Association of initial opioid prescription duration and an opioid refill by pain diagnosis: Evidence from outpatient settings in ten US health systems.

OBJECTIVE: The Centers for Disease Control and Prevention's 2022 Clinical Practice Guideline for Prescribing Opioids for Pain cautioned that inflexible opioid prescription duration limits may harm patients. Information about the relationship between initial opioid prescription duration and a subsequent refill could inform prescribing policies and practices to optimize patient outcomes. We assessed the association between initial opioid duration and an opioid refill prescription. METHODS: We conducted a retrospective cohort study of adults ≥19 years of age in 10 US health systems between 2013 and 2018 from outpatient care with a diagnosis for back pain without radiculopathy, back pain with radiculopathy, neck pain, joint pain, tendonitis/bursitis, mild musculoskeletal pain, severe musculoskeletal pain, urinary calculus, or headache. Generalized additive models were used to estimate the association between opioid days' supply and a refill prescription. RESULTS: Overall, 220,797 patients were prescribed opioid analgesics upon an outpatient visit for pain. Nearly a quarter (23.5%) of the cohort received an opioid refill prescription during follow-up. The likelihood of a refill generally increased with initial duration for most pain diagnoses. About 1 to 3 fewer patients would receive a refill within 3 months for every 100 patients initially prescribed 3 vs. 7 days of opioids for most pain diagnoses. The lowest likelihood of refill was for a 1-day supply for all pain diagnoses, except for severe musculoskeletal pain (9 days' supply) and headache (3-4 days' supply). CONCLUSIONS: Long-term prescription opioid use increased modestly with initial opioid prescription duration for most but not all pain diagnoses examined.

Prescription Opioid Dose Reductions and Potential Adverse Events: a Multi-site Observational Cohort Study in Diverse US Health Systems.

BACKGROUND: In response to the opioid crisis in the United States, population-level prescribing of opioids has been decreasing; there are concerns, however, that dose reductions are related to potential adverse events. OBJECTIVE: Examine associations between opioid dose reductions and risk of 1-month potential adverse events (emergency department (ED) visits, opioid overdose, benzodiazepine prescription fill, all-cause mortality). DESIGN: This observational cohort study used electronic health record and claims data from eight United States health systems in a prescription opioid registry (Clinical Trials Network-0084). All opioid fills (excluding buprenorphine) between 1/1/2012 and 12/31/2018 were used to identify baseline periods with mean morphine milligram equivalents daily dose of  ≥ 50 during six consecutive months. PATIENTS: We identified 60,040 non-cancer patients with  ≥ one 2-month dose reduction period (600,234 unique dose reduction periods). MAIN MEASURES: Analyses examined associations between dose reduction levels (1- < 15%, 15- < 30%, 30- < 100%, 100% over 2 months) and potential adverse events in the month following a dose reduction using logistic regression analysis, adjusting for patient characteristics. KEY RESULTS: Overall, dose reduction periods involved mean reductions of 18.7%. Compared to reductions of 1- < 15%, dose reductions of 30- < 100% were associated with higher odds of ED visits (OR 1.14, 95% CI 1.10, 1.17), opioid overdose (OR 1.41, 95% CI 1.09-1.81), and all-cause mortality (OR 1.39, 95% CI 1.16-1.67), but lower odds of a benzodiazepine fill (OR 0.83, 95% CI 0.81-0.85). Dose reductions of 15- < 30%, compared to 1- < 15%, were associated with higher odds of ED visits (OR 1.08, 95% CI 1.05-1.11) and lower odds of a benzodiazepine fill (OR 0.93, 95% CI 0.92-0.95), but were not associated with opioid overdose and all-cause mortality. CONCLUSIONS: Larger reductions for patients on opioid therapy may raise risk of potential adverse events in the month after reduction and should be carefully monitored.

Implementation-effectiveness trial of systematic family health history based risk assessment and impact on clinical disease prevention and surveillance activities.

BACKGROUND: Systematically assessing disease risk can improve population health by identifying those eligible for enhanced prevention/screening strategies. This study aims to determine the clinical impact of a systematic risk assessment in diverse primary care populations. METHODS: Hybrid implementation-effectiveness trial of a family health history-based health risk assessment (HRA) tied to risk-based guideline recommendations enrolling from 2014-2017 with 12 months of post-intervention survey data and 24 months of electronic medical record (EMR) data capture. SETTING: 19 primary care clinics at four geographically and culturally diverse U.S. healthcare systems. PARTICIPANTS: any English or Spanish-speaking adult with an upcoming appointment at an enrolling clinic. METHODS: A personal and family health history based HRA with integrated guideline-based clinical decision support (CDS) was completed by each participant prior to their appointment. Risk reports were provided to patients and providers to discuss at their clinical encounter. OUTCOMES: provider and patient discussion and provider uptake (i.e. ordering) and patient uptake (i.e. recommendation completion) of CDS recommendations. MEASURES: patient and provider surveys and EMR data. RESULTS: One thousand eight hundred twenty nine participants (mean age 56.2 [SD13.9], 69.6% female) completed the HRA and had EMR data available for analysis. 762 (41.6%) received a recommendation (29.7% for genetic counseling (GC); 15.2% for enhanced breast/colon cancer screening). Those with recommendations frequently discussed disease risk with their provider (8.7%-38.2% varied by recommendation, p-values ≤ 0.004). In the GC subgroup, provider discussions increased referrals to counseling (44.4% with vs. 5.9% without, P < 0.001). Recommendation uptake was highest for colon cancer screening (provider = 67.9%; patient = 86.8%) and lowest for breast cancer chemoprevention (0%). CONCLUSIONS: Systematic health risk assessment revealed that almost half the population were at increased disease risk based on guidelines. Risk identification resulted in shared discussions between participants and providers but variable clinical action uptake depending upon the recommendation. Understanding the barriers and facilitators to uptake by both patients and providers will be essential for optimizing HRA tools and achieving their promise of improving population health. TRIAL REGISTRATION: Clinicaltrials.gov number NCT01956773 , registered 10/8/2013.

Development and implementation of a prescription opioid registry across diverse health systems.

Objective: Develop and implement a prescription opioid registry in 10 diverse health systems across the US and describe trends in prescribed opioids between 2012 and 2018. Materials and Methods: Using electronic health record and claims data, we identified patients who had an outpatient fill for any prescription opioid, and/or an opioid use disorder diagnosis, between January 1, 2012 and December 31, 2018. The registry contains distributed files of prescription opioids, benzodiazepines and other select medications, opioid antagonists, clinical diagnoses, procedures, health services utilization, and health plan membership. Rates of outpatient opioid fills over the study period, standardized to health system demographic distributions, are described by age, gender, and race/ethnicity among members without cancer. Results: The registry includes 6 249 710 patients and over 40 million outpatient opioid fills. For the combined registry population, opioid fills declined from a high of 0.718 per member-year in 2013 to 0.478 in 2018, and morphine milligram equivalents (MMEs) per fill declined from 985 MMEs per fill in 2012 to 758 MMEs in 2018. MMEs per member declined from 692 MMEs per member in 2012 to 362 MMEs per member in 2018. Conclusion: This study established a population-based opioid registry across 10 diverse health systems that can be used to address questions related to opioid use. Initial analyses showed large reductions in overall opioid use per member among the combined health systems. The registry will be used in future studies to answer a broad range of other critical public health issues relating to prescription opioid use.

Validity of an Automated Algorithm to Identify Cirrhosis Using Electronic Health Records in Patients with Primary Biliary Cholangitis.

BACKGROUND: Biopsy remains the gold standard for determining fibrosis stage in patients with primary biliary cholangitis (PBC), but it is unavailable for most patients. We used data from the 11 US health systems in the FibrOtic Liver Disease Consortium to explore a combination of biochemical markers and electronic health record (EHR)-based diagnosis/procedure codes (DPCs) to identify the presence of cirrhosis in PBC patients. METHODS: Histological fibrosis staging data were obtained from liver biopsies. Variables considered for the model included demographics (age, gender, race, ethnicity), total bilirubin, alkaline phosphatase, albumin, aspartate aminotransferase (AST) to platelet ratio index (APRI), Fibrosis 4 (FIB4) index, AST to alanine aminotransferase (ALT) ratio, and >100 DPCs associated with cirrhosis/decompensated cirrhosis, categorized into ten clusters. Using least absolute shrinkage and selection operator regression (LASSO), we derived and validated cutoffs for identifying cirrhosis. RESULTS: Among 4328 PBC patients, 1350 (32%) had biopsy data; 121 (9%) were staged F4 (cirrhosis). DPC clusters (including codes related to cirrhosis and hepatocellular carcinoma diagnoses/procedures), Hispanic ethnicity, ALP, AST/ALT ratio, and total bilirubin were retained in the final model (AUROC=0.86 and 0.83 on learning and testing data, respectively); this model with two cutoffs divided patients into three categories (no cirrhosis, indeterminate, and cirrhosis) with specificities of 81.8% (for no cirrhosis) and 80.3% (for cirrhosis). A model excluding DPCs retained ALP, AST/ALT ratio, total bilirubin, Hispanic ethnicity, and gender (AUROC=0.81 and 0.78 on learning and testing data, respectively). CONCLUSION: An algorithm using laboratory results and DPCs can categorize a majority of PBC patients as cirrhotic or noncirrhotic with high accuracy (with a small remaining group of patients' cirrhosis status indeterminate). In the absence of biopsy data, this EHR-based model can be used to identify cirrhosis in cohorts of PBC patients for research and/or clinical follow-up.

Chronic pain diagnoses and opioid dispensings among insured individuals with serious mental illness.

BACKGROUND: Individuals with major depressive disorder (MDD) and bipolar disorder (BD) have particularly high rates of chronic non-cancer pain (CNCP) and are also more likely to receive prescription opioids for their pain. However, there have been no known studies published to date that have examined opioid treatment patterns among individuals with schizophrenia. METHODS: Using electronic medical record data across 13 Mental Health Research Network sites, individuals with diagnoses of MDD (N = 65,750), BD (N = 38,117) or schizophrenia or schizoaffective disorder (N = 12,916) were identified and matched on age, sex and Medicare status to controls with no documented mental illness. CNCP diagnoses and prescription opioid medication dispensings were extracted for the matched samples. Multivariate analyses were conducted to evaluate (1) the odds of receiving a pain-related diagnosis and (2) the odds of receiving opioids, by separate mental illness diagnosis category compared with matched controls, controlling for age, sex, Medicare status, race/ethnicity, income, medical comorbidities, healthcare utilization and chronic pain diagnoses. RESULTS: Multivariable models indicated that having a MDD (OR = 1.90; 95% CI = 1.85-1.95) or BD (OR = 1.71; 95% CI = 1.66-1.77) diagnosis was associated with increased odds of a CNCP diagnosis after controlling for age, sex, race, income, medical comorbidities and healthcare utilization. By contrast, having a schizophrenia diagnosis was associated with decreased odds of receiving a chronic pain diagnosis (OR = 0.86; 95% CI = 0.82-0.90). Having a MDD (OR = 2.59; 95% CI = 2.44-2.75) or BD (OR = 2.12; 95% CI = 1.97-2.28) diagnosis was associated with increased odds of receiving chronic opioid medications, even after controlling for age, sex, race, income, medical comorbidities, healthcare utilization and chronic pain diagnosis; having a schizophrenia diagnosis was not associated with receiving chronic opioid medications. CONCLUSIONS: Individuals with serious mental illness, who are most at risk for developing opioid-related problems, continue to be prescribed opioids more often than their peers without mental illness. Mental health clinicians may be particularly well-suited to lead pain assessment and management efforts for these patients. Future research is needed to evaluate the effectiveness of involving mental health clinicians in these efforts.

Randomized, double-blind trial of 220 mg zinc sulfate twice daily in the treatment of rosacea.

A 2006 article published in the International Journal of Dermatology reported that oral zinc sulfate 100 mg three times daily was associated with improvement in the severity of facial rosacea (Sharquie et al. 2006; 45: 857-861). The current study was undertaken to further assess the role of zinc in the management of rosacea. This was a randomized, double-blind trial of 220 mg of zinc sulfate twice daily for 90 days in patients with moderately severe facial rosacea at baseline. Subjects were recruited in the Upper Midwest USA between August 2006 and April 2008, and followed until July 2008. Forty-four subjects completed the trial (22 in each arm). Rosacea improved in both groups. There were no differences in magnitude of improvement based on rosacea severity scores between subjects receiving zinc sulfate and subjects receiving placebo (P=0.284). Serum zinc levels were higher in subjects receiving zinc (P<0.001). Oral zinc sulfate was not associated with greater improvement in rosacea severity compared with placebo in this study. Additional studies are needed to determine what role oral zinc may have in the management of rosacea.

Utilization of medical services at the end of life in older adults with cognitive impairment: focus on outliers.

BACKGROUND: The use of intensive medical care near end of life is often questioned because of potential burden to patients, their families, and society. Efforts to moderate intensive end-of-life care may be facilitated by early identification of those at greatest risk for receiving such care. OBJECTIVE: To examine factors associated with intensive end-of-life medical care utilization in nursing home residents with severe cognitive impairment. DESIGN: Retrospective review of existing Medicare data: 1998-2001 Minimum Data Set (MDS), Medicare Denominator, MedPAR, and hospice files. METHODS: Subjects were Minnesota and Texas nursing home residents from rural and urban counties (USDA metro-nonmetro continuum codes: 0-2 urban, 6-9 rural), who had severe cognitive impairment and who died during 2000-2001. Hospice and managed care enrollees were excluded. High medical care users were defined as subjects with 7+ intensive care unit (ICU) days in the last 90 days of life. Measures of end-of-life medical care utilization intensity included tube feeding on the last MDS report, number of hospital and ICU days, and total hospital charges during the study period. RESULTS: The study population included 1494 nursing home residents who were hospitalized within 90 days prior to death; 82 (5%) met the high medical care user criteria. In multivariable analysis: urban location (p < 0.001), lack of do-not-resuscitate directive (p = 0.002), non-white race (p = 0.021), and having 3+ comorbidities (p = 0.021) were independently associated with high medical care utilization. CONCLUSIONS: Urban nursing home location and lack of do-not-resuscitate directives were the strongest predictors of high medical care utilization near the end of life.

Rural-urban differences in cancer care: results from the Lake Superior Rural Cancer Care Project.

Past studies have shown significant differences between rural and urban cancer patients in many measures of cancer care. There is little recent information about this disparity, which generally has shown disadvantages in rural populations. This study reports the rural and urban differences in cancer care using data from the Lake Superior Rural Cancer Care Project. The study used a prospective, population-based design that included all incident cases of breast, colorectal, lung, and prostate cancers diagnosed in northeastern Minnesota, northwestern Wisconsin, and the western portion of Michigan's Upper Peninsula from 1992 to 1997. The outcome measures were 9 endpoints that represented state-of-the-art cancer care during the study. Rural cancer patients as compared with their urban counterparts were disadvantaged in proportion staged, stage at diagnosis, initial management procedures, post-treatment surveillance testing, and participation in cancer clinical trials. These findings are similar to previously published studies. Further research is needed to determine more clearly the barriers in rural cancer care and to find more effective strategies.

Ethical wills and suffering in patients with cancer: a pilot study.

INTRODUCTION: Suffering at the end of life may be caused by many factors, including pain and other symptoms, concern about family and friends, and loss of control of one's life. Several authors have suggested that loss of meaning is pivotal in suffering. An ethical will (EW) is a statement, usually written, capturing one's values, wisdom, hopes, and advice. EWs have been suggested as a vehicle for finding meaning as the end of life approaches. This pilot study of EWs examined methods for exploring the role of EWs in reducing suffering at the end of life. METHODS: Oncology clinic patients 65+ years of age in active therapy for cancer were randomly assigned to one of two arms: EW or control. Subjects in both arms had writing assignments, three home visits, and exit interviews. Suffering was measured at baseline and at the time of the exit interview, using a series of Likert-like scales. RESULTS: Twenty-four subjects (10 EW and 14 control) completed the study. Among EW subjects, trends toward reduced suffering were noted in "concern for loved ones," "unfinished business," and "fear of the future." Several methodological issues were identified by this pilot study, including selection of population for studying suffering, placebo effect, and randomization. CONCLUSIONS: EW may be valuable in alleviating suffering; a larger study will be needed to examine efficacy. The study of interventions designed to reduce suffering at the end of life requires careful attention to the definition and measurement of suffering, study design, and subject selection.

Health-related quality of life (HRQoL) in patients with cancer and other concurrent illnesses.

This study analyzed the impact of eight common chronic medical conditions on cancer patients' health-related quality of life (HRQoL) as measured by the functional living index-cancer (FLIC). The FLIC was administered to a population of 405 people in 14 communities in the North Central US within 4-8 weeks of diagnosis with breast or colorectal cancer. At that time, patients also self-reported any other health conditions for which they had been receiving medical treatment. The impact of the selected chronic conditions on the FLIC scores was analyzed using Student's t-tests and linear multiple regression. In the bivariate analysis, patients with heart/circulation problems had lower FLIC total scores (p < 0.05), physical well-being subscale scores (p < 0.05), and nausea subscale scores (p < 0.01). Patients with diabetes had lower nausea subscale scores (p < 0.05). The social well-being subscale score was higher with the report of arthritis/joint problems (p = 0.001). In multivariate analysis adjusted for age, arthritis/joint problems were predictive of the social well-being (p < 0.01) and hardship due to cancer (p < 0.05) subscale scores; heart/circulation problems (p < 0.001) and diabetes were predictive of the nausea subscale scores. ECOG performance status was significant predictor for the FLIC total and all of the subscale scores. HRQoL as measured with the FLIC scores in patients with cancer is impacted by the presence of other concurrent health conditions; this finding has implications for HRQoL theory and application.

Improving rural cancer patients' outcomes: a group-randomized trial.

CONTEXT: Significant barriers exist in the delivery of state-of-the-art cancer care to rural populations. Rural providers' knowledge and practices, their rural health care delivery systems, and linkages to cancer specialists are not optimal; therefore, rural cancer patient outcomes are less than achievable. PURPOSE: To test the effects of a strategy targeting rural providers and their practice environment on patient travel for care, satisfaction, economic barriers, and health-related quality of life. METHODS: A group-randomized trial was conducted with 18 rural communities in the north-central United States. Twelve of these communities were included and defined as the unit of analysis for the patient outcomes portion of the study. The intervention targeted rural providers and their practice environment. The subjects were patients with breast, colorectal, lung, and prostate cancers from the rural communities. The main outcomes were patients' travel to obtain health care, satisfaction with care, perceptions of economic barriers to care, and health-related quality of life. In total, 881 patients were included. RESULTS: Group randomization was balanced. Travel for health care was significantly reduced in the community group exposed to the intervention during months 13 to 24 following cancer diagnosis. The mean miles traveled per patient were 1,326 (SE = 306) for the experimental group and 2,186 (SE = 347) for the control group (P = 0.03). No significant differences in satisfaction with care, economic barriers to care, or health-related quality of life were found. CONCLUSIONS: The intervention significantly reduced cancer patient travel for health care, which suggests that access to care improved in the experimental group. The results of this study do not allow conclusion that there was no effect on other patient outcomes. The results supported the study's conceptual framework and many of its hypotheses.

Tacrolimus effect on rosacea.

Twenty-four patients with erythrotelangiectatic or papulopustular rosacea were treated with 0.1% tacrolimus topical ointment in a 12-week open-label trial. Erythema was significantly improved in both rosacea subtypes (P<.05). There was no decrease in the number of papulopustular lesions. Side effects were consistent with those on the tacrolimus topical ointment labeling.

Preventing cardiovascular disease in women: an intervention-control randomized study.

This 1-year, group-randomized, intervention-control study looked at the effectiveness of a primary prevention, community-based program for reducing cardiovascular (CV) risk factors in women. Women between the ages of 20 and 50 were recruited through community contacts, including religious and academic institutions, health clinics, and large local employers in the Duluth, Minnesota, and Superior, Wisconsin, area. All study activities took place in neighborhood places of worship. Screenings at baseline and 12 months included physical and laboratory measurements addressing CV risk factors and assessment of the women's knowledge about CV disease in women. All participants received an individualized review of their CV risk factors and recommendations for modifying them, along with educational literature about CV disease in women. The control group had limited follow-up compared with the intervention group, who participated in general CV health classes and received a follow-up phone call and information about health resources. The study showed that education and one-on-one follow-up significantly change behavior. Comprehensive community-based screening and individualized review decrease women's risk for CV disease.

Dying of old age: an examination of death certificates of Minnesota centenarians.

OBJECTIVES: To compare how causes of death are recorded on the death certificates of centenarians with those who die in their 70s, 80s, and 90s. We also examined direct and indirect acknowledgment of age as a cause of death. DESIGN: Retrospective review of death certificates. SETTING: State of Minnesota. PARTICIPANTS: The death certificates of 26,415 individuals aged 70 and over who died in Minnesota in 1998 were examined for underlying causes of death. Of these, 449 were for individuals who were aged 100 and older at the time of their death. MEASUREMENTS: Causes of death. RESULTS: Diabetes mellitus, chronic obstructive pulmonary disease, cirrhosis, myocardial infarction, and most cancers decreased in frequency as reported causes of death with advancing age. Conversely, congestive heart failure, atherosclerosis, and neurological/mental and poorly defined conditions increased in frequency with age. CONCLUSIONS: Centenarians appear to "outlive" the risks for many of the conditions that are common causes of death for those who die in their 70s, 80s, and 90s, such as cancer and myocardial infarction. Conditions associated with aging, such as congestive heart failure and degenerative neurological conditions become more prominent as reported causes of death in the oldest individuals. The guidelines for the completion of death certificates should be modified to facilitate direct acknowledgment of age-related frailty as a contributing cause of death.

Lake Superior Rural Cancer Care Project, Part III: provider practice.

PURPOSE: Effective methods that encourage rural primary-care physicians to adopt state-of-the-art cancer-management practices are needed. The purpose of this study was to evaluate educational and systems strategies to improve rural primary-care physicians' cancer practice behaviors. DESCRIPTION OF STUDY: The Lake Superior Rural Cancer Care Project was a group-randomized, controlled trial conducted with 18 rural communities in the North Central United States over 4 years. Although the unit of analysis was the community, the subjects were 104 primary-care physicians and 2089 rural patients with cancer. The intervention was educational and comprised systems strategies that targeted rural primary-care physicians and their healthcare delivery systems. The outcome measures reported here were physician practice behaviors regarding cancer diagnosis, staging, treatment, clinical trial participation, and post-treatment surveillance. RESULTS: The intervention significantly improved 5 of the 37 cancer practice end points. The overall result of the study did not support the majority of the study hypotheses. Because 16 practice end points were found to be at acceptable performance levels, the possibility of a measurable intervention effect was limited. CLINICAL IMPLICATIONS: Earlier, the authors reported the results of the intervention on providers' cancer management knowledge, which showed significant improvement. The present study findings demonstrated that improving provider knowledge does not necessarily improve practice performance. Changing practice behaviors requires much more effort. Furthermore, interventions found to be effective in other diseases, types of providers, or settings may not work on rural providers for cancer management.