rTMS for post-covid-19 condition: A sham-controlled case series involving iTBS-300 and iTBS-600.

Post-Covid-19 Condition (PCC) is a syndrome comprised of symptoms persisting 3 months or more beyond SARS-CoV-2 primary infection. It is typically characterized by fatigue, cognitive problems and psychiatric symptoms, as well as cardiac symptoms that contribute to exercise intolerance in many. Despite the high prevalence of PCC among those with a prior SARS-CoV-2 infection, there is currently no widely accepted rehabilitation strategy, and many conventional modalities are movement-based. Non-invasive brain stimulation methods such as repetitive transcranial magnetic stimulation (rTMS) may have some potential to alleviate the cognitive and affective symptoms of PCC without reliance on exercise. The purpose of the present study was to explore the feasibility and tolerability of using rTMS to treat symptoms of "brain fog" and affective disturbance among those living with PCC, using a case series design. We enrolled four individuals with PCC following a confirmed SARS-CoV-2 infection, at least 3 months after the resolution of the primary infection. Participants were randomized to 4 sessions of active and 2 sessions of sham intermittent theta-burst stimulation (iTBS); two intensities of iTBS were evaluated: iTBS-300 and iTBS-600. No adverse events occurred in active or sham stimulation; 2 participants reported tingling sensation on the scalp but no other tolerability issues. Trends in symptoms suggested improvements in cognitive interference, quality of life, and anxiety in the majority of participants. In summary, in this case series iTBS was well tolerated among 4 individuals with PCC; active stimulation was associated with positive trends in some primary symptom clusters as compared with sham stimulation. Future studies should examine the effects of iTBS on PCC symptoms in the context of experimental studies and randomized controlled trials.

Diabetes status and cognitive function in middle-aged and older adults in the Canadian longitudinal study on aging.

Objectives: Diabetes is recognized as a significant risk factor for cognitive impairment. However, this association has not been thoroughly examined using large-scale population-based datasets in the Canadian context. The objective of this study was to investigate the potential association between cognitive function and diabetes in a large population-based sample of middle-aged and older Canadians. Methods: We utilized baseline data from the Canadian Longitudinal Study on Aging (N=30,097) to test our hypotheses, using five indicators of cognitive function (animal fluency, Stroop interference, reaction time, immediate and delayed memory recall). We conducted multivariate multivariable linear regression and subsequently performed tests for moderation analysis with lifestyle factors and health status. Results: The analysis revealed that type 2 diabetes (T2DM) was associated with lower performance on most cognitive tasks, including those assessing executive function (b=0.60, 95% CI 0.31 to 0.90), reaction time (b=16.94, 95% CI 9.18 to 24.70), immediate memory recall (b=-0.10, 95% CI -0.18 to -0.02), and delayed memory recall (b=-0.12, 95% CI -0.21 to -0.02). However, no significant association was observed between other types of diabetes and cognitive performance. Moderation effects were largely null for T2DM, with the exception of alcohol intake for reaction time, and physical activity for animal fluency. Conclusions: The study showed that individuals with T2DM exhibit poor performance on tasks that assess executive function, reaction time, and memory. Therefore, optimizing cognitive health among individuals with T2DM should be a priority in primary care. Additionally, further studies should examine this association using longitudinal data.

Bidirectional Associations Between Adiposity and Cognitive Function and Mediation by Brain Morphology in the ABCD Study.

Importance: Most epidemiologic studies examine the brain as an outcome in relation to adiposity (ie, the brain-as-outcome perspective), but it is also a potential risk factor associated with adiposity accumulation over time (ie, the brain-as-risk factor perspective). The bidirectionality hypothesis has not been fully explored in adolescent samples previously. Objective: To assess bidirectional associations between adiposity and cognitive function in youth and test mediational pathways through brain morphology (specifically the lateral prefrontal cortex [LPFC]), lifestyle behaviors, and blood pressure. Design, Setting, and Participants: This cohort study uses data (wave 1-3; 2 years of follow-up) from the Adolescent Brain Cognitive Development (ABCD) Study, a long-term longitudinal investigation of brain development in the United States launched in 2015, which recruited 11 878 children aged 9 to 10 years at inception. Data analysis was performed from August 2021 to June 2022. Main Outcomes and Measures: Multivariate multivariable regression analyses were used to assess bidirectional associations of indicators of cognitive function (eg, executive function, processing speed, episodic memory, receptive vocabulary and reading skills) and adiposity (eg, body mass index z scores [zBMI] and waist circumference [WC]). Mediators considered for this investigation were lifestyle variables (eg, diet and physical activity), blood pressure, and the morphology of the LPFC and its subregions. Results: A total of 11 103 individuals (mean [SD] age, 9.91 [0.6] years; 5307 females [48%]; 8293 White individuals [75%] and 2264 Hispanic individuals [21%]) were included in the current study. Multivariate multivariable regression analyses revealed that higher baseline zBMI and WC were associated with worse follow-up episodic memory (ß, -0.04; 95% CI, -0.07 to -0.01) and better vocabulary (ß, 0.03; 95% CI, 0.002 to 0.06) task performance, in covariate adjusted models. Similarly, superior baseline executive function (zBMI: ß, -0.03; 95% CI, -0.06 to -0.01; WC: ß, -0.04; 95% CI, -0.07 to -0.01) and episodic memory (zBMI: ß, -0.04; 95% CI, -0.07 to -0.02; WC: ß, -0.03; 95% CI, -0.06 to -0.002) task performance were associated with better follow-up adiposity status in covariate adjusted models. Cross-lagged panel models with latent variable modeling had a bidirectional association with executive function task performance (brain-as-outcome: ß, -0.02; 95% CI, -0.05 to -0.001; brain-as-risk factor: ß, -0.01; 95% CI, -0.02 to -0.003). The hypothesized associations were statistically mediated by LPFC volume and thickness, physical activity, and blood pressure. Conclusions and Relevance: In this cohort study, executive function and episodic memory were bidirectionally associated with adiposity indices over time in this adolescent sample. These findings suggest that the brain can be both a risk factor and an outcome of adiposity; this complex bidirectional association should be taken into account in future research and clinical practice.

Cognitive Function Is Associated With Multiple Indices of Adiposity in the Canadian Longitudinal Study on Aging: A Cross-Sectional Analysis.

OBJECTIVE: Prior studies have suggested reciprocal relationships between cognitive function and adiposity, but this has not been investigated with population representative data sets. The purpose of this study was to examine the association between cognitive function and adiposity in a large population-based sample of middle-aged and older adults. It was hypothesized that better scores on tests of cognitive function would be associated with lower adiposity, and this association would be primarily mediated through life-style behavior and physical health status. METHODS: Using baseline data from the Canadian Longitudinal Study on Aging ( N = 30,097), we tested our hypotheses using three indicators of cognitive function (animal fluency, Stroop interference, and reaction time) and four indicators of adiposity (body mass index, total fat mass, waist circumference, and waist-hip ratio). Hierarchical multivariable linear regression modeling was conducted followed by tests for moderation by socioeconomic status and mediation through diet, physical activity, hypertension, and diabetes status. RESULTS: All measures of cognitive indicators were significantly associated with adiposity after adjusting for confounders. In general, superior performance on animal fluency, Stroop, and reaction time tasks were associated with lower adiposity by most metrics. Stroop interference was associated with lower adiposity across all metrics, including body mass index ( b = - 0.04, 95 % confidence interval [CI] = - 0.06 to - 0.01), total fat mass ( b = 19.35, 95 % CI = 8.57 to 30.12), waist circumference ( b = 33.83, 95 % CI = 10.08 to 57.58), and waist-hip ratio ( b = 0.13, 95 % CI = 0.01 to 0.24). These associations were more substantial for moderate- and high-income subpopulations. Mediation analyses suggested that the aforementioned effects were mediated through life-style behavior (e.g., diet and physical activity) and physical health conditions (e.g., diabetes and hypertension). CONCLUSIONS: Reliable associations exist between cognitive function and adiposity in middle-aged and older adults. The associations seem to be mediated through life-style behavior and physical health conditions.

Layperson-Led vs Professional-Led Behavioral Interventions for Weight Loss in Pediatric Obesity: A Systematic Review and Meta-analysis.

Importance: The appropriate approach for weight loss among children and adolescents with overweight and obesity remains unclear. Objective: To evaluate the difference in the treatment outcomes associated with behavioral weight loss interventions led by laypersons and professionals in comparison with unsupervised control arms among children and adolescents with overweight and obesity. Data Sources: For this systematic review and meta-analysis, the Medical Literature Analysis and Retrieval System Online (MEDLINE), Embase, the Cochrane Library, and Cumulative Index of Nursing and Allied Health Literature (CINAHL) databases were searched from January 1, 1996, to June 1, 2019. Study Selection: Included in this study were randomized clinical trials (RCTs) of behavioral interventions lasting at least 12 weeks for children and adolescents (aged 5-18 years) with overweight and obesity. Exclusion criteria included non-RCT studies, interventions lasting less than 12 weeks, adult enrollment, participants with other medical diagnoses, pharmacological treatment use, and articles not written in English. Two of 6 reviewers independently screened all citations. Of 25 586 citations, after duplicate removal, 78 RCTs (5780 participants) met eligibility criteria. Data Extraction and Synthesis: A bayesian framework and Markov chain Monte Carlo simulation methods were used to combine direct and indirect associations. Random-effects and fixed-effect network meta-analysis models were used with the preferred model chosen by comparing the deviance information criteria. This study was registered with the International Prospective Register of Systematic Reviews (PROSPERO) and followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Main Outcomes and Measures: The immediate and sustained changes in weight and body mass index (BMI) standardized mean difference (SMD) were primary outcomes planned before data collection began, whereas waist circumference and percent body fat were secondary outcomes. The hypothesis being tested was formulated before the data collection. Results: Of 25 586 citations retrieved, we included 78 RCTs (5780 participants), with a follow-up of 12 to 104 weeks. Compared with the control condition, random-effects models revealed that professional-led weight loss interventions were associated with reductions in weight (mean difference [MD], -1.60 kg [95% CI, -2.30 to -0.99 kg]; 68 trials; P < .001) and BMI (SMD, -0.30 [95% CI, -0.39 to -0.20]; 59 trials; P < .001) that were not sustained long term (weight MD, -1.02 kg [95% CI, -2.20 to 0.34 kg]; 21 trials; P = .06; BMI SMD, -0.12 [95% CI, -0.46 to 0.21]; 20 trials; P < .001). There was no association between layperson-led interventions and weight loss in the short-term (MD, -1.40 kg [95% CI, -3.00 to 0.26 kg]; 5 trials; P = .05) or long-term (MD, -0.98 kg [95% CI, -3.60 to 1.80 kg]; 1 trial; P = .23) compared with standard care. No difference was found in head-to-head trials (professional vs layperson MD, -0.25 kg [95% CI -1.90 to 1.30 kg]; 5 trials; P = .38). Conclusions and Relevance: This systematic review and meta-analysis found that professional-led weight loss interventions were associated with short-term but not sustained weight reduction among children and adolescents with overweight or obesity, and the evidence for layperson-led approaches was insufficient to draw firm conclusions.

Considerations for an Individual-Level Population Notification System for Pandemic Response: A Review and Prototype.

The outbreak of the coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, spread worldwide after its emergence in China. Whether rich or poor, all nations are struggling to cope with this new global health crisis. The speed of the threat's emergence and the quick response required from public health authorities and the public itself makes evident the need for a major reform in pandemic surveillance and notification systems. The development and implementation of a graded, individual-level pandemic notification system could be an effective tool to combat future threats of epidemics. This paper describes a prototype model of such a notification system and its potential advantages and challenges for implementation. Similar to other emergency alerts, this system would include a number of threat levels (level 1-5) with a higher level indicating increasing severity and intensity of safety measures (eg, level 1: general hygiene, level 2: enhanced hygiene, level 3: physical distancing, level 4: shelter in place, and level 5: lockdown). The notifications would be transmitted to cellular devices via text message (for lower threat levels) or push notification (for higher threat levels). The notification system would allow the public to be informed about the threat level in real time and act accordingly in an organized manner. New Zealand and the United Kingdom have recently launched similar alert systems designed to coordinate the ongoing COVID-19 pandemic response more efficiently. Implementing such a system, however, faces multiple challenges. Extensive preparation and coordination among all levels of government and relevant sectors are required. Additionally, such systems may be effective primarily in countries where there exists at least moderate trust in government. Advance and ongoing public education about the nature of the system and its steps would be an essential part of the system, such that all members of the public understand the meaning of each step in advance, similar to what has been established in systems for other emergency responses. This educational component is of utmost importance to minimize adverse public reaction and unintended consequences. The use of mass media and local communities could be considered where mobile phone penetration is low. The implementation of such a notification system would be more challenging in developing countries for several reasons, including inadequate technology, limited use of data plans, high population density, poverty, mistrust in government, and tendency to ignore or failure to understand the warning messages. Despite the challenges, an individual-level pandemic notification system could provide added benefits by giving an additional route for notification that would be complementary to existing platforms.

Correction: Considerations for an Individual-Level Population Notification System for Pandemic Response: A Review and Prototype.

[This corrects the article DOI: 10.2196/19930.].

The prevalence of multimorbidity and associations with lifestyle factors among middle-aged Canadians: an analysis of Canadian Longitudinal Study on Aging data.

BACKGROUND: Multimorbidity can be defined as the presence of more than one chronic condition in an individual. Research on multimorbidity has predominantly focused on older adults and few studies have examined multimorbidity in middle-aged people. The objectives of this study were to: 1) examine the prevalence of multimorbidity among middle-aged Canadians; and 2) examine the association between lifestyle factors (smoking, alcohol intake, physical activity) and multimorbidity in this age group. METHODS: In this analysis of the Canadian Longitudinal Study on Aging (CLSA) baseline data, we extracted data from 29,841 participants aged 45-64 years from a database of 51,338 people aged 45-85 years. Self-reported data on 27 chronic physical health conditions were used to derive different multimorbidity definitions. We estimated the prevalence of 3+ to 5+ chronic physical health conditions in different subgroups for descriptive purposes. Multivariable logistic regression analyses were performed to determine the association between socio-demographic and lifestyle factors, and multimorbidity using a 3+ multimorbidity case definition. RESULT: We found that 39.6% (99% CI 38.4-40.7) of participants had three or more chronic conditions with a mean number of chronic condition of 2.41 (99% CI 2.37-2.46). The prevalence of multimorbidity increased with age from 29.7% in the 45-49-year-old age group to 52% in individuals aged 60-64 years. The prevalence of 4+ and 5+ chronic conditions was 24.5 and 14.2% respectively. Analyses indicated that female sex and low income were associated with higher odds of multimorbidity, whereas daily or weekly alcohol intake were associated with lower odds of multimorbidity. Exercise was not associated with multimorbidity. Results were similar when analyses were conducted separately for women and men. CONCLUSIONS: Multimorbidity is not limited to older adults, but is a common phenomenon among middle-aged people. Longitudinal research is needed to better understand the temporal relationship between lifestyle factors and multimorbidity.