Novotny, Paul J.

Objective: Predictors of long-term functional impairment in acute respiratory failure of all causes are poorly understood. Our objective was to assess the frequency and predictors of long-term functional impairment or death after invasive mechanical ventilation for acute respiratory failure of all causes. Design: Population-based, observational cohort study. Setting: Eight adult ICUs of a single center. Patients: All adult patients from Olmsted County, Minnesota, without baseline functional impairment who received mechanical ventilation in ICUs for acute respiratory failure of all causes from 2005 through 2009. Interventions: None. Measurements and Main Results: In total, 743 patients without baseline functional impairment received mechanical ventilation in the ICU. At 1- and 5-year follow-up, the rates of survival with return to baseline functional ability were 61% (366/597) and 53% (356/669). Among 71 patients with new functional impairment at 1 year, 55% (39/71) had recovered and were alive without functional impairment at 5 years. Factors predictive of new functional impairment or death at 1 year were age, comorbidities, discharge to other than home, mechanical ventilation of 7 days or longer, and stroke. Of factors known at the time of intubation, the following are predictive of new functional impairment or death: age, comorbidities, nonsurgical condition, Acute Physiology and Chronic Health Evaluation III score, stroke, and sepsis. Post hoc sensitivity analyses revealed no significant change in predictor variables in patient populations when stroke was excluded or who received more than 48 hours of mechanical ventilation. Conclusions: At 1- and 5-year follow-up, many patients who received mechanical ventilation for acute respiratory failure from all causes are no longer alive or have new moderate-to-severe functional impairment. Functional recovery between year 1 and year 5 is possible and common. Sepsis, stroke, illness severity, age, and comorbidities predict long-term functional outcome at intubation.

Purpose: To evaluate a healthy eating and physical activity intervention for immigrant families, derived through community-based participatory research. Design: The Healthy Immigrant Families study was a randomized controlled trial with delayed intervention control group, with families as the randomization unit. Setting: US Midwest city. Participants: Participants were recruited by community partners from Hispanic, Somali, and Sudanese immigrant communities. Intervention: Family health promoters from participating communities delivered 6 healthy eating modules, 4 physical activity modules, and 2 modules synthesizing information in 12 home visits (60-90 minutes) within the first 6 months. Up to 12 follow-up phone calls to each participant occurred within the second 6 months. Measures: Primary measures were dietary quality measured with weekday 24-hour recall and reported as Healthy Eating Index score (0-100) and physical activity measured with accelerometers (14 wear days) at baseline, 6, 12, and 24 months. Results: In total, 151 persons (81 adolescents and 70 adults; 44 families) were randomly assigned. At 12 months, significant improvement occurred in Healthy Eating Index scores for adults in the intervention group compared with controls (change, +8.6 vs −4.4; P < .01) and persisted at 24 months (+7.4 from baseline; P < .01). No differences were observed for adolescents and no significant differences occurred between groups for physical activity. Conclusion: This intervention produced sustained dietary quality improvement among adults but not among adolescents. Program outcomes are relevant to communities working to decrease cardiovascular risk among immigrant populations.

Purpose Skeletal-related events (SREs) such as pathologic fracture, spinal cord compression, or the necessity for radiation or surgery to bone metastasis cause considerable morbidity, decrements in quality of life, and costs to the health care system. The results of a recent large randomized trial (Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology [CALGB/Alliance 70604]) showed that zoledronic acid (ZA) every 3 months was noninferior to monthly ZA in reducing the risks of SREs. We sought to determine the cost-effectiveness (CE) of monthly ZA, ZA every 3 months, and monthly denosumab in women with breast cancer and skeletal metastases. Methods Using a Markov model, costs per SRE avoided were calculated for the three treatments. Sensitivity analyses were performed where denosumab SRE probabilities were assumed to be 50%, 75%, and 90% lower than the ZA SRE probabilities. Quality-adjusted life-years were also calculated. The analysis was from the US payer perspective. Results The mean costs of the denosumab treatment strategy are nine-fold higher than generic ZA every 3 months. Quality-adjusted life-years were virtually identical in all the three treatment arms; hence, the optimal treatment would be ZA every 3 months because it was the least costly treatment. The sensitivity analyses showed that relative to ZA every 3 months, the incremental costs per mean SRE avoided for denosumab ranged from $162,918 to $347,655. Conclusion ZA every 3 months was more CE in reducing the risks of SRE than monthly denosumab. This analysis was one of the first to incorporate the costs of generic ZA and one of the first independent CE analyses not sponsored by either Novartis or Amgen, the makers of ZA and denosumab, respectively. ZA every 3 months is the more CE option and more reasonable alternative to monthly denosumab.

Background In view of the large number of families engaged in caregiving, this study was initiated to describe informal cancer care provision from the perspective of the caregiver. Methods A professional data collection site was used to convene focus groups in four cities. Participants included 63 caregivers, 87% of whom were female, mean age of 56 years. Caregivers responded to an open-ended question regarding the challenges of providing care. The study utilized qualitative analysis of verbatim transcripts. Transcript coding with four independent raters, using an iterative process, achieved a high inter-rater reliability. Results The project elucidates self-reported concerns confronted in cancer caregiving. Five primary themes emerged: supportive care demands, emotional toll, impact on health status, coping strategies, and rewards and affirmation. Providing supportive care introduced a balancing act in caregivers’ lives as they attempted to address complex and overlapping roles. They felt alone in their decisions, were under-prepared for tasks they assumed, and tried to shield the care recipient. Conclusions This qualitative approach confirmed past research while identifying novel concepts related to maintaining well-being and a sense of purpose despite caregiving hardships. Some aspects of caregiver suffering were identified. Caregiver self-regulation strategies revealed by this work suggest ideas for psychosocial interventions caregivers could use to protect themselves and the care recipient from impending distress.

Purpose The purpose of this pilot feasibility project was to examine the potential effectiveness of a digital storytelling intervention designed through a community-based participatory research (CBPR) approach for immigrants and refugees with type 2 diabetes mellitus (T2DM). Methods The intervention was a 12-minute culturally and linguistically tailored video consisting of an introduction, 4 stories, and a concluding educational message. A structured interview was used to assess the intervention for acceptability, interest level, and usefulness among 25 participants with T2DM (15 Latino, 10 Somali) across 5 primary care clinical sites. After watching the video, participants rated their confidence and motivation about managing T2DM as a result of the intervention. Baseline A1C and follow-up values (up to 6 months) were abstracted from medical records. Results All participants reported that the intervention got their attention, was interesting, and was useful; 96% reported that they were more confident about managing their T2DM than before they watched the video, and 92% reported that the video motivated them to change a specific behavior related to T2DM self-management. The mean baseline A1C level for the intervention participants was 9.3% (78 mmol/mol). The change from baseline to first follow-up A1C level was −0.8% (−10 mmol/mol) ( P < .05). Conclusions Implementation of a digital storytelling intervention for T2DM among immigrant populations in primary care settings is feasible and resulted in self-rated improvement in psychosocial constructs that are associated with healthy T2DM self-management behaviors, and there was some evidence of improvement in glycemic control. A large-scale efficacy trial of the intervention is warranted.

PURPOSE: A meta-analysis of six North Central Cancer Treatment Group (NCCTG) trials involving patients receiving their first ever fluorouracil (5-FU)–based chemotherapy was undertaken to explore the association of sex with reports of the incidence and severity of stomatitis. PATIENTS AND METHODS: Data were obtained on a total of 731 patients (402 men and 329 women). Comparisons of incidence and severity rates and average stomatitis across sex were performed using standard binomial testing and t tests, respectively. Logistic regression analysis and a weighted analysis using data summarized to study level served as evidence of cross-validation. RESULTS: Women reported stomatitis both more often and with greater severity than did men. The incidence of any stomatitis for women was 63% versus 52% for men (P = .002). The incidence of severe or very severe stomatitis for men and women was 22% and 12%, respectively (P = .0006). On average, women reported stomatitis of roughly 0.4 points higher than men on a 0 to 4 ordinal scale (P < .00001). Comparison of results across treatment and placebo arms was carried out to validate the initial findings. Logistic regression modelling further confirmed the results conditional on the presence of a number of potentially confounding covariates. Women were also 11% more likely than men to experience leukopenia of common toxicity criteria grade ≥ 1, (70% v 59%, respectively; P < .00001) and grade 3+ (18% v 11%, respectively; P = .004). CONCLUSION: More women than men reported 5-FU–induced stomatitis. The precise mechanism resulting in different degrees of stomatitis across sex is not evident.

PURPOSE: Hot flashes can be a prominent problem in women with a history of breast cancer. Given concerns regarding the use of hormonal therapies in such patients, other nonhormonal means for treating hot flashes are required. Based on anecdotal information regarding the efficacy of fluoxetine and other newer antidepressants for treating hot flashes, the present trial was developed. PATIENTS AND METHODS: This trial used a double-blinded, randomized, two-period (4 weeks per period), cross-over methodology to study the efficacy of fluoxetine (20 mg/d) for treating hot flashes in women with a history of breast cancer or a concern regarding the use of estrogen (because of breast cancer risk). Eligible patients had to have reported that they averaged at least 14 hot flashes per week; they could have received tamoxifen or raloxifene as long as they were on a stable dose. The major outcome measure was a bivariate construct representing hot flash frequency and hot flash score, analyzed by a classic sums and differences cross-over analysis. RESULTS: Eighty-one randomized women began protocol therapy. By the end of the first treatment period, hot flash scores (frequency × average severity) decreased 50% in the fluoxetine arm versus 36% in the placebo arm. Cross-over analysis demonstrated a significantly greater marked hot flash score improvement with fluoxetine than placebo (P = .02). The results were not adjusted for potential confounding influences, including age and tamoxifen use. The fluoxetine was well tolerated. CONCLUSION: This dose of fluoxetine resulted in a modest improvement in hot flashes.

PURPOSE: The toxicity profile of fluorouracil (5-FU)–based chemotherapy given on 5 consecutive days at doses of 370 to 450 mg/m2 has been well documented. A meta-analysis of six North Central Cancer Treatment Group (NCCTG) cancer control trials involving 786 patients indicated that women treated with this type of regimen experienced more severe stomatitis and leukopenia than men. After these findings, an additional meta-analysis of the toxicity profiles on five NCCTG colorectal cancer treatment trials was undertaken. METHODS: Data for 1,093 women and 1,355 men from 12 different treatment arms were included. The primary end points were the incidence of stomatitis, leukopenia, alopecia, diarrhea, nausea, and vomiting, recorded with standard National Cancer Institute common toxicity criteria. Fisher’s exact test was used to compare incidence and severity across sexes, supplemented by Forrest meta-analysis plots and logistic regression. RESULTS: The incidence of four out of six toxicities studied was significantly greater for women than men; the exceptions were severe nausea and vomiting. Overall, almost half of the women compared with a third of the men experienced severe toxicity (P < .0001). Logistic regression confirmed the univariate findings while adjusting for the effects of study, dose, body mass index, and age. The differences were consistent across treatment cycles. Response rates and survival distributions were the same for both sexes. CONCLUSION: This study confirms an earlier finding that women receiving 5-FU–based chemotherapy in a 5-day bolus schedule experience toxicity more frequently and with more severity than men. These data raise the question of whether the recommended initial dose of 5-FU–based chemotherapy for women should be lower than that for men.