Testosterone therapy and cancer risks among men in the SEER-Medicare linked database.

BACKGROUND: We examined associations between two forms of testosterone therapy (TT) and risks of seven cancers among men. METHODS: SEER-Medicare combines cancer registry data from the Surveillance, Epidemiology, and End Results programme with Medicare claims. Our population-based case-control study included incident cancer cases diagnosed between 1992-2015: prostate (n = 130,713), lung (n = 105,466), colorectal (n = 56,433), bladder (n = 38,873), non-Hodgkin lymphoma (n = 17,854), melanoma (n = 14,241), and oesophageal (n = 9116). We selected 100,000 controls from a 5% random sample of Medicare beneficiaries and used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: TT was associated with lower risk of distant-stage prostate cancer (injection/implantation OR = 0.72, 95% CI: 0.60-0.86; topical OR = 0.50, 95% CI: 0.24-1.03). We also observed inverse associations for distant-stage colorectal cancer (injection/implantation OR = 0.75, 95% CI: 0.62-0.90; topical OR = 0.11, 95% CI: 0.05-0.24). Risks of distant-stage colorectal and prostate cancers decreased with time after initiating TT by injection/implantation. By contrast, TT was positively associated with distant-stage melanoma (injection/implantation OR = 1.70, 95% CI: 1.37-2.11). TT was not associated with bladder cancer, oesophageal cancer, lung cancer or non-Hodgkin lymphoma. CONCLUSION: TT was inversely associated with distant-stage prostate and colorectal cancers but was positively associated with distant-stage melanoma. These observations may suggest an aetiologic role for TT or the presence of residual confounding.

Deintensification of Treatment With Sulfonylurea and Insulin After Severe Hypoglycemia Among Older Adults With Diabetes.

Importance: Practice guidelines recommend deintensification of hypoglycemic agents among older adults with diabetes who are at high risk of hypoglycemia, yet real-world treatment deintensification practices are not well characterized. Objective: To examine the incidence of sulfonylurea and insulin deintensification after a hypoglycemia-associated emergency department (ED) visit or hospitalization among older adults with diabetes and to identify factors associated with deintensification of treatment. Design, Setting, and Participants: This retrospective cohort study included a random sample of 20% of nationwide fee-for-service US Medicare beneficiaries aged 65 years and older with concurrent Medicare parts A, B, and D coverage between January 1, 2007, and December 31, 2017. Individuals with diabetes who had at least 1 hypoglycemia-associated ED visit or hospitalization were included. Data were analyzed from August 1, 2020, to August 1, 2021. Exposures: Baseline medication for the treatment of diabetes (sulfonylurea, insulin, or both). Main Outcomes and Measures: Incidence of treatment deintensification (yes or no) in the 100 days after a severe hypoglycemic episode requiring an ED visit or hospitalization, with treatment deintensification defined as (1) a decrease in sulfonylurea dose, (2) a change from long-acting to short-acting sulfonylurea (glipizide), (3) discontinuation of sulfonylurea, or (4) discontinuation of insulin based on pharmacy dispensing claims. Results: Among 76 278 distinct Medicare beneficiaries who had a hypoglycemia-associated ED visit or hospitalization, the mean (SD) age was 76.6 (7.6) years. Of 106 293 total hypoglycemic episodes requiring hospital attention, 69 084 (65.0%) occurred among women, 26 056 (24.5%) among Black individuals; 4761 (4.5%) among Hispanic individuals; 69 704 (65.6%) among White individuals; and 5772 (5.4%) among individuals of other races and ethnicities (comprising Asian, North American Native, unknown race or ethnicity, and unspecified race or ethnicity). A total of 32 074 episodes (30.2%) occurred among those receiving sulfonylurea only, 60 350 (56.8%) occurred among those receiving insulin only, and 13 869 (13.0%) occurred among those receiving both sulfonylurea and insulin. Treatment deintensification rates were highest among individuals receiving both sulfonylurea and insulin therapies at the time of their hypoglycemic episode (6677 episodes [48.1%]), followed by individuals receiving sulfonylurea only (14 192 episodes [44.2%]) and insulin only (14 495 episodes [24.0%]). Treatment deintensification rates increased between 2007 and 2017 (sulfonylurea only: from 41.4% to 49.7%; P < .001 for trend; insulin only: from 21.3% to 25.9%; P < .001 for trend; sulfonylurea and insulin: from 45.9% to 49.6%; P = .005 for trend). Lower socioeconomic status (as indicated by the receipt of low-income subsidies) was associated with lower odds of deintensification, regardless of baseline hypoglycemic regimen (sulfonylurea only: adjusted odds ratio [AOR], 0.74 [95% CI, 0.70-0.78]; insulin only: AOR, 0.71 [95% CI, 0.68-0.75]; sulfonylurea and insulin: AOR, 0.72 [95% CI, 0.66-0.78]). A number of patient factors were associated with higher odds of treatment deintensification: higher frailty (eg, ≥40% probability of needing assistance with activities of daily living among those receiving sulfonylurea and insulin: AOR, 1.50; 95% CI, 1.32-1.71), chronic kidney disease (eg, sulfonylurea and insulin: AOR, 1.29; 95% CI, 1.19-1.40), a history of falls (eg, sulfonylurea and insulin: AOR, 1.20; 95% CI, 1.09-1.33), and depression (eg, sulfonylurea and insulin: AOR, 1.11; 95% CI, 1.02-1.20). Conclusions and Relevance: In this cohort study, deintensification of sulfonylurea and/or insulin therapy within 100 days after a hypoglycemia-associated ED visit or hospitalization occurred in fewer than 50% of older adults with diabetes; however, these deintensification rates may be increasing over time, and deintensification of insulin was likely underestimated because of challenges in capturing changes to insulin dosing using administrative claims data. These results suggest that greater efforts are needed to identify individuals at high risk of hypoglycemia to encourage appropriate treatment deintensification in accordance with current evidence.

Similar Breast Cancer Risk in Women Older Than 65 Years Initiating Glargine, Detemir, and NPH Insulins.

OBJECTIVE: To assess whether initiation of insulin glargine (glargine), compared with initiation of NPH or insulin detemir (detemir), was associated with an increased risk of breast cancer in women with diabetes. RESEARCH DESIGN AND METHODS: This was a retrospective new-user cohort study of female Medicare beneficiaries aged ≥65 years initiating glargine (203,159), detemir (67,012), or NPH (47,388) from September 2006 to September 2015, with follow-up through May 2017. Weighted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for incidence of breast cancer according to ever use, cumulative duration of use, cumulative dose of insulin, length of follow-up time, and a combination of dose and length of follow-up time. RESULTS: Ever use of glargine was not associated with an increased risk of breast cancer compared with NPH (HR 0.97; 95% CI 0.88-1.06) or detemir (HR 0.98; 95% CI 0.92-1.05). No increased risk was seen with glargine use compared with either NPH or detemir by duration of insulin use, length of follow-up, or cumulative dose of insulin. No increased risk of breast cancer was observed in medium- or high-dose glargine users compared with low-dose users. CONCLUSIONS: Overall, glargine use was not associated with an increased risk of breast cancer compared with NPH or detemir in female Medicare beneficiaries.

Interventions to improve the appropriate use of polypharmacy for older people.

BACKGROUND: Inappropriate polypharmacy is a particular concern in older people and is associated with negative health outcomes. Choosing the best interventions to improve appropriate polypharmacy is a priority, hence interest in appropriate polypharmacy, where many medicines may be used to achieve better clinical outcomes for patients, is growing. This is the second update of this Cochrane Review. OBJECTIVES: To determine which interventions, alone or in combination, are effective in improving the appropriate use of polypharmacy and reducing medication-related problems in older people. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL and two trials registers up until 7 February 2018, together with handsearching of reference lists to identify additional studies. SELECTION CRITERIA: We included randomised trials, non-randomised trials, controlled before-after studies, and interrupted time series. Eligible studies described interventions affecting prescribing aimed at improving appropriate polypharmacy in people aged 65 years and older, prescribed polypharmacy (four or more medicines), which used a validated tool to assess prescribing appropriateness. These tools can be classified as either implicit tools (judgement-based/based on expert professional judgement) or explicit tools (criterion-based, comprising lists of drugs to be avoided in older people). DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed abstracts of eligible studies, extracted data and assessed risk of bias of included studies. We pooled study-specific estimates, and used a random-effects model to yield summary estimates of effect and 95% confidence intervals (CIs). We assessed the overall certainty of evidence for each outcome using the GRADE approach. MAIN RESULTS: We identified 32 studies, 20 from this update. Included studies consisted of 18 randomised trials, 10 cluster randomised trials (one of which was a stepped-wedge design), two non-randomised trials and two controlled before-after studies. One intervention consisted of computerised decision support (CDS); and 31 were complex, multi-faceted pharmaceutical-care based approaches (i.e. the responsible provision of medicines to improve patient's outcomes), one of which incorporated a CDS component as part of their multi-faceted intervention. Interventions were provided in a variety of settings. Interventions were delivered by healthcare professionals such as general physicians, pharmacists and geriatricians, and all were conducted in high-income countries. Assessments using the Cochrane 'Risk of bias' tool, found that there was a high and/or unclear risk of bias across a number of domains. Based on the GRADE approach, the overall certainty of evidence for each pooled outcome ranged from low to very low.It is uncertain whether pharmaceutical care improves medication appropriateness (as measured by an implicit tool), mean difference (MD) -4.76, 95% CI -9.20 to -0.33; 5 studies, N = 517; very low-certainty evidence). It is uncertain whether pharmaceutical care reduces the number of potentially inappropriate medications (PIMs), (standardised mean difference (SMD) -0.22, 95% CI -0.38 to -0.05; 7 studies; N = 1832; very low-certainty evidence). It is uncertain whether pharmaceutical care reduces the proportion of patients with one or more PIMs, (risk ratio (RR) 0.79, 95% CI 0.61 to 1.02; 11 studies; N = 3079; very low-certainty evidence). Pharmaceutical care may slightly reduce the number of potential prescribing omissions (PPOs) (SMD -0.81, 95% CI -0.98 to -0.64; 2 studies; N = 569; low-certainty evidence), however it must be noted that this effect estimate is based on only two studies, which had serious limitations in terms of risk bias. Likewise, it is uncertain whether pharmaceutical care reduces the proportion of patients with one or more PPOs (RR 0.40, 95% CI 0.18 to 0.85; 5 studies; N = 1310; very low-certainty evidence). Pharmaceutical care may make little or no difference in hospital admissions (data not pooled; 12 studies; N = 4052; low-certainty evidence). Pharmaceutical care may make little or no difference in quality of life (data not pooled; 12 studies; N = 3211; low-certainty evidence). Medication-related problems were reported in eight studies (N = 10,087) using different terms (e.g. adverse drug reactions, drug-drug interactions). No consistent intervention effect on medication-related problems was noted across studies. AUTHORS' CONCLUSIONS: It is unclear whether interventions to improve appropriate polypharmacy, such as reviews of patients' prescriptions, resulted in clinically significant improvement; however, they may be slightly beneficial in terms of reducing potential prescribing omissions (PPOs); but this effect estimate is based on only two studies, which had serious limitations in terms of risk bias.

Interventions to improve the appropriate use of polypharmacy for older people.

BACKGROUND: Inappropriate polypharmacy is a particular concern in older people and is associated with negative health outcomes. Choosing the best interventions to improve appropriate polypharmacy is a priority, hence interest in appropriate polypharmacy, where many medicines may be used to achieve better clinical outcomes for patients, is growing. OBJECTIVES: This review sought to determine which interventions, alone or in combination, are effective in improving the appropriate use of polypharmacy and reducing medication-related problems in older people. SEARCH METHODS: In November 2013, for this first update, a range of literature databases including MEDLINE and EMBASE were searched, and handsearching of reference lists was performed. Search terms included 'polypharmacy', 'medication appropriateness' and 'inappropriate prescribing'. SELECTION CRITERIA: A range of study designs were eligible. Eligible studies described interventions affecting prescribing aimed at improving appropriate polypharmacy in people 65 years of age and older in which a validated measure of appropriateness was used (e.g. Beers criteria, Medication Appropriateness Index (MAI)). DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed abstracts of eligible studies, extracted data and assessed risk of bias of included studies. Study-specific estimates were pooled, and a random-effects model was used to yield summary estimates of effect and 95% confidence intervals (CIs). The GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach was used to assess the overall quality of evidence for each pooled outcome. MAIN RESULTS: Two studies were added to this review to bring the total number of included studies to 12. One intervention consisted of computerised decision support; 11 complex, multi-faceted pharmaceutical approaches to interventions were provided in a variety of settings. Interventions were delivered by healthcare professionals, such as prescribers and pharmacists. Appropriateness of prescribing was measured using validated tools, including the MAI score post intervention (eight studies), Beers criteria (four studies), STOPP criteria (two studies) and START criteria (one study). Interventions included in this review resulted in a reduction in inappropriate medication usage. Based on the GRADE approach, the overall quality of evidence for all pooled outcomes ranged from very low to low. A greater reduction in MAI scores between baseline and follow-up was seen in the intervention group when compared with the control group (four studies; mean difference -6.78, 95% CI -12.34 to -1.22). Postintervention pooled data showed a lower summated MAI score (five studies; mean difference -3.88, 95% CI -5.40 to -2.35) and fewer Beers drugs per participant (two studies; mean difference -0.1, 95% CI -0.28 to 0.09) in the intervention group compared with the control group. Evidence of the effects of interventions on hospital admissions (five studies) and of medication-related problems (six studies) was conflicting. AUTHORS' CONCLUSIONS: It is unclear whether interventions to improve appropriate polypharmacy, such as pharmaceutical care, resulted in clinically significant improvement; however, they appear beneficial in terms of reducing inappropriate prescribing.

Infection control strategies for preventing the transmission of meticillin-resistant Staphylococcus aureus (MRSA) in nursing homes for older people.

BACKGROUND: Nursing homes for older people provide an environment likely to promote the acquisition and spread of meticillin-resistant Staphylococcus aureus (MRSA), putting residents at increased risk of colonisation and infection. It is recognised that infection prevention and control strategies are important in preventing and controlling MRSA transmission. OBJECTIVES: To determine the effects of infection prevention and control strategies for preventing the transmission of MRSA in nursing homes for older people. SEARCH METHODS: In August 2013, for this third update, we searched the Cochrane Wounds Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), Database of Abstracts of Reviews of Effects (DARE, The Cochrane Library), Ovid MEDLINE, OVID MEDLINE (In-process and Other Non-Indexed Citations), Ovid EMBASE, EBSCO CINAHL, Web of Science and the Health Technology Assessment (HTA) website. Research in progress was sought through Current Clinical Trials, Gateway to Reseach, and HSRProj (Health Services Research Projects in Progress). SELECTION CRITERIA: All randomised and controlled clinical trials, controlled before and after studies and interrupted time series studies of infection prevention and control interventions in nursing homes for older people were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed the results of the searches. Another review author appraised identified papers and undertook data extraction which was checked by a second review author. MAIN RESULTS: For this third update only one study was identified, therefore it was not possible to undertake a meta-analysis. A cluster randomised controlled trial in 32 nursing homes evaluated the effect of an infection control education and training programme on MRSA prevalence. The primary outcome was MRSA prevalence in residents and staff, and a change in infection control audit scores which measured adherence to infection control standards. At the end of the 12 month study, there was no change in MRSA prevalence between intervention and control sites, while mean infection control audit scores were significantly higher in the intervention homes compared with control homes. AUTHORS' CONCLUSIONS: There is a lack of research evaluating the effects on MRSA transmission of infection prevention and control strategies in nursing homes. Rigorous studies should be conducted in nursing homes, involving residents and staff to test interventions that have been specifically designed for this unique environment.

Effectiveness of medicines review with web-based pharmaceutical treatment algorithms in reducing potentially inappropriate prescribing in older people in primary care: a cluster randomized trial (OPTI-SCRIPT study protocol).

BACKGROUND: Potentially inappropriate prescribing in older people is common in primary care and can result in increased morbidity, adverse drug events, hospitalizations and mortality. In Ireland, 36% of those aged 70 years or over received at least one potentially inappropriate medication, with an associated expenditure of over €45 million.The main objective of this study is to determine the effectiveness and acceptability of a complex, multifaceted intervention in reducing the level of potentially inappropriate prescribing in primary care. METHODS/DESIGN: This study is a pragmatic cluster randomized controlled trial, conducted in primary care (OPTI-SCRIPT trial), involving 22 practices (clusters) and 220 patients. Practices will be allocated to intervention or control arms using minimization, with intervention participants receiving a complex multifaceted intervention incorporating academic detailing, medicines review with web-based pharmaceutical treatment algorithms that provide recommended alternative treatment options, and tailored patient information leaflets. Control practices will deliver usual care and receive simple patient-level feedback on potentially inappropriate prescribing. Routinely collected national prescribing data will also be analyzed for nonparticipating practices, acting as a contemporary national control. The primary outcomes are the proportion of participant patients with potentially inappropriate prescribing and the mean number of potentially inappropriate prescriptions per patient. In addition, economic and qualitative evaluations will be conducted. DISCUSSION: This study will establish the effectiveness of a multifaceted intervention in reducing potentially inappropriate prescribing in older people in Irish primary care that is generalizable to countries with similar prescribing challenges. TRIAL REGISTRATION: Current controlled trials ISRCTN41694007.

Interventions to improve the appropriate use of polypharmacy for older people.

BACKGROUND: Inappropriate polypharmacy is a particular concern in older people and is associated with negative health outcomes. Choosing the best interventions to improve appropriate polypharmacy is a priority, hence there is growing interest in appropriate polypharmacy, where many medicines may be used to achieve better clinical outcomes for patients. OBJECTIVES: This review sought to determine which interventions alone, or in combination, are effective in improving the appropriate use of polypharmacy and reducing medication-related problems in older people. SEARCH METHODS: A range of literature databases including MEDLINE and EMBASE were searched in addition to handsearching reference lists. Search terms included polypharmacy, Beers criteria, medication appropriateness and inappropriate prescribing. SELECTION CRITERIA: A range of study designs were eligible. Eligible studies described interventions affecting prescribing aimed at improving appropriate polypharmacy in people aged 65 years and older where a validated measure of appropriateness was used (e.g. Beers criteria or Medication Appropriateness Index - MAI). DATA COLLECTION AND ANALYSIS: Three authors independently reviewed abstracts of eligible studies, extracted data and assessed risk of bias of included studies. Study specific estimates were pooled, using a random-effects model to yield summary estimates of effect and 95% confidence intervals. MAIN RESULTS: Electronic searches identified 2200 potentially relevant citations, of which 139 were examined in detail. Following assessment, 10 studies were included. One intervention was computerised decision support and nine were complex, multifaceted pharmaceutical care provided in a variety of settings. Appropriateness of prescribing was measured using the MAI score postintervention (seven studies) and/or Beers criteria (four studies). The interventions included in this review demonstrated a reduction in inappropriate medication use. A mean difference of -6.78 (95% CI -12.34 to -1.22) in the change in MAI score in favour of the intervention group (four studies). Postintervention pooled data (five studies) showed a mean reduction of -3.88 (95% CI -5.40 to -2.35) in the summated MAI score and a mean reduction of -0.06 (95% CI -0.16 to 0.04) in the number of Beers drugs per patient (three studies). Evidence of the effect of the interventions on hospital admissions (four studies) was conflicting. Medication-related problems, reported as the number of adverse drug events (three studies), reduced significantly (35%) postintervention. AUTHORS' CONCLUSIONS: It is unclear if interventions to improve appropriate polypharmacy, such as pharmaceutical care, resulted in a clinically significant improvement; however, they appear beneficial in terms of reducing inappropriate prescribing and medication-related problems.

Potentially inappropriate prescribing and cost outcomes for older people: a cross-sectional study using the Northern Ireland Enhanced Prescribing Database.

PURPOSE: We sought to estimate the prevalence of potentially inappropriate prescribing (PIP) in the Northern Ireland (NI) population aged ≥70 years, to investigate factors associated with PIP and to calculate total gross cost of PIP. METHODS: A retrospective cross-sectional population study was carried out in those aged ≥70 years in 2009/2010 who were in primary care in NI. Data were extracted from the Enhanced Prescribing Database, which provides details of prescribed and dispensed medications for each individual registered with a general practitioner. Twenty-eight PIP indicators from the Screening Tool of Older Persons potentially inappropriate Prescriptions (STOPP) criteria were applied to these data. PIP prevalence according to individual STOPP criteria and the overall prevalence of PIP were estimated. The relationship between PIP and polypharmacy, age and gender was examined using logistic regression. Gross cost of PIP was ascertained. RESULTS: The overall prevalence of PIP in the study population (n = 166,108) was 34 %. The most common examples of PIP identified were proton pump inhibitors at maximum therapeutic dose for >8 weeks (17,931 patients, 11 %), non-steroidal anti-inflammatory drugs >3 months (14,545 patients, 9 %) and long-term long-acting benzodiazepines (10,147 patients, 6 %). PIP was strongly associated with polypharmacy, with those receiving seven different medications being fivefold more likely to be exposed to PIP than those on zero to three medications (odds ratio 5.04, 95 % confidence interval 4.84-5.25) The gross cost of PIP was estimated to be 6,098,419 CONCLUSIONS: Consistent with other research, the prevalence of PIP was high among the study cohort, increased with polypharmacy and was associated with significant cost.

Infection control strategies for preventing the transmission of meticillin-resistant Staphylococcus aureus (MRSA) in nursing homes for older people.

BACKGROUND: Nursing homes for older people provide an environment likely to promote the acquisition and spread of meticillin-resistant Staphylococcus aureus (MRSA), putting residents at increased risk of colonisation and infection. It is recognised that infection prevention and control strategies are important in preventing and controlling MRSA transmission. OBJECTIVES: To determine the effects of infection prevention and control strategies for preventing the transmission of MRSA in nursing homes for older people. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2011, Issue 2), the Cochrane Wounds Group Specialised Register (searched May 27th, 2011). We also searched Ovid MEDLINE (from 1950 to April Week 2 2011), OVID MEDLINE (In-process and Other Non-Indexed Citations, April 26th 2011) Ovid EMBASE (1980 to 2011 Week 16), EBSCO CINAHL (1982 to April 21st 2011), DARE (1992 to 2011, week 16), Web of Science (1981 to May 2011), and the Health Technology Assessment (HTA) website (1988 to May 2011). Research in progress was sought through Current Clinical Trials (www.controlled-trials.com), Medical Research Council Research portfolio, and HSRPRoj (current USA projects). SELECTION CRITERIA: All randomised and controlled clinical trials, controlled before and after studies and interrupted time series studies of infection prevention and control interventions in nursing homes for older people were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed the results of the searches. Another review author appraised identified papers and undertook data extraction which was checked by a second review author. MAIN RESULTS: For this second update only one study was identified, therefore it was not possible to undertake a meta-analysis. A cluster randomised controlled trial in 32 nursing homes evaluated the effect of an infection control education and training programme on MRSA prevalence. The primary outcome was MRSA prevalence in residents and staff, and a change in infection control audit scores which measured adherence to infection control standards. At the end of the 12 month study, there was no change in MRSA prevalence between intervention and control sites, while mean infection control audit scores were significantly higher in the intervention homes compared with control homes. AUTHORS' CONCLUSIONS: There is a lack of research evaluating the effects on MRSA transmission of infection prevention and control strategies in nursing homes. Rigorous studies should be conducted in nursing homes, to test interventions that have been specifically designed for this unique environment.