the youth, and those with low education.

PMID:35213668 | DOI:10.1371/journal.pone.0264441

PLoS One. 2022 Feb 25;17(2):e0264504. doi: 10.1371/journal.pone.0264504. eCollection 2022.

ABSTRACT

BACKGROUND: The predictive role of hematological indexes of mean platelet volume (MPV) and red cell distribution width (RDW) has been demonstrated in cardiovascular disease concomitant with psoriasis. This meta-analysis is intended to assess whether MPV and RDW can also serve as biomarkers for the early diagnosis and disease severity assessment of psoriasis.

MATERIAL AND METHODS: 13 studies which enrolled 1331 psoriasis patients and 919 healthy volunteers were included after screening the search results from PubMed, Embase and the Cochrane Library since inception to Mar 14, 2020. MPV of psoriasis participants and their counterparts was assessed in 10 studies, and RDW was evaluated in 4 studies, while the disease severity was measured by the Psoriasis Area and Severity Index (PASI) in 11 studies. Random-effect model analysis was applied to calculate pooled standard mean difference (SMD) with 95% confidence interval (95% CI).

RESULTS: Associations of MPV and RDW with the presence of psoriasis were demonstrated (MPV: SMD = 0.503, 95% CI: 0.242-0.765; RDW: SMD = 0.522, 95% CI: 0.228-0.817), but no statistically significant correlation of MPV and disease severity of psoriasis was found in meta-regression analysis (p = 0.208). Subgroup analysis revealed that the diagnosis value of MPV and RDW was consistent regardless of PASI and study type. Heterogeneity analysis between studies was implemented by chi-squared test and I2 statistics. Begg’s and Egger’s test were utilized for the evaluation of publication bias. The sensitivity analysis revealed no significant alteration no matter which study was excluded.

CONCLUSION: MPV and RDW could serve as promising predictive diagnostic biomarkers of psoriasis.

PMID:35213665 | DOI:10.1371/journal.pone.0264504

PLoS One. 2022 Feb 25;17(2):e0264455. doi: 10.1371/journal.pone.0264455. eCollection 2022.

ABSTRACT

The pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) took the world by surprise. Following the first outbreak of COVID-19 in December 2019, several models have been developed to study and understand its transmission dynamics. Although the spread of COVID-19 is being slowed down by vaccination and other interventions, there is still a need to have a clear understanding of the evolution of the pandemic across countries, states and communities. To this end, there is a need to have a clearer picture of the initial spread of the disease in different regions. In this project, we used a simple SEIR model and a Bayesian inference framework to estimate the basic reproduction number of COVID-19 across Africa. Our estimates vary between 1.98 (Sudan) and 9.66 (Mauritius), with a median of 3.67 (90% CrI: 3.31-4.12). The estimates provided in this paper will help to inform COVID-19 modeling in the respective countries/regions.

PMID:35213645 | DOI:10.1371/journal.pone.0264455

PLoS One. 2022 Feb 25;17(2):e0264410. doi: 10.1371/journal.pone.0264410. eCollection 2022.

ABSTRACT

The economic, environmental and social sustainability of Dutch dairy farms have attracted increasing societal concern in the past decades. In this paper, we propose a recently developed dynamic Luenberger indicator based on the by-production model to measure dynamic productivity growth in the economic, environmental and social dimensions of sustainability of Dutch dairy farms. Subsequently, we investigate the statistical associations between productivity growth and socio-economic factors using the OLS bootstrap regression model. We find that dairy farms have suffered a decline in dynamic sustainable productivity growth, especially in the environmental dimension where it is more pronounced than in the economic and social dimensions. Furthermore, we find that both technical and scale inefficiency change contribute to the decline of environmental productivity growth. Specialization and government support are associated with a higher economic and environmental sustainability productivity growth, and with, a decreased growth of social sustainable productivity. We found no significant association between the age of the oldest entrepreneur, financial structure, farm size or cost of advisory service and dynamic productivity growth in the three sustainability dimensions. The results provide insights into potential pathways towards improving the three pillars of sustainability.

PMID:35213644 | DOI:10.1371/journal.pone.0264410