Examining Sex Differences in Autism Heritability.

Importance: Autism spectrum disorder (ASD) is a neurodevelopmental disorder more prevalent in males than in females. The cause of ASD is largely genetic, but the association of genetics with the skewed sex ratio is not yet understood. To our knowledge, no large population-based study has provided estimates of heritability by sex. Objective: To estimate the sex-specific heritability of ASD. Design, Setting, and Participants: This was a population-based, retrospective analysis using national health registers of nontwin siblings and cousins from Sweden born between January 1, 1985, and December 31, 1998, with follow-up to 19 years of age. Data analysis occurred from August 2022 to November 2023. Main Outcomes and Measures: Models were fitted to estimate the relative variance in risk for ASD occurrence owing to sex-specific additive genetics, shared environmental effects, and a common residual term. The residual term conceptually captured other factors that promote individual behavioral variation (eg, maternal effects, de novo variants, rare genetic variants not additively inherited, or gene-environment interactions). Estimates were adjusted for differences in prevalence due to birth year and maternal and paternal age by sex. Results: The sample included 1 047 649 individuals in 456 832 families (538 283 males [51.38%]; 509 366 females [48.62%]). Within the entire sample, 12 226 (1.17%) received a diagnosis of ASD, comprising 8128 (1.51%) males and 4098 (0.80%) females. ASD heritability was estimated at 87.0% (95% CI, 81.4%-92.6%) for males and 75.7% (95% CI, 68.4%-83.1%) for females with a difference in heritability estimated at 11.3% (95% CI, 1.0%-21.6%). There was no support for shared environmental contributions. Conclusions and Relevance: These findings suggest that the degree of phenotypic variation attributable to genetic differences (heritability) differs between males and females, indicating that some of the underlying causes of the condition may differ between the 2 sexes. The skewed sex ratio in ASD may be partly explained by differences in genetic variance between the sexes.

Five-Year Clinical Trial of the Low-Concentration Atropine for Myopia Progression (LAMP) Study: Phase 4 Report.

PURPOSE: To evaluate (1) the long-term efficacy of low-concentration atropine over 5 years, (2) the proportion of children requiring re-treatment and associated factors, and (3) the efficacy of pro re nata (PRN) re-treatment using 0.05% atropine from years 3 to 5. DESIGN: Randomized, double-masked extended trial. PARTICIPANTS: Children 4 to 12 years of age originally from the Low-Concentration Atropine for Myopia Progression (LAMP) study. METHODS: Children 4 to 12 years of age originally from the LAMP study were followed up for 5 years. During the third year, children in each group originally receiving 0.05%, 0.025%, and 0.01% atropine were randomized to continued treatment and treatment cessation. During years 4 and 5, all continued treatment subgroups were switched to 0.05% atropine for continued treatment, whereas all treatment cessation subgroups followed a PRN re-treatment protocol to resume 0.05% atropine for children with myopic progressions of 0.5 diopter (D) or more over 1 year. Generalized estimating equations were used to compare the changes in spherical equivalent (SE) progression and axial length (AL) elongation among groups. MAIN OUTCOMES MEASURES: (1) Changes in SE and AL in different groups over 5 years, (2) the proportion of children who needed re-treatment, and (3) changes in SE and AL in the continued treatment and PRN re-treatment groups from years 3 to 5. RESULTS: Two hundred seventy (82.8%) of 326 children (82.5%) from the third year completed 5 years of follow-up. Over 5 years, the cumulative mean SE progressions were -1.34 ± 1.40 D, -1.97 ± 1.03 D, and -2.34 ± 1.71 D for the continued treatment groups with initial 0.05%, 0.025%, and 0.01% atropine, respectively (P = 0.02). Similar trends were observed in AL elongation (P = 0.01). Among the PRN re-treatment group, 87.9% of children (94/107) needed re-treatment. The proportion of re-treatment across all studied concentrations was similar (P = 0.76). The SE progressions for continued treatment and PRN re-treatment groups from years 3 to 5 were -0.97 ± 0.82 D and -1.00 ± 0.74 D (P = 0.55) and the AL elongations were 0.51 ± 0.34 mm and 0.49 ± 0.32 mm (P = 0.84), respectively. CONCLUSIONS: Over 5 years, the continued 0.05% atropine treatment demonstrated good efficacy for myopia control. Most children needed to restart treatment after atropine cessation at year 3. Restarted treatment with 0.05% atropine achieved similar efficacy as continued treatment. Children should be considered for re-treatment if myopia progresses after treatment cessation. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Cost effectiveness of nonpharmacological prevention programs for diabetes: A systematic review of trial-based studies.

Trial-based economic value of prevention programs for diabetes is inexplicit. We aimed to review the cost-effectiveness of nonpharmacological interventions to prevent type-2 diabetes mellitus (T2DM) for high-risk people. Six electronic databases were searched up to March 2022. Studies assessing both the cost and health outcomes of nonpharmacological interventions for people at high-risk of T2DM were included. The quality of the study was assessed by the Consolidated Health Economic Evaluation Reporting Standards 2022 checklist. The primary outcome for synthesis was incremental cost-effectiveness ratios (ICER) for quality-adjusted life years (QALYs), and costs were standardized in 2022 US dollars. Narrative synthesis was performed, considering different types and delivery methods of interventions. Sixteen studies included five based on the US diabetes prevention program (DPP), six on non-DPP-based lifestyle interventions, four on health education, and one on screening plus lifestyle intervention. Compared with usual care, lifestyle interventions showed higher potential of cost-effectiveness than educational interventions. Among lifestyle interventions, DPP-based programs were less cost-effective (median of ICERs: $27,077/QALY) than non-DPP-based programs (median of ICERs: $1395/QALY) from healthcare perspectives, but with larger decreases in diabetes incidence. Besides, the cost-effectiveness of interventions was more possibly realized through the combination of different delivery methods. Different interventions to prevent T2DM in high-risk populations are both cost-effective and feasible in various settings. Nevertheless, economic evidence from low- and middle-income countries is still lacking, and interventions delivered by trained laypersons and combined with peer support sessions or mobile technologies could be potentially a cost-effective solution in such settings with limited resources.

Age-dependent association of central blood pressure with cardiovascular outcomes: a cohort study involving 34 289 participants using the UK biobank.

BACKGROUND: It remained unclear whether central blood pressures (BP) was more closely associated with cardiovascular disease (CVD) than brachial BP in different age groups. OBJECTIVES: To investigate the age-stratified association of CVD with brachial and central BPs, and to evaluate corresponding improvement in model performance. METHODS: This cohort study included 34 289 adults without baseline CVD from the UK Biobank dataset. Participants were categorized into middle-aged and older aged groups using the cut-off of age 65 years. The primary endpoint was a composite cardiovascular outcome consisting of cardiovascular mortality combined with nonfatal coronary events, heart failure and stroke. Multivariable-adjusted hazard ratios expressed CVD risks associated with BP increments of 10 mmHg. Akaike Information Criteria (AIC) was used for model comparisons. RESULTS: In both groups, CVD events were associated with brachial or central SBP ( P  ≤ 0.002). Model fit was better for central SBP in middle-aged adults (AIC 4427.2 vs. 4429.5), but model fit was better for brachial SBP in older adults (AIC 10 246.7 vs. 10 247.1). Central SBP remained significantly associated to CVD events [hazard ratio = 1.05; 95% confidence interval (CI) 1.0-1.1] and improved model fit (AIC = 4426.6) after adjustment of brachial SBP only in the middle-aged adults. These results were consistent for pulse pressure (PP). CONCLUSION: In middle-aged adults, higher central BPs were associated with greater risks of CVD events, even after adjusting for brachial BP indexes. For older adults, the superiority of central BP was not observed. Additional trials with adequate follow-up time will confirm the role of central BP in estimating CVD risk for middle-aged individuals.

Cost-Effectiveness Analysis of Myopia Progression Interventions in Children.

Importance: Several interventions exist for treating myopia progression in children. While these interventions' efficacy has been studied, their cost-effectiveness remains unknown and has not been compared. Objective: To determine cost-effective options for controlling myopia progression in children. Design, Setting, and Participants: In this cost-effectiveness analysis, a Markov model was designed to compare the cost-effectiveness of interventions for controlling myopia progression over 5 years from a societal perspective in a simulated hypothetical cohort of patients aged 10 years with myopia. Myopia interventions considered included atropine eye drops, 0.05% and 0.01%, defocus incorporated multiple segment spectacles, outdoor activity, soft contact lenses (daily disposable and multifocal), rigid gas-permeable contact lenses, progressive addition lenses, bifocal spectacle lenses, orthokeratology, highly aspherical lenslets (HALs), and red light therapy; all interventions were compared with single-vision lenses. Deterministic and probabilistic sensitivity analysis determined the association of model uncertainties with the cost-effectiveness. Costs were obtained from the charges of the Hospital Authority of Hong Kong and The Chinese University of Hong Kong Eye Center. Main Outcome and Measures: The mean costs (in US dollars) per child included the cost of hospital visits, medications, and optical lenses. The outcomes of effectiveness were the annual spherical equivalent refraction (SER) and axial length (AL) reductions. Incremental cost-effectiveness ratios (ICERs) were calculated for each strategy relative to single-vision lenses over a time horizon of 5 years. Results: Outdoor activity, atropine (0.05%), red light therapy, HALs, and orthokeratology were cost-effective. The ICER of atropine, 0.05%, was US $220/SER reduction; red light therapy, US $846/SER reduction; and HALs, US $448/SER reduction. Outdoor activity yielded a savings of US $5/SER reduction and US $8/AL reduction. Orthokeratology resulted in an ICER of US $2376/AL reduction. Conclusions and Relevance: These findings suggest that atropine eye drops, 0.05%, and outdoor activity are cost-effective for controlling myopia progression in children. Though more expensive, red light therapy, HALs, and orthokeratology may also be cost-effective. The use of these interventions may help to control myopia in a cost-effective way.

Cost-effectiveness of virtual reality and wet laboratory cataract surgery simulation.

PURPOSE: To evaluate the cost-effectiveness of phacoemulsification simulation training in virtual reality simulator and wet laboratory on operating theater performance. METHODS: Residents were randomized to a combination of virtual reality and wet laboratory phacoemulsification or wet laboratory phacoemulsification. A reference control group consisted of trainees who had wet laboratory training without phacoemulsification. All trainees were assessed on operating theater performance in 3 sequential cataract patients. International Council of Ophthalmology Surgical Competency Assessment Rubric-phacoemulsification (ICO OSCAR phaco) scores by 2 masked independent graders and cost data were used to determine the incremental cost-effectiveness ratio (ICER). A decision model was constructed to indicate the most cost-effective simulation training strategy based on the willingness to pay (WTP) per ICO OSCAR phaco score gained. RESULTS: Twenty-two trainees who performed phacoemulsification in 66 patients were analyzed. Trainees who had additional virtual reality simulation achieved higher mean ICO OSCAR phaco scores compared with trainees who had wet laboratory phacoemulsification and control (49.5 ± standard deviation [SD] 9.8 vs 39.0 ± 15.8 vs 32.5 ± 12.1, P < .001). Compared with the control group, ICER per ICO OSCAR phaco of wet laboratory phacoemulsification was $13,473 for capital cost and $2209 for recurring cost. Compared with wet laboratory phacoemulsification, ICER per ICO OSCAR phaco of additional virtual reality simulator training was US $23,778 for capital cost and $1879 for recurring cost. The threshold WTP values per ICO OSCAR phaco score for combined virtual reality simulator and wet laboratory phacoemulsification to be most cost-effective was $22,500 for capital cost and $1850 for recurring cost. CONCLUSIONS: Combining virtual reality simulator with wet laboratory phacoemulsification training is effective for skills transfer in the operating theater. Despite of the high capital cost of virtual reality simulator, its relatively low recurring cost is more favorable toward cost-effectiveness.

Dimensional structure of one-year post-COVID-19 neuropsychiatric and somatic sequelae and association with role impairment.

This study examined the latent structure of the broad range of complex neuropsychiatric morbidities occurring 1 year after COVID-19 infection. As part of the CU-COVID19 study, 248 (response rate=39.3%) of 631 adults hospitalized for COVID-19 infection in Hong Kong completed an online survey between March-2021 and January-2022. Disorder prevalence was compared against a random non-infected household sample (n=1834). 248 surveys were received on average 321 days post-infection (Mean age: 48.9, 54% female, moderate/severe/critical infection: 58.2%). 32.4% were screened to have at least one mental disorder, 78.7% of whom had concurrent fatigue/subjective cognitive impairment (SCI). Only PTSD (19.1%) was significantly more common than control (14%, p=0.047). Latent profile analysis classified individuals into P1 (12·4%)-no current neuropsychiatric morbidities, P2 (23.1%)-SCI/fatigue, P3 (45.2%)-anxiety/PTSD, P4 (19.3%)-depression. SCI and fatigue pervaded in all profiles (P2-4) with neuropsychiatric morbidities one-year post-infection. PTSD, anxiety and depressive symptoms were most important in differentiating P2-4. Past mental health and P4 independently predicted functional impairment. Neuropsychiatric morbidity was associated with past mental health, reduced resilience, financial problems, but not COVID-19 severity. Their confluence with depressive and anxiety symptoms predicted impairment and are associated with psychological and environmental factors.

Cost-effectiveness analysis of myopia management: A systematic review.

The rising prevalence of myopia is a major global public health concern. Economic evaluation of myopia interventions is critical for maximizing the benefits of treatment and the healthcare system. This systematic review aimed to evaluate the cost-effectiveness of interventions for treating myopia. Five databases were searched - Embase, Emcare, PubMed, Web of Science, and ProQuest - from inception to July 2022 and a total of 2,099 articles were identified. After careful assessments, 6 studies met the eligibility criteria. The primary outcomes of this systematic review were costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). The secondary outcomes included utility values and net monetary benefits (NMB). One study determined the cost-effectiveness of photorefractive screening plus treatment with 0.01% atropine, 2 studies examined cost-effectiveness of corneal refractive surgery, and 3 studies evaluated cost-effectiveness of commonly used therapies for pathologic myopia. Corneal refractive surgeries included laser in situ keratomileusis (LASIK), femtosecond laser-assisted in situ keratomileusis (FS-LASIK), photorefractive keratectomy (PRK), and small-incision lenticule extraction (SMILE). Interventions for pathologic myopia included ranibizumab, conbercept, and photodynamic therapy (PDT). At an incremental cost of NZ$ 18 (95% CI 15, 20) (US$ 11) per person, photorefractive screening plus 0.01% atropine resulted in an ICER of NZ$ 1,590/QALY (US$ 1,001/QALY) (95% CI NZ$ 1,390, 1,791) for an incremental QALY of 0.0129 (95% CI 0.0127, 0.0131). The cost of refractive surgery in Europe ranged from €3,075 to €3,123 ([US$4,046 to $4,109 - adjusted to 2021 inflation). QALYs associated with these procedures were 23 (FS-LASIK) and 24 (SMILE and PRK) with utility values of 0.8 and ICERs ranging from approximately €14 (US$17)/QALY to €19 (US$23)/QALY. The ICER of LASIK was US$683/diopter gained (inflation-adjusted). The ICER of ranibizumab and PDT were £8,778 (US$12,032)/QALY and US$322,460/QALY respectively, with conbercept yielding a saving of 541,974 RMB (US$80,163)/QALY, respectively. The use of 0.01% atropine and corneal refractive surgery were cost-effective for treating myopia. Treating pathologic myopia with ranibizumab and conbercept were more cost-effective than PDT. Prevention of myopia progression is more cost-effective than treating pathologic myopia.

Effect of Low-Concentration Atropine Eyedrops vs Placebo on Myopia Incidence in Children: The LAMP2 Randomized Clinical Trial.

Importance: Early onset of myopia is associated with high myopia later in life, and myopia is irreversible once developed. Objective: To evaluate the efficacy of low-concentration atropine eyedrops at 0.05% and 0.01% concentration for delaying the onset of myopia. Design, Setting, and Participants: This randomized, placebo-controlled, double-masked trial conducted at the Chinese University of Hong Kong Eye Centre enrolled 474 nonmyopic children aged 4 through 9 years with cycloplegic spherical equivalent between +1.00 D to 0.00 D and astigmatism less than -1.00 D. The first recruited participant started treatment on July 11, 2017, and the last participant was enrolled on June 4, 2020; the date of the final follow-up session was June 4, 2022. Interventions: Participants were assigned at random to the 0.05% atropine (n = 160), 0.01% atropine (n = 159), and placebo (n = 155) groups and had eyedrops applied once nightly in both eyes over 2 years. Main Outcomes and Measures: The primary outcomes were the 2-year cumulative incidence rate of myopia (cycloplegic spherical equivalent of at least -0.50 D in either eye) and the percentage of participants with fast myopic shift (spherical equivalent myopic shift of at least 1.00 D). Results: Of the 474 randomized patients (mean age, 6.8 years; 50% female), 353 (74.5%) completed the trial. The 2-year cumulative incidence of myopia in the 0.05% atropine, 0.01% atropine, and placebo groups were 28.4% (33/116), 45.9% (56/122), and 53.0% (61/115), respectively, and the percentages of participants with fast myopic shift at 2 years were 25.0%, 45.1%, and 53.9%. Compared with the placebo group, the 0.05% atropine group had significantly lower 2-year cumulative myopia incidence (difference, 24.6% [95% CI, 12.0%-36.4%]) and percentage of patients with fast myopic shift (difference, 28.9% [95% CI, 16.5%-40.5%]). Compared with the 0.01% atropine group, the 0.05% atropine group had significantly lower 2-year cumulative myopia incidence (difference, 17.5% [95% CI, 5.2%-29.2%]) and percentage of patients with fast myopic shift (difference, 20.1% [95% CI, 8.0%-31.6%]). The 0.01% atropine and placebo groups were not significantly different in 2-year cumulative myopia incidence or percentage of patients with fast myopic shift. Photophobia was the most common adverse event and was reported by 12.9% of participants in the 0.05% atropine group, 18.9% in the 0.01% atropine group, and 12.2% in the placebo group in the second year. Conclusions and Relevance: Among children aged 4 to 9 years without myopia, nightly use of 0.05% atropine eyedrops compared with placebo resulted in a significantly lower incidence of myopia and lower percentage of participants with fast myopic shift at 2 years. There was no significant difference between 0.01% atropine and placebo. Further research is needed to replicate the findings, to understand whether this represents a delay or prevention of myopia, and to assess longer-term safety. Trial Registration: Chinese Clinical Trial Registry: ChiCTR-IPR-15006883.

Global Burden, Regional Differences, Trends, and Health Consequences of Medication Nonadherence for Hypertension During 2010 to 2020: A Meta-Analysis Involving 27 Million Patients.

Background Nonadherence to antihypertensive medications is the leading cause of poor blood pressure control and thereby cardiovascular diseases and mortality worldwide. Methods and Results We investigated the global epidemiology, regional differences, and trend of antihypertensive medication nonadherence via a systematic review and meta-analyses of data from 2010 to 2020. Multiple medical databases and clinicaltrials.gov were searched for articles. Observational studies reporting the proportion of patients with anti-hypertensive medication nonadherence were included. The proportion of nonadherence, publication year, year of first recruitment, country, and health outcomes attributable to antihypertensive medication nonadherence were extracted. Two reviewers screened abstracts and full texts, classified countries according to levels of income and locations, and extracted data. The Joanna Briggs Institute prevalence critical appraisal tool was used to rate the included studies. Prevalence meta-analyses were conducted using a fixed-effects model, and trends in prevalence were analyzed using meta-regression. The certainty of evidence concerning the effect of health consequences of nonadherence was rated according to Grading of Recommendations, Assessment, Development and Evaluations. A total of 161 studies were included. Subject to different detection methods, the global prevalence of anti-hypertensive medication nonadherence was 27% to 40%. Nonadherence was more prevalent in low- to middle-income countries than in high-income countries, and in non-Western countries than in Western countries. No significant trend in prevalence was detected between 2010 and 2020. Patients with antihypertensive medication nonadherence had suboptimal blood pressure control, complications from hypertension, all-cause hospitalization, and all-cause mortality. Conclusions While high prevalence of anti-hypertensive medication nonadherence was detected worldwide, higher prevalence was detected in low- to middle-income and non-Western countries. Interventions are urgently required, especially in these regions. Current evidence is limited by high heterogeneity. Registration URL: www.crd.york.ac.uk/prospero/; Unique identifier: CRD42021259860.

Sensitivity and specificity of automated blood pressure devices to detect atrial fibrillation: A systematic review and meta-analysis of diagnostic accuracy.

Background: Atrial fibrillation (AF) is a prevalent and preventable cause of stroke and mortality. Aim: This systematic review and meta-analysis aimed to investigate the sensitivity and specificity of office and out-of-office automated blood pressure (BP) devices to detect AF. Methods: Diagnostic studies, extracted from databases such as Ovid Medline and Embase, on AF detection by BP device(s), electrocardiography, and reported sensitivity and specificity, were included. Screening of abstracts and full texts, data extraction, and quality assessment were conducted independently by two investigators using Covidence software. The sensitivity and specificity of the BP devices were pooled using a random-effects model. Results: Sixteen studies including 10,158 participants were included. Only a few studies were conducted in primary care (n = 3) or with a low risk of bias (n = 5). Office BP devices, which utilised different algorithms to detect AF, had a sensitivity and specificity of 96.2 and 94%, respectively. Specificity was reduced when only one positive result was considered among consecutive BP measurements. Only a few studies (n = 3) investigated out-of-office BP. Only one study (n = 100) suggested the use of ≥79 and ≥26% of positive readings on 24-h ambulatory BP measurements to detect AF and paroxysmal AF, respectively. Conclusions: Office BP devices can be used clinically to screen for AF in high-risk populations. Clinical trials are needed to determine the effect of AF screening using office BP devices in reducing stroke risk and mortality. Further studies are also required to guide out-of-office use of BP devices for detecting paroxysmal AF or AF. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022319541, PROSPERO CRD42022319541.

Metformin use and the risk of total knee replacement among diabetic patients: a propensity-score-matched retrospective cohort study.

Metformin has been shown to modulate meta-inflammation, an important pathogenesis in knee osteoarthritis (OA). The study aimed to test the association between regular metformin use with total knee replacement (TKR) in patients with diabetes. This is a retrospective study with electronic records retrieved in Hong Kong public primary care. Patients with diabetes aged ≥ 45 who visited during 2007 to 2010, were followed up for a four-year period from 2011 to 2014 to determine the incidence of TKR. Propensity score matching based on age, sex, co-medications and chronic conditions was conducted to adjust for confounding. Cox regression was implemented to examine the association between metformin use and TKR. In total, 196,930 patients were eligible and 93,330 regular metformin users (defined as ≥ 4 prescriptions over the previous year) and non-users were matched. Among 46,665 regular users, 184 TKRs were conducted, 17.1% fewer than that among non-users. Cox regression showed that regular metformin users had a 19%-lower hazard of TKR [hazard ratio (HR) = 0.81, 95% confidence interval: 0.67 to 0.98, P = 0.033], with a dose-response relationship. Findings suggest a potential protective effect of metformin on knee OA progression and later TKR incidence among diabetic patients.

Cost-effectiveness of pharmacological therapies for people with Alzheimer's disease and other dementias: a systematic review and meta-analysis.

OBJECTIVES: This study aims to synthesize the empirical economic evidence of pharmaceutical therapies for people with dementia. STUDY DESIGN: Systematic review and meta-analysis. Literature evaluating the costs and effects of drug therapies for dementia was indexed until December 2021. Quality of study was assessed using the Cochrane Risk of Bias Tool and Consensus on Health Economic Criteria list. Cost data were standardized to 2020 US dollars and analyzed from healthcare service and societal perspectives. Random-effects models were used to synthesize economic and clinical data, based on mean differences (MDs) and standardized MDs. RESULTS: Ten unique studies were identified from 11,771 records. Acetylcholinesterase inhibitors (AChEIs) and memantine improved dementia-related symptoms, alongside nonsignificant savings in societal cost (AChEIs: MD-2002 [- 4944 ~ 939]; memantine: MD-6322 [- 14355 ~ 1711]). Despite decreases in cost, antidepressants of mirtazapine and sertraline and second-generation antipsychotics were limited by their significant side effects on patients' cognitive and activity functions. Subgroup analysis indicated that the impacts of AChEIs on cost were affected by different analytical perspectives, follow-up periods, and participant age. CONCLUSIONS: AChEIs and memantine are cost-effective with improvements in dementia-related symptoms and trends of cost-savings. More empirical evidence with non-industrial sponsorships and rigorous design in different settings is warranted.

Effectiveness of Peri-Discharge Complex Interventions for Reducing 30-Day Readmissions among COPD Patients: Overview of Systematic Reviews and Network Meta-Analysis.

BACKGROUND: An overview of systematic reviews(SRs) and network meta-analysis(NMA) were conducted to evaluate the comparative effectiveness of peri-discharge complex interventions for reducing 30-day readmissions among chronic obstructive pulmonary disease(COPD) patients. METHODS: Five databases were searched for SRs of randomized controlled trials(RCTs). An additional search was conducted for updated RCTs from database inception until Jun 2020. Pooled effect of peri-discharge complex interventions was assessed using random-effect pairwise meta-analyses. Comparative effectiveness across different peri-discharge complex interventions was evaluated using NMA. RESULTS: Nine SRs and 11 eligible RCTs(n = 1,422) assessing eight different peri-discharge complex interventions were included. For reducing 30-day all-cause readmissions, pairwise meta-analysis showed no significant difference between peri-discharge complex interventions and usual care, while NMA indicated no significant differences among different peri-discharge complex interventions as well as usual care. For reducing 30-day COPD-related readmissions, peri-discharge complex interventions were significantly more effective than usual care (pooled RR = 0.45, 95% CI:0.24-0.84). CONCLUSIONS: Peri-discharge complex interventions may not differ from usual care in reducing 30-day all-cause readmissions among COPD patients but some are more effective for lowering 30-day COPD-related readmission. Thus, complex intervention comprising core components of patient education, self-management, patient-centred discharge instructions, and telephone follow up may be considered for implementation, but further evaluation is warranted.

Sociodemographic moderation of the association between depression and stroke incidence in a retrospective cohort of 0.4 million primary care recipients with hypertension.

BACKGROUND: Previous research has suggested an association between depression and subsequent acute stroke incidence, but few studies have examined any effect modification by sociodemographic factors. In addition, no studies have investigated this association among primary care recipients with hypertension. METHODS: We examined the anonymized records of all public general outpatient visits by patients aged 45+ during January 2007-December 2010 in Hong Kong to extract primary care patients with hypertension for analysis. We took the last consultation date as the baseline and followed them up for 4 years (until 2011-2014) to observe any subsequent acute hospitalization due to stroke. Mixed-effects Cox models (random intercept across 74 included clinics) were implemented to examine the association between depression (ICPC diagnosis or anti-depressant prescription) at baseline and the hazard of acute stroke (ICD-9: 430-437.9). Effect modification by age, sex, and recipient status of social security assistance was examined in extended models with respective interaction terms specified. RESULTS: In total, 396 858 eligible patients were included, with 9099 (2.3%) having depression, and 10 851 (2.7%) eventually hospitalized for stroke. From the adjusted analysis, baseline depression was associated with a 17% increased hazard of acute stroke hospitalization [95% confidence interval (CI) 1.03-1.32]. This association was suggested to be even stronger among men than among women (hazard ratio = 1.29, 95% CI 1.00-1.67). CONCLUSION: Depression is more strongly associated with acute stroke incidence among male than female primary care patients with hypertension. More integrated services are warranted to address their needs.

Comparing drawing under instructions with image copying for mild cognitive impairment (MCI) or dementia screening: a meta-analysis of 92 diagnostic studies.

OBJECTIVES: Drawing is a major component of cognitive screening for dementia. It can be performed without language restriction. Drawing pictures under instructions and copying images are different screening approaches. The objective of this study was to compare the diagnostic performance between drawing under instructions and image copying for MCI and dementia screening. METHOD: A literature search was carried out in the OVID databases with keywords related to drawing for cognitive screening. Study quality and risk of bias were assessed by QUADAS-2. The level of diagnostic accuracy across different drawing tests was pooled by bivariate analysis in a random effects model. The area under the hierarchical summary receiver-operating characteristic curve (AUC) was constructed to summarize the diagnostic performance. RESULTS: Ninety-two studies with sample size of 22,085 were included. The pooled results for drawing under instructions showed a sensitivity of 79% (95% CI: 76 - 83%) and a specificity of 80% (95% CI: 77 - 83%) with AUC of 0.87 (95% CI: 0.83 - 0.89). The pooled results for image copying showed a sensitivity of 71% (95% CI: 62 - 79%) and a specificity of 83% (95% CI: 72 - 90%) with AUC of 0.83 (95% CI: 0.80 - 0.86). Clock-drawing test was the screening test used in the majority of studies. CONCLUSION: Drawing under instructions showed a similar diagnostic performance when compared with image copying for cognitive screening and the administration of image copying is relatively simpler. Self-screening for dementia is feasible to be done at home in the near future.

Evaluation of Digital Drawing Tests and Paper-and-Pencil Drawing Tests for the Screening of Mild Cognitive Impairment and Dementia: A Systematic Review and Meta-analysis of Diagnostic Studies.

Digital drawing tests have been proposed for cognitive screening over the past decade. However, the diagnostic performance is still to clarify. The objective of this study was to evaluate the diagnostic performance among different types of digital and paper-and-pencil drawing tests in the screening of mild cognitive impairment (MCI) and dementia. Diagnostic studies evaluating digital or paper-and-pencil drawing tests for the screening of MCI or dementia were identified from OVID databases, included Embase, MEDLINE, CINAHL, and PsycINFO. Studies evaluated any type of drawing tests for the screening of MCI or dementia and compared with healthy controls. This study was performed according to PRISMA and the guidelines proposed by the Cochrane Diagnostic Test Accuracy Working Group. A bivariate random-effects model was used to compare the diagnostic performance of these drawing tests and presented with a summary receiver-operating characteristic curve. The primary outcome was the diagnostic performance of clock drawing test (CDT). Other types of drawing tests were the secondary outcomes. A total of 90 studies with 22,567 participants were included. In the screening of MCI, the pooled sensitivity and specificity of the digital CDT was 0.86 (95% CI = 0.75 to 0.92) and 0.92 (95% CI = 0.69 to 0.98), respectively. For the paper-and-pencil CDT, the pooled sensitivity and specificity of brief scoring method was 0.63 (95% CI = 0.49 to 0.75) and 0.77 (95% CI = 0.68 to 0.84), and detailed scoring method was 0.63 (95% CI = 0.56 to 0.71) and 0.72 (95% CI = 0.65 to 0.78). In the screening of dementia, the pooled sensitivity and specificity of the digital CDT was 0.83 (95% CI = 0.72 to 0.90) and 0.87 (95% CI = 0.79 to 0.92). The performances of the digital and paper-and-pencil pentagon drawing tests were comparable in the screening of dementia. The digital CDT demonstrated better diagnostic performance than paper-and-pencil CDT for MCI. Other types of digital drawing tests showed comparable performance with paper-and-pencil formats. Therefore, digital drawing tests can be used as an alternative tool for the screening of MCI and dementia.

Comparative accuracies of automated and manual office blood pressure measurements in a Chinese population.

We aimed to assess the difference in the accuracy of readings from automated office blood pressure machines with each other or with manual office blood pressure measurements in Chinese individuals. We collected awake 48-h ambulatory blood pressure monitoring, two automated office blood pressure device (BpTRU and WatchBP) readings, and manual office blood pressure measurements in Chinese patients (n = 135) with hypertension in a randomized sequence. Differences were compared using paired t-tests and Bland-Altman plots. The sensitivity and specificity of the techniques for detecting elevated blood pressure were calculated using awake ambulatory blood pressure monitoring as the reference standard. The WatchBP device's and awake ambulatory blood pressure readings were similar. The BpTRU device provided significantly lower mean systolic (P < 0.001) and diastolic (P < 0.001) blood pressure readings, while manual office BP provided significantly higher mean systolic (P = 0.008) and diastolic (P < 0.001) blood pressure readings than the awake automated office blood pressure readings. Automated and manual office blood pressure measurements showed similar sensitivity, specificity, and 95% limits of agreement as based on Bland-Altman plots. The mean systolic (P < 0.001) and diastolic (P < 0.02) blood pressure readings of WatchBP and BpTRU differed, and their diagnostic performances were not superior than those of manual office blood pressure measurements in Chinese patients. Therefore, automated office blood pressure measurements cannot be routinely recommended for Chinese individuals in clinical practice. More studies are needed to confirm these results.

Three-Year Clinical Trial of Low-Concentration Atropine for Myopia Progression (LAMP) Study: Continued Versus Washout: Phase 3 Report.

PURPOSE: (1) To compare the efficacy of continued and stopping treatment for 0.05%, 0.025%, and 0.01% atropine during the third year. (2) To evaluate the efficacy of continued treatment over 3 years. (3) To investigate the rebound phenomenon and its determinants after cessation of treatment. DESIGN: A randomized, double-masked extended trial. PARTICIPANTS: A total of 350 of 438 children aged 4 to 12 years originally recruited into the Low-Concentration Atropine for Myopia Progression (LAMP) study. METHODS: At the beginning of the third year, children in each group were randomized at a 1:1 ratio to continued treatment and washout subgroups. Cycloplegic spherical equivalent (SE) refraction and axial length (AL) were measured at 4-month intervals. MAIN OUTCOME MEASURES: Changes in SE and AL between groups. RESULTS: A total of 326 children completed 3 years of follow-up. During the third year, SE progression and AL elongation were faster in the washout subgroups than in the continued treatment groups across all concentrations: -0.68 ± 0.49 diopters (D) versus -0.28 ± 0.42 D (P < 0.001) and 0.33 ± 0.17 mm versus 0.17 ± 0.14 mm (P < 0.001) for the 0.05%; -0.57 ± 0.38 D versus -0.35 ± 0.37 D (P = 0.004) and 0.29 ± 0.14 mm versus 0.20 ± 0.15 mm (P = 0.001) for the 0.025%; -0.56 ± 0.40 D versus -0.38 ± 0.49 D (P = 0.04) and 0.29 ± 0.15 mm versus 0.24 ± 0.18 mm (P = 0.13) for the 0.01%. Over the 3-year period, SE progressions were -0.73 ± 1.04 D, -1.31 ± 0.92 D, and -1.60 ± 1.32 D (P = 0.001) for the 0.05%, 0.025%, and 0.01% groups in the continued treatment subgroups, respectively, and -1.15 ± 1.13 D, -1.47 ± 0.77 D, and -1.81 ± 1.10 D (P = 0.03), respectively, in the washout subgroup. The respective AL elongations were 0.50 ± 0.40 mm, 0.74 ± 0.41 mm, and 0.89 ± 0.53 mm (P < 0.001) for the continued treatment subgroups and 0.70 ± 0.47 mm, 0.82 ± 0.37 mm, and 0.98 ± 0.48 mm (P = 0.04) for the washout subgroup. The rebound SE progressions during washout were concentration dependent, but their differences were clinically small (P = 0.15). Older age and lower concentration were associated with smaller rebound effects in both SE progression (P < 0.001) and AL elongation (P < 0.001). CONCLUSIONS: During the third year, continued atropine treatment achieved a better effect across all concentrations compared with the washout regimen. 0.05% atropine remained the optimal concentration over 3 years in Chinese children. The differences in rebound effects were clinically small across all 3 studied atropine concentrations. Stopping treatment at an older age and lower concentration are associated with a smaller rebound.