Nevin Manimala

J Prev Alzheimers Dis. 2023;10(1):133-136. doi: 10.14283/jpad.2022.91.

ABSTRACT

OBJECTIVES: Whole grains (WG) have been widely recognized as healthy foods but few prospective studies have examined WG foods consumption and all-cause dementia and Alzheimer’s disease (AD) dementia. This pilot study aimed to investigate the relationship between WG and dementia.

METHODS: 2958 subjects from the Framingham Offspring cohort were included with the Food Frequency Questionnaire (FFQ) to assess their diet intake. And multivariate Cox proportional regression was conducted to examine the relations.

RESULTS: After an average follow-up of 12.6 years, 322 all-cause dementia were documented, including 247 AD dementia. In the fully adjusted model, participants in the highest vs. the lowest quintiles of WG consumption had lower risks of all-cause dementia (HR, 0.72; 95% CI, 0.53-0.84; P for trend <0.001) and AD dementia (HR, 0.64; 95% CI, 0.47-0.80; P for trend <0.001).

CONCLUSIONS: High consumption of WG foods is associated with decreased risks of all-cause dementia and AD dementia.t disease mortality. Our findings are from a preliminary study and need to be confirmed in comprehensive settings and integrated statistical methods.

PMID:36641618 | DOI:10.14283/jpad.2022.91

J Prev Alzheimers Dis. 2023;10(1):25-33. doi: 10.14283/jpad.2022.84.

ABSTRACT

BACKGROUND: Previously we reported the clinical safety and pharmacological activity of buntanetap (known as Posiphen or ANVS401) in healthy volunteers and mild cognitive impaired (MCI) patients (21). The data supported continued clinical evaluation of buntanetap for treating Alzheimer’s Disease (AD). Neurodegenerative diseases such as AD and Parkinson’s disease (PD) share several pathological manifestations, including increased levels of multiple neurotoxic protein aggregates. Therefore, a treatment strategy that targets toxic species common to both disorders can potentially provide better clinical outcomes than attacking one neurotoxic protein alone. To test this hypothesis, we recently completed a clinical study in early AD and early PD participants and report the data here.

OBJECTIVES: We evaluated safety, pharmacokinetics, biomarkers, and efficacy of buntanetap in treating early AD and PD patients.

DESIGN: Double-blind, placebo-controlled, multi-center study.

SETTING: 13 sites in the US participated in this clinical trial. The registration number is NCT04524351 at ClinicalTrials.gov.

PARTICIPANTS: 14 early AD patients and 54 early PD patients.

INTERVENTION: AD patients were given either 80mg buntanetap or placebo QD. PD patients were given 5mg, 10mg, 20mg, 40mg, 80mg buntanetap or placebo QD.

MEASUREMENTS: Primary endpoint is safety and tolerability; secondary endpoint is pharmacokinetics of buntanetap in plasma; exploratory endpoints are 1) biomarkers in cerebrospinal fluid (CSF) in both AD and PD patients 2) psychometric tests specific for AD (ADAS-Cogs and WAIS coding test) or PD (MDS-UPDRS and WAIS coding test).

RESULTS: Buntanetap was safe and well tolerated. Biomarker data indicated a trend in lowering levels of neurotoxic proteins and inflammatory factors and improving axonal integrity and synaptic function in both AD and PD cohorts. Psychometric tests showed statistically significant improvements in ADAS-Cog11 and WAIS coding in AD patients and MDS-UPDRS and WAIS coding in PD patients.

CONCLUSIONS: Buntanetap is well tolerated and safe at doses up to 80mg QD in both AD and PD patients. Cmax and AUC increase with dose without evidence for a plateau up to 80mg QD. The drug shows promising evidence in exploratory biomarker and efficacy measures. Further evaluation of buntanetap in larger, longer-term clinical trials for the treatment of AD and PD are warranted.

PMID:36641607 | DOI:10.14283/jpad.2022.84

J Prev Alzheimers Dis. 2023;10(1):7-8. doi: 10.14283/jpad.2022.104.

NO ABSTRACT

PMID:36641604 | DOI:10.14283/jpad.2022.104

BMC Health Serv Res. 2023 Jan 14;23(1):33. doi: 10.1186/s12913-023-09025-2.

ABSTRACT

BACKGROUND: Equity and efficiency are basic value dimensions to evaluate the effectiveness of China’s medical and health service system (MHS) reform and development. Coordinated development of equity and efficiency is necessary to realize high-quality development of medical and health services. This study aims to evaluate the equity, efficiency, and combined efforts in coordinating the MHS during 1991-2020 reform.

METHODS: Data on China’s MHS were obtained from the China Statistical Yearbook 1992-2021. Ratios of urban to rural residents’ medical expenditure and number of medical professionals per 10,000 people were employed to evaluate MHS’s equity. The data envelopment analysis-Malmquist model was employed to evaluate MHS’s efficiency. We constructed a combined-efforts-in-coordination model to examine the coordination degree between equity and efficiency.

RESULTS: Equity of medical expenditure burden significantly improved from during 1991-2007. Urban residents’ 1991 medical expenditure burden was 87.8% of that of rural residents, which increased to 100.1% in 2007. Urban areas’ mean medical expenditure burden was 105.94% of that in rural areas during 1991-2007. The gap in equity of medical expenditure burden between urban and rural areas slowly widened after 2007, with urban areas’ mean burden being 68.52% of that in rural areas during 2007-2020. Medical and health resources allocation shows an alarming inequity during this period, with mean number of medical professionals per 10,000 people in urban areas being 238.30% of that in rural areas. Efficiency experienced several fluctuations before 2008. Since 2008, efficiency was high (0.915) and remained stable, except in 2020. The combined-efforts-in-coordination score for medical expenditure burden was less than 0.2 for 80% of the years, while that for in medical and health resources was more than 0.5 for 99.67% of the years.

CONCLUSIONS: MHS inequity remains between urban and rural China, primarily because of disproportionate allocation of medical and health resources. The government should enhance rural medical professionals’ salary and welfare and provide medical subsidies for rural residents to adjust resource allocation levels in urban and rural areas, control differences in medical expenditure burden between urban and rural residents to a reasonable range, and continuously improve urban and rural residents’ equity level.

PMID:36641525 | DOI:10.1186/s12913-023-09025-2

Commun Biol. 2023 Jan 14;6(1):49. doi: 10.1038/s42003-023-04443-8.

ABSTRACT

Pulmonary function is an indicator of well-being, and pulmonary pathologies are the third major cause of death worldwide. We analysed the UK Biobank genome-wide association summary statistics of pulmonary function for Europeans and individuals of recent African descent to identify variants associated with the trait in the two ancestries. Here, we show 627 variants in Europeans and 3 in Africans associated with three pulmonary function parameters. In addition to the 110 variants in Europeans previously reported to be associated with phenotypes related to pulmonary function, we identify 279 novel loci, including an ISX intergenic variant rs369476290 on chromosome 22 in Africans. Remarkably, we find no shared variants among Africans and Europeans. Furthermore, enrichment analyses of variants separately for each ancestry background reveal significant enrichment for terms related to pulmonary phenotypes in Europeans but not Africans. Further analysis of studies of pulmonary phenotypes reveals that individuals of European background are disproportionally overrepresented in datasets compared to Africans, with the gap widening over the past five years. Our findings extend our understanding of the different variants that modify the pulmonary function in Africans and Europeans, a promising finding for future GWASs and medical studies.

PMID:36641522 | DOI:10.1038/s42003-023-04443-8

Environ Health. 2023 Jan 14;22(1):7. doi: 10.1186/s12940-023-00961-4.

ABSTRACT

BACKGROUND: While it is known that exposure to traffic-related air pollution causes an enormous global toll on human health, neurobiological underpinnings therein remain elusive. The study addresses this gap in knowledge.

METHODS: We performed the first controlled human exposure study using functional MRI with an efficient order-randomized double-blind crossover study of diesel exhaust (DE) and control (filtered air; FA) in 25 healthy adults (14 males, 11 females; 19-49 years old; no withdrawals). Analyses were carried out using a mixed effects model in FLAME. Z (Gaussianised T/F) statistic images were thresholded non-parametrically using clusters determined by Z > 2.3 and a (corrected) cluster significance threshold of p = 0.05.

RESULTS: All 25 adults went through the exposures and functional MRI imaging were collected. Exposure to DE yielded a decrease in functional connectivity compared to exposure to FA, shown through the comparison of DE and FA in post-exposure measurement of functional connectivity.

CONCLUSION: We observed short-term pollution-attributable decrements in default mode network functional connectivity. Decrements in brain connectivity causes many detrimental effects to the human body so this finding should guide policy change in air pollution exposure regulation.

TRIAL REGISTRATION: University of British Columbia Clinical Research Ethics Board (# H12-03025), Vancouver Coastal Health Ethics Board (# V12-03025), and Health Canada’s Research Ethics Board (# 2012-0040).

PMID:36641507 | DOI:10.1186/s12940-023-00961-4

J Prosthodont. 2023 Jan 14. doi: 10.1111/jopr.13648. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the effect of different in vitro aging protocols on the optical properties and crystalline structure of high-translucency zirconia.

MATERIALS AND METHODS: Thirty-six specimens of high-translucency (HT) and extra-high translucency (XT) zirconia were divided into three groups: control (CO) – no treatment; hydrothermal aging (HA) – autoclave aging for 12.5 hours at 134°C, 2 bar; clinically-related aging (CRA) – aging in the chewing simulator for 1.2 million cycles, followed by 50,000 thermocycles (5-55°C) and immersion in HCl (pH 1.2) for 15 hours. Optical properties, crystalline structure, and surface roughness were analyzed and compared using Analysis of Variance (5% significance level).

RESULTS: There was no statistically significant effect of aging on translucency (p = 0.10), but CRA promoted the development of a high contrast ratio (p = 0.03). Aging did not cause significant color changes for HT (p = 0.65) or XT (p = 0.36). The proportion of monoclinic crystals increased to 40% for HT-zirconia after HA and 5% after CRA. No monoclinic crystals were detected for XT groups. There was no effect of aging on surface roughness (p = 0.77).

CONCLUSION: Although hydrothermal aging has been widely used to verify zirconia crystalline stability, it did not generate an effect similar to clinically-related aging on the optical properties and crystalline structure of zirconia. Hydrothermal aging affected the crystalline structure of HT-zirconia, and clinically-related aging compromised the optical properties of XT zirconia. This article is protected by copyright. All rights reserved.

PMID:36641491 | DOI:10.1111/jopr.13648

Subst Abuse Treat Prev Policy. 2023 Jan 14;18(1):4. doi: 10.1186/s13011-022-00510-1.

ABSTRACT

BACKGROUND: Medication for opioid use disorder (MOUD) is the gold standard treatment for opioid use disorder. Traditionally, “success” in MOUD treatment is measured in terms of program retention, adherence to MOUD, and abstinence from opioid and other drug use. While clinically meaningful, these metrics may overlook other aspects of the lives of people with opioid use disorder (OUD) and surprisingly do not reflect the diagnostic criteria for OUD.

METHODS: Authors identified items for a pilesorting task to identify participant-driven measures of MOUD treatment success through semi-structured interviews. Interviews were transcribed verbatim and coded in Nvivo using directed and conventional content analysis to identify measures related to treatment success and quality of life goals. Participants of a low-threshold MOUD program were recruited and asked to rank identified measures in order of importance to their own lives. Multidimensional scaling (MDS) compared the similarity of items while non-metric MDS in R specified a two-dimensional solution. Descriptive statistics of participant demographics were generated in SPSS.

RESULTS: Sixteen semi-structured interviews were conducted between June and August 2020 in Philadelphia, PA, USA, and 23 measures were identified for a pilesorting activity. These were combined with 6 traditional measures for a total list of 29 items. Data from 28 people were included in pilesorting analysis. Participants identified a combination of traditional and stakeholder-defined recovery goals as highly important, however, we identified discrepancies between the most frequent and highest ranked items within the importance categories. Measures of success for participants in MOUD programs were complex, multi-dimensional, and varied by the individual. However, some key domains such as emotional well-being, decreased drug use, and attendance to basic functioning may have universal importance. The following clusters of importance were identified: emotional well-being, decreased drug use, and human functioning.

CONCLUSIONS: Outcomes from this research have practical applications for those working to provide services in MOUD programs. Programs can use aspects of these domains to both provide patient-centered care and to evaluate success. Specifics from the pilesorting results may also inform approaches to collaborative goal setting during treatment.

PMID:36641478 | DOI:10.1186/s13011-022-00510-1

BMC Pregnancy Childbirth. 2023 Jan 14;23(1):28. doi: 10.1186/s12884-023-05370-6.

ABSTRACT

OBJECTIVE: We previously described a technique for repair of the myometrial defect at repeat Caesarean section which increases residual myometrial thickness thereby potentially reducing future niche-related complications. Here we describe how this technique can be modified for use for placenta accreta spectrum disorders, in line with emerging evidence that this is more a disorder of myometrial deficiency than morbid adherence.

DESIGN: The surgical performance of peripartum hysterectomy was compared with that of the modified technique in all women having repeat Caesarean delivery for placenta accreta spectrum disorder in a tertiary unit in Singapore between December 2019 and October 2021.

METHODS: Modification of the original technique involved the systematic delivery of the placenta starting from its most posterior attachment after uterine exteriorization. This is followed by the identification, mobilization, and apposition of the boundaries of myometrial defects as described previously.

RESULTS: Ten women had Caesarean hysterectomy and ten had Caesarean section using the modified approach. Age and gestational age at delivery were similar for the two groups. Women in the modified technique group had had fewer prior Caesarean sections and had a lower body mass index. Operating time, estimated blood loss and need for transfusion were all lower in the myometrial repair group but without statistical significance. There were no visceral injuries in the repair group but there was one bladder injury in the hysterectomy group.

CONCLUSION: The modified approach provides an effective alternative to peripartum hysterectomy with favourable surgical profile and allows uterine conservation with restoration of myometrial thickness.

PMID:36641463 | DOI:10.1186/s12884-023-05370-6

BMC Health Serv Res. 2023 Jan 14;23(1):31. doi: 10.1186/s12913-022-09011-0.

ABSTRACT

OBJECTIVES: To determine whether exempting people (with high health needs and living in areas of high deprivation) from a $5 prescription charge reduces hospital use.

DESIGN: Two-group parallel prospective randomised controlled trial.

SETTING: People living in the community in various regions of New Zealand.

PARTICIPANTS: One thousand sixty one people who lived in areas of high socioeconomic deprivation, and either took medicines for diabetes, took antipsychotic medicines, or had chronic obstructive pulmonary disease (COPD). Of the 1053 who completed the study, just under half (49%) were Māori.

INTERVENTIONS: Participants were individually randomized (1-1 ratio) to either be exempted from the standard $5 charge per prescription item for one year (2019-2020) (n = 591) or usual care (n = 469). Those in the intervention group did not pay the standard NZ$5 charge, and pharmacies billed the study for these. Participants continued to pay any other costs for prescription medicines. Those in the control group continued to pay all prescription charges for the year although they may have received one-off assistance from other agencies.

MAIN OUTCOME MEASURES: The primary outcome was length of stay (hospital bed-days). Secondary outcomes presented in this paper included: all-cause hospitalisations, hospitalisations for diabetes/mental health problems/COPD, deaths, and emergency department visits.

RESULTS: The trial was under-powered because the recruitment target was not met. There was no statistically significant reduction in the primary outcome, hospital bed-days (IRR = 0.68, CI: 0.54 to 1.05). Participants in the intervention group were significantly less likely to be hospitalised during the study year than those in the control group (OR = 0.70, CI: 0.54 to 0.90). There were statistically significant reductions in the number of hospital admissions for mental health problems (IRR = 0.39, CI: 0.17 to 0.92), the number of admissions for COPD (IRR = 0.37, CI: 0.16 to 0.85), and length of stay for COPD (IRR 0.20, CI: 0.07 to 0.60). Apart from all-cause mortality and diabetes length of stay, all measures were better for the intervention group than the control group.

CONCLUSIONS: Eliminating a small co-payment appears to have had a substantial effect on patients’ risk of being hospitalised. Given the small amount of revenue gathered from the charges, and the comparative large costs of hospitalisations, the results suggest that these charges are likely to increase the overall cost of healthcare, as well as exacerbate ethnic inequalities.

TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12618001486213 registered on 04/09/2018.

PMID:36641460 | DOI:10.1186/s12913-022-09011-0