Effect of Multimodal Prehabilitation on Reducing Postoperative Complications and Enhancing Functional Capacity Following Colorectal Cancer Surgery: The PREHAB Randomized Clinical Trial.

Importance: Colorectal surgery is associated with substantial morbidity rates and a lowered functional capacity. Optimization of the patient's condition in the weeks prior to surgery may attenuate these unfavorable sequelae. Objective: To determine whether multimodal prehabilitation before colorectal cancer surgery can reduce postoperative complications and enhance functional recovery. Design, Setting, and Participants: The PREHAB randomized clinical trial was an international, multicenter trial conducted in teaching hospitals with implemented enhanced recovery after surgery programs. Adult patients with nonmetastasized colorectal cancer were assessed for eligibility and randomized to either prehabilitation or standard care. Both arms received standard perioperative care. Patients were enrolled from June 2017 to December 2020, and follow-up was completed in December 2021. However, this trial was prematurely stopped due to the COVID-19 pandemic. Interventions: The 4-week in-hospital supervised multimodal prehabilitation program consisted of a high-intensity exercise program 3 times per week, a nutritional intervention, psychological support, and a smoking cessation program when needed. Main Outcomes and Measures: Comprehensive Complication Index (CCI) score, number of patients with CCI score more than 20, and improved walking capacity expressed as the 6-minute walking distance 4 weeks postoperatively. Results: In the intention-to-treat population of 251 participants (median [IQR] age, 69 [60-76] years; 138 [55%] male), 206 (82%) had tumors located in the colon and 234 (93%) underwent laparoscopic- or robotic-assisted surgery. The number of severe complications (CCI score >20) was significantly lower favoring prehabilitation compared with standard care (21 of 123 [17.1%] vs 38 of 128 [29.7%]; odds ratio, 0.47 [95% CI, 0.26-0.87]; P = .02). Participants in prehabilitation encountered fewer medical complications (eg, respiratory) compared with participants receiving standard care (19 of 123 [15.4%] vs 35 of 128 [27.3%]; odds ratio, 0.48 [95% CI, 0.26-0.89]; P = .02). Four weeks after surgery, 6-minute walking distance did not differ significantly between groups when compared with baseline (mean difference prehabilitation vs standard care 15.6 m [95% CI, -1.4 to 32.6]; P = .07). Secondary parameters of functional capacity in the postoperative period generally favored prehabilitation compared with standard care. Conclusions and Relevance: This PREHAB trial demonstrates the benefit of a multimodal prehabilitation program before colorectal cancer surgery as reflected by fewer severe and medical complications postoperatively and an optimized postoperative recovery compared with standard care. Trial Registration: trialregister.nl Identifier: NTR5947.

Frailty and the impacts of the COVID-19 pandemic on community-living middle-aged and older adults: an analysis of data from the Canadian Longitudinal Study on Aging (CLSA).

BACKGROUND: frailty imparts a higher risk for hospitalisation, mortality and morbidity due to COVID-19 infection, but the broader impacts of the pandemic and associated public health measures on community-living people with frailty are less known. METHODS: we used cross-sectional data from 23,974 Canadian Longitudinal Study on Aging participants who completed a COVID-19 interview (Sept-Dec 2020). Participants were included regardless of whether they had COVID-19 or not. They were asked about health, resource, relationship and health care access impacts experienced during the pandemic. Unadjusted and adjusted prevalence of impacts was estimated by frailty index quartile. We further examined if the relationship with frailty was modified by sex, age or household income. RESULTS: community-living adults (50-90 years) with greater pre-pandemic frailty reported more negative impacts during the first year of the pandemic. The frailty gradient was not explained by socio-demographic or health behaviour factors. The largest absolute difference in adjusted prevalence between the most and least frail quartiles was 15.1% (challenges accessing healthcare), 13.3% (being ill) and 7.4% (increased verbal/physical conflict). The association between frailty and healthcare access differed by age where the youngest age group tended to experience the most challenges, especially for those categorised as most frail. CONCLUSION: although frailty has been endorsed as a tool to inform estimates of COVID-19 risk, our data suggest it may have a broader role in primary care and public health by identifying people who may benefit from interventions to reduce health and social impacts of COVID-19 and future pandemics.

Frailty differences across population characteristics associated with health inequality: a cross-sectional analysis of baseline data from the Canadian Longitudinal Study on Aging (CLSA).

OBJECTIVE: To evaluate the pattern of frailty across several of social stratifiers associated with health inequalities. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional baseline data on 51 338 community-living women and men aged 45-85 years from the population-based Canadian Longitudinal Study on Aging (collected from September 2011 to May 2015) were used in this study. PRIMARY OUTCOMES AND MEASURES: A Frailty Index (FI) was constructed using self-reported chronic conditions, psychological function and cognitive status and physical functioning variables. Social stratifiers were chosen based on the Pan-Canadian Health Inequalities Reporting Initiative, reflecting key health inequalities in Canada. Unadjusted and adjusted FIs and domain-specific FIs (based on chronic conditions, physical function, psychological/cognitive deficits) were examined across population strata. RESULTS: The overall mean FI was 0.13±0.08. It increased with age and was higher in women than men. Higher mean FIs were found among study participants with low income (0.20±0.10), who did not complete secondary education (0.17±0.09) or had low perceived social standing (0.18±0.10). Values did not differ by Canadian province of residence or urban/rural status. After simultaneously adjusting for population characteristics and other covariates, income explained the most heterogeneity in frailty, especially in younger age groups; similar patterns were found for men and women. The average frailty for people aged 45-54 in the lowest income group was greater than that for those aged 75-85 years. The heterogeneity in the FI among income groups was greatest for the psychological/cognitive domain. CONCLUSIONS: Our results suggest that especially in the younger age groups, psychological/cognitive deficits are most highly associated with both overall frailty levels and the gradient in frailty associated with income. If this is predictive of later increases in the other two domains (and overall frailty), it raises the question whether targeting mental health factors earlier in life might be an effective approach to mitigating frailty.

Association between markers of immune response at hospital admission and COVID-19 disease severity and mortality: A meta-analysis and meta-regression.

BACKGROUND: To determine the utility of admission laboratory markers in the assessment and prognostication of coronavirus disease-2019 (COVID-19), a systematic review and meta-analysis were conducted on the association between admission laboratory values in hospitalized COVID-19 patients and subsequent disease severity and mortality. MATERIAL AND METHODS: Searches were conducted in MEDLINE, Pubmed, Embase, and the WHO Global Research Database from December 1,2019 to May 1, 2020 for relevant articles. A random effects meta-analysis was used to calculate the weighted mean difference (WMD) and 95% confidence interval (95% CI) for each of 27 laboratory markers. The impact of age and sex on WMDs was estimated using meta-regression techniques for 11 markers. RESULTS: In total, 64 studies met the inclusion criteria. The most marked WMDs were for neutrophils (ANC) at 3.82 × 109 /L (2.76, 4.87), lymphocytes (ALC) at -0.34 × 109 /L (-0.45, -0.23), interleukin-6 (IL-6) at 32.59 pg/mL (23.99, 41.19), ferritin at 814.14 ng/mL (551.48, 1076.81), C-reactive protein (CRP) at 66.11 mg/L (52.16, 80.06), D-dimer at 5.74 mg/L (3.91, 7.58), LDH at 232.41 U/L (178.31, 286.52), and high sensitivity troponin I at 90.47 pg/mL (47.79, 133.14) when comparing fatal to nonfatal cases. Similar trends were observed comparing severe to non-severe groups. There were no statistically significant associations between age or sex and WMD for any of the markers included in the meta-regression. CONCLUSION: The results highlight that hyper inflammation, blunted adaptive immune response, and intravascular coagulation play key roles in the pathogenesis of COVID-19. Markers of these processes are good candidates to identify patients for early intervention and, importantly, are likely reliable regardless of age or sex in adult patients.

How did governmental interventions affect the spread of COVID-19 in European countries?

BACKGROUND: To reduce the transmission of the severe acute respiratory syndrome coronavirus 2 in its first wave, European governments have implemented successive measures to encourage social distancing. However, it remained unclear how effectively measures reduced the spread of the virus. We examined how the effective-contact rate (ECR), the mean number of daily contacts for an infectious individual to transmit the virus, among European citizens evolved during this wave over the period with implemented measures, disregarding a priori information on governmental measures. METHODS: We developed a data-oriented approach that is based on an extended Susceptible-Exposed-Infectious-Removed (SEIR) model. Using the available data on the confirmed numbers of infections and hospitalizations, we first estimated the daily total number of infectious-, exposed- and susceptible individuals and subsequently estimated the ECR with an iterative Poisson regression model. We then compared change points in the daily ECRs to the moments of the governmental measures. RESULTS: The change points in the daily ECRs were found to align with the implementation of governmental interventions. At the end of the considered time-window, we found similar ECRs for Italy (0.29), Spain (0.24), and Germany (0.27), while the ECR in the Netherlands (0.34), Belgium (0.35) and the UK (0.37) were somewhat higher. The highest ECR was found for Sweden (0.45). CONCLUSIONS: There seemed to be an immediate effect of banning events and closing schools, typically among the first measures taken by the governments. The effect of additionally closing bars and restaurants seemed limited. For most countries a somewhat delayed effect of the full lockdown was observed, and the ECR after a full lockdown was not necessarily lower than an ECR after (only) a gathering ban.

Evaluation of 10 years of parainfluenza virus, human metapneumovirus, and respiratory syncytial virus infections in lung transplant recipients.

Respiratory tract infection with pneumoviruses (PVs) and paramyxoviruses (PMVs) are increasingly associated with chronic lung allograft dysfunction (CLAD) in lung transplant recipients (LTRs). Ribavirin may be a treatment option but its effectiveness is unclear, especially with respect to infection severity. We retrospectively analyzed 10 years of PV/PMV infections in LTRs. The main end points were forced expiratory volume in 1 second (FEV1 ) at 3 and 6 months postinfection, expressed as a percentage of pre-infection FEV1 and incidence of new or progressed CLAD 6 months postinfection. A total of 139 infections were included: 88 severe infections (63%) (defined as >10% FEV1 loss at infection) and 51 mild infections (37%) (≤10% FEV1 loss). Overall postinfection CLAD incidence was 20%. Associations were estimated on postinfection FEV1 for ribavirin vs no ribavirin (+13.2% [95% CI: 7.79; 18.67]) and severe vs mild infection (-11.1% [95% CI: -14.76; -7.37]). Factors associated with CLAD incidence at 6 months were ribavirin treatment (odds ratio (OR [95% CI]) 0.24 [0.10; 0.59]), severe infection (OR [95% CI] 4.63 [1.66; 12.88]), and mycophenolate mofetil use (OR [95% CI] 0.38 [0.14; 0.97]). These data provide valuable information about the outcomes of lung transplant recipients with these infections and suggests possible associations of ribavirin use and infection severity with long-term outcomes. Well-designed prospective trials are needed to confirm these findings.