Long-term quality of life, work limitation, physical activity, economic cost and disease burden following ACL and meniscal injury: a systematic review and meta-analysis for the OPTIKNEE consensus.

OBJECTIVE: Determine the long-term health-related quality-of-life (HRQoL), work limitation, physical activity, health/economic cost and disease burden of traumatic ACL and/or meniscal injury. Findings will inform OPTIKNEE evidence-based consensus recommendations. DESIGN: Random-effects meta-analysis evaluated HRQoL (SF-36/SF-12/VR-12 Physical Component Scores (PCS) and Mental Component Scores (MCS), EuroQol-5D (EQ-5D)) stratified by time postinjury, and pooled mean differences (95% CI) between ACL-injured and uninjured controls. Other outcomes were synthesised descriptively. Risk-of-bias (RoB) and certainty of evidence (Grading of Recommendations Assessment, Development and Evaluation) were assessed. DATA SOURCES: MEDLINE, EMBASE, CENTRAL, SPORTDiscus, CINAHL searched inception: 22 November 2021. ELIGIBILITY: Studies reporting HRQoL, work limitations, physical activity levels, health/economic costs or disease burden, ≥2 years post-ACL and/or meniscal injury. RESULTS: Fifty studies were included (10 high-RoB, 28 susceptible-to-some-bias and 12 low-RoB). Meta-analysis (27 studies, very low certainty of evidence) estimated a pooled mean (95% CI) PCS of 52.4 (51.4 to 53.4) and MCS of 54.0 (53.0 to 55.0) 2-14 years post-ACL injury. Pooled PCS scores were worse >10 years (50.8 (48.7 to 52.9)) compared with 2-5 years (53.9 (53.1 to 54.7)) postinjury. Excluding high-RoB studies, PCS scores were worse in ACL-injured compared with uninjured controls (-1.5 (-2.9 to -0.1)). Six studies (low certainty of evidence) informed a pooled EQ-5D score of 0.83 (0.81 to 0.84). Some individuals experienced prolonged work absenteeism and modified activities ≥2 years post-ACL injury. ACL injury was associated with significant direct and indirect costs, and early ACL reconstruction may be less cost-effective than rehabilitation. Only three studies evaluated meniscal injury outcomes (all evaluated HRQoL). CONCLUSION: There is a very-low certainty of evidence that PCS scores ≥2 years post-ACL injury are worse than uninjured controls and decline over time, whereas MCS scores remain high. ACL injury can result in prolonged work absenteeism and high health/economic costs. Further studies are needed to determine the long-term burden of traumatic meniscal injury.

Immune checkpoint Inhibitor-Induced diarrhea and Colitis: Incidence and Management. A systematic review and Meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have improved cancer outcomes. However, immune-related adverse effects are common. The aim was to investigate the incidence of diarrhea and colitis of ICIs alone and in combination with chemotherapy or tyrosine kinase inhibitors (TKIs), histopathological findings, and management. METHODS: Two separate studies, including meta-analyses, were performed. Key inclusion criteria were for Study I) phase I-IV trials, and data on diarrhea and/or colitis; for Study II) studies describing histopathologic and endoscopic findings and/or biologic treatment for ICI-induced colitis. RESULTS: The incidence of anti-PD-1/PD-L1 antibody-induced diarrhea and colitis was 10% and 2%, respectively, with no clinically relevant differences between the compounds. The CTLA-4 inhibitor, ipilimumab, induced diarrhea and colitis in 33% and 7% of patients, respectively, whereas the incidence of diarrhea and colitis following ipilimumab combined with nivolumab was 21%-37% and 4%-8%, depending on regimen. The incidence of all-grade diarrhea following ICIs combined with chemotherapy or TKIs was high (17%-56%), whereas only 0.5% of patients developed severe (≥grade 3) colitis. The main patterns of histopathologic presentation after PD-1/CTLA-4 inhibitor mono- or combination therapy were acute and chronic active colitis and microscopic colitis-like. Infliximab and vedolizumab were equally effective against ICI-induced colitis. CONCLUSION: Expanding treatment options include combinations of ICIs and chemotherapy/TKI with a high incidence of diarrhea and a low incidence of colitis; thus, a potential risk of overtreatment with corticosteroids exists. We suggest a more tailored approach, particularly for the management of low-grade diarrhea. Prospective clinical trials are needed to refine management.

The MIPAM trial: a 12-week intervention with motivational interviewing and physical activity monitoring to enhance the daily amount of physical activity in community-dwelling older adults - a study protocol for a randomized controlled trial.

BACKGROUND: Physical Activity Monitors (PAMs) have been shown to effectively enhance level of physical activity (PA) in older adults. Motivational interviewing is a person-centred model where participants are guided using self-reflection and counselling, and addresses the behavioural and psychological aspects of why people initiate health behaviour change by prompting increases in motivation and self-efficacy. The addition of motivational interviewing to PA interventions may increase the effectiveness of PAMs for older adults. METHODS: This motivational interviewing and PA monitoring trial is designed as an investigator-blinded, two arm parallel group, randomized controlled superiority trial with primary endpoint after 12 weeks of intervention. The intervention group will receive a PAM-based intervention and motivational interviewing and the control group will only receive the PAM-based intervention. The primary outcome is PA, objectively measured as the average daily number of steps throughout the intervention period. Secondary outcome measures include self-reported PA health-related quality of life, loneliness, self-efficacy for exercise, outcome expectancy for exercise, and social relations. The outcomes will be analysed with a linear regression model investigating between-group differences, adjusted for baseline scores. Following the intention to treat principle, multiple imputation will be performed to handle missing values. DISCUSSION: A moderate effect of daily PA measured using PAMs is expected in this superiority RCT investigating the effect of adding motivational interviewing to a PAM intervention. According to the World Health Organization, walking and cycling are key activities in regular PA and should be promoted. To increase the general public health and lower the burden of inactivity in older adults, cost-beneficial solutions should be investigated further. If this RCT shows that motivational interviewing can enhance the effect of PAM-based interventions, it might be included as an add-on intervention when appropriate. No matter what the results of this study will be, the conclusions will be relevant for clinicians as the dependence on technology is increasing, especially in relation to public health promotion. TRIAL REGISTRATION: NCT03906162 , April 1, 2019.