Is the association between social jetlag and BMI mediated by lifestyle? A cross-sectional survey study in the Dutch general population.

OBJECTIVE: Social jetlag is a discordance between the social and biological rhythm and is associated with higher HbA1c, higher BMI, and higher odds of obesity. The pathways that could explain these associations are still debated. This study aims to assess the mediating role of several lifestyle factors in the cross-sectional association between social jetlag and BMI. METHODS: We used cross-sectional data from 1784 adults from urban areas in the Netherlands, collected in 2019. Social jetlag (difference in midpoint of sleep between week and weekend nights) was categorized as low(<1 h), moderate(1-2h), and high(>2 h). BMI(kg/m2) was calculated from self-reported height and weight. The association between social jetlag and BMI was assessed using linear regression, adjusted for sex, age, education, and sleep duration and stratified for the effect modifier stress (high vs. low). Mediation analysis was performed for self-reported smoking, physical activity, alcohol consumption, and adherence to a healthy diet. RESULTS: High social jetlag was associated with higher BMI (0.69 kg/m2,95%CI 0.05;1.33). This association was stronger in people with high stress (0.93 kg/m2,95%CI 0.09;1.76). Social jetlag was also associated with higher odds of smoking, lower physical activity, higher alcohol consumption, and lower healthy diet adherence. In people with high stress, these factors mediated 10-15% of the association between social jetlag and BMI. CONCLUSIONS: Social jetlag is associated with higher BMI and this association is stronger in people with high stress. In people with high stress, healthy diet adherence mediated 12% of this association. Other pathways involved in this association should be further investigated.

The development of fatigue after treatment for pediatric brain tumors does not differ between tumor locations.

BACKGROUND: Children and adolescents treated for a brain tumor suffer from more fatigue than survivors of other types of childhood cancer. As tumor location might be predictive of fatigue, our aim was to investigate the longitudinal development of fatigue in children with brain tumors and risk factors for fatigue separately for different tumor locations. METHODS: Fatigue was assessed 1235 times for 425 participants. Self-report versions of PedsQL Multidimensional Fatigue Scale were used to repeatedly assess fatigue from the end of treatment up to 8 years later. Mixed models were used to analyze fatigue over time and determinants separately for infratentorial (N = 205), supratentorial hemispheric (N = 91), and supratentorial midline tumors (N = 129). RESULTS: Cognitive fatigue worsened with time, while sleep-rest and general fatigue first decreased and then increased. There was no difference in fatigue between the tumor locations, but the risk factors differed when stratified by location. Radiotherapy was associated with more fatigue for infratentorial tumors, and centralization of care was associated with less fatigue for the supratentorial midline tumors. For supratentorial hemispheric tumors, female sex was associated with more fatigue. Higher parental education was associated with less fatigue regardless of tumor location. CONCLUSIONS: The development of fatigue seems to be more related to sociodemographic and treatment variables than to tumor location. Healthcare providers need to be aware that fatigue may develop in the years following end of treatment, and that patients with a low/middle educational family background might be more vulnerable and in need of targeted support.

Differences in the organization of the primary motor cortex in people with and without low back pain and associations with motor control and sensory tests.

Differences in organization of the primary motor cortex and altered trunk motor control (sensing, processing and motor output) have been reported in people with low back pain (LBP). Little is known to what extent these differences are related. We investigated differences in 1) organization of the primary motor cortex and 2) motor and sensory tests between people with and without LBP, and 3) investigated associations between the organization of the primary motor cortex and motor and sensory tests. We conducted a case-control study in people with (N=25) and without (N=25) LBP. The organization of the primary motor cortex (Center of Gravity (CoG) and Area of the cortical representation of trunk muscles) was assessed using neuronavigated transcranial magnetic stimulation, based on individual MRIs. Sensory tests (quantitative sensory testing, graphaesthesia, two-point discrimination threshold) and a motor test (spiral-tracking test) were assessed. Participants with LBP had a more lateral and lower location of the CoG and a higher temporal summation of pain. For all participants combined, better vibration test scores were associated with a more anterior, lateral, and lower CoG and a better two-point discrimination threshold was associated with a lower CoG. A small subset of variables showed significance. Although this aligns with the concept of altered organization of the primary motor cortex in LBP, there is no strong evidence of the association between altered organization of the primary motor cortex and motor and sensory test performance in LBP. Focusing on subgroup analyses regarding pain duration can be a topic for future research.

Sleep disturbances in hospitalized children: a wake-up call.

Although sleep is essential for (recovery of) health, it is adversely affected by hospitalization, due to disease discomfort, environmental noise, and care routines, causing reduced sleep and increased disturbances. This study evaluates factors affecting sleep quality and quantity in hospitalized children and compares inpatient sleep with sleep at home. Using an observational, prospective study design, we assessed sleep in hospitalized children aged 1-12 years, admitted to a tertiary center, and compared this with home 6-8 weeks after discharge. We measured total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), sleep efficiency, awakenings, and subjective sleep quality, using actigraphy, sleep diaries, and PROMIS questionnaires. We explored an array of sleep-disturbing factors. Regression analyses identified key determinants affecting sleep patterns, while mixed linear models compared sleep in hospital to sleep at home. Out of 621 eligible patients, 467 were invited, and 272 (58%) consented to participate. Key determinants of sleep included pain, number of previous admissions, (underlying) chronic illness, and environment-, staff-, and disease-related factors. Parents reported lower perceived sleep quality in the hospital compared to at home, 97-min (SE 9) lower TST, 100-min (5) longer WASO, more difficulties with falling asleep, lower sleep satisfaction, and more awakenings. Actigraphy outcomes revealed shorter TST (20 min (6)), but better sleep efficiency and fewer awakenings in the hospital. Conclusion: Sleep in hospital was compromised in comparison to sleep at home, primarily due to disturbances related to treatment, environment, and staff. These findings underscore the necessity and potential of relative simple interventions to improve sleep quality and minimize sleep disturbances in hospitalized children.

The effects of individual music therapy in nursing home residents with dementia to improve general well-being: study protocol of a randomized controlled trial.

BACKGROUND: Dementia is often associated with Neuropsychiatric Symptoms (NPS) such as agitation, depression, hallucinations, anxiety, that can cause distress for the resident with dementia in long-term care settings and can impose emotional burden on the environment. NPS are often treated with psychotropic drugs, which, however, frequently cause side effects. Alternatively, non-pharmacological interventions can improve well-being and maintain an optimal quality of life (QoL) of those living with dementia. Other QoL related outcomes, such as pain, discomfort and sleep disruption are relevant outcomes in music trials as well. Music therapy is a non-pharmacological intervention that can reduce NPS and improve well-being, and its associated symptoms in dementia. METHODS: The research will be conducted at eight nursing home facilities of a health care organization in the Netherlands. A sample size of 30 in each group (experimental and control group) is required, totalling 60 residents increased to 80 when considering expected drop out to follow up. The participants in the intervention group receive 30 min of individual music therapy (MT) in their own room by a music therapist twice a week for 12 weeks. The participants in the control group will receive 30 min of individual attention in their own room by a volunteer twice a week for 12 weeks. Assessments will be done at baseline, 6 weeks and 12 weeks. An independent observer, blinded for the intervention or control condition, will assess directly observed well-being (primary outcome) and pain (secondary outcome) before and after the sessions. Nurses will assess other secondary outcomes unblinded, i.e., perceived quality of life and NPS, both assessed with validated scales. The sleep duration will be indirectly assessed by a wrist device called MotionWatch. Information about psychotropic drug use will be derived from electronic medical chart review. DISCUSSION: The main purpose of this study is to assess the effects of individual music therapy on directly observed well-being controlled for individual attention in nursing home residents with dementia with NPS. The outcomes refer to both short-term and long-term effects consistent with therapeutic goals of care for a longer term. We hope to overcome limitations of previous study designs such as not blinded designs and music facilitators that were not only music therapists but also occupational therapists and nurses. This study should lead to more focused recommendations for practice and further research into non-pharmacological interventions in dementia such as music therapy. TRIAL REGISTRATION: The trial is registered at the International Clinical Trials Registry Platform (ICTRP) search portal in the Netherlands Trial Registration number NL7708, registration date 04-05-2019.

Methylphenidate dose-response in children with ADHD: evidence from a double-blind, randomized placebo-controlled titration trial.

Methylphenidate (MPH) is highly efficacious in reducing symptoms of attention-deficit/hyperactivity disorder (ADHD) in children. Generally increased doses are found to result in better symptom control; however, it remains unclear whether this pattern can be observed at the individual level, given the large heterogeneity in individual dose-response relationships and observed placebo responses. A double-blind, randomized, placebo-controlled cross-over trial was used to compare weekly treatment with placebo and 5, 10, 15 and 20 mg of MPH twice daily on parent and teacher ratings of child ADHD symptoms and side effects. Participants were 5-13-year-old children with a DSM-5 diagnosis of ADHD (N = 45). MPH response was assessed at group and individual levels and predictors of individual dose-response curves were examined. Mixed model analysis showed positive linear dose-response curves at group level for parent and teacher rated ADHD symptoms and parent rated side effects, but not for teacher rated side effects. Teachers reported all dosages to improve ADHD symptoms compared to placebo, while parents only reported > 5 mg/dose as effective. At the individual level, most (73-88%) children, but not all, showed positive linear dose-response curves. Higher severity of hyperactive-impulsive symptoms and lower internalizing problems, lower weight, younger age and more positive opinions towards diagnosis and medication partly predicted steeper linear individual dose-response curves. Our study confirms that increased doses of MPH yield greater symptom control at a group level. However, large interindividual variation in the dose-response relationship was found and increased doses did not lead to greater symptom improvement for all children. This trial was registered in the Netherlands trial register (# NL8121).

Effects of a 1 year aerobic and strength training on cognitive functioning after transient ischemic attack or minor stroke: A randomized controlled trial.

OBJECTIVES: Patients who have recently suffered a transient ischemic attack (TIA) or minor ischemic stroke are at increased risk of cognitive impairment. In the present study, we aimed to investigate the effect of a 1-year exercise intervention on cognitive functioning up to 2 years post intervention. MATERIAL AND METHODS: We conducted a single-blind randomized controlled trial to investigate the effect of an exercise intervention on cognitive functioning, compared with usual care, for up to 2 years. Patients with a TIA or minor stroke were randomly allocated to an intervention group receiving the 1-year exercise intervention (n = 60) or to usual care (n = 59). Outcome measures were assessed at baseline and after 1 and 2 years. We measured cognition with neuropsychological tests on three domains: (1) executive functioning, (2) attention-psychomotor speed, and (3) memory. Linear mixed models were used for longitudinal data to determine the effect of the exercise intervention on cognitive functioning. Statistical analyses were performed using IBM SPSS software 24.0. RESULTS: We found that over the two years study period -and corrected for age, sex, and educational level- the intervention group on average improved significantly more in executive functioning than the control group (ß = 0.13; 95 % CI [0.02 to 0.25]; p = 0.03). No significant intervention effects were found on either memory or attention-psychomotor speed. CONCLUSIONS: Our data show that a 1-year exercise intervention significantly improved executive functioning over time, compared to usual care. We recommend that health care professionals consider broadening standard secondary stroke prevention treatment in patients with TIA/minor stroke by adding exercise and physical activity.

Multicenter Evaluation of AI-generated DIR and PSIR for Cortical and Juxtacortical Multiple Sclerosis Lesion Detection.

Background Cortical multiple sclerosis lesions are clinically relevant but inconspicuous at conventional clinical MRI. Double inversion recovery (DIR) and phase-sensitive inversion recovery (PSIR) are more sensitive but often unavailable. In the past 2 years, artificial intelligence (AI) was used to generate DIR and PSIR from standard clinical sequences (eg, T1-weighted, T2-weighted, and fluid-attenuated inversion-recovery sequences), but multicenter validation is crucial for further implementation. Purpose To evaluate cortical and juxtacortical multiple sclerosis lesion detection for diagnostic and disease monitoring purposes on AI-generated DIR and PSIR images compared with MRI-acquired DIR and PSIR images in a multicenter setting. Materials and Methods Generative adversarial networks were used to generate AI-based DIR (n = 50) and PSIR (n = 43) images. The number of detected lesions between AI-generated images and MRI-acquired (reference) images was compared by randomized blinded scoring by seven readers (all with >10 years of experience in lesion assessment). Reliability was expressed as the intraclass correlation coefficient (ICC). Differences in lesion subtype were determined using Wilcoxon signed-rank tests. Results MRI scans of 202 patients with multiple sclerosis (mean age, 46 years ± 11 [SD]; 127 women) were retrospectively collected from seven centers (February 2020 to January 2021). In total, 1154 lesions were detected on AI-generated DIR images versus 855 on MRI-acquired DIR images (mean difference per reader, 35.0% ± 22.8; P < .001). On AI-generated PSIR images, 803 lesions were detected versus 814 on MRI-acquired PSIR images (98.9% ± 19.4; P = .87). Reliability was good for both DIR (ICC, 0.81) and PSIR (ICC, 0.75) across centers. Regionally, more juxtacortical lesions were detected on AI-generated DIR images than on MRI-acquired DIR images (495 [42.9%] vs 338 [39.5%]; P < .001). On AI-generated PSIR images, fewer juxtacortical lesions were detected than on MRI-acquired PSIR images (232 [28.9%] vs 282 [34.6%]; P = .02). Conclusion Artificial intelligence-generated double inversion-recovery and phase-sensitive inversion-recovery images performed well compared with their MRI-acquired counterparts and can be considered reliable in a multicenter setting, with good between-reader and between-center interpretative agreement. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Zivadinov and Dwyer in this issue.

Percutaneous coronary intervention of native coronary artery versus saphenous vein graft in patients with prior coronary artery bypass graft surgery: Rationale and design of the multicenter, randomized PROCTOR trial.

BACKGROUND: Patients with prior coronary artery bypass grafting (CABG) frequently require repeat percutaneous revascularization due to advanced age, progressive coronary artery disease and bypass graft failure. Percutaneous coronary intervention (PCI) of either the bypass graft or the native coronary artery may be performed. Randomized trials comparing native vessel PCI with bypass graft PCI are lacking and long-term outcomes have not been reported. METHODS: PROCTOR (NCT03805048) is a prospective, multicenter, randomized controlled trial, that will include 584 patients presenting with saphenous vein graft (SVG) failure and a clinical indication for revascularization, as determined by the local Heart Team. The trial is designed to compare the clinical and angiographic outcomes in patients randomly allocated in a 1:1 fashion to either a strategy of native vessel PCI or SVG PCI. The primary study endpoint is a 3-year composite of major adverse cardiac events (MACE: all-cause mortality, non-fatal target coronary territory myocardial infarction [MI], or clinically driven target coronary territory revascularization). At 3-years, after evaluation of the primary endpoint, follow-up invasive coronary angiography will be performed. Secondary endpoints comprise individual components of MACE at 1, 3 and 5 years follow-up, PCI-related MI, MI >48 hours after index PCI, target vessel failure, target lesion revascularization, renal failure requiring renal-replacement therapy, angiographic outcomes at 3-years and quality of life (delta Seattle Angina Questionnaire, Canadian Cardiovascular Society Grading Scale and Rose Dyspnea Scale). CONCLUSION: PROCTOR is the first randomized trial comparing an invasive strategy of native coronary artery PCI with SVG PCI in post-CABG patients presenting with SVG failure.

A multidisciplinary lifestyle program for metabolic syndrome-associated osteoarthritis: the "Plants for Joints" randomized controlled trial.

OBJECTIVE: To determine the effectiveness of the "Plants for Joints" multidisciplinary lifestyle program in patients with metabolic syndrome-associated osteoarthritis (MSOA). DESIGN: Patients with hip or knee MSOA were randomized to the intervention or control group. The intervention group followed a 16-week program in addition to usual care based on a whole food plant-based diet, physical activity, and stress management. The control group received usual care. The patient-reported Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) total score (range 0-96) was the primary outcome. Secondary outcomes included other patient-reported, anthropometric, and metabolic measures. An intention-to-treat analysis with a linear-mixed model adjusted for baseline values was used to analyze between-group differences. RESULTS: Of the 66 people randomized, 64 completed the study. Participants (84% female) had a mean (SD) age of 63 (6) years and body mass index of 33 (5) kg/m2. After 16 weeks, the intervention group (n = 32) had a mean 11-point larger improvement in WOMAC-score (95% CI 6-16; p = 0.0001) compared to the control group. The intervention group also lost more weight (-5 kg), fat mass (-4 kg), and waist circumference (-6 cm) compared to the control group. Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue, pain interference, C-reactive protein, hemoglobin A1c, fasting glucose, and low-density lipoproteins improved in the intervention versus the control group, while other PROMIS measures, blood pressure, high-density lipoproteins, and triglycerides did not differ significantly between the groups. CONCLUSION: The "Plants for Joints" lifestyle program reduced stiffness, relieved pain, and improved physical function in people with hip or knee MSOA compared to usual care.

A multidisciplinary lifestyle program for rheumatoid arthritis: the 'Plants for Joints' randomized controlled trial.

OBJECTIVE: To determine the effect of a multidisciplinary lifestyle program in patients with RA with low-moderate disease activity. METHODS: In the 'Plants for Joints' (PFJ) parallel-arm, assessor-blind randomized controlled trial, patients with RA and 28-joint DAS (DAS28) ≥2.6 and ≤5.1 were randomized to the PFJ or control group. The PFJ group followed a 16-week lifestyle program based on a whole-food plant-based diet, physical activity and stress management. The control group received usual care. Medication was kept stable 3 months before and during the trial whenever possible. We hypothesized that PFJ would lower disease activity (DAS28). Secondary outcomes included anthropometric, metabolic and patient-reported measures. An intention-to-treat analysis with a linear mixed model adjusted for baseline values was used to analyse between-group differences. RESULTS: Of the 83 people randomized, 77 completed the study. Participants were 92% female with mean (s.d.) age of 55 (12) years, BMI of 26 (4) kg/m2 and mean DAS28 of 3.8 (0.7). After 16 weeks the PFJ group had a mean 0.9-point greater improvement of DAS28 vs the control group (95% CI 0.4, 1.3; P < 0.0001). The PFJ intervention led to greater decreases in body weight (difference -3.9 kg), fat mass (-2.8 kg), waist circumference (-3 cm), HbA1c (-1.3 mmol/mol) and low-density lipoprotein (-0.32 mmol/l), whereas patient-reported outcome measures, blood pressure, glucose and other lipids did not change. CONCLUSION: The 16-week PFJ multidisciplinary lifestyle program substantially decreased disease activity and improved metabolic status in people with RA with low-moderate disease activity. TRIAL REGISTRATION: International Clinical Trials Registry Platform; https://www.who.int/clinical-trials-registry-platform; NL7800.

Phosphorylated tau in the retina correlates with tau pathology in the brain in Alzheimer's disease and primary tauopathies.

The retina is a potential source of biomarkers for the detection of neurodegenerative diseases. Accumulation of phosphorylated tau (p-tau) in the brain is a pathological feature characteristic for Alzheimer's disease (AD) and primary tauopathies. In this study the presence of p-tau in the retina in relation to tau pathology in the brain was assessed. Post-mortem eyes and brains were collected through the Netherlands Brain Bank from donors with AD (n = 17), primary tauopathies (n = 8), α-synucleinopathies (n = 13), other neurodegenerative diseases including non-tau frontotemporal lobar degeneration (FTLD) (n = 9), and controls (n = 15). Retina cross-sections were assessed by immunohistochemistry using antibodies directed against total tau (HT7), 3R and 4R tau isoforms (RD3, RD4), and phospho-epitopes Ser202/Thr205 (AT8), Thr217 (anti-T217), Thr212/Ser214 (AT100), Thr181 (AT270), Ser396 (anti-pS396) and Ser422 (anti-pS422). Retinal tau load was compared to p-tau Ser202/Thr205 and p-tau Thr217 load in various brain regions. Total tau, 3R and 4R tau isoforms were most prominently present in the inner plexiform layer (IPL) and outer plexiform layer (OPL) of the retina and were detected in all cases and controls as a diffuse and somatodendritic signal. Total tau, p-tau Ser202/Thr205 and p-tau Thr217 was observed in amacrine and horizontal cells of the inner nuclear layer (INL). Various antibodies directed against phospho-epitopes of tau showed immunoreactivity in the IPL, OPL, and INL. P-tau Ser202/Thr205 and Thr217 showed significant discrimination between AD and other tauopathies, and non-tauopathy cases including controls. Whilst immunopositivity was observed for p-tau Thr212/Ser214, Thr181 and Ser396, there were no group differences. P-tau Ser422 did not show any immunoreactivity in the retina. The presence of retinal p-tau Ser202/Thr205 and Thr217 correlated with Braak stage for NFTs and with the presence of p-tau Ser202/Thr205 in hippocampus and cortical brain regions. Depending on the phospho-epitope, p-tau in the retina is a potential biomarker for AD and primary tauopathies.

Impact of cardiac history and myocardial scar on increase of myocardial perfusion after revascularization.

PURPOSE: We sought to assess the impact of coronary revascularization on myocardial perfusion and fractional flow reserve (FFR) in patients without a cardiac history, with prior myocardial infarction (MI) or non-MI percutaneous coronary intervention (PCI). Furthermore, we studied the impact of scar tissue. METHODS: Symptomatic patients underwent [15O]H2O positron emission tomography (PET) and FFR before and after revascularization. Patients with prior CAD, defined as prior MI or PCI, underwent scar quantification by magnetic resonance imaging late gadolinium enhancement. RESULTS: Among 137 patients (87% male, age 62.2 ± 9.5 years) 84 (61%) had a prior MI or PCI. The increase in FFR and hyperemic myocardial blood flow (hMBF) was less in patients with prior MI or non-MI PCI compared to those without a cardiac history (FFR: 0.23 ± 0.14 vs. 0.20 ± 0.12 vs. 0.31 ± 0.18, p = 0.02; hMBF: 0.54 ± 0.75 vs. 0.62 ± 0.97 vs. 0.91 ± 0.96 ml/min/g, p = 0.04). Post-revascularization FFR and hMBF were similar across patients without a cardiac history or with prior MI or non-MI PCI. An increase in FFR was strongly associated to hMBF increase in patients without a cardiac history or with prior MI/non-MI PCI (r = 0.60 and r = 0.60, p < 0.01 for both). Similar results were found for coronary flow reserve. In patients with prior MI scar was negatively correlated to hMBF increase and independently predictive of an attenuated CFR increase. CONCLUSIONS: Post revascularization FFR and perfusion were similar among patients without a cardiac history, with prior MI or non-MI PCI. In patients with prior MI scar burden was associated to an attenuated perfusion increase.

The course of health-related quality of life after the diagnosis of childhood cancer: a national cohort study.

BACKGROUND: Comprehensive insight in the longitudinal development of health-related quality of life (HRQOL) after childhood cancer diagnosis could improve quality of care. Thus, we aimed to study the course and biopsychosocial determinants of HRQOL in a unique national cohort of children with cancer. METHODS: HRQOL of 2154 children with cancer was longitudinally reported (median: 3 reports) between diagnosis and 5 years after, using the pediatric quality of life inventory generic core scales (PedsQL). HRQOL was modelled over time since diagnosis using mixed model analysis for children 2-7 years (caregiver-reports) and ≥ 8 years (self-reports). Differences in the course between hematological, solid and central nervous system malignancies were studied. Additional associations of demographics, disease characteristics (age at diagnosis, relapse, diagnosis after the national centralization of childhood cancer care and treatment components) and caregiver distress (Distress thermometer) were studied. RESULTS: Overall, HRQOL improved with time since diagnosis, mostly in the first years. The course of HRQOL differed between diagnostic groups. In children aged 2-7 years, children with a solid tumor had most favorable HRQOL. In children aged ≥ 8 years, those with a hematological malignancy had lower HRQOL around diagnosis, but stronger improvement over time than the other diagnostic groups. In both age-groups, the course of HRQOL of children with a CNS tumor showed little or no improvement. Small to moderate associations (ß: 0.18 to 0.67, p < 0.05) with disease characteristics were found. Centralized care related to better HRQOL (ß: 0.25 to 0.44, p < 0.05). Caregiver distress was most consistently associated with worse HRQOL (ß: - 0.13 to - 0.48, p < 0.01). CONCLUSIONS: The HRQOL course presented can aid in identifying children who have not fully recovered their HRQOL following cancer diagnosis, enabling early recognition of the issue. Future research should focus on ways to support children, especially those with a CNS tumor, for example by decreasing distress in their caregivers.

Which patients benefit from adding short-term psychodynamic psychotherapy to antidepressants in the treatment of depression? A systematic review and meta-analysis of individual participant data.

BACKGROUND: Adding short-term psychodynamic psychotherapy (STPP) to antidepressants increases treatment efficacy, but it is unclear which patients benefit specifically. This study examined efficacy moderators of combined treatment (STPP + antidepressants) v. antidepressants for adults with depression. METHODS: For this systematic review and meta-analysis (PROSPERO registration number: CRD42017056029), we searched PubMed, PsycINFO, Embase.com, and the Cochrane Library from inception to 1 January 2022. We included randomized clinical trials comparing combined treatment (antidepressants + individual outpatient STPP) v. antidepressants in the acute-phase treatment of depression in adults. Individual participant data were requested and analyzed combinedly using mixed-effects models (adding Cochrane risk of bias items as covariates) and an exploratory machine learning technique. The primary outcome was post-treatment depression symptom level. RESULTS: Data were obtained for all seven trials identified (100%, n = 482, combined: n = 238, antidepressants: n = 244). Adding STPP to antidepressants was more efficacious for patients with high rather than low baseline depression levels [B = -0.49, 95% confidence interval (CI) -0.61 to -0.37, p < 0.0001] and for patients with a depressive episode duration of >2 years rather than <1 year (B = -0.68, 95% CI -1.31 to -0.05, p = 0.03) and than 1-2 years (B = -0.86, 95% CI -1.66 to -0.06, p = 0.04). Heterogeneity was low. Effects were replicated in analyses controlling for risk of bias. CONCLUSIONS: To our knowledge, this is the first study that examines moderators across trials assessing the addition of STPP to antidepressants. These findings need validation but suggest that depression severity and episode duration are factors to consider when adding STPP to antidepressants and might contribute to personalizing treatment selection for depression.

Longitudinal associations between self-reported sleep duration and cardiometabolic disease risk in corporate executives.

OBJECTIVE: This study aimed to determine the longitudinal associations between self-reported sleep duration and cardiometabolic disease (CMD) risk in corporate executives. METHODS: Self-reported sleep duration and lifestyle, occupational, psychological, and anthropometrical, blood pressure and blood marker variables were obtained from 1512 employees at annual health risk assessments in South Africa between 2016 and 2019. Gender-stratified linear mixed models, adjusting for age, lifestyle, occupational and psychological covariates were used to explore these longitudinal associations. RESULTS: Among women, shorter sleep duration was associated with higher body mass index (BMI) covarying for age only (ß with 95% confidence intervals: -0.19 [-0.36, -0.03]), age and occupational factors (-0.20 [-0.36, -0.03]) and age and psychological factors (-0.20 [-0.37, -0.03]). Among men, shorter sleep was associated with both BMI and waist circumference (WC) covarying for age only (BMI: -0.15 [-0.22; -0.08]; WC: -0.62 [-0.88; -0.37]); age and lifestyle factors (BMI: -0.12 [-0.21; -0.04]); WC: -0.016 [-0.92; -0.29], age and occupational factors (BMI: -0.20 [-0.22; 0.08]; WC: -0.62 [-0.88; -0.36]), and age and psychological factors (BMI: -0.15 [-0.22; -0.07]; WC: -0.59 [-0.86; -0.33]). Among men, shorter sleep was also longitudinally associated with higher CMD risk scores in models adjusted for age and lifestyle factors (CMD: -0.12 [-0.20; -0.04]) and age and psychological factors (CMD: -0.08 [-0.15; -0.01]). CONCLUSION: Corporate executives who report shorter sleep durations may present with poorer CMD risk profiles, independent of age, lifestyle, occupational and psychological factors. Addressing sleep health in workplace health programmes may help mitigate the development of CMD in such employees.

Misspecification of confounder-exposure and confounder-outcome associations leads to bias in effect estimates.

BACKGROUND: Confounding is a common issue in epidemiological research. Commonly used confounder-adjustment methods include multivariable regression analysis and propensity score methods. Although it is common practice to assess the linearity assumption for the exposure-outcome effect, most researchers do not assess linearity of the relationship between the confounder and the exposure and between the confounder and the outcome before adjusting for the confounder in the analysis. Failing to take the true non-linear functional form of the confounder-exposure and confounder-outcome associations into account may result in an under- or overestimation of the true exposure effect. Therefore, this paper aims to demonstrate the importance of assessing the linearity assumption for confounder-exposure and confounder-outcome associations and the importance of correctly specifying these associations when the linearity assumption is violated. METHODS: A Monte Carlo simulation study was used to assess and compare the performance of confounder-adjustment methods when the functional form of the confounder-exposure and confounder-outcome associations were misspecified (i.e., linearity was wrongly assumed) and correctly specified (i.e., linearity was rightly assumed) under multiple sample sizes. An empirical data example was used to illustrate that the misspecification of confounder-exposure and confounder-outcome associations leads to bias. RESULTS: The simulation study illustrated that the exposure effect estimate will be biased when for propensity score (PS) methods the confounder-exposure association is misspecified. For methods in which the outcome is regressed on the confounder or the PS, the exposure effect estimate will be biased if the confounder-outcome association is misspecified. In the empirical data example, correct specification of the confounder-exposure and confounder-outcome associations resulted in smaller exposure effect estimates. CONCLUSION: When attempting to remove bias by adjusting for confounding, misspecification of the confounder-exposure and confounder-outcome associations might actually introduce bias. It is therefore important that researchers not only assess the linearity of the exposure-outcome effect, but also of the confounder-exposure or confounder-outcome associations depending on the confounder-adjustment method used.

Implant supported overdentures in Sjögren's disease patients: a multicentre prospective cohort study.

OBJECTIVES: To prospectively investigate patient-reported outcomes and clinical performance of implant supported overdentures in edentulous Sjögren's disease (SjD) patients compared to subjects without SjD. METHODS: 51 implants were placed in 12 patients with SjD and 50 implants in 12 non-SjD patients to support overdentures. Clinical performance, marginal bone-level changes, patient satisfaction and oral health related quality of life (OHRQoL) were assessed at 1 (T1), 6 (T6), 12 (T12) and 18 (T18) months after placement of the overdenture. Patient satisfaction, ability to chew and OHRQoL were assessed with validated questionnaires. Marginal bone-level changes were measured on standardised dental radiographs. Clinical parameters included implant and overdenture survival, plaque, bleeding and gingival indices, and probing depth. RESULTS: OHRQoL in patients with SjD improved significantly after placement of implant supported overdentures at all measuring moments compared to baseline (p<0.05). Nevertheless, ability to chew tough and hard food was significantly better for non-SjD patients at all timepoints after placement of an implant supported overdenture (p<0.05). Implant survival at T18 was 100% in the patients with SjD and 98% in the non-SS group. Mean marginal bone loss at T18 did not differ between patients with SjD and non-SS patients, 1.12±0.74 mm and 1.43±1.66 mm, respectively (p=0.58). Clinical performance was good with no differences between the groups for all outcome measures (p>0.05). CONCLUSIONS: Implant-supported overdentures have a positive effect on OHRQoL and dental implants can be successfully applied in edentulous patients with SjD with nearly similar outcomes as in non-SjD subjects.

Post-discharge light physical activity indicates recovery in acutely hospitalized older adults - the Hospital-ADL study.

BACKGROUND: Physical activity (PA) levels might be a simple overall physical function indicator of recovery in acutely hospitalized older adults; however it is unknown which amount and level of PA is associated with recovery. Our objective was to evaluate the amount and level of post discharge PA and its optimum cut-off values associated with recovery among acutely hospitalized older adults and stratified for frailty. METHODS: We performed a prospective observational cohort study including acutely hospitalized older adults (≥ 70 years). Frailty was assessed using Fried's criteria. PA was assessed using Fitbit up to one week post discharge and quantified in steps and minutes light, moderate or higher intensity. The primary outcome was recovery at 3-months post discharge. ROC-curve analyses were used to determine cut-off values and area under the curve (AUC), and logistic regression analyses to calculate odds ratios (ORs). RESULTS: The analytic sample included 174 participants with a mean (standard deviation) age of 79.2 (6.7) years of whom 84/174 (48%) were frail. At 3-months, 109/174 participants (63%) had recovered of whom 48 were frail. In all participants, determined cut-off values were 1369 steps/day (OR: 2.7, 95% confidence interval [CI]: 1.3-5.9, AUC 0.7) and 76 min/day of light intensity PA (OR: 3.9, 95% CI: 1.8-8.5, AUC 0.73). In frail participants, cut-off values were 1043 steps/day (OR: 5.0, 95% CI: 1.7-14.8, AUC 0.72) and 72 min/day of light intensity PA (OR: 7.2, 95% CI: 2.2-23.1, AUC 0,74). Determined cut-off values were not significantly associated with recovery in non-frail participants. CONCLUSIONS: Post-discharge PA cut-offs indicate the odds of recovery in older adults, especially in frail individuals, however are not equipped for use as a diagnostic test in daily practice. This is a first step in providing a direction for setting rehabilitation goals in older adults after hospitalization.

The influence of apical periodontitis on circulatory inflammatory mediators in peripheral blood: A prospective case-control study.

AIM: To explore the influence of apical periodontitis (AP) on inflammatory markers in blood of otherwise healthy individuals and to depict the inflammatory profile of the healing after dental extraction. METHODOLOGY: This is a prospective case-control intervention study, during which, individuals with a diagnosis of AP of one affected tooth were included, along with a control group matched for age and gender. A broad panel of blood inflammatory mediators was examined longitudinally in all subjects during six visits. In the case of the AP subjects, the tooth with AP was extracted at the third visit. Results were analysed by linear regression analyses and linear mixed-model analyses. RESULTS: A total of 53 subjects were included in the study, 27 with AP and 26 without. Fifteen females and 12 males were included in the AP group, and 14 females and 12 males in the control group. At baseline, granulocyte colony-stimulating factor (p < .001), interleukin (IL)-1ß (p = .03) and IL-4 (p = .01) were significantly lower in AP subjects than in controls. Comparison of the differences between baseline and the last visit, i.e. 3 months after the tooth extraction, showed a significant reduction in IL-10 (p = .03) and IL-12p70 (p = .01). CONCLUSIONS: The immunologic profile of chronic AP in one tooth and its healing profile reveals a systemic low-grade inflammation through compensatory immunosuppression. A larger lesion or multiple lesions could disrupt the balance that the system is trying to maintain, resulting in loss of homeostasis.