MMWR Morb Mortal Wkly Rep. 2023 Jan 6;72(1):16. doi: 10.15585/mmwr.mm7201a4.
NO ABSTRACT
PMID:36602935 | DOI:10.15585/mmwr.mm7201a4
Tag: statistics
Cochrane Database Syst Rev. 2023 Jan 5;1:CD013856. doi: 10.1002/14651858.CD013856.pub2.
ABSTRACT
BACKGROUND: Physical exercise is effective in managing Parkinson’s disease (PD), but the relative benefit of different exercise types remains unclear.
OBJECTIVES: To compare the effects of different types of physical exercise in adults with PD on the severity of motor signs, quality of life (QoL), and the occurrence of adverse events, and to generate a clinically meaningful treatment ranking using network meta-analyses (NMAs).
SEARCH METHODS: An experienced information specialist performed a systematic search for relevant articles in CENTRAL, MEDLINE, Embase, and five other databases to 17 May 2021. We also searched trial registries, conference proceedings, and reference lists of identified studies up to this date.
SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing one type of physical exercise for adults with PD to another type of exercise, a control group, or both.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. A third author was involved in case of disagreements. We categorized the interventions and analyzed their effects on the severity of motor signs, QoL, freezing of gait, and functional mobility and balance up to six weeks after the intervention using NMAs. Two review authors independently assessed the risk of bias using the risk of bias 2 (RoB 2) tool and rated the confidence in the evidence using the CINeMA approach for results on the severity of motor signs and QoL. We consulted a third review author to resolve any disagreements. Due to heterogeneous reporting of adverse events, we summarized safety data narratively and rated our confidence in the evidence using the GRADE approach.
MAIN RESULTS: We included 156 RCTs with a total of 7939 participants with mostly mild to moderate disease and no major cognitive impairment. The number of participants per study was small (mean 51, range from 10 to 474). The NMAs on the severity of motor signs and QoL included data from 71 (3196 participants), and 55 (3283 participants) trials, respectively. Eighty-five studies (5192 participants) provided safety data. Here, we present the main results. We observed evidence of beneficial effects for most types of physical exercise included in our review compared to a passive control group. The effects on the severity of motor signs and QoL are expressed as scores on the motor scale of the Unified Parkinson Disease Rating Scale (UPDRS-M) and the Parkinson’s Disease Questionnaire 39 (PDQ-39), respectively. For both scales, higher scores denote higher symptom burden. Therefore, negative estimates reflect improvement (minimum clinically important difference: -2.5 for UPDRS-M and -4.72 for PDQ-39). Severity of motor signs The evidence from the NMA (71 studies; 3196 participants) suggests that dance has a moderate beneficial effect on the severity of motor signs (mean difference (MD) -10.32, 95% confidence interval (CI) -15.54 to -4.96; high confidence), and aqua-based, gait/balance/functional, and multi-domain training might have a moderate beneficial effect on the severity of motor signs (aqua-based: MD -7.77, 95% CI -13.27 to -2.28; gait/balance/functional: MD -7.37, 95% CI -11.39 to -3.35; multi-domain: MD -6.97, 95% CI -10.32 to -3.62; low confidence). The evidence also suggests that mind-body training and endurance training might have a small beneficial effect on the severity of motor signs (mind-body: MD -6.57, 95% CI -10.18 to -2.81; endurance: MD -6.43, 95% CI -10.72 to -2.28; low confidence). Flexibility training might have a trivial or no effect on the severity of motor signs (MD 2.01, 95% CI -4.82 to 8.98; low confidence). The evidence is very uncertain about the effects of strength/resistance training and “Lee Silverman Voice training BIG” (LSVT BIG) on the severity of motor signs (strength/resistance: MD -6.97, 95% CI -11.93 to -2.01; LSVT BIG: MD -5.49, 95% CI -14.74 to 3.62; very low confidence). Quality of life The evidence from the NMA (55 studies; 3283 participants) suggests that aqua-based training probably has a large beneficial effect on QoL (MD -14.98, 95% CI -23.26 to -6.52; moderate confidence). The evidence also suggests that endurance training might have a moderate beneficial effect, and that gait/balance/functional and multi-domain training might have a small beneficial effect on QoL (endurance: MD -9.16, 95% CI -15.68 to -2.82; gait/balance/functional: MD -5.64, 95% CI -10.04 to -1.23; multi-domain: MD -5.29, 95% CI -9.34 to -1.06; low confidence). The evidence is very uncertain about the effects of mind-body training, gaming, strength/resistance training, dance, LSVT BIG, and flexibility training on QoL (mind-body: MD -8.81, 95% CI -14.62 to -3.00; gaming: MD -7.05, 95% CI -18.50 to 4.41; strength/resistance: MD -6.34, 95% CI -12.33 to -0.35; dance: MD -4.05, 95% CI -11.28 to 3.00; LSVT BIG: MD 2.29, 95% CI -16.03 to 20.44; flexibility: MD 1.23, 95% CI -11.45 to 13.92; very low confidence). Adverse events Only 85 studies (5192 participants) provided some kind of safety data, mostly only for the intervention groups. No adverse events (AEs) occurred in 40 studies and no serious AEs occurred in four studies. AEs occurred in 28 studies. The most frequently reported events were falls (18 studies) and pain (10 studies). The evidence is very uncertain about the effect of physical exercise on the risk of adverse events (very low confidence). Across outcomes, we observed little evidence of differences between exercise types.
AUTHORS’ CONCLUSIONS: We found evidence of beneficial effects on the severity of motor signs and QoL for most types of physical exercise for people with PD included in this review, but little evidence of differences between these interventions. Thus, our review highlights the importance of physical exercise regarding our primary outcomes severity of motor signs and QoL, while the exact exercise type might be secondary. Notably, this conclusion is consistent with the possibility that specific motor symptoms may be treated most effectively by PD-specific programs. Although the evidence is very uncertain about the effect of exercise on the risk of adverse events, the interventions included in our review were described as relatively safe. Larger, well-conducted studies are needed to increase confidence in the evidence. Additional studies recruiting people with advanced disease severity and cognitive impairment might help extend the generalizability of our findings to a broader range of people with PD.
PMID:36602886 | DOI:10.1002/14651858.CD013856.pub2
Biometrics. 2023 Jan 5. doi: 10.1111/biom.13822. Online ahead of print.
ABSTRACT
Publication bias is a major concern in conducting systematic reviews and meta-analyses. Various sensitivity analysis or bias-correction methods have been developed based on selection models, and they have some advantages over the widely used trim-and-fill bias-correction method. However, likelihood methods based on selection models may have difficulty in obtaining precise estimates and reasonable confidence intervals, or require a rather complicated sensitivity analysis process. Herein, we develop a simple publication bias adjustment method by utilizing the information on conducted but still unpublished trials from clinical trial registries. We introduce an estimating equation for parameter estimation in the selection function by regarding the publication bias issue as a missing data problem under the missing not at random assumption. With the estimated selection function, we introduce the inverse probability weighting (IPW) method to estimate the overall mean across studies. Furthermore, the IPW versions of heterogeneity measures such as the between-study variance and the measure are proposed. We propose methods to construct confidence intervals based on asymptotic normal approximation as well as on parametric bootstrap. Through numerical experiments, we observed that the estimators successfully eliminated bias, and the confidence intervals had empirical coverage probabilities close to the nominal level. On the other hand, the confidence interval based on asymptotic normal approximation is much wider in some scenarios than the bootstrap confidence interval. Therefore, the latter is recommended for practical use. This article is protected by copyright. All rights reserved.
PMID:36602873 | DOI:10.1111/biom.13822
JCI Insight. 2023 Jan 5:e156049. doi: 10.1172/jci.insight.156049. Online ahead of print.
ABSTRACT
HIV non-progression despite persistent viraemia is rare among antiretroviral therapy (ART)-naïve adults, but relatively common among ART-naïve children. Previous studies indicate that ART-naïve paediatric slow-progressors (PSPs) adopt immune evasion strategies similar to those described in the SIV natural hosts. However, the mechanisms underlying this immunophenotype are not well understood. In a cohort of early-treated infants who underwent analytical treatment interruption (ATI) after 12 months of ART, expression of PD-1 on CD8+ T-cells immediately prior to ATI was the main predictor of slow progression during ATI (r=0.77, p=0.002). PD-1+ CD8+ T-cell frequency was also negatively correlated with CCR5 (r=-0.74, p=0.005) and HLA-DR (r=-0.63, p=0.02) expression on CD4+ T-cells and predicted stronger HIV-specific T-lymphocyte responses. In the CD8+ T-cell compartment of PSPs, we identified an enrichment of stem-like TCF-1+PD-1+ memory cells, whereas paediatric progressors and viraemic adults were populated with a terminally exhausted PD-1+CD39+ population. TCF-1+PD-1+ expression on CD8+ T-cells was associated with higher proliferative activity (r=0.41, p=0.03) and stronger Gag-specific effector functionality. These data prompt the hypothesis that the proliferative burst potential of stem-like HIV-specific cytotoxic cells could be exploited in therapeutic strategies to boost the antiviral response and facilitate remission in early-ART-treated infants with a preserved and non-exhausted T-cell compartment.
PMID:36602861 | DOI:10.1172/jci.insight.156049
Pol Arch Intern Med. 2023 Jan 5:16405. doi: 10.20452/pamw.16405. Online ahead of print.
ABSTRACT
INTRODUCTION: The SARS-CoV-2 infection is associated with an increased risk of thromboembolic complications.
OBJECTIVES: We aimed to compare patient characteristics, and 12-month clinical outcomes of myocardial infarction with non-obstructive coronary arteries (MINOCA) before and during the COVID-19 pandemic.
PATIENTS AND METHODS: We retrospectively analyzed data of 51,734 patients with acute myocardial infarction registered in the nationwide PL-ACS database in 2019 and 2020, finally including 3,178 MINOCA patients. We compared baseline characteristics, management strategies, and 12-month clinical outcomes of MINOCA patients before (2019) and during (2020) the COVID-19 pandemic.
RESULTS: The MINOCA percentage was higher in 2019 than 2020 (6.3% vs. 5.9%, P = 0.03). The groups did not differ apart from the higher hypercholesterolemia rate before the pandemic (33.9% vs. 28.2%, P < 0.001). We observed in-hospital stroke more frequently during pandemic (0 vs. 0.3%, P = 0.01). However, other in-hospital complications were similar between groups. Most patients were discharged on aspirin (85.6%), beta-blocker (73.1%), angiotensin convertase enzyme inhibitor/angiotensin receptor blocker (70.2%), and statin (62.7%), but only 50.6% of patients received P2Y12 inhibitor. There was no statistical difference in 12-month all-cause mortality in patients with MINOCA before and during pandemic (total population 9.9%; 9.2% [2019] vs. 11.0% [2020], P = 0.09).
CONCLUSIONS: We observed a lower percentage of MINOCA cases and higher in-hospital stroke rates in MINOCA patients during the COVID-19 pandemic. The possible association between worse clinical outcomes of MINOCA patients during the COVID-19 pandemic and thromboembolic complications of SARS-CoV-2 infection needs further evaluation.
PMID:36602860 | DOI:10.20452/pamw.16405
Pol Arch Intern Med. 2023 Jan 5:16403. doi: 10.20452/pamw.16403. Online ahead of print.
ABSTRACT
INTRODUCTION: Coronavirus disease 2019 to this day caused more than 6 million deaths worldwide. So far five variants of concerns have been identified with Delta and Omicron being the subject of our analysis.
OBJECTIVES: We aim to compare baseline characteristics and outcomes of patients hospitalized during Delta and Omicron predominance in Poland.
PATIENTS AND METHODS: The study population consisted of 2,225 patients divided into two groups depending on the variant with which they were infected during the corresponding period of the pandemic.
RESULTS: During the Delta wave, the median age of patients was significantly lower (65 vs. 73 years, p<0.001), and the cohort was significantly less burdened by comorbidities than during the Omicron surge. Omicron-infected patients presented significantly less often in an unstable symptomatic state with SpO2 ≤90% on admission (49.9% vs. 29.9%, p<0.001). Regardless of the pandemic period, the two most common early symptoms of COVID-19 were fever and cough. In-hospital treatment consisted of antiviral drugs, more frequently used in the Omicron wave, and immunomodulatory drugs more frequently used during the Delta wave. The risk of mechanical ventilation was significantly lower in patients infected with Omicron (7.2% vs. 3.1%, p<0.001). For the age group >80 years the risk of death was significantly higher during the Delta wave as compared to Omicron wave. The risk of death was statistically significantly lower in patients treated with antiviral drugs regardless of the pandemic wave.
CONCLUSIONS: The Delta variant causes a more severe clinical course of the disease and a higher risk of death compared to the Omicron variant.
PMID:36602857 | DOI:10.20452/pamw.16403
JMIR Form Res. 2023 Jan 5;7:e40062. doi: 10.2196/40062.
ABSTRACT
BACKGROUND: Despite the increasing prevalence of obesity, the use of pharmacotherapy treatment remains low. Telehealth platforms have the potential to facilitate access to pharmacotherapy interventions, but little is known about telehealth patients.
OBJECTIVE: This study describes a large patient population taking Plenity, an oral superabsorbent hydrogel (OSH) used in the treatment of excess weight or obesity (BMI 25-40 kg/m2). The analysis compared differences in weight loss practices and in-person access to obesity care among telehealth patients with preobesity and obesity.
METHODS: This was a cross-sectional assessment of a random sample of 20,000 telehealth patients who completed a structured, web-based visit and received at least one prescription of OSH. Patients were eligible to receive care via telehealth if they were adults, were not pregnant, and had a BMI ≥25 kg/m2. During the visit, patients provided baseline health information including comorbidities, diet, and exercise habits. Their zip code of residence was used to determine their proximity to an obesity medicine provider. Descriptive statistical analysis and tests of differences (chi-square and 2-tailed t tests) were used to compare patients with preobesity (BMI 25-29.9 kg/m2) and obesity (BMI 30-40 kg/m2).
RESULTS: Most (15,576/20,000, 77.88%) of the cohort were female, with a mean age of 44 (SD 11) years and a mean BMI of 32.4 (SD 4.1) kg/m2. Among the cohort, 32.13% (6426/20,000) had preobesity, and 40.18% (8036/20,000) of all patients had ≥1 weight-related comorbidity. Almost all (19,732/20,000, 98.66%) patients attempted 1 weight loss method before OSH and half (10,067/20,000, 50.34%) tried ≥4 different methods. Exercise and low-calorie diets were the most attempted weight loss methods, and 28.76% (5752/20,000) of patients reported a prior prescription of weight loss medication. Patients with obesity were more likely than patients with preobesity to have previously tried commercial weight loss plans (7294/13,574, 53.74% vs 2791/6426, 43.43%; P<.001), specialized diets (8493/13,574, 62.57% vs 3799/6426, 59.12%; P<.001), over-the-counter supplements (6807/13,574, 50.15% vs 2876/6426, 44.76%; P<.001), and prescription weight loss medications (4407/13,574, 32.47% vs 1345/6426, 20.93%; P<.001). Females were more likely to seek treatment for preobesity (5332/15,576, 34.23% vs 1094/4424, 24.73% male; P<.001) and reported fewer comorbidities (5992/15,576, 38.47% vs 2044/4424, 46.2% male; P<.001), despite >90% of both sexes reporting the belief that excess weight negatively affected their health (14,247/15,576, 91.47% female participants, 4116/4424, 93.04% male participants). Moreover, 29.25% (5850/20,000) of patients lived in the same zip code and 85.15% (17,030/20,000) lived in the same county as an obesity medicine provider.
CONCLUSIONS: Data from this large patient cohort supports the potential for telehealth to provide prescriptive weight management treatment to a population seeking care. Patients with preobesity are an undertreated population who actively seek new weight management options. Female participants sought weight management treatment earlier in the disease continuum than males, despite reporting fewer comorbidities.
PMID:36602855 | DOI:10.2196/40062
JMIR Res Protoc. 2023 Jan 5;12:e38603. doi: 10.2196/38603.
ABSTRACT
BACKGROUND: Mobile health apps have the potential to motivate people to adopt healthier behavior, but many fail to maintain this behavior over time. However, it has been suggested that long-term adherence can be improved by personalizing the proposed interventions. Based on the literature, we created a conceptual framework for selecting appropriate functionalities according to the user’s profile.
OBJECTIVE: This cross-sectional study aims to investigate if the relationships linking functionalities and profiles proposed in our conceptual framework are confirmed by user preferences.
METHODS: A web-based questionnaire comprising several sections was developed to determine the mobile app functionalities most likely to promote healthier behavior. First, participants completed questionnaires to define the user profile (Big Five Inventory-10, Hexad Scale, and perception of the social norm using dimensions of the Theory of Planned Behavior). Second, participants were asked to select the 5 functionalities they considered to be the most relevant to motivate healthier behavior and to evaluate them on a score ranging from 0 to 100. We will perform logistic regressions with the selected functionalities as dependent variables and with the 3 profile scales as predictors to allow us to understand the effect of the participants’ scores on each of the 3 profile scales on the 5 selected functionalities. In addition, we will perform logistic ordinal regressions with the motivation score of the functionalities chosen as dependent variables and with scores of the 3 profile scales as predictors to determine whether the scores on the different profile scales predict the functionality score.
RESULTS: Data collection was conducted between July and December 2021. Analysis of responses began in January 2022, with the publication of results expected by the end of 2022.
CONCLUSIONS: This study will allow us to validate our conceptual model by defining the preferred functionalities according to user profiles.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/38603.
PMID:36602850 | DOI:10.2196/38603
Am J Respir Crit Care Med. 2023 Jan 5. doi: 10.1164/rccm.202207-1331OC. Online ahead of print.
ABSTRACT
RATIONALE: Idiopathic pulmonary fibrosis is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to non-genetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF. However, the extent to which rare variants genome-wide may contribute to the risk of IPF remains unknown.
OBJECTIVES: We used whole-genome sequencing to investigate the role of rare variants, genome-wide, on IPF risk.
METHODS: As part of the Trans-Omics for Precision Medicine Program, we sequenced 2,180 cases of IPF. Association testing focused on the aggregated effect of rare variants (minor allele frequency ≤0.01) within genes or regions. We also identified individual variants that are influential within genes and estimated the heritability of IPF based on rare and common variants.
MEASUREMENTS AND MAIN RESULTS: Rare variants in both TERT and RTEL1 were significantly associated with IPF. A single rare variant in each of the TERT and RTEL1 genes was found to consistently influence the aggregated test statistics. There was no significant evidence of association with other previously reported rare variants. The SNP-heritability of IPF was estimated to be 32% (s.e. 3%).
CONCLUSIONS: Rare variants within the TERT and RTEL1 genes and well-established common variants have the largest contribution to IPF risk overall. Efforts in risk profiling or development of therapies for IPF that focus on TERT, RTEL1, common variants, and environmental risk factors are likely to have the largest impact on this complex disease.
PMID:36602845 | DOI:10.1164/rccm.202207-1331OC
J Med Internet Res. 2023 Jan 5;25:e43601. doi: 10.2196/43601.
ABSTRACT
BACKGROUND: Telemedicine has a long history; however, its efficacy has been reported with mixed reviews. Studies have reported a wide range of quality implications when using the telemedicine modality of care.
OBJECTIVE: This study aimed to analyze the effectiveness of telemedicine through 6 domains of quality through an analysis of randomized controlled trials (RCTs) published in the literature published, to date, in 2022.
METHODS: A total of 4 databases were searched using a standard Boolean string. The 882,420 results were reduced to 33 for analysis through filtering and randomization. The systematic literature review was conducted in accordance with the Kruse Protocol and reported in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses; 2020).
RESULTS: The Cohen κ statistic was calculated to show agreement between the reviewers (Cohen κ=0.90, strong). Medical outcomes associated with the telemedicine modality were 100% effective with a weighted average effect size of 0.21 (small effect). Many medical outcomes were positive but not statistically better than treatment as usual. RCTs have reported positive outcomes for physical and mental health, medical engagement, behavior change, increased quality of life, increased self-efficacy, increased social support, and reduced costs. All 6 domains of quality were identified in the RCTs and 4 were identified in 100% of the studies. Telemedicine is highly patient-centered because it meets digital preferences, is convenient, avoids stigma, and enables education at one’s own pace. A few barriers exist to its wide adoption, such as staff training and cost, and it may not be the preferred modality for all.
CONCLUSIONS: The effectiveness of telemedicine is equal to or greater than that of traditional care across a wide spectrum of services studied in this systematic literature review. Providers should feel comfortable offering this modality of care as a standard option to patients where it makes sense to do so. Although barriers exist for wide adoption, the facilitators are all patient facing.
TRIAL REGISTRATION: PROSPERO CRD42022343478; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=343478.
PMID:36602844 | DOI:10.2196/43601