Category: Nevin Manimala

Biomed Chromatogr. 2022 Jun 2:e5421. doi: 10.1002/bmc.5421. Online ahead of print.

ABSTRACT

Alzheimer’s disease (AD) is regarded as a progressive neurodegenerative dementia, characterized by degeneration of distinct neuronal populations. A case-control study was carried out by using high resolution mass spectrometry to explore AD associated urinary metabolic biomarkers from 30 AD patients and 30 cognitively normal (CN) individuals, respectively. In total, 49 metabolites were determined and validated as known compounds by LC/MS analysis. With two sample t-test statistical analysis (p<0.05), 19 metabolites were shown to be significantly differed from AD to CN. A diagnostic model of receiver-operator characteristic (ROC) curve was constructed with a combination of 9 selected metabolites and yielded a separation with an area under the curve value of 0.976 between two groups. This study indicated urinary metabolites showed a significant expression between AD and CN. AD related metabolites enable to satisfy the diagnostic power of disease discrimination. Additionally, as a non-invasive approach, urine collection provides its convenience in clinical diagnosis of AD.

PMID:35653409 | DOI:10.1002/bmc.5421

PLoS One. 2022 Jun 2;17(6):e0269387. doi: 10.1371/journal.pone.0269387. eCollection 2022.

ABSTRACT

BACKGROUND: The single patient (n-of-1) trial can be used to resolve therapeutic uncertainty for the individual patient. Treatment alternatives are systematically tested against each other, generating patient-specific data used to inform an individualized treatment plan. We hypothesize that clinical decisions informed by n-of-1 trials improve patient outcomes compared to usual care. Our objective was to provide an overview of the clinical trial evidence on the effect of n-of-1 trials on clinical outcomes.

METHODS: A systematic search of medical databases, trial registries, and gray literature was performed to identify trials assessing clinical outcomes in a group of patients undergoing an n-of-1 trial compared to those receiving usual care for any clinical condition. We abstracted elements related to study design and results and assessed risk of bias for both the overall randomized trials and the n-of-1 trials. The review was registered on PROSPERO. (CRD: 42020166490).

FINDINGS: Twelve randomized trials of the n-of-1 approach were identified in conditions spanning chronic pain, osteoarthritis, chronic irreversible airflow limitation, attention-deficit hyperactivity disorder, hyperlipidemia, atrial fibrillation, statin intolerance, and hypertension. One trial showed a statistically significant benefit in the primary outcome. Only one reached the pre-specified sample size target. Secondary outcomes showed modest benefits, including decreasing medication use, fewer atrial fibrillation episodes, and improved patient satisfaction.

INTERPRETATION: Very few trials have been undertaken to assess the effectiveness of n-of-1 trials in improving clinical outcomes, and most trials were underpowered for the primary outcome. Barriers to enrollment and retention in these trials should be explored, as well-powered randomized trials are needed to clarify the clinical impact of n-of-1 trials and assess their utility in clinical practice.

PMID:35653405 | DOI:10.1371/journal.pone.0269387

PLoS Comput Biol. 2022 Jun 2;18(6):e1010172. doi: 10.1371/journal.pcbi.1010172. Online ahead of print.

ABSTRACT

Gene-based association analysis is an effective gene-mapping tool. Many gene-based methods have been proposed recently. However, their power depends on the underlying genetic architecture, which is rarely known in complex traits, and so it is likely that a combination of such methods could serve as a universal approach. Several frameworks combining different gene-based methods have been developed. However, they all imply a fixed set of methods, weights and functional annotations. Moreover, most of them use individual phenotypes and genotypes as input data. Here, we introduce sumSTAAR, a framework for gene-based association analysis using summary statistics obtained from genome-wide association studies (GWAS). It is an extended and modified version of STAAR framework proposed by Li and colleagues in 2020. The sumSTAAR framework offers a wider range of gene-based methods to combine. It allows the user to arbitrarily define a set of these methods, weighting functions and probabilities of genetic variants being causal. The methods used in the framework were adapted to analyse genes with large number of SNPs to decrease the running time. The framework includes the polygene pruning procedure to guard against the influence of the strong GWAS signals outside the gene. We also present new improved matrices of correlations between the genotypes of variants within genes. These matrices estimated on a sample of 265,000 individuals are a state-of-the-art replacement of widely used matrices based on the 1000 Genomes Project data.

PMID:35653402 | DOI:10.1371/journal.pcbi.1010172

PLoS One. 2022 Jun 2;17(6):e0269192. doi: 10.1371/journal.pone.0269192. eCollection 2022.

ABSTRACT

Adding abiraterone acetate (AA) plus prednisolone (P) to standard of care (SOC) improves survival in newly diagnosed advanced prostate cancer (PC) patients starting hormone therapy. Our objective was to determine the value for money to the English National Health Service (NHS) of adding AAP to SOC. We used a decision analytic model to evaluate cost-effectiveness of providing AAP in the English NHS. Between 2011-2014, the STAMPEDE trial recruited 1917 men with high-risk localised, locally advanced, recurrent or metastatic PC starting first-line androgen-deprivation therapy (ADT), and they were randomised to receive SOC plus AAP, or SOC alone. Lifetime costs and quality-adjusted life-years (QALYs) were estimated using STAMPEDE trial data supplemented with literature data where necessary, adjusting for baseline patient and disease characteristics. British National Formulary (BNF) prices (£98/day) were applied for AAP. Costs and outcomes were discounted at 3.5%/year. AAP was not cost-effective. The incremental cost-effectiveness ratio (ICER) was £149,748/QALY gained in the non-metastatic (M0) subgroup, with 2.4% probability of being cost-effective at NICE’s £30,000/QALY threshold; and the metastatic (M1) subgroup had an ICER of £47,503/QALY gained, with 12.0% probability of being cost-effective. Scenario analysis suggested AAP could be cost-effective in M1 patients if priced below £62/day, or below £28/day in the M0 subgroup. AAP could dominate SOC in the M0 subgroup with price below £11/day. AAP is effective for non-metastatic and metastatic disease but is not cost-effective when using the BNF price. AAP currently only has UK approval for use in a subset of M1 patients. The actual price currently paid by the English NHS for abiraterone acetate is unknown. Broadening AAP’s indication and having a daily cost below the thresholds described above is recommended, given AAP improves survival in both subgroups and its cost-saving potential in M0 subgroup.

PMID:35653395 | DOI:10.1371/journal.pone.0269192

J Interpers Violence. 2022 Jun 2:8862605221101185. doi: 10.1177/08862605221101185. Online ahead of print.

ABSTRACT

All forms of family violence may negatively affect a child’s development. However, research on child maltreatment is primarily focused on the child who is directly maltreated and does not often account for how other children in the family experience the abuse. The central aim of our study was to better understand how children’s direct experience of physical abuse and exposure to physical abuse influence their academic outcomes. Data were taken from the Minnesota Departments of Education and Human Services. The sample was developed from a population-level cohort of 8-10 years old children (N = 1740) from two groups: Child Protective Service (CPS)-involved (a child who allegedly experienced physical abuse or a child who was exposed to the alleged physical abuse of another child in their household) and the matched comparison. Exposure to intimate partner violence (IPV) was also measured for CPS-involved children. School attendance and academic achievement were examined over 4 years. Descriptive statistics and Generalized Estimating Equations (GEE) were used to answer the three research questions. Over time, declines in attendance for children exposed to physical abuse were significantly greater than those of their matched peers. Exposure to IPV for CPS-involved children resulted in further declines in attendance. Math proficiency of children who experienced physical abuse declined at a significantly faster rate than their matched peers. The decline in reading proficiency of both children who experienced physical abuse and children exposed to physical abuse was more significantly pronounced than that of their matched peers. Differences in math and reading proficiency were eliminated when IPV exposure was taken into account. Child protection workers and school professionals should be aware of negative effects of experiences of and exposures to child maltreatment and work collaboratively to provide academic support, counseling, and other interventions to support children’s academic stability.

PMID:35653186 | DOI:10.1177/08862605221101185

JMIR Form Res. 2022 Jun 2;6(6):e32147. doi: 10.2196/32147.

ABSTRACT

BACKGROUND: Heart failure (HF) is a costly health condition and a major public health problem. It is estimated that 2%-3% of the population in developed countries has HF, and the prevalence increases to 8% among patients aged ≥75 years. Home telemonitoring is a form of noninvasive, remote patient monitoring that aims to improve the care and management of patients with chronic HF. Telehealth for Emergency-Community Continuity of Care Connectivity via Home-Telemonitoring (TEC4Home) is a project that implements and evaluates a comprehensive home monitoring protocol designed to support patients with HF as they transition from the emergency department to home.

OBJECTIVE: The aim of this study is to assess the cost of using the home monitoring platform (TEC4Home) relative to usual care for patients with HF.

METHODS: This study is a cost-consequence analysis of the TEC4Home pilot study. The analysis was conducted from a partial societal perspective, including direct and indirect health care costs. The aim is to assess the costs of the home monitoring platform relative to usual care and track costs related to health care utilization during the 90-day postdischarge period.

RESULTS: Economic analysis of the TEC4Home pilot study showed a positive trend in cost savings for patients using TEC4Home. From both the health system perspective (Pre TEC4Home cost per patient: CAD $2924 vs post TEC4Home cost per patient: CAD $1293; P=.01) and partial societal perspective (Pre TEC4Home cost per patient: CAD $2411 vs post TEC4Home cost per patient: CAD $1108; P=.01), we observed a statistically significant cost saving per patient.

CONCLUSIONS: In line with the advantages of conducting an economic analysis alongside a feasibility study, the economic analysis of the TEC4Home pilot study facilitated the piloting of patient questionnaires and informed the methodology for a full clinical trial.

PMID:35653179 | DOI:10.2196/32147

J Med Internet Res. 2022 Jun 2;24(6):e35947. doi: 10.2196/35947.

ABSTRACT

BACKGROUND: Although preventive interventions for eating disorders in general have shown promise, interventions specifically targeting individuals at risk for anorexia nervosa (AN) are lacking.

OBJECTIVE: The aim of this study was to determine the efficacy of a guided, indicated web-based prevention program for women at risk for AN.

METHODS: We conducted a randomized controlled efficacy trial for women at risk for AN. Assessments were carried out at baseline (before the intervention), after the intervention (10 weeks after baseline), and at 6- and 12-month follow-ups (FUs). A total of 168 women with low body weight (17.5 kg/m²≤BMI≤19 kg/m²) and high weight concerns or with normal body weight (19 kg/m²<BMI≤25 kg/m²), high weight concerns, and high restrained eating were recruited from 3 German universities as well as on the web and randomized to Student Bodies-AN (SB-AN; intervention group [IG]) or a wait-list control group (CG). The exclusion criteria were current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-based full-syndrome eating disorders and serious medical or mental problems. The interventions were a cognitive-behavioral guided web-based prevention program (SB-AN) over 10 weeks (IG) and a wait-list CG. The primary outcomes were clinically significant changes in disordered eating attitudes and behaviors and change in BMI at 12-month FU in the group of participants who were underweight. The secondary outcomes were new onset of eating disorders, symptoms of disordered eating, and associated psychopathology.

RESULTS: Data were available for 81.5% (137/168) of the women after the intervention and for 69% (116/168) of the women at 12-month FU. At 12-month FU, the IG participants showed larger decreases in Eating Disorder Examination total scores (38/48, 79% vs 33/58, 57%) than the CG participants and the IG participants who were underweight also showed larger clinically relevant increases in BMI (15/31, 49% vs 10/32, 32%) than the CG participants, but these differences were not significant. In addition, after the intervention and at 12-month FU, we found a significant increase in continuously measured BMI for the participants who were underweight and significant improvements in disordered eating attitudes and behaviors (eg, restrained eating as well as weight and shape concerns). At all time points, the rates of new-onset eating disorder cases were (nonsignificantly) lower in the IG than in the CG and the reductions in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-based eating disorder syndromes were (nonsignificantly) higher in the IG than in the CG.

CONCLUSIONS: SB-AN is the first preventive intervention shown to significantly reduce specific risk factors for, and symptoms of, AN and shows promise for reducing full-syndrome AN onset.

TRIAL REGISTRATION: ISRCTN Registry ISRCTN70380261; https://www.isrctn.com/ISRCTN70380261.

PMID:35653174 | DOI:10.2196/35947

JAMA Netw Open. 2022 Jun 1;5(6):e2215863. doi: 10.1001/jamanetworkopen.2022.15863.

ABSTRACT

IMPORTANCE: Gender minority adults experience higher rates of sexual violence (SV) than cisgender adults. How this disparity extends to youths, including perpetration rates, is unknown.

OBJECTIVE: To compare rates of experience and perpetration of SV by gender identity and investigate characteristics associated with odds of perpetration within gender identity categories.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used baseline data from a national online longitudinal survey collected in 2018 to 2020. Eligible participants were youths ages 14 to 16 years who read English and had internet access. Data were analyzed in November 2021 and March 2022.

EXPOSURES: Youth characteristics included stressors associated with being marginalized (eg, internalized transphobia), general stressors (eg, trauma not associated with experiencing SV), other marginalized statuses (eg, identifying as a girl), factors associated with protection (eg, social support), environmental characteristics (eg, community violence exposure), and risk factors associated with SV (eg, consumption of violent pornography).

MAIN OUTCOMES AND MEASURES: Self-reported rates of experiencing and perpetrating SV, defined as sexual assault, rape, attempted rape, and coercive sex, among cisgender, transgender, and nonbinary youths.

RESULTS: Among 4193 youths in the sample (mean [SD] age, 14.8 [0.7] years), 3282 participants (78.3%) were cisgender, 329 participants (7.9%) were transgender, and 582 participants (13.9%) were nonbinary. The odds of SV perpetration were not statistically significantly different for transgender boys and girls (odds ratio [OR], 0.90; 95% CI, 0.57-1.41; P = .64) or nonbinary youths (OR, 0.78; 95% CI, 0.54-1.12; P = .18) compared with cisgender boys and girls. By contrast, transgender boys and girls (OR, 2.31; 95% CI, 1.83-2.91; P < .001) and nonbinary youths (OR, 2.37; 95% CI, 1.98-2.83; P < .001) were more than 2-fold as likely as cisgender boys and girls to report experiencing SV. Aggressive behavior was associated with higher odds of SV perpetration for transgender boys and girls (adjusted OR [aOR], 1.87; 95% CI, 0.75-4.65; P = .18) and nonbinary youths (aOR, 1.61; 95% CI, 0.78-3.32; P = .20). Indications of hostile masculinity were associated with higher odds of SV perpetration among cisgender youths (ie, positive attitudes for boys to engage in rape behaviors: aOR per unit increase in score, 1.15; 95% CI, 1.07-1.25; P < .001; sexual dominance: aOR per unit increase in score, 1.03; 95% CI, 1.01-1.04; P < .001) but not among transgender or nonbinary youths.

CONCLUSION AND RELEVANCE: These findings may suggest an important foundation for the development of inclusive, research-based SV prevention programs and methods for incorporating gender identity effectively into SV research.

PMID:35653152 | DOI:10.1001/jamanetworkopen.2022.15863

JAMA Netw Open. 2022 Jun 1;5(6):e2212449. doi: 10.1001/jamanetworkopen.2022.12449.

ABSTRACT

IMPORTANCE: Resettled refugees in high-income countries represent a vulnerable population. It is known that refugees have high rates of trauma-related mental health issues; however, ad hoc research has generally revealed low rates of health services use among refugees. Such research usually samples a population at a single point in time and is based on targeted surveys. Because refugee populations change over time, such research becomes expensive and time-consuming for agencies interested in routinely publishing statistics of mental health services use among refugees. The linking of large administrative data sets to establish rates of use of mental health services among resettled refugees is a flexible and relatively inexpensive approach.

OBJECTIVE: To use data linkage to establish rates of mental health services use among resettled refugees relative to the general population.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study implemented data linkage from the Refugee Health Nurse Program for 10 050 refugees who resettled in Sydney, Australia, from October 23, 2012, to June 8, 2017, with data concerning use of community mental health services and mental health hospitalization from New South Wales Health databases. Data were analyzed between June 1, 2019, and December 31, 2021.

MAIN OUTCOMES AND MEASURES: Rates of service contacts with community mental health services among the resettled refugees were compared with those of the general population by age, sex, and the most common International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnosis codes. Length of community mental health service sessions and rates of mental health hospitalizations were also compared.

RESULTS: Among the 255 resettled refugees who had contacts with community mental health care services and were not missing data (median age, 35 [range, 4-80] years; 117 [64%] male and 138 [54%] female), 153 (60%) were born in Iraq and 156 (61%) were Arabic speaking. This population was less likely to use mental health services than the general population and had shorter community mental health consultations. The rate of contacts with community mental health services for depressive disorders among the resettled refugee population was 40% (95% CI, 33%-46%) lower than that among the general population. Rates of same-day hospitalization per 10 000 person-years were not significantly different between the refugee population (4 [95% CI, 2-8]) and the general Australian population (7 [95% CI, 7-7]). However, the refugee population was 17% (95% CI, 6%-29%) more likely than the general Australian population to interact with the community mental health system for severe stress- and adjustment disorder-related diagnoses.

CONCLUSIONS AND RELEVANCE: These findings suggest that refugees who have resettled in Australia tend to use fewer mental health services than the general population except for services devoted to stress- and adjustment disorder-related diagnoses. These findings also suggest that it is possible to successfully leverage data linkage to study patterns of mental health services use among resettled refugees.

PMID:35653157 | DOI:10.1001/jamanetworkopen.2022.12449

JAMA Ophthalmol. 2022 Jun 2. doi: 10.1001/jamaophthalmol.2022.1640. Online ahead of print.

ABSTRACT

IMPORTANCE: After the Age-Related Eye Disease Study 2 (AREDS2) study, the beta carotene component was replaced by lutein/zeaxanthin for the development of the revised AREDS supplement. However, it is unknown if the increased risk of lung cancer observed in those assigned beta carotene persists beyond the conclusion of the AREDS2 trial and if there is a benefit of adding lutein/zeaxanthin to the original AREDS supplement that can be observed with long-term follow-up.

OBJECTIVE: To assess 10-year risk of developing lung cancer and late age-related macular degeneration (AMD).

DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter epidemiologic follow-up study of the AREDS2 clinical trial, conducted from December 1, 2012, to December 31, 2018. Included in the analysis were participants with bilateral or unilateral intermediate AMD for an additional 5 years after clinical trial. Eyes/participants were censored at the time of late AMD development, death, or loss to follow-up. Data were analyzed from November 2019 to March 2022.

INTERVENTIONS: During the clinical trial, participants were randomly assigned primarily to lutein/zeaxanthin and/or ω-3 fatty acids or placebo and secondarily to no beta carotene vs beta carotene and low vs high doses of zinc. In the epidemiologic follow-up study, all participants received AREDS2 supplements with lutein/zeaxanthin, vitamins C and E, and zinc plus copper. Outcomes were assessed at 6-month telephone calls. Analyses of AMD progression and lung cancer development were conducted using proportional hazards regression and logistic regression, respectively.

MAIN OUTCOMES AND MEASURES: Self-reported lung cancer and late AMD validated with medical records.

RESULTS: This study included 3882 participants (mean [SD] baseline age, 72.0 [7.7] years; 2240 women [57.7%]) and 6351 eyes. At 10 years, the odds ratio (OR) of having lung cancer was 1.82 (95% CI, 1.06-3.12; P = .02) for those randomly assigned to beta carotene and 1.15 (95% CI, 0.79-1.66; P = .46) for lutein/zeaxanthin. The hazard ratio (HR) for progression to late AMD comparing lutein/zeaxanthin with no lutein/zeaxanthin was 0.91 (95% CI, 0.84-0.99; P = .02) and comparing ω-3 fatty acids with no ω-3 fatty acids was 1.01 (95% CI, 0.93-1.09; P = .91). When the lutein/zeaxanthin main effects analysis was restricted to those randomly assigned to beta carotene, the HR was 0.80 (95% CI, 0.68-0.92; P = .002). A direct analysis of lutein/zeaxanthin vs beta carotene showed the HR for late AMD was 0.85 (95% CI, 0.73-0.98; P = .02). The HR for low vs high zinc was 1.04 (95% CI, 0.94-1.14; P = .49), and the HR for no beta carotene vs beta carotene was 1.04 (95% CI, 0.94-1.15; P = .48).

CONCLUSIONS AND RELEVANCE: Results of this long-term epidemiologic follow-up study of the AREDS2 cohort suggest that lutein/zeaxanthin was an appropriate replacement for beta carotene in AREDS2 supplements. Beta carotene usage nearly doubled the risk of lung cancer, whereas there was no statistically significant increased risk with lutein/zeaxanthin. When compared with beta carotene, lutein/zeaxanthin had a potential beneficial association with late AMD progression.

PMID:35653117 | DOI:10.1001/jamaophthalmol.2022.1640