Comparison of Five Lists to Identify Potentially Inappropriate Use of Non-Steroidal Anti-Inflammatory Drugs in Older Adults.

OBJECTIVE: To compare the prevalence of potentially inappropriate non-steroidal anti-inflammatory drugs (NSAIDs) among NSAIDs users defined with frequently used potentially inappropriate medication (PIM) lists and to identify the determinants of their use. DESIGN AND SETTING: Cross-sectional survey among community-dwelling older adults from Germany. SUBJECTS: N = 284 NSAIDs users aged 65-89 years. METHODS: All currently regularly or as-needed used drugs were recorded during a home visit. Multivariate logistic regression models were applied to assess the potential determinants of potentially inappropriate NSAIDs use. RESULTS: Prevalence of potentially inappropriate NSAIDs use was 54.2%, 45.4%, 29.9%, 20.4%, and 3.5% when applying the STOPP, 2019 Beers, EU(7)-PIM, FORTA, and PRISCUS list, respectively. No study participant was identified as a potentially inappropriate NSAIDs user by all five lists simultaneously. The majority (68%) were identified only by one or two lists. Merely the STOPP and Beers criteria had a moderate inter-instrument agreement. Lower pain severity, gout, peptic ulcer (PU), cardiovascular disease (CVD), and chronic kidney disease (CKD) were statistically significantly associated with potentially inappropriate NSAIDs use defined by the STOPP criteria and the latter three conditions also with the 2019 Beers criteria. CONCLUSIONS: The STOPP and Beers criteria may be superior to the other lists because they more frequently identify potentially inappropriate NSAIDs use in conditions implying a high risk for NSAIDs' adverse events (i.e., PUD, CKD and CVD). We developed a harmonized, country-independent PIM list for NSAIDs with the same advantages as observed for the STOOP and 2019 Beers criteria and recommended its use.

Protocol of the VICTORIA study: personalized vitamin D supplementation for reducing or preventing fatigue and enhancing quality of life of patients with colorectal tumor - randomized intervention trial.

BACKGROUND: Cancer-related fatigue represents one major cause of reduced quality of life in cancer patients and can seriously affect the physical, emotional, and cognitive functioning impeding coping with the disease. Options for effective treatment of cancer-related fatigue are limited, consisting only of non-pharmacologic interventions like physical activity, psychosocial, and mind-body interventions. Recent evidence suggests that vitamin D3 supplementation might alleviate cancer-related fatigue. However, confirmation in a randomized controlled trial is needed. METHODS: In this multicenter, randomized, double-blind, placebo-controlled trial, 456 colorectal cancer (CRC) patients aged 18 years and older are being recruited in three German rehabilitation clinics. Study inclusion requires hospitalization of at least 3 weeks at such a clinic, a diagnosis of non-metastatic CRC (stage I-III), surgical removal of the tumor within the past 9 months, and season-adapted vitamin D insufficiency or deficiency. Eligible patients are randomly assigned to a personalized regimen of vitamin D3 or placebo for 12 weeks. In the intervention group, a loading dose of 20,000 or 40,000 IU vitamin D3 will be administered daily during the first 11 days, followed by a maintenance dose of 2000 IU daily. Patients will complete questionnaires for secondary outcomes (fatigue subdomains, quality of life and subdomains, depression, functional well-being, and infection frequency). Blood and urine samples will be collected for analyses of safety parameters (hypervitaminosis D, hypercalcemia, hypercalciuria, and renal impairment) and efficacy biomarkers (25-hydroxyvitamin D, HbA1c, white blood cell count, leukocyte subtype counts, serum C-reactive protein, uric acid, creatinine, triglycerides, total, low- and high-density lipoprotein cholesterol). DISCUSSION: This trial tests whether a personalized vitamin D3 dosing regimen reduces or prevents fatigue among non-metastatic CRC patients by treating the underlying vitamin D deficiency/insufficiency. If efficacy can be confirmed, personalized vitamin D3 supplementation could be used as a tertiary prevention measure in addition to non-pharmacological treatments of cancer-related fatigue in CRC patients. We expect to detect an effect of vitamin D3 supplementation on secondary outcomes like quality of life, depression, functional well-being, infections, inflammatory biomarkers, diabetes mellitus, and dyslipidemia. TRIAL REGISTRATION: European Clinical Trials Database: EudraCT-No: 2019-000502-30, January 21, 2019; German Clinical Trials Register (DRKS): DRKS00019907 , April 30, 2019.

Pain severity and analgesics use in the community-dwelling older population: a drug utilization study from Germany.

PURPOSE: Chronic pain is common in the older population and a significant public health concern. However, comprehensive studies on analgesics use in this age group from Germany are scarce. This study aims to give a comprehensive overview on the use of the most common therapeutic groups of analgesics in community-dwelling older adults from Germany. METHODS: A cross-sectional study was carried out using data from a German cohort of 2038 community-dwelling adults aged 63-89 years. Descriptive statistics and logistic regression models were applied to assess the utilization of analgesics by age, sex, pain severity, pain duration, and locations. RESULTS: One out of four study participants was suffering from high-intensity or disabling pain. Approximately half of those taking analgesics still reported to suffer from high-intensity or disabling pain. Among analgesics users, occasional non-steroidal anti-inflammatory drugs (NSAIDs) use was the most frequent pain therapy (in 43.6% of users), followed by metamizole (dipyrone) use (16.1%), regular NSAIDs use (12.9%), strong opioids use (12.7%), and weak opioids use (12.0%). In multivariate logistic regression models, higher age, higher pain severity, longer pain duration, abdominal pain, and back pain were statistically significantly associated with opioids use. Metamizole use was also statistically significantly associated with higher pain severity but inversely associated with pain duration. CONCLUSIONS: A significant number of older German adults are affected by high-intensity and disabling chronic pain despite receiving analgesics. Long-term studies are needed to compare the effectiveness and safety of different treatments for chronic pain in older adults.

Association of Comedication Quality With Chemotherapy-Related Adverse Drug Reactions and Survival in Older Colorectal Cancer Patients.

BACKGROUND: Evidence about the clinical relevance of appropriate comedication among older colorectal cancer (CRC) patients is sparse. METHODS: A cohort study was conducted with 3239 CRC patients aged 65 years and older. To assess comedication quality, we calculated the total Fit fOR The Aged (FORTA) score and its subscores for medication overuse, underuse, and potentially inappropriate medication use. Multivariable Cox proportional hazards or logistic regression models were performed to evaluate the association of comedication quality with up to 5-year overall survival, CRC-specific survival, and chemotherapy-related adverse drug reactions. RESULTS: Overall, 3239 and 1209 participants were included in analyses on survival and adverse drug reactions, respectively. The hazard ratios [95% confidence intervals] for the total FORTA score ≥ 7 versus 0-1 points were 1.83 [1.40-2.40] and 1.76 [1.22-2.52] for up to 5-year overall and CRC-specific survival, respectively. Worse up to 5-year overall survival and CRC-specific survival was also evident for FORTA subscores for potentially inappropriate medication use and overuse, whereas no association was observed for underuse. Although results for the total FORTA and potentially inappropriate medication score were much stronger among patients receiving chemotherapy, no significant associations with chemotherapy-related adverse drug reactions were observed. Moreover, associations were particularly strong among men and rectal cancer patients as compared to women and colon cancer patients. CONCLUSIONS: Poor total comedication quality was significantly associated with worse up to 5-year overall and CRC-specific survival. Randomized controlled trials are needed to test whether improved cancer comedication management in older CRC patients prolongs survival.

Efficacy and Safety of a Personalized Vitamin D3 Loading Dose Followed by Daily 2000 IU in Colorectal Cancer Patients with Vitamin D Insufficiency: Interim Analysis of a Randomized Controlled Trial.

A personalized vitamin D3 loading dose has not yet been tested in cancer patients. This interim analysis of the randomized, placebo-controlled VICTORIA trial analyzed the first recruited 74 German adults with nonmetastatic colorectal cancer, a tumor surgery within the past year, and 25-hydroxyvitamin D levels (25(OH)D) < 50 nmol/L. Study participants received a loading dose tailored for a baseline 25(OH)D level and BMI in the first 11 days, followed by a maintenance dose of 2000 IU of vitamin D3 daily until end of trial week 12. The mean 25(OH)D levels were 27.6, 31.0, and 34.1 nmol/L in the placebo group and 25.9, 63.1, and 75.5 nmol/L in the verum group during screening, visit 1 (end of loading dose), and visit 2 (end of maintenance dose), respectively. The prevalence of 25(OH)D) ≥ 50 nmol/L at visits 1 and 2 was 3.5% and 17.4% in the placebo group and 80.0% and 100% in the verum group. No events of 25(OH)D > 150 nmol/L or hypercalcemia were observed. Hypercalciuria events at visit 1 (n = 5 in verum and n = 1 in the placebo group; p = 0.209) receded after discontinuation of the study medication. The personalized loading dose effectively and safely increased the 25(OH)D levels, and 2000 IU of vitamin D3 daily sustained the achieved levels.

Systematic Review and Meta-Analysis on the Associations of Polypharmacy and Potentially Inappropriate Medication With Adverse Outcomes in Older Cancer Patients.

BACKGROUND: Both polypharmacy and potentially inappropriate medication (PIM) intake are highly prevailing in older cancer patients. However, only studies on the association of polypharmacy and postoperative complications have been meta-analyzed previously. METHODS: A systematic review and a meta-analysis of prospective/retrospective observational studies reporting associations of polypharmacy or PIM with at least one out of five predefined adverse health outcomes in a population of older cancer patients (≥60 years) were carried out. PubMed and Web of Science were used to search for relevant studies published between January 1991 and March 2020. Data were pooled by adopting a random-effects model. RESULTS: Overall, 42 publications were included in the systematic review. Meta-analyses could be performed on 39 studies about polypharmacy and 13 studies about PIM. Polypharmacy was found to be statistically significantly associated with all-cause mortality (risk ratio [95% confidence interval]: 1.37 [1.25-1.50]), hospitalization (1.53 [1.37-1.71]), treatment-related toxicity (1.22 [1.01-1.47]), and postoperative complications (1.73 [1.36-2.20]). The association of polypharmacy with prolongation of hospitalization was not statistically significant at the p < .05 significance level (1.62 [0.98-2.66]). With respect to PIM, a statistically significant association with all-cause mortality (1.43 [1.08-1.88]) was observed but not with other adverse outcomes. CONCLUSIONS: Polypharmacy was found to be associated with several adverse outcomes and PIM use with all-cause mortality in older cancer patients. However, these results should be interpreted with caution because about three-quarters of the studies identified did not adjust for comorbidity and are prone to confounding by indication.

Probiotic/Synbiotic Treatment and Postoperative Complications in Colorectal Cancer Patients: Systematic Review and Meta-analysis of Randomized Controlled Trials.

Colorectal cancer (CRC) is a leading cause of morbidity and mortality. Post-CRC resection complications and lower quality of life (QoL) are associated with a lower long-term survival. Perioperative administration of probiotics/synbiotics might lower prevalence of side effects and improve QoL and survival among CRC patients. Medline, Web of Science, Cochrane database, Embase, and clinical trials registries were searched in January 2020. Altogether, 16 randomized placebo-controlled probiotic/synbiotic clinical trials that included patients undergoing CRC surgery and investigated postoperative complications and QoL side effects were found. Meta-analyses using random-effects model were performed on data from 11 studies to calculate the effects of probiotics/synbiotics on common CRC resection postoperative side effects and complications. Perioperative probiotics/synbiotics administration was associated with lower infection incidence (odds ratio [OR] = 0.34, P < 0.001), lower diarrheal incidence (OR = 0.38, P < 0.001), faster return to normal gut function (mean difference [MD] -0.66 days, P < 0.001), shorter postoperative antibiotics use (MD -0.64 days, P < 0.001), lower incidence of septicemia (OR = 0.31, P < 0.001), and shorter length of hospital stay (MD -0.41 days, P = 0.110). The results support the hypothesis that short-term perioperative administration of probiotics/synbiotics, which are easy to administer, have few side-effects, and are low cost compared with alternatives, might help to alleviate gastrointestinal symptoms and postoperative complications among CRC patients.

Factors associated with high oxidative stress in patients with type 2 diabetes: a meta-analysis of two cohort studies.

OBJECTIVE: Our objective is to identify the potential factors associated with serum Diacron's reactive oxygen metabolites test (D-ROM) levels of patients with type 2 diabetes mellitus (T2DM) by conducting cross-sectional and longitudinal analyses in two large cohorts and further strengthening these results by performing a meta-analysis. METHODS: Serum D-ROM concentrations were measured in 1045 and 1101 patients with T2DM from two independent cohort studies from Germany at baseline and repeatedly 3-4 years later. The cross-sectional and longitudinal associations of various potential determinants with D-ROM levels were assessed with a backwards selection algorithm in multivariable adjusted models. RESULTS: In the meta-analysis of the cross-sectional analysis, female sex, low education, obesity, smoking, high total cholesterol, hemoglobin A1c ≥7%, no diabetes medication, a history of myocardial infarction, heart failure, a history of cancer and C reactive protein levels (CRP) >3 mg/L were statistically significantly associated with increased D-ROM levels in patients with T2DM. The meta-analysis of the longitudinal analysis revealed that old age, female sex, obesity, smoking, physical inactivity, high alcohol consumption, ≥5 years since diabetes diagnosis and CRP levels between 3 mg/L and 10 mg/L were statistically significantly associated with D-ROM levels measured 3-4 years later. CONCLUSIONS VALIDITY, LIMITATIONS AND CLINICAL APPLICABILITY: This comprehensive analysis confirmed that several modifiable risk factors are being associated with oxidative stress in patients with T2DM within an observational study design. We discuss potential prevention measures against these risk factors that might help to reduce oxidative stress and to prevent some cases of premature mortality in patients with T2DM.