Mean Difference Research Articles

Traumatic brain injury (TBI) is associated with widespread disruptions in functional connectivity (FC), yet how these alterations vary by injury severity remains unclear. Traditional classification systems fail to capture network-level dysfunction, limiting prognostic accuracy and targeted rehabilitation strategies. The aim of this study was to systematically evaluate fMRI-detected FC alterations after mild, moderate-severe, and severe TBI using coordinate-based meta-analysis and network-level mapping. A systematic search of MEDLINE/PubMed, Embase, and Web of Science was conducted to identify studies examining FC changes in TBI using fMRI. This review was not funded or prospectively registered. Studies were stratified by TBI severity and time since injury. Significant peak Montreal Neurological Institute coordinates were extracted, matched to the Yeo-17 brain network atlas, and analyzed using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI). Study quality and evidence level were assessed using an adapted NIH Quality Assessment Tool and the Oxford Centre for Evidence-Based Medicine criteria. Eligible studies included adult participants with TBI assessed using resting-state or task-based fMRI; studies lacking severity classification or involving pediatric populations were excluded. Seventy-six studies were included, totaling 5,064 participants (2,993 patients with TBI, 1,914 controls; mean age 35.5 vs 35.0 years; 37.6% female overall). Mild TBI (mTBI) was the most common severity (n = 59 studies; 77.6%). Twenty-two studies contributed data for meta-analysis: 15 with resting-state fMRI and 7 with task-based fMRI. Aggregated peak coordinates most frequently mapped to subcomponents of the default mode (22.9%), ventral attention (18.8%), and somatomotor (10.1%) networks in mTBI and to the frontoparietal (36%), ventral attention (20%), and dorsal attention (14.7%) networks in moderate-severe/severe TBI. SDM-PSI identified uncorrected clusters in default mode and frontoparietal regions in mTBI and moderate-severe/severe TBI, respectively, but no clusters survived family-wise error rate correction (standardized mean difference Z score range -1.986 to 3.911, p < 0.05 uncorrected). Heterogeneity was low across analyses (I2 < 21%). FC changes after TBI potentially involve large-scale brain networks such as the default mode, attention, and executive control networks in a severity-dependent and phase-dependent manner. Although meta-analysis revealed consistent patterns, corrected statistical significance was not achieved, highlighting the need for larger, harmonized data sets and standardized analysis pipelines in future research.

Abstract Objectives In rheumatoid arthritis (RA) patients with an insufficient response to conventional synthetic DMARDs (csDMARDs), both biological DMARDs and low-to-moderate dose glucocorticoids are effective treatment options. However, direct comparative evidence on their relative effectiveness and safety is lacking. Methods This investigator-initiated, open-label, randomised trial compared 10 mg daily prednisone to weekly subcutaneous tocilizumab (TCZ, 162 mg), both added to stable csDMARD therapy, in a 12-month treat-to-target strategy. If treatment response was inadequate at 3 months, patients switched to the alternative arm. The primary end point was Clinical Disease Activity Index (CDAI) averaged over months 6–12. Secondary outcomes included the Glucocorticoid Toxicity Index (GTI), TCZ-related adverse events, and radiographic progression. Results Sixty-five patients with established RA were included in the intention-to-treat population. TCZ was superior in reducing CDAI over months 6–12 (mean difference on square root scale: −0.64; 95% CI: −1.18 to − 0.09). Treatment was switched in 28% (TCZ) and 52% (prednisone). No significant differences were observed in toxicity (GTI: p= 0.922; TCZ related-AEs: p= 1.00) or in radiographic progression (p= 0.376). On-treatment analyses yielded similar results. Conclusion TCZ led to greater improvement in disease activity than prednisone. There was no significant difference in joint damage progression over 12 months and there were no major differences in adverse events. Clinical trial registration EudraCT Number: 2017–003037-28

Post-operative delirium (POD) is an acute deterioration in cognitive function and highly prevalent after cardiac surgery (CS; up to 55%). Perioperative sleep disorders (PSD) are also commonly noted in surgical patients (up to 60%). The primary aim of our systematic review is to determine the association between PSD and POD in CS patients during their hospital stay. We searched five databases (PubMed, CINAHL, Web of Science, Scopus, and EMBASE) to identify studies evaluating the association between PSD and POD amongst CS (any open-heart CS) patients, without time and geographic restriction. Original articles that focused on adults undergoing cardiac surgeries and assessed sleep and POD were included. We conducted a meta-analysis using a random effects model to determine the effect of sleep quality on POD. Thirty-three studies were included (63% observational designs); most studies originated from China (33%). The most frequently used subjective and objective sleep assessment tools were the Pittsburgh Sleep Quality Index (PSQI) (33%) and polysomnography (18%). After pooling observational data, we identified an incidence of POD ranging from 3.6% to 73%. Increased PSQI scores (standard threshold > 5) were associated with a greater likelihood of POD occurrence (standardised mean difference [SMD] = 0.73, p > 0.05). Lower total sleep time (SMD = -0.68, p < 0.05) was associated with an increased risk of POD. Poor sleep quality, insomnia, and sleep-disordered breathing are prevalent forms of PSD and are major risk factors for POD following CS. Additional research is warranted to clarify when sleep quality normalises after cardiac surgery and how targeted interventions can accelerate this recovery.

Voice Alterations in Multiple Sclerosis: ASystematic Review and Meta-analysis of Acoustic Parameters.

A comprehensive assessment of its effectiveness and evidence base is lacking. Therefore, this systematic review and meta-analysis attempts to systematically investigate the therapeutic effect of traditional Chinese exercises (TCEs) on limb motor function, activity of daily living, and balance function in stroke patients with hemiplegia through rigorous meta-analysis methods. Our aim is to verify whether TCEs are effective for the treatment of hemiplegia and provide evidence to support the clinic application of TCEs through synthesizing the existing literature and differences in research methods. The randomized controlled trials of treatment for stroke patients with hemiplegia using the TCEs were searched from seven databases up to September 2024, including CNKI, CBM, VIP, WanFang Data, PubMed, Cochrane, and Embase. The clinical effectiveness and Fugl-Meyer Assessment (FMA) score were chosen as the primary outcomes; the Modified Barthel Index (MBI) score and Berg Balance Scale (BBS) score were defined as the secondary outcomes. Two researchers conducted the literature screening and evaluated the risk of bias and quality of the included literature according to the Cochrane Handbook 5.1 independently. The RevMan 5.7 was used for meta-analysis. Twenty-eight randomized trials involving 2826 participants met the inclusion criteria and were used for meta-analysis in this study. The results showed that the TCEs significantly improved all of the measured outcomes in this study compared with the control group, including the clinical efficacy, the upper limb FMA score, lower limb FMA score, MBI score, and BBS score: The clinical efficacy: mean difference (MD) = 4.83, 95% confidence interval (CI) (3.17, 7.37), Z = 7.34, P < .00001; upper extremity FMA score: MD = 7.94, 95% CI (7.50, 8.37), Z = 35.52, P < .00001; lower extremity FMA score: MD = 4.49, 95% CI (4.25, 4.73), Z = 37.36, P < .00001; MBI score: MD = 8.15, 95% CI (7.47, 8.84), Z = 23.36, P < .00001; BBS score: MD = 6.62, 95% CI (6.17, 7.07), Z = 28.69, P < .00001. Our results revealed that TCE could improve the motor function, ability to live independently, and balance function of the limbs in patients with hemiplegia after stroke. However, the lack of standards for TCEs may lead to bias and heterogeneity. Well-designed, large-sample, multicenter randomized high-quality clinical studies should be conducted to verify the efficacy.

Evidence supporting the benefits of music therapy for preterm infants during neonatal care is growing. This study aimed to compare the effects of live-performed sansula music (SM) to storytelling (ST) as an alternative caregiving intervention on physiological and behavioral responses. The study was conducted as a randomized controlled trial (RCT), enrolling preterm infants born from 32 + 0 to 36 + 6 weeks of gestation. Infants were block-randomized to either receive SM or ST. Both interventions were performed live and provided three to four times per week on average. Vital signs and behavioral state (assessed using the COMFORTneo scale) were documented before, during, and after each intervention. Sixty preterm infants were enrolled in the study: 30 received SM and 30 received ST. We observed positive effects on vital signs and behavioral state in both groups, although the effects were importantly less pronounced in the ST group compared to the SM group. Heart rate decreased during both SM and ST interventions (mean difference (MD) (baseline-after): SM -9.90bpm (95% CI -11.14 to -8.66); ST -2.85bpm (-3.79 to -1.92)). Respiratory rate also decreased for both groups (MD: SM -8.60 breaths/min (-9.60 to -7.60); ST -2.49 breaths/min (-3.30 to -1.68)). Oxygen saturation increased (MD: SM +1.01% (0.82 to 1.20); ST +0.25% (0.11 to 0.39)). The COMFORTneo score decreased (MD: SM -5.40 (-5.95 to -4.86); ST -2.26 (-2.74 to -1.77)). Both, live-performed sansula music as a therapeutic intervention and storytelling, positively impacted the immediate well-being of preterm infants. However, the benefits of live-performed sansula music on physiological and behavioral parameters compared to storytelling as a caregiving alternative were significantly higher.

Breast cancer surgery is often associated with unpleasant postoperative symptoms, including pain, nausea, fatigue, and emotional distress, which can reduce quality of life and prolong recovery times. This study aimed to test the efficacy of preoperative hypnosis in reducing postoperative symptoms following breast cancer surgery. A total of 203 women scheduled for breast cancer surgery at Oslo University Hospital, Norway, participated in a randomized controlled trial. Patients were randomized to receive either a single session of preoperative hypnosis or of mindfulness within two hours prior to their scheduled surgery. Primary outcomes were postoperative pain, fatigue, nausea, discomfort, and emotional distress, measured using 100mm visual analogue scales on the day of surgery following recovery from general anesthesia. Additional measures included amount of intraoperative and postoperative anesthesia and analgesia, as well as surgery duration (extracted from patients' medical records). Patients receiving preoperative hypnosis reported significantly lower postoperative fatigue (mean difference (MD) 6.4, 95% CI 0.40 - 12.4, Cohen's d=0.30) and emotional distress (MD 5.7, 95% CI 0.24 - 11.2, d=0.24) when compared to patients in a mindfulness control group. There was also a significant reduction in postoperative fentanyl use among those patients receiving preoperative hypnosis (MD -0.03, 95% CI -0.047 - -0.005, d=0.54). Preoperative anxiety moderated the effect of hypnosis on postoperative emotional distress, showing a more pronounced benefit for patients with high levels of preoperative anxiety. However, no significant differences were found in postoperative pain, nausea, or discomfort between the hypnosis and mindfulness groups. No adverse events attributed to the interventions were reported. A brief preoperative hypnosis session before breast cancer surgery appears to be more effective than mindfulness in reducing postoperative fatigue, emotional distress, and fentanyl dose. Hypnosis stands out as a promising, non-pharmacological, and safe intervention for reducing certain postoperative symptoms.

Sleep disturbances are common and debilitating non-motor symptoms (NMS) in Parkinson's disease (PD), profoundly affecting quality of life. Despite emerging evidence suggesting that monoamine oxidase B (MAO-B) and catechol-O-methyltransferase (COMT) inhibitors may alleviate NMS, their specific effects on sleep remain unclear. This network meta-analysis (NMA) aimed to compare the efficacy of these inhibitors on sleep problems in PD. Following a systematic search of PubMed, Cochrane, and EMBASE, studies comparing MAO-B or COMT inhibitors and assessing sleep outcomes in PD were identified. An NMA was conducted using data from the seven studies that met our inclusion criteria. Outcomes included subjective sleep quality, daytime sleepiness, and objective polysomnography (PSG) parameters. No statistically significant differences were found among MAO-B and COMT inhibitors in improving subjective sleep quality or daytime sleepiness. However, in analyses of objective PSG data, safinamide was found to significantly increase REM sleep duration (mean difference, 5.70 [95% CI, 2.26, 9.14]) and decrease wake time after sleep onset (mean difference, -10.20 [-19.38, -1.02]) compared to rasagiline and placebo. These findings suggest that safinamide may offer additional value for managing sleep disruptions beyond its known motor benefits in patients with PD. Given the limited number and small scale of available trials, the overall evidence should be interpreted cautiously. Nonetheless, this analysis highlights the need for further high-quality trials focused on sleep outcomes to guide personalized use of MAO-B and COMT inhibitors for sleep disturbances in PD.

Abstract Introduction Knee osteoarthritis (KNOA) is a chronic and burdensome disease associated with chronic pain, reduced physical function and increased joint stiffness [1]. KNOA’s clinical management is complex, and there remains considerable debate about the comparative performance of pharmacotherapeutics for core outcomes, including physical function and joint stiffness, which are essential in clinical decision making to improve patient outcomes. This Network Meta-analysis (NMA) addresses this critical gap in the clinical literature. Aim To evaluate the relative effectiveness of pharmacological interventions for joint stiffness and physical function among adult patients with KNOA using standard NMA and additive component NMA (CNMA). Methodology We performed a comprehensive search of major electronic databases and trial registries from inception to January 2021 for randomised controlled trials (RCTs) that evaluated treatments for KNOA listed in NICE guidelines [2] including: paracetamol, NSAIDs, COX2-inhibitors, opioids, duloxetine, capsaicin, hyaluronic acid (HA) and corticosteroids (CS), administered via oral, topical, transdermal or intra-articular (IA) routes at four time windows: immediate, short, medium and long term. A random-effects NMA and additive CNMA estimated relative treatment effects within a frequentist framework using mean differences (MD) on a 0–10 scale [3]. Certainty of evidence was evaluated using the Confidence in Network Meta-Analysis (CINeMA) with risk of bias (RoB) assessed using the revised Cochrane RoB2 tool. This study does not require ethical approval as it is a systematic review and CNMA of already approved trials and is registered with PROSPERO, CRD42020184192[4]. Results Of 33298 citations, 202 RCTs were eligible for inclusion after a full-text review. Of these, 202 reported on pain, 126 on physical function, and 98 on stiffness. We have previously reported findings for pain[5]. Here, we report findings on physical function and joint stiffness. For physical function, in the immediate-term (32 RCTs), significant improvements were observed only for IACS (MD, -1.05 [95% confidence interval, -1.48, -0.61), oral NSAIDs -0.68 (-0.89, -0.46), and COX2 inhibitors -0.60 (-0.82, -0.38); IACS ranked highest, IAHA lowest. In the short-term (105 RCTs), all interventions except IAHA+oral NSAIDs/gastroprotection demonstrated significant effects, topical+oral NSAIDs ranked highest and oral opioids lowest. In the medium (28 RCTs) and long-term (6 RCTs), only IAHA showed a significant benefit, while IACS showed a non-significant worsening; however, evidence was sparse and of very low certainty. For stiffness, in the immediate-term (26 RCTs), topical and oral NSAIDs, COX2 inhibitors, and duloxetine showed significant effects. Oral NSAIDs ranked first, followed by COX2 inhibitors, while IAHA ranked lowest with MDs of -0.76 (-1.06, -0.46), -0.68 (-1.02, -0.34), and 0.22 (-0.39, 0.83), respectively. In the short-term (78 RCTs), all interventions except IACS, IAHA+oral NSAIDs/gastroprotection, and paracetamol were associated with a significant improvement. In the medium (20 RCTs) and long-term (4 RCTs), only IAHA significantly improved stiffness; however, evidence was sparse and of very low certainty. Discussion Results suggest that anti-inflammatories are the optimal pharmacotherapeutic options, with oral NSAIDs, topical NSAIDs and COX2 inhibitors superior for up to three months, and IACS as a single injection only. Findings serve as a foundation to guide prescribing practices and inform future guidelines, but should be interpreted cautiously given few trials with low risk of bias and the complex nature of KNOA in clinical practice.

To compare the effects of different rehabilitation therapies on the scores of Fugl-Meyer assessment of motor recovery (FMA), the action research arm test (ARAT), and modified Barthel index in hemiplegic patients with stroke by a network meta-analysis. We searched Embase, PubMed, Web of Science, and Cochrane Library from their inception until April 1, 2024 for randomized controlled trials (RCTs) on the effects of rehabilitation therapies on upper extremity motor function and activities of daily living in hemiplegic patients with stroke. Data analyses were conducted using R software. Seventeen RCTs were included, involving 901 patients and 10 rehabilitation therapies. The network meta-analysis revealed that mirror therapy (mean difference [MD] = 4.94, 95% confidence interval [CI]: 4.3-5.59, P < .05), neuromuscular electrical stimulation (NMES) + robotic therapy (RT) (MD = 7.1, 95% CI: 3.15-11.10, P < .05), RT (MD = 4.7, 95% CI: 0.98-8.41, P < .05), and transcranial direct current stimulation (MD = -4.92, 95% CI: -6.12 to -3.72, P < .05) outperformed conventional therapies in the improvement of FMA. NMES + RT (MD = 4.6, 95% CI: 0.42-8.76, P < .05) and repetitive facilitative exercise (RFE) + botulinum toxin type A (BoNT-A) (MD = 8, 95% CI: 4.43-11.52, P < .05) outperformed conventional therapies in the improvement of ARAT. Action observation (AO) (MD = 6, 95% CI: 0.11-11.85, P < .05) was superior to conventional therapies in the improvement of activities of daily living. RFE + BoNT-A had the highest surface under the cumulative ranking curve value for FMA improvement and ARAT improvement. The surface under the cumulative ranking curve value for modified Barthel index improvement was the highest for AO. RFE + BoNT-A and AO exhibit advantages in improving upper extremity motor function and AO, respectively. Due to some limitations in this study, more high-quality RCTs are still required to validate our findings.

Patients' perception of their health outcomes after surgery has become increasingly important in perioperative medicine. This study aimed to evaluate whether emergence delirium in the postanesthesia care unit (PACU) has a relevant impact on self-reported quality of recovery on the first postoperative day. This prospective observational cohort study was conducted in a German tertiary care university hospital. Patients ≥60 years, scheduled for elective noncardiac surgery were included. Patients were screened for the presence of delirium signs 30 minutes after arrival in the PACU using the 3-Minute Diagnostic Interview for CAM-defined Delirium (3D-CAM). Self-reported quality of recovery after surgery was assessed with the German version of the Quality of Recovery-15 questionnaire (QoR-15GE), which patients completed preoperatively and on the first postoperative day. The association between emergence delirium and self-reported quality of recovery was analyzed using a linear multivariable regression model taking into account covariates with a potential impact on recovery after surgery. A total of 428 patients were tested for emergence delirium. Of these, 397 were assessed for self-reported quality of recovery on the first postoperative day. The incidence of emergence delirium was 32.9% (141/428). Patients with emergence delirium showed a greater decline in QoR-15GE sum scores from pre- to postoperative (difference between preoperative and postoperative QoR-15GE sum scores [ΔQoR-15GE]), with a mean difference (± standard deviation [SD]) of 32.8 ± 25.3, compared to 21.6 ± 26.6 in patients without emergence delirium. The between-group difference was 11.2 points (95% confidence interval [CI], 5.5-16.8; P < .001). After adjusting for potentially confounding covariates, the negative impact of emergence delirium on ΔQoR-15GE (adjusted effect 10.11 [95% CI, 4.99-15.23]; P < .001) remained significant. In a heterogeneous cohort of elderly patients who underwent elective noncardiac surgery, we found a significant negative impact of emergence delirium on self-reported quality of recovery on the first postoperative day. Our findings suggest that the presence of delirium symptoms in the PACU may be an important determinant of patient comfort after surgery.

Weaning from mechanical ventilation is a critical process in the intensive care unit (ICU), and extubation failure remains associated with poor outcomes. ICU-acquired weakness has been identified as a risk factor for delayed weaning. Maximal handgrip strength (HGS) is a simple bedside measure proposed as a surrogate marker of global muscle strength. This systematic review and meta-analysis aimed to assess the association between HGS and weaning outcomes in ICU patients. A systematic search of MEDLINE, EMBASE, CINAHL, and Cochrane Library was conducted up to December 2024. We included prospective cohort studies assessing maximal HGS prior to extubation in mechanically ventilated adults, and its association with extubation failure, spontaneous breathing trial (SBT) failure, or weaning classification (simple, difficult, or prolonged). Meta-analyses pooled mean differences in HGS between outcome groups, and diagnostic accuracy was evaluated using a hierarchical summary ROC model. Risk of bias was assessed using the QUIPS tool. Seven studies were included in the review (n = 707 patients), and six in the meta-analysis. No significant difference in HGS was found between extubation failure and success (mean difference: - 3.62kg; 95% CI: - 7.92 to 0.62). However, significantly lower HGS was associated with SBT failure (-3.00kg; 95% CI: - 4.64 to - 1.36) and non-simple weaning (-3.94kg; 95% CI: - 5.31 to - 2.58). Pooled sensitivity and specificity of HGS were 72% and 60% respectively, in predicting either extubation failure or non-simple weaning. Negative predictive values ranged from 90% to 95%, for 10% and 20% pre-test probability. Maximal HGS does not appear to significantly differentiate extubation success from failure Given the limited number of studies and their heterogeneity, further high-quality research is needed to clarify its prognostic value across different patient subgroups and timeframes.

Information security is a critical challenge in the digital age, especially for hospitals, which are prime targets for cyberattacks due to the monetary worth of sensitive medical data. Given the distinctive security risks faced by health care professionals, tailored Security Education, Training, and Awareness (SETA) programs are needed to increase both their ability and willingness to integrate security practices into their workflows. This study investigates the effectiveness of a video-based security training, which was customized for hospital settings and enriched with motivational framing strategies to build information security skills among health care professionals. The training stands out from conventional interventions in this context, particularly by incorporating a dual-motive model to differentiate between self- and other-oriented goals as stimuli for skill acquisition. The appeal to the professional values of responsible health care work, whether absent or present, facilitates a nuanced examination of differential framing effects on training outcomes. A randomized controlled trial was conducted with 130 health care professionals from 3 German university hospitals. Participants within 2 intervention groups received either a self-oriented framing (focused on personal data protection) or an other-oriented framing (focused on patient data protection) at the beginning of a security training video. A control group watched the same video without any framing. Skill assessments using situational judgment tests before and after the training served to evaluate skill growth in all 3 groups. Members of the other-oriented intervention group, who were motivated to protect patients, exhibited the highest increase in security skills (ΔM=+1.13, 95% CI 0.82-1.45), outperforming both the self-oriented intervention group (ΔM=+0.55, 95% CI 0.24-0.86; P=.04) and the control group (ΔM=+0.40, 95% CI 0.10-0.70; P=.004). Conversely, the self-oriented framing of the training content, which placed emphasis on personal privacy, did not yield significantly greater improvements in security skills over the control group (mean difference=+0.15, 95% CI -0.69 to 0.38; P>.99). Further exploratory analyses suggest that the other-oriented framing was particularly impactful among participants who often interact with patients personally, indicating that a higher frequency of direct patient contact may increase receptiveness to this framing strategy. This study underscores the importance of aligning SETA programs with the professional values of target groups, in addition to adapting these programs to specific contexts of professional action. In the investigated hospital setting, a motivational framing that resonates with health care professionals' sense of responsibility for patient safety has proven to be effective in promoting skill growth. The findings offer a pragmatic pathway with a theoretical foundation for implementing beneficial motivational framing strategies in SETA programs within the health care sector.

Adolescence and early adulthood represent a critical phase for management of chronic diseases, including obesity. To improve transition of care in adolescents and young adults with obesity (AYALwO), the main goal was to summarize the current evidence on transition of care interventions (T-interventions) for obesity management. Anticipating a lack of evidence on T-interventions for AYALwO, we expanded the patient population to include individuals with other chronic diseases that can be appropriately transferred, such as diabetes. We searched three databases and one trial registry from 01/2013-07/2025 onwards and screened reference lists of included trials, i.e. randomized-controlled trials (RCTs) and non-randomized-controlled studies of interventions (NRSI) enrolling AYALwO, type 1 (T1D)/ 2 diabetes and RCTs only for inflammatory bowel disease (IBD), arthritis or asthma (effects for these populations were considered transferable in case of lack of trials in AYALwO). We evaluated outcomes of T-interventions, e.g. HbA1c, quality of life, self-management or transition readiness. The review process was completed by two reviewers, independently. Results were summarized via random-effects meta-analysis or descriptively. We included 14 RCTs (n=9 T1D, n=2 mixed population, n=1 IBD, n=1 arthritis, n=1 asthma) and four NRSI (n=2 T1D, n=2 mixed population). Prespecified outcomes were mostly reported infrequently and/or heterogeneously. Effect measures were mostly inconclusive or not meaningful. No effect was shown for HbA1c in seven RCTs (mean difference 0.12% [95%-confidence interval -0.59; 0.83]) or in two NRSI. A higher transfer rate by appointment reminders (one RCT) or consultation at the same physician for pediatric and adult care (one RCT) and an improvement of transition readiness for transition-oriented patient education programs (one RCT, one NSRI) was found. Certainty of evidence (CoE) was very low for all outcomes, mainly due to a high risk of bias, indirectness and imprecision. We found no trial for AYALwO. Evidence on other chronic diseases was limited, showing that T-interventions lead to improvements in transfer rate or transition readiness (very low CoE). This highlights the need for future research regarding T-interventions in AYALwO. CRD42024513411.

Paternal use of valproate during spermatogenesis has been associated with increased risk of neurodevelopmental disorders (NDDs) in offspring, yet the role of genetic confounding is unclear. Using data from the Norwegian Mother, Father, and Child Cohort Study (MoBa), we assessed genetic susceptibility to epilepsy, ADHD and autism spectrum disorders (ASD) in fathers with epilepsy treated with valproate (n = 41), lamotrigine or levetiracetam (n = 37), other anti-seizure medications (ASMs; n = 80), and healthy controls (n = 54,752). Fathers using valproate had significantly higher polygenic risk scores (PRSs) for epilepsy compared to those using lamotrigine or levetiracetam (mean difference: 0.66, 95% CI: 0.21-1.11, p ≈ 0.005), other ASMs (0.41, 95% CI: 0.02-0.81, p ≈ 0.04) and controls (0.85, 95% CI: 0.54-1.15, p = 5.8 × 10⁻⁸). No robust associations were found between paternal ASM use or epilepsy PRS and child neurodevelopmental outcomes. Significant genetic overlap was found among the top 1% of weighted SNPs in the PRSs for epilepsy, ADHD and ASD (428 genes, p ≈ 0.0001), enriched for neurodevelopmental pathways. These results emphasize the importance of considering shared genetic susceptibility when assessing risks of paternal valproate exposure.

Poorer psychological and social well-being has been linked to increased mortality. To delineate the trajectories of psychological and social well-being during the last two decades of life. Within the Rush Memory and Aging Project, 1971 older adults were followed up for up to 22 years. Aspects of psychological well-being (ie, depression symptoms, loneliness and purpose in life) and social well-being (ie, cognitive activity, social activity and social network) were annually measured through structured interviews. Survival status was tracked during the follow-up period. Data were analysed using Cox regression and mixed-effect models with a backward timescale. During the follow-up, 1119 (56.77%) participants died. In multiadjusted Cox regression models, higher depression symptoms and poor social activity were associated with increased mortality. Compared with survivors, decedents showed steeper declines in psychological and social well-being, leading to significant differences up to 13 years before death for purpose in life (mean difference: -0.14 (-0.26, -0.01)), 9 years for depression symptoms (0.35 (0.10, 0.60)) and social activity (-0.16 (-0.26, -0.06)), 6 years for loneliness (0.13 (0.05, 0.21)), 4 years for social network (-1.06 (-1.77, -0.36)), and 3 years for cognitive activity (-0.12 (-0.21, -0.04)). Among decedents, the terminal phase began 11 years before death for purpose in life, 10 years for cognitive activity, 9 years for social activity and depression symptoms and 6 years for loneliness. Psychological and social well-being may begin to exhibit terminal decline approximately 6-11 years prior to death. Longitudinal surveillance of well-being should be incorporated into the context of geriatric medical care.

This study aimed to identify phenotypes of long COVID symptoms in adults following Omicron infection and assess their association with health-related quality of life (HRQoL). We analyzed three prospective observational studies in Brazil, enrolling adult patients who sought care for symptomatic Omicron infection between December 2021 and March 2023. The infection was confirmed by either an antigen test or reverse transcriptase polymerase chain reaction. Long COVID symptoms were assessed three months after enrollment through structured interviews. Phenotypes of Long COVID-19 were identified using a machine learning-based clustering approach. Exploratory analyses were conducted to examine predisposing factors and health-related quality of life utilities, measured by EQ-5D-3L, associated with each phenotype. A total of 2,989 patients were analyzed (39% women, median age 41 years, and 96% had completed the primary series of COVID-19 vaccination). Long COVID symptoms at three months were reported by 1,155 (38.6%) patients. Three phenotypes were identified: cluster 1 (n = 459 [39.7%]), characterized by a median of three symptoms (IQR, 2-5) with memory loss (80.4%), concentration problems (38.3%) and fatigue (35.7%) being most common; cluster 2 (n = 549 [47.5%]), characterized by a median of two symptoms (IQR, 1-4) with fatigue (43.7%), other symptoms (42.3%), and cough (20.6%) being most common; and cluster 3 (n = 147, 12.7%), characterized by a higher number of symptoms (median, 8; IQR, 7-10), with fatigue (89.9%), memory loss (88.4%), and anxiety (64.6%) as the most common. The mean EQ-5D-3L utility at 3 months was 0.75 for cluster 1, 0.73 for cluster 2, and 0.59 for cluster 3 (p < 0.001). After adjusted regression analysis, cluster 3 was independently associated with the lowest EQ-5D-3L utilities (mean difference, -0.21; 95%CI, -0.24 to -0.18; p < 0.001). Distinct phenotypic presentations of Long COVID following Omicron infection in Brazil were identified, with significant differences in quality of life. Not applicable.

Chronic low back pain (CLBP) significantly impairs quality of life and increases mortality among older adults, making its effective management essential for healthy aging. This quasi-randomized trial compared Pain Neuroscience Education emphasizing physical activity (PNE-PA) with traditional biomechanical treatments (BM) in older women with CLBP over 12 weeks. Community-dwelling women aged 65-90 years with CLBP were assigned to either group based on recruitment timing, using a double-blinded design. PNE-PA aimed to reduce pain-related fear by educating patients about pain neuroscience and encouraging physical activity. Outcomes included physical function, pain intensity, self-reported disability and psychological factors. Analyses used intention-to-treat and bootstrap resampling methods. Between-group differences were assessed using mean differences, 95% confidence intervals (CI), and Cohen's d. The PNE-PA group (n = 24) showed significantly greater improvements than the BM group (n = 18) in Chair Stand Test (95% CI: 1.53to7.76, d = 0.88), step count (95% CI: 475.97to2550.42, d = 0.87), pain catastrophizing (95% CI: -10.64 to-1.95, d = -0.87), and fear-avoidance beliefs (95% CI: -7.40 to-0.14, d = -0.65). These findings suggest that Pain Neuroscience Education emphasizing physical activity was associated with better physical and psychological outcomes among older women with chronic low back pain.

When we consider the treatment of polycystic ovary syndrome (PCOS), one of our treatment options is metformin, which reduces free testosterone levels in PCOS patients. We were interested to know what happens to the free testosterone levels of male type 2 diabetes mellitus (T2DM) patients when we use metformin. The effect of metformin on testosterone level, fertility, and sexual activity in males has been issues of interest to researchers. This study was conducted to observe the effect of metformin on free testosterone levels in male T2DM patients. One hundred fifty male patients (mean age, 40-46 years; SD, 1.2), newly diagnosed with T2DM and drug-naïve, were enrolled. Initially, the baseline-free testosterone level was measured. Then, 75 of them were given metformin, and 75 of them were treated with other antidiabetics. After treatment for 30 days, the free testosterone level was measured again. In both groups, the mean value of free testosterone change in 1 month was calculated. Then, a comparison between the mean change in the 2 groups was done. Baseline-free testosterone of metformin (mean = 7.9, SD = 2.2) and non-metformin (mean = 8.1, SD = 1.9) groups were compared, and no significant difference was seen between them (P = .264). After 30 days of treatment, there was an increased level of free testosterone in both groups (mean metformin = 9.75, non-metformin = 10.77). But. free testosterone rise in non-metformin group(M = 2.63,SD = 1.07) was significantly higher (mean difference = .80,95% CI) than metformin group (M = 1.82,SD = .99,t = 4.76, P < .001). Metformin is inferior to other antidiabetic medications in raising free testosterone levels. Larger multicenter studies are further warranted.

The effect of flow-controlled ventilation (FCV) as compared with volume-controlled ventilation (VCV) on oxygenation and respiratory system mechanics in patients undergoing one-lung ventilation (OLV) is unknown. To test the hypothesis that FCV would improve oxygenation and respiratory system mechanics compared with VCV during OLV. Two-centre, two-arm, randomised controlled clinical trial. University hospital and speciality hospital for pulmonary diseases in Germany. A total of 78 thoracic surgery patients undergoing OLV for more than 30 min. Patients were randomly assigned to OLV with FCV (n = 39), or VCV (n = 39). In both groups, OLV was conducted with tidal volume of 5 ml kg-1, positive end-expiratory pressure of 5 cmH2O, respiratory rate to normocapnia, and inspiratory oxygen fraction of 1.0. The primary outcome was the arterial partial pressure of oxygen (PaO2) 20 min after initiation of OLV. The secondary outcomes included respiratory system mechanics, the need for rescue due to hypoxaemia, and clinical outcome variables. The partial pressure of arterial oxygen did not differ between FCV and VCV at 20 min after starting OLV (PaO2: 24.8 ± 14.8 kPa vs. 26.1 ± 15.9 kPa, mean difference -1.2 (95% confidence interval -8.2 to 5.7), P = 0.721), while mechanical power was lower during FCV compared with VCV. Other variables did not differ at any time thereafter, except for the compliance of the respiratory system at end of surgery. The need for rescue manoeuvres due to hypoxemia or hypercapnia during OLV did not differ between the groups. The incidence of postoperative pulmonary and extrapulmonary complications, as well as the number of hospital-free days at day 30 after surgery, did not differ between FCV and VCV. Compared with VCV in thoracic surgery patients, FCV did not improve oxygenation or respiratory system mechanics during OLV, nor was it associated with improved outcomes.