Progression of Frailty and Cardiovascular Outcomes Among Medicare Beneficiaries.

Background: Frailty is associated with adverse cardiovascular outcomes independent of age and comorbidities, yet the independent influence of frailty progression remains uncertain. Methods: Medicare Fee-for-service beneficiaries ≥ 65 years at cohort inception with continuous enrollment from 2003-2015 were included. Frailty trajectory was measured by annualized change in a validated claims-based frailty index (CFI) over a 5-year period. Linear mixed effects models, adjusting for baseline frailty, were used to estimate CFI change over a 5-year period. Survival analysis was used to evaluate associations of frailty progression and future health outcomes (major adverse cardiovascular and cerebrovascular events [MACCE], all-cause death, heart failure, myocardial infarction, ischemic stroke, and days alive at home [DAH] within the following calendar year). Results: 26.4 million unique beneficiaries were included (mean age 75.4 ± 7.0 years, 57% female, 13% non-White). In total, 20% had frailty progression, 66% had no change in frailty, and 14% frailty regression over median follow-up of 2.4 years. Compared to those without a change in CFI, when adjusting for baseline frailty, those with frailty progression had significantly greater risk of incident MACCE (hazard ratio [HR] 2.30, 95% confidence interval [CI] 2.30-2.31), all-cause mortality (HR 1.59, 95% CI 1.58-1.59), acute myocardial infarction (HR 1.78, 95% CI 1.77-1.79), heart failure (HR 2.78, 95% CI 2.77-2.79), and stroke (HR 1.78, 95% CI 1.77-1.79). There was also a graded increase in risk of each outcome with more rapid progression and significantly fewer DAH with the most rapid vs. the slowest progression group (270.4 ± 112.3 vs. 308.6 ± 93.0 days, rate ratio 0.88, 95% CI 0.87-0.88, p < 0.001). Conclusions: In this large, nationwide sample of Medicare beneficiaries, frailty progression, independent of baseline frailty, was associated with fewer DAH and a graded risk of MACCE, all-cause mortality, myocardial infarction, heart failure, and stroke compared to those without progression.

Cost-Effectiveness of Surgical Weight-Loss Interventions for Patients With Knee Osteoarthritis and Class III Obesity.

OBJECTIVE: Class III obesity (body mass index [BMI] ≥40 kg/m2 ) is associated with worse knee pain and total knee replacement (TKR) outcomes. Because bariatric surgery yields sustainable weight loss for individuals with BMI ≥40 kg/m2 , our objective was to establish the value of Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG) in conjunction with usual care for knee osteoarthritis (OA) patients with BMI ≥40 kg/m2 . METHODS: We used the Osteoarthritis Policy model to assess long-term clinical benefits, costs, and cost-effectiveness of RYGB and LSG. We derived model inputs for efficacy, costs, and complications associated with these treatments from published data. Primary outcomes included quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs), all discounted at 3%/year. This analysis was conducted from a health care sector perspective. We performed sensitivity analyses to evaluate uncertainty in input parameters. RESULTS: The usual care + RYGB strategy increased the quality-adjusted life expectancy by 1.35 years and lifetime costs by $7,209, compared to usual care alone (ICER = $5,300/QALY). The usual care + LSG strategy yielded less benefit than usual care + RYGB and was dominated. Relative to usual care alone, both usual care + RYGB and usual care + LSG reduced opioid use from 13% to 4%, and increased TKR usage from 30% to 50% and 41%, respectively. For cohorts with BMI between 38 and 41 kg/m2 , usual care + LSG dominated usual care + RYGB. In the probabilistic sensitivity analysis, at a willingness-to-pay threshold of $50,000/QALY, usual care + RYGB and usual care + LSG were cost-effective in 70% and 30% of iterations, respectively. CONCLUSION: RYGB offers good value among knee OA patients with BMI ≥40 kg/m2 , while LSG may provide good value among those with BMI between 35 and 41 kg/m2 .

Posterior reversible encephalopathy syndrome after first rituximab transfusion for treatment of granulomatosis with polyangiitis.

A woman in her 60s developed acute onset headache, blurry vision and encephalopathy a few hours after rituximab infusion, given to treat granulomatosis with polyangiitis. CT scan showed oedema in the posterior circulation area suggesting the diagnosis of posterior reversible encephalopathy syndrome, and an MRI confirmed it. After being treated with aggressive blood pressure control and other supportive measures, her symptoms improved over 3-4 days. This case highlights the need for awareness and early recognition of this rare but serious adverse effect of rituximab. CT scan can be helpful in diagnosis (also to rule out bleeding), but the MRI provides the most accurate diagnosis.

Thoracic surgery with geriatric assessment and collaboration can prepare frail older adults for lung cancer surgery.

BACKGROUND AND OBJECTIVES: We assessed frailty, measured by a comprehensive geriatric assessment-based frailty index (FI-CGA), and its association with postoperative outcomes among older thoracic surgical patients. METHODS: Patients aged ≥65 years evaluated in the geriatric-thoracic clinic between June 2016 through May 2020 who underwent lung surgery were included. Frailty was defined as FI-CGA > 0.2, and "occult frailty", a level not often recognized by surgical teams, as 0.2 < FI-CGA < 0.4. A qualitative analysis of geriatric interventions was performed. RESULTS: Seventy-three patients were included, of which 45 (62%) were nonfrail and 28 (38%) were frail. "Occult frailty" was present in 23/28 (82%). Sixty-one (84%) had lung malignancy. Geriatric interventions included delirium management, geriatric-specific pain and bowel regimens, and frailty optimization. More sublobar resections versus lobectomies (61% vs. 25%) were performed among frail patients. Frailty was not significantly associated with overall complications (odds ratio [OR]: 2.4; 95% confidence interval [CI]: 0.88-6.44; p = 0.087), major complications (OR: 2.33; 95% CI: 0.48-12.69; p = 0.293), discharge disposition (OR: 2.8; 95% CI: 0.71-11.95; p = 0.141), or longer hospital stay (1.3 more days; p = 0.18). CONCLUSION: Frailty and "occult frailty" are prevalent in patients undergoing lung surgery. However, with integrated geriatric management, these patients can safely undergo surgery.

Validation of the Fitbit Charge 2 compared to the ActiGraph GT3X+ in older adults with knee osteoarthritis in free-living conditions.

OBJECTIVE: To evaluate physical activity (PA) and sedentary time in subjects with knee osteoarthritis (OA) measured by the Fitbit Charge 2 (Fitbit) and a wrist-worn ActiGraph GT3X+ (AGW) compared to the hip-worn ActiGraph (AGH). DESIGN: We recruited a cohort of subjects with knee OA from rheumatology clinics. Subjects wore the AGH for four weeks, AGW for two weeks, and Fitbit for two weeks over a four-week study period. We collected accelerometer counts (ActiGraphs) and steps (ActiGraphs, Fitbit) and calculated time spent in sedentary, light, and moderate-to-vigorous activity. We used triaxial PA intensity count cut-points from the literature for ActiGraph and a stride length-based cadence algorithm to categorize Fitbit PA. We compared Fitbit wear times calculated from a step-based algorithm and a novel algorithm that incorporates steps and heart rate (HR). RESULTS: We enrolled 15 subjects (67% female, mean age 68 years). Relative to AGH, Fitbit, on average, overestimated steps by 39% and sedentary time by 37% and underestimated MVPA by 5 minutes. Relative to AGH, AGW overestimated steps 116%, underestimated sedentary time by 66%, and captured 281 additional MVPA minutes. The step-based wear time Fitbit algorithm captured 14% less wear time than the HR-based algorithm. CONCLUSIONS: Fitbit overestimates steps and underestimates MVPA in knee OA subjects. Cut-offs validated for AGW should be developed to support the use of AGW for PA assessment. The HR-based Fitbit algorithm captured more wear time than the step-based algorithm. These data provide critical insight for researchers planning to use commercially-available accelerometers in pragmatic studies.

Financial incentives for objectively-measured physical activity or weight loss in adults with chronic health conditions: A meta-analysis.

OBJECTIVE: We conducted a meta-analysis and systematic review of published randomized controlled trials (RCTs) to evaluate the impact of financial incentives (FI) on objectively-measured physical activity (PA) and weight loss (WL) in adults with sedentary behavior or chronic health conditions. EVIDENCE REVIEW: We performed a systematic search for RCTs published in English indexed in PubMed, Embase, or Web of Science through July 27, 2017. We limited our search to RCTs that involved an FI intervention with a monetary component, objectively-measured PA or WL outcomes, samples with either sedentary lifestyles or chronic health conditions, and a comparator group that did not receive performance-contingent FI. We calculated the mean difference and standardized mean difference (SMD) for each study and used a random effects model to summarize intervention efficacy. We used the Jadad scoring tool to assess the quality of the identified articles. RESULTS: We abstracted data from 11 RCTs. Two of the 11 included studies focused on PA, totaling 126 intervention and 116 control subjects. Nine RCTs evaluated the effect of FI on WL, totaling 1,799 intervention and 1,483 control subjects. The combined estimate for change in daily steps was 940 (95%CI [306-1,574]) more in PA intervention groups than in control groups and 2.36 (95%CI [1.80-2.93]) more kilograms lost by WL intervention groups compared to control groups. The overall estimated SMD for both outcomes combined was 0.395 (95%CI [0.243-0.546; p<0.001]), favoring FI interventions. CONCLUSION: FI interventions are efficacious in increasing PA and WL in adults with chronic conditions or sedentary adults. Public health programs to increase PA or prevent chronic disease should consider incorporating FI to improve outcomes.

Endogenous Two-Photon Excited Fluorescence Imaging Characterizes Neuron and Astrocyte Metabolic Responses to Manganese Toxicity.

As neurodegenerative conditions are increasingly linked to mitochondrial dysfunction, methods for studying brain cell metabolism at high spatial resolution are needed to elucidate neurodegeneration mechanisms. Two-photon excited fluorescence (TPEF) imaging is a non-destructive, high-resolution technique for studying cell metabolism via endogenous fluorescence of reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD). We employed TPEF to study the metabolism of primary rat astrocyte and neuronal cultures under normal growth conditions and in response to manganese (Mn) treatment. Histograms of pixel-wise optical redox ratio, defined as FAD/(FAD + NAD(P)H), revealed three distinct redox distributions and significant differences in their relative weights between astrocytes and neurons. When treated with Mn, both cell types exhibited redox ratio shifts consistent with increased oxidative stress. However, the manner in which the redox distributions was affected was distinct for the two cell types. Furthermore, NAD(P)H fluorescence lifetime imaging revealed an increase in bound NAD(P)H fraction upon Mn treatment for neurons, consistent with enhanced apoptosis. Astrocytes showed a decrease in bound fraction, possibly due to a shift towards glycolytic metabolism in response to impaired respiration. These results exhibit TPEF's utility for characterizing detailed metabolic changes of different brain cell types in response to neurotoxins.