An Analysis of 5 Years of Randomized Trials in Gastroenterology and Hepatology Reveals 52 Medical Reversals.

BACKGROUND AND AIMS: One manifestation of low-value medical practice is the medical reversal, a practice in widespread use that, once subjected to a randomized controlled trial (RCT), is found to be no better-or worse-than a prior established standard of care. We aimed to determine the prevalence of medical reversals in gastroenterology (GI) journals and characterize these reversals. METHODS: We searched the American Journal of Gastroenterology, Clinical Gastroenterology and Hepatology, Gastroenterology, Gut, Hepatology, and the Journal of Hepatology, reviewing studies published in 2015-2019. We identified RCTs that tested an established clinical practice and produced negative results, considered tentative reversals. Any systematic review or meta-analysis that included the article was categorized as confirming the reversal, refuting the reversal, or providing insufficient data. RESULTS: During the 5-year period, we identified 5,898 original articles, of which 212 tested an established practice and 52 were categorized as unrefuted medical reversals (25% of articles testing standard of care). Of the reversals, 21 (40%) tested procedures and devices, 15 (29%) tested medications, and 8 (15%) tested vitamins/supplements/diet. Twenty-three (44%) considered the alimentary tract, 12 (23%) considered the liver, pancreas, or biliary tract, and 17 (33%) considered endoscopy. Thirty-eight (73%) were funded exclusively by non-industry sources. CONCLUSION: This review reveals a total of 52 reversals across all subfields of GI and medical, procedural, screening, and diagnostic interventions, occurring in 25% of randomized trials testing an established practice. More research is needed to determine the optimal way to engage stakeholders and remove reversed practices from medical care.

The frequency of assessment of progression in randomized oncology clinical trials.

BACKGROUND: Progression in tumor assessments is often detected at a follow-up appointment rather than when actual change in progression has occurred, which can bias PFS outcomes. AIM: We sought to evaluate the frequency of tumor assessment scans in clinical trials of anti-cancer interventions and to compare this to recommended (National Comprehensive Cancer Network) and real-world frequencies of tumor assessments. METHODS: In a cross-sectional analysis, we searched for articles published in the three top oncology journals between July 2017 and June 2020. We included articles that were RCTs of patients that had unresectable or metastatic solid tumors and used an intervention that was designed to be anti-tumor. We abstracted median PFS survival for each group, the PFS hazard ratio, frequency of tumor assessment scans, tumor type, intervention type, and information regarding the study. RESULTS: We found that, in the 182 comparisons (163 articles), less frequent tumor assessment (occurring more than 9 weeks between assessments) was associated with higher median PFS values for both the intervention group (p < .0001) and the control group (p < .0001). PFS hazard ratios for studies scanning for tumors every 10 or more weeks were no different than for studies scanning for tumors more frequently (p = .88). Data on the frequency of tumor assessments in the real world is sparse. CONCLUSION: We found that less frequent tumor assessment frequency was associated with longer median PFS in both intervention and control groups of clinical oncology trials but was not associated with differences in PFS hazard ratios. Future research is needed to compare real world to trial assessment.

Estimation of US patients with cancer who may respond to cytotoxic chemotherapy.

AIMS PATIENTS & METHODS: In this retrospective review, we sought to estimate the proportion of patients in the USA with advanced or metastatic cancer who are eligible for and may respond to recommended first-line cytotoxic chemotherapy based on National Comprehensive Cancer Network treatment guidelines. RESULTS: Among 609,640 patients, we estimate 479,823 (78.7%, 95% CI: 78.6-78.8%) may be eligible for cytotoxic chemotherapy while 189,159 out of 609,640 patients (31.0%, 95% CI: 30.9-31.1%) may have achieved treatment response. The average objective response rate from these regimens was 48.6% (range 9.2 to 90.6%). CONCLUSION: Given the large role of cytotoxic agents in cancer, drug development in this space may remain of interest in specific cancer types, and regulatory approval of novel oncology drugs may justify head-to-head comparisons against cytotoxic regimens.

Relationship between Meditation and Waking Salivary Cortisol Secretion among Long-Term MBSR Instructors.

BACKGROUND: A potential relationship between long-term meditation practice and stress reduction remains virtually unexplored. The purpose of this study was to characterize stress using salivary waking cortisol in a group of long-term meditators with training in the Mindfulness-Based Stress Reduction (MBSR) program. MATERIALS AND METHODS: Four salivary cortisol samples were collected from meditators (n = 84) during the first hour of awakening. The waking cortisol rhythm was summarized using cortisol area under the curve (AUC) with respect to increased secretion above baseline (AUCI) and cortisol AUC above ground (above zero, AUCG); data on meditation duration and depth, perceived stress, and other covariates were collected via self-reported questionnaire. RESULTS: Individuals in the highest quartile of years meditating (> 26 years) had statistically significantly elevated AUCG values (p = 0.01) as compared to individuals in the lowest quartile of years meditating (≤10 years). This relationship was more pronounced among individuals waking at or before 6: 30 a.m. CONCLUSIONS: Overall, an increasing number of years of meditation practice was related to a higher waking cortisol response. These intriguing findings warrant additional exploration, as the stress response can be complex.

Survey to Assess Interest in a Mindfulness Intervention at a Midwifery and Women's Health Clinic.

We conducted a voluntary survey among ethnically and socioeconomically diverse women. About half of the respondents reported experiencing at least one health issue; over half were interested in attending a mindfulness class to reduce stress. Our study suggests interest in participating in a mindfulness intervention, primarily among those with more health issues.

Relationship Between Meditation Depth and Waking Salivary Alpha-Amylase Secretion Among Long-Term MBSR Instructors.

The purpose of this study was to characterize sympathetic activity by using waking salivary alpha-amylase (sAA) concentrations in a group of long-term meditation instructors and to examine the association between meditation (depth, dose and duration) and the waking alpha-amylase response. Salivary alpha-amylase samples were collected (immediately upon waking and at 15-min, 30-min and 45-min intervals after waking) from mindfulness-based stress reduction instructors to determine both the area under the curve and the awakening slope (difference in alpha-amylase concentrations between waking and 30-min post-waking). It was determined through general linear models that neither years of meditation nor meditation dose were associated with the awakening sAA slope, but higher scores for meditation depth (greater depth) was associated with a more negative (or steeper) awakening slope [Quartile (Q)1: -7 versus Q4: -21 U/mL; p = 0.06], in fully adjusted models. Older age (p = 0.04) and a later time of waking (p < 0.01) also were associated with less negative awakening slope values. Smoking was associated with lower area under the curve values (smokers: 1716 U/mL versus nonsmokers: 2107 U/mL; p = 0.05) in fully adjusted models. The results suggest a 'healthy' sAA waking slope among individuals who meditate more deeply. Copyright © 2016 John Wiley & Sons, Ltd.

Polychlorinated biphenyls and omega-3 fatty acid exposure from fish consumption, and thyroid cancer among New York anglers.

Fish from the Great Lakes contain polychlorinated biphenyls (PCBs) which have been shown to disrupt endocrine function and mimic thyroid hormones, but they also contain beneficial omega-3 fatty acids that may offer protection against endocrine cancers. The purpose of this study was to examine the effects of Lake Ontario fish consumption and the estimated consumption of PCBs and omega-3 fatty acids on the risk of thyroid cancer in a group of sport fishermen. Anglers from the New York State Angler Cohort Study were followed for cancer incidence from 1991-2008. Twenty-seven cases of incident thyroid cancer and 108 controls were included in the analyses. Total estimated fish consumption, estimated omega-3 fatty acid consumption, and estimated PCB consumption from Lake Ontario fish were examined for an association with the incidence of thyroid cancer, while matching on sex, and controlling for age and smoking status. Results from logistic regression indicate no significant associations between fish consumption, short-term estimated omega-3 fatty acids, or estimated PCB consumption from Great Lakes fish and the development of thyroid cancer, but it was suggested that long-term omega-3 fatty acid from Great Lakes fish may be protective of the development of thyroid cancer. In conclusion, fish consumption, with the possible concomitant PCBs, from the Great Lakes does not appear to increase the risk of thyroid cancer in New York anglers. Further research is needed in order to separate the individual health effects of PCBs from omega-3 fatty acids contained within the fish.

Prevalence and predictors of anemia in a population-based study of octogenarians and centenarians in Georgia.

BACKGROUND: Anemia has been associated with increased physical and financial costs and occurs more frequently in older individuals. Therefore, the primary objectives of this study were to examine the prevalence and possible predictors of anemia in the very old. METHODS: Hemoglobin was used to identify those with anemia in a group of centenarians and near centenarians (98+, n = 185) and octogenarians (n = 69), who were recruited as part of the population-based multidisciplinary Georgia Centenarian Study. Blood markers, including ferritin, vitamin B12, red blood cell folate, methylmalonic acid, creatinine, and C-reactive protein, demographic variables, and medication and/or supplement usage were used to determine possible predictors of anemia. RESULTS: The prevalence of anemia was 26.2% in octogenarians and 52.1% in centenarians. Low serum albumin (<3.6 g/dL) and decreased estimated glomerular filtration rate (<45 mL/min/m(2)) were predictors of anemia in centenarians. CONCLUSIONS: Anemia is a major health issue, particularly as people age. Because of the high prevalence of anemia in older individuals, awareness of the predictors associated with anemia becomes increasingly important so as to reduce the negative consequences associated with it and allow for the identification of steps that can be taken to correct anemia, including managing chronic disease.