Associations between frailty and cancer-specific mortality among older women with breast cancer.

PURPOSE: Frailty is assessed when making treatment decisions among older women with breast cancer (BC), which in turn impacts survival. We evaluated associations between pre-diagnosis frailty and risks of BC-specific and all-cause mortality in older women. METHODS: We conducted a retrospective cohort study of Medicare beneficiaries ages ≥ 65 years with stage I-III BC using the Surveillance, Epidemiology and End Results-Medicare Health Outcome Survey Data Resource. Frailty was measured using the deficit-accumulation frailty index, categorized as robust, pre-frail, or frail, at baseline and during follow-up. Fine and Gray competing risk and Cox proportional hazards models were used to estimate subdistribution hazard ratios (SHR) and hazard ratios (HR) with 95% confidence intervals (CI) for BC-specific and all-cause mortality, respectively. RESULTS: Among 2411 women with a median age of 75 years at BC diagnosis, 49.5% were categorized as robust, 29.4% were pre-frail and 21.1% were frail. Fewer frail women compared to robust women received breast-conserving surgery (52.8% vs. 61.5%, frail vs. robust, respectively) and radiation (43.5% vs. 51.8%). In multivariable analyses, degree of frailty was not associated with BC-specific mortality (frail vs robust SHR 1.47, 95% CI 0.97-2.24). However, frail women with BC had higher risks of all-cause mortality compared to robust women with BC (HR 2.32, 95% CI 1.84-2.92). CONCLUSION: Among a cohort of older women with BC, higher degrees of frailty were associated with higher risk of all-cause mortality, but not BC-specific mortality. Future study should examine if preventing progression of frailty may improve all-cause mortality.

Clinical pharmacists in diabetes management: What do minority patients with uncontrolled diabetes have to say?

OBJECTIVE: Clinical pharmacist support for patients with type 2 diabetes mellitus (T2DM) can optimize patient outcomes and medication adherence. However, there is limited understanding of what pharmacist roles patients perceive as most helpful in T2DM management interventions. This study describes experiences of minority patients with uncontrolled T2DM in terms of perceived pharmacist helpfulness and specific roles found to be most helpful within diabetes management. DESIGN: A secondary analysis of a 2-year randomized, crossover trial was conducted. SETTING AND PARTICIPANTS: This study included 244 African American and Hispanic adults with uncontrolled T2DM who received clinical pharmacist support within a team-based model. OUTCOME MEASURES: The patients completed a mixed-methods survey regarding their experience with the intervention that included a general helpfulness rating on a 10-point unipolar Likert scale and described the support qualitatively, including their perception of the pharmacist roles. Thematic analysis guided coding of the responses. RESULTS: One hundred forty-seven (60%) patients completed the survey and had at least 1 encounter with a clinical pharmacist. Of these, 108 (74%) were African American, 39 (27%) were Hispanic, and 101 (69%) were women. The median rating of clinical pharmacist helpfulness was 10 (very helpful). Only 10 (7%) participants rated pharmacist helpfulness as 1 (not at all helpful). "Medication education and management" was the most frequently perceived supportive role of the clinical pharmacists, followed by "non-medication-related patient education," "social support," and "care coordination." Miscommunication related to scheduling was the most common reason cited for not meeting with the clinical pharmacist. CONCLUSION: This sample of minority patients with uncontrolled T2DM recognized many roles outlined within the American Pharmacists Association Medication Therapy Management framework. Patient experiences with clinical pharmacist T2DM support are crucial for developing effective programs, maximizing patient engagement, satisfying patient needs, and ensuring that a program's intended purpose aligns with the patient perspective.

Risk for Mortality in High versus Low Antiparkinsonian Therapy Dose During the First Year of Parkinson's Disease: A Real-World Study.

INTRODUCTION: Early, simple predictors for long-term survival in Parkinson's disease (PD) may help identify patients at elevated risk and are crucial for more personalized treatment. METHODS: This large, retrospective study examined whether higher levodopa equivalent daily dose (LEDD) a year after diagnosis predicts long-term survival. RESULTS: Mortality risk was increased among 292 patients receiving ≥ 600 mg LEDD versus 2233 patients receiving < 600 mg LEDD (hazard ratio 1.5; 95% confidence interval 1.3-1.7), particularly among patients aged < 75 years (1.8; 1.4-2.4). CONCLUSION: In PD, higher LEDD can be an early risk marker of increased mortality, probably because it reflects more severe disease.

The Relationship Between Signature Time and Functional Health Literacy: Results from a Prospective Study of an Urban Low-Income Population Receiving Long-Term Anticoagulation.

INTRODUCTION: Low health literacy (HL) is consistently associated with worse health outcomes. Routine clinical screening with available instruments is impractical because of added time and effort. Prior findings suggested that signature time may be a reliable alternative measure of HL among general medicine patients. METHODS: Our aim was to assess the screening performance of signature time and explore optimal thresholds for identifying patients with limited HL in a chronically anticoagulated population. English-speaking patients receiving long-term anticoagulation therapy were recruited. HL was assessed using the Short Test of Functional Health Literacy in Adults (STOFHLA). Signature time was measured using a stopwatch. Logistic regression models and receiver-operating characteristic (ROC) curves were used to evaluate the association and accuracy of signature time compared to HL, respectively. RESULTS: Of 139 enrolled patients, mean age was 60.1 years, 70.5% were African-American, 48.9% reported < $25,000 income, and 27.3% had marginal or inadequate HL. Overall, median time to sign was 6.1 s. Signature time was longest with inadequate HL (median 9.5 s) compared to adequate HL (5.7 s; p < 0.01). Longer signature time was significantly associated with lower HL after adjusting for age and education (aOR 0.77, 95% CI: 0.68-0.88, p < 0.01). Signature time demonstrated high accuracy (area under the curve [AUC] > 0.8) in identifying HL levels. Thresholds of 5.1 s and 9.0 s showed appropriate screening performance in distinguishing patients with adequate vs. marginal and marginal vs. inadequate HL, respectively. CONCLUSION: Signature time demonstrated strong screening performance and may offer a quick and practical approach to assessing HL among patients receiving long-term anticoagulation management.

Cost-effectiveness of full and partial opioid agonists for opioid use disorder in outpatient settings: United States healthcare sector perspective.

INTRODUCTION: Studies show that medications for opioid use disorder (MOUD) reduce illicit opioid use, emergency healthcare services, opioid-related overdose, and death. However, few studies have investigated the long-term cost-effectiveness of MOUD in office-based opioid treatment (OBOT) and opioid treatment program (OTP) settings. We aimed to estimate the cost, utility, quality-adjusted life years gained (QALYs), and incremental cost-effectiveness ratios (ICERs) of three MOUD compared to each other and counseling without medication from a US healthcare sector perspective. METHODS: Our study developed a Markov model to conduct a cost-effectiveness analysis of counseling and three MOUD in the OBOT and OTP settings: sublingual buprenorphine/naloxone (BUPNX), buprenorphine extended-release (XR-BUP) injection, and oral methadone. The model included five health states representing combinations of receiving or off treatment while either using or not actively using illicit opioids, and death. The cycle length was one month; the time-horizon was ten years. The study obtained model inputs from systematic reviews of published literature and public data. A 3 % annual discount rate was applied to cost and utility calculation. The primary outcomes included total costs, life-years (LYs), QALYs, and ICERs. We also conducted a scenario analysis using a hypothetical OBOT outpatient setting with methadone. RESULTS: In the base-case OBOT setting, the total costs and QALYs, respectively, were counseling $22,848, 5.60; BUPNX $29,875, 5.82; and XR-BUP $63,936, 5.87. ICERs were $32,345/QALY (BUPNX vs. counseling) and $625,858/QALY (XR-BUP vs BUPNX). In the OTP setting, the total costs of counseling, methadone, BUPNX, and XR-BUP were $20,124, $27,000, $33,500, and $75,272, respectively. QALYs of methadone were 5.86. QALYs of counseling, BUPNX, and XR-BUP remained the same as in the OBOT setting. Incremental ICERs were $26,714/QALY (methadone vs counseling) and $3,337,623/QALY (XR-BUP vs methadone). BUPNX was dominated by methadone. In the scenario analysis, BUPNX was also dominated by methadone. CONCLUSIONS: Outpatient MOUD resulted in important gains in quality of life and life expectancy. In both OBOT and OTP settings, XR-BUP was not cost-effective. BUPNX was cost-effective in the OBOT setting, while it was dominated by methadone in the OTP setting. The cost-effectiveness of BUPNX and XR-BUP could be enhanced if the costs of these medications were reduced.

Changes in antibiotic prescribing by dentists in the United States, 2012-2019.

OBJECTIVES: Dentists prescribe 10% of all outpatient antibiotics in the United States and are the top specialty prescriber. Data on current antibiotic prescribing trends are scarce. Therefore, we evaluated trends in antibiotic prescribing rates by dentists, and we further assessed whether these trends differed by agent, specialty, and by patient characteristics. DESIGN: Retrospective study of dental antibiotic prescribing included data from the IQVIA Longitudinal Prescription Data set from January 1, 2012 to December 31, 2019. METHODS: The change in the dentist prescribing rate and mean days' supply were evaluated using linear regression models. RESULTS: Dentists wrote >216 million antibiotic prescriptions between 2012 and 2019. The annual dental antibiotic prescribing rate remained steady over time (P = .5915). However, the dental prescribing rate (antibiotic prescriptions per 1,000 dentists) increased in the Northeast (by 1,313 antibiotics per 1,000 dentists per year), among oral and maxillofacial surgeons (n = 13,054), prosthodontists (n = 2,381), endodontists (n = 2,255), periodontists (n = 1,961), and for amoxicillin (n = 2,562; P < .04 for all). The mean days' supply significantly decreased over the study period by 0.023 days per 1,000 dentists per year (P < .001). CONCLUSIONS: From 2012 to 2019, dental prescribing rates for antibiotics remained unchanged, despite decreases in antibiotic prescribing nationally and changes in guidelines during the study period. However, mean days' supply decreased over time. Dental specialties, such as oral and maxillofacial surgeons, had the highest prescribing rate with increases over time. Antibiotic stewardship efforts to improve unnecessary prescribing by dentists and targeting dental specialists may decrease overall antibiotic prescribing rates by dentists.

Healthcare resource utilization and device-aided therapy discussions with eligible patients across the Parkinson's disease continuum: Revelations from the MANAGE-PD validation cohort.

INTRODUCTION: Device-aided therapy may improve the quality of life (QoL) for people with advanced Parkinson's disease (PD) and poorly controlled symptoms with oral therapy. MANAGE-PD is a validated tool classifying patients based on symptom control and advanced treatment eligibility. This study focused on patient/caregiver reported outcomes and healthcare resource utilization among patients grouped by MANAGE-PD categories. METHODS: Device-aided therapy-naïve patients receiving oral treatments were identified from the Adelphi Parkinson's Disease Programme. Patients were categorized (category 1 to 3) using MANAGE-PD. PD-specific QoL (PDQ-39), care partner burden (ZBI), satisfaction with current treatment, healthcare resource utilization, associated healthcare costs, and future treatment discussion with providers were measured. Categories were compared using ANOVA, t-test, chi square and adjusted regression analyses. RESULTS: Of the analytical sample (n = 2709), 18.9% were inadequately controlled on current therapy and potentially eligible for device-aided therapies (category 3). As expected, they had worse patient/caregiver reported outcomes versus patients in categories 1 or 2. However, the degree of difference in healthcare resource utilization, including: greater number of hospitalizations, emergency room (ER) visits and consultations, higher likelihood of being recipients of respite care, and greater PD treatment burden, was unexpected. Importantly, of patients in category 3 and their care partners, >40% did not report discussions with providers about device-aided therapies. CONCLUSION: MANAGE-PD category 3 patients had significantly higher burden on healthcare resources versus patients well-controlled with oral treatment or requiring only oral medication adjustments; yet almost half had no discussion on device-aided therapies with providers. Device-aided therapies may be considered in these patients.

Long-term results of carbidopa/levodopa enteral suspension across the day in advanced Parkinson's disease: Post-hoc analyses from a large 54-week trial.

Introduction: Carbidopa/levodopa enteral suspension (CLES) previously demonstrated reduction in total daily OFF from baseline by over 4 hours in advanced Parkinson's disease patients across 54 weeks. Evidence on CLES's long-term effectiveness on patterns of motor-symptom control throughout the day remains limited. Methods: We present post-hoc analyses of a large, open-label study of CLES monotherapy (N = 289). Diary data recorded patients' motor states at 30-minute intervals over 3 days at baseline and weeks 4, 12, 24, 36, and 54. Adjusted generalized linear mixed models assessed changes from baseline at each timepoint for four outcome measures: time to ON without troublesome dyskinesia (ON-woTD) after waking, motor-symptom control as measured by motor states' durations throughout the day, number of motor-state transitions, and presence of extreme fluctuations (OFF to ON with TD). Results: Patients demonstrated short-term (wk4) and sustained (wk54) improvement in all outcomes compared to baseline. At weeks 4 and 54, patients were more likely to reach ON-woTD over the course of their day (HR: 1.86 and 2.51, both P < 0.0001). Across 4-hour intervals throughout the day, patients also experienced increases in ON-woTD (wk4: 58-65 min; wk54: 60-78 min; all P < 0.0001) and reductions in OFF (wk4: 50-61 min; wk54: 56-68 min; all P < 0.0001). At weeks 4 and 54, patients' motor-state transitions were reduced by about half (IRR: 0.53 and 0.49, both P < 0.0001), and fewer patients experienced extreme fluctuations (OR: 0.22 and 0.15, both P < 0.0001). Conclusion: CLES monotherapy was associated with significant long-term reductions in motor-state fluctuations, faster time to ON-woTD upon awakening, and increased symptom control throughout the day.

Comparative Effectiveness of Carbidopa/Levodopa Enteral Suspension and Deep Brain Stimulation on Pill Burden Reduction in Medicare Fee-for-Service Patients with Advanced Parkinson's Disease.

INTRODUCTION: Complex polypharmacy regimens to manage persistent motor fluctuations result in significant pill burden for patients with advanced Parkinson's disease (APD). This study evaluated the effectiveness of carbidopa/levodopa enteral suspension (CLES) and deep brain stimulation (DBS) on reducing pill burden in APD patients. METHODS: We utilized 100% Medicare fee-for-service claims from 2014 to 2018 linked to CLES Patient Support Program (PSP) data. CLES initiators (CLES-I) were propensity matched 1:1 with patients enrolled in PSP who did not initiate treatment (CLES-NI) (N = 188) or undergo DBS, and 1:3 with patients who received DBS (N = 204, N = 612). Average daily pill burden and levodopa equivalent daily dosage (LEDD) were measured at baseline, 0-6 months and 7-12 months follow-up. RESULTS: CLES-I and CLES-NI had higher pill burden than DBS patients at baseline. However, at 6 months post-treatment, CLES-I had significantly fewer pills/day than CLES-NI (4.7 versus 11.4, p < 0.05) and DBS (4.8 versus 7.4, p < 0.05). A significant reduction in pill burden was observed at 0-6 months (46.3%) and 7-12 months (68.3%) follow-up for CLES-I (p < 0.001) versus increased burden for CLES-NI (+10.5%, p < 0.05 and +8.2%, p > 0.05) and insignificant reductions for DBS (-3.9% and -6.1%, p > 0.05). Mean adjusted pill burden showed 57.3% fewer pills at 0-6 months and 74.1% at 7-12 months among CLES-I compared with CLES-NI, and 49.6% and 70.1% reduction compared with DBS. CLES-I showed a decrease in LEDD at 7-12 months compared with baseline (935 to 237 mg) and to CLES-NI (237 mg versus 1112 mg) and DBS patients (236 mg versus 594 mg). CONCLUSION: CLES led to a significant reduction in pill burden and oral LEDD compared with CLES-NI and DBS patients. Pill burden reduction could be considered a treatment goal for patients with APD challenged by complex polypharmacy regimens that interfere with activities of daily living and quality of life.

Management of uncontrollable motor movements in patients with advanced Parkinson's disease rely on oral levodopa-based treatments. Non-motor symptoms such as depression and anxiety are managed with additional oral medications. Over time, higher and more frequent dosing of oral medications is required, resulting in complex medication regimens that impact quality of life and adherence.A real-world study of 10,752 Parkinson's disease patients between 2014 and 2018 evaluated the effectiveness of two device-aided therapies to reduce pill burden, carbidopa/levodopa enteral suspension and deep brain stimulation. Carbidopa/levodopa suspension treatment involves continuous delivery of levodopa to the intestines through a surgical port attached to a portable pump. Brain stimulation involves surgery to attach metal wires to the brain to send electrical pulses via an implanted stimulator.As Parkinson's disease predominately affects the elderly, we compared Medicare patients on carbidopa/levodopa suspension to a matched control group receiving no suspension and to those receiving brain stimulation. Average pill burden/day was measured prior to receiving a device-aided treatment (baseline) and at 0­6 months and 7­12 months post-treatment (follow-up).The top graph shows that by 6-months post-treatment, patients on carbidopa/levodopa suspension required fewer pills than those without suspension (4.7 versus 11.4), with further pill reduction at 12 months (3.5 versus 11.1). The bottom graph shows that by 6 months, patients on carbidopa/levodopa suspension required fewer pills than patients treated with brain stimulation (4.8 versus 7.4), with further reduction at 12 months (3.6 versus 7.0). The reduction in oral pill burden suggests that the carbidopa/levodopa suspension may present an opportunity to simplify treatment regimens.

Physical functioning, frailty and risks of locally-advanced breast cancer among older women.

OBJECTIVE: Women with multiple comorbidities have competing health needs that may delay screening for early detection of breast cancer. Our objective was to determine associations between physical functioning and frailty with risk of locally-advanced breast cancer (BC). METHODS: We conducted a retrospective cohort study of women 65 years and older diagnosed with first primary stage I-III BC using the Surveillance, Epidemiology and End Results Medicare Health Outcome Survey Data Resource. Physical health-related quality of life was measured using Veterans RAND 12 Item Health Survey scales within two years before diagnosis; frailty was determined by calculating deficit-accumulation frailty index (DAFI) scores. Multivariable modified Poisson regression models were used to estimate rate ratios (RR) and 95% confidence intervals (CI) for risk of locally-advanced (stage III) versus early-stage (I-II) BC. RESULTS: Among 2411 women with a median age of 75 years at BC diagnosis, 2189 (91%) were diagnosed with incident stage I-II BC and 222 (9%) were diagnosed at stage III. Compared to women with early-stage disease, women with locally-advanced BC had lower physical component scores (37.8 vs. 41.4) and more classified as pre-frail or frail (55% vs. 50%). In multivariable models, frailty was not associated with increased risk of locally-advanced disease. However, worse physical function subscale scores (lowest vs. upper quartile; RR = 1.56, 95% CI 1.04-2.34) were associated with risk of locally-advanced BC. CONCLUSIONS: Breast cancer screening among non-frail older women should be personalized to include women with limited physical functioning if the benefits of screening and early detection outweigh the potential harms.

Comparative Effectiveness of Carbidopa-Levodopa Enteral Suspension and Deep Brain Stimulation on Parkinson's Disease-Related Pill Burden Reduction in Advanced Parkinson's Disease: A Retrospective Real-World Cohort Study.

INTRODUCTION: In advanced Parkinson's disease (PD), a high pill burden is associated with poor compliance, reduced control of symptoms, and decreased quality of life. We assessed the impact of carbidopa-levodopa enteral suspension (CLES) and deep brain stimulation (DBS) on PD-related pill burden. METHODS: A retrospective cohort analysis was conducted in the IBM MarketScan and Medicare Supplemental databases. Patients with advanced PD, taking only PD medications, and initiating CLES or DBS between 9 January 2015 and 31 July 2019 were identified. CLES patients were matched to DBS patients in a 1:3 ratio based on a propensity score to balance patient characteristics. Pill burden was measured as a 30-day average number of PD-related pills per day and was captured monthly. Pill-free status was evaluated as the percentage of patients receiving CLES or DBS monotherapy. Descriptive statistics were used to compare pill counts and assess the proportion of patients on monotherapy at 6 and 12 months after initiating CLES or DBS. RESULTS: The cohorts included 34 CLES patients matched to 97 DBS patients. A significant reduction in PD-related pill burden was observed at 6 months after initiation of CLES or DBS (∆CLES: -5.62, p < 0.0001; ∆DBS: -1.48, p = 0.0022). PD-related pill burden reduction in CLES patients was significantly greater than in matched DBS patients at 6 months (∆: -4.14, p < 0.0001), which was sustained at 12 months after initiation. At 12 months, nearly three times more CLES patients were pill free than DBS patients (29.41% and 10.31%, respectively, p = 0.0123). CONCLUSIONS: Device-aided therapies such as CLES and DBS are effective in significantly reducing PD-related pill burden. Patients treated with CLES were more likely to achieve pill-free status than patients receiving DBS.

Barriers to and facilitators of opioid prescribing by dentists in the United States: A qualitative study.

BACKGROUND: Dentists in the United States frequently prescribe opioids for dental-related pain, although evidence shows superior efficacy of nonopioids for pain management. A national sample of US dentists was interviewed to understand the barriers and facilitators to opioid prescribing. METHODS: Semistructured one-on-one telephone interviews were conducted with dentists sampled from the 6 regions of The National Dental Practice-Based Research Network. Responses were coded into the domains of the Capability, Opportunity and Motivation Model of Behavior. Potential behavior change interventions were identified for targeted themes. RESULTS: Seventy-three interviews were qualitatively analyzed. Most of those interviewed were general dentists (86.3%) and on average (SD) were in practice for 24.3 (13.0) years. Ten themes were identified within the Capability, Opportunity and Motivation Model of Behavior. Dentists' knowledge of opioid risk, ability to identify substance use disorder behavior, and capability of communicating pain management plans to patients or following clinic policies or state and federal regulations were linked with judicious opioid prescribing. Dentists reported prescribing opioids if they determined clinical necessity or feared negative consequences for refusing to prescribe opioids. CONCLUSIONS: Dentists' opioid decision making is influenced by a range of real-world practice experiences and patient and clinic factors. Education and training that target dentists' knowledge gaps and changes in dentists' practice environment can encourage effective communication of pain management strategies with patients and prescribing of nonopioids as first-line analgesics while conserving opioid use. PRACTICAL IMPLICATIONS: Identified knowledge gaps in dentistry can be targets for education, clinical guidelines, and policy interventions to ensure safe and appropriate prescribing of opioids.

Trends in Opioid Prescribing by General Dentists and Dental Specialists in the U.S., 2012-2019.

INTRODUCTION: Evidence suggests that U.S. dentists prescribe opioids excessively. There are limited national data on recent trends in opioid prescriptions by U.S. dentists. In this study, we examined trends in opioid prescribing by general dentists and dental specialists in the U.S. from 2012 to 2019. METHODS: Dispensed prescriptions for oral opioid analgesics written by dentists were identified from IQVIA Longitudinal Prescription Data from January 2012 through December 2019. Autoregressive integrated moving average and joinpoint regression models described monthly population-based prescribing rates (prescriptions/100,000 individuals), dentist-based prescribing rates (prescriptions/1,000 dentists), and opioid dosages (mean daily morphine milligram equivalents/day). All analyses were performed in 2020. RESULTS: Over the 8 years, dentists prescribed >87.2 million opioid prescriptions. Population- and dentist-based prescribing rates declined monthly by -1.97 prescriptions/100,000 individuals (95% CI= -9.98, -0.97) and -39.12 prescriptions/1,000 dentists (95% CI= -58.63, -17.65), respectively. Opioid dosages declined monthly by -0.08 morphine milligram equivalents/day (95% CI= -0.13, -0.04). Joinpoint regression identified 4 timepoints (February 2016, May 2017, December 2018, and March 2019) at which monthly prescribing rate trends were often decreasing in greater magnitude than those in the previous time segment. CONCLUSIONS: Following national trends, dentists became more conservative in prescribing opioids. A greater magnitude of decline occurred post 2016 following the implementation of strategies aimed to further regulate opioid prescribing. Understanding the factors that influence prescribing trends can aid in development of tailored resources to encourage and support a conservative approach by dentists, to prescribing opioids.

Comparative Effectiveness of Device-Aided Therapies on Quality of Life and Off-Time in Advanced Parkinson's Disease: A Systematic Review and Bayesian Network Meta-analysis.

INTRODUCTION: Research comparing levodopa/carbidopa intestinal gel (LCIG), deep brain stimulation (DBS), and continuous subcutaneous apomorphine infusion (CSAI) for advanced Parkinson's disease (PD) is lacking. This network meta-analysis (NMA) assessed the comparative effectiveness of LCIG, DBS, CSAI and best medical therapy (BMT) in reducing off-time and improving quality of life (QoL) in patients with advanced PD. METHODS: A systematic literature review was conducted for randomized controlled trials (RCTs), observational and interventional studies from January 2003 to September 2019. Data extracted at baseline and 6 months were off-time, as reported by diary or Unified Parkinson's Disease Rating Scale Part IV item 39, and QoL, as reported by Parkinson's Disease Questionnaire (PDQ-39/PDQ-8). Bayesian NMA was performed to estimate pooled treatment effect sizes and to rank treatments in order of effectiveness. RESULTS: A total of 22 studies fulfilled the inclusion criteria (n = 2063 patients): four RCTs, and 16 single-armed, one 2-armed and one 3-armed prospective studies. Baseline mean age was between 55.5-70.9 years, duration of PD was 9.1-15.3 years, off-time ranged from 5.4 to 8.7 h/day in 9 studies, and PDQ scores ranged from 28.8 to 67.0 in 19 studies. Levodopa/carbidopa intestinal gel and DBS demonstrated significantly greater improvement in off-time and QoL at 6 months compared with CSAI and BMT (p < 0.05). There was no significant difference in the effects of LCIG and DBS, but DBS was ranked first for reduction in off-time, and LCIG was ranked first for improvement in QoL. CONCLUSIONS: This NMA found that LCIG and DBS were associated with superior improvement in off-time and PD-related QoL compared with CSAI and BMT at 6 months after treatment initiation. This comparative effectiveness research may assist providers, patients, and caregivers in the selection of the optimal device-aided therapy.

Serious opioid-related adverse outcomes associated with opioids prescribed by dentists.

ABSTRACT: Although nonsteroidal anti inflammatory drugs are superior to opioids in dental pain management, opioids are still prescribed for dental pain in the United States. Little is known about the serious adverse outcomes of short-acting opioids within the context of dental prescribing. The objective of this study was to evaluate adverse outcomes and persistent opioid use (POU) after opioid prescriptions by dentists, based on whether opioids were overprescribed or within recommendations. A cross-sectional analysis of adults with a dental visit and corresponding opioid prescription (index) from 2011 to 2018 within a nationwide commercial claims database was conducted. Opioid overprescribing was defined as >120 morphine milligram equivalents per Centers for Disease Control and Prevention guidelines. Generalized estimating equation models were used to assess adverse outcomes (emergency department visits, hospitalizations, newly diagnosed substance use disorder, naloxone administration, or death within 30 days from index) and POU (≥1 prescription 4-90 days postindex). Predicted probabilities are reported. Of 633,387 visits, 2.6% experienced an adverse outcome and 16.6% had POU. Adverse outcome risk was not different whether opioids were overprescribed or within recommendations (predicted probability 9.0%, confidence interval [CI]: 8.0%-10.2% vs 9.1%, CI: 8.1-10.3), but POU was higher when opioids were overprescribed (predicted probability 27.4%, CI: 26.1%-28.8% vs 25.2%, CI: 24.0%-26.5%). Visits associated with mild pain and those with substance use disorders had the highest risk of both outcomes. Findings from this study demonstrate that dental prescribing of opioids was associated with adverse outcomes and POU, even when prescriptions were concordant with guidelines. Additional efforts are required to improve analgesic prescribing in dentistry, especially in groups at high risk of opioid-related adverse outcomes.

Association between transportation barriers and anticoagulation control among an inner-city, low-income population: A prospective observational cohort study.

BACKGROUND: Anticoagulation with warfarin represents a transportation-sensitive treatment state. Transportation barrier is a common reason for not using health care services. OBJECTIVE: To assess the association between transportation barriers to anticoagulation clinic and anticoagulation control (AC) among an inner-city, low-income population. PATIENTS/METHODS: Adults expected to be on chronic warfarin therapy were recruited from an ambulatory anticoagulation clinic. Participants completed a validated questionnaire that assessed transportation barriers to clinic, defined as self-reported trouble getting transportation to a clinic and a composite score of the presence of transportation barriers. Suboptimal AC was defined as time in therapeutic range (TTR) <60% over 6 months. Prevalence ratios with 95% confidence intervals (CIs), adjusted for age, sex, and annual household income, described the association of transportation trouble and barriers with AC. RESULTS: Of 133 participants, 42.9% had suboptimal AC. Mean age was 60.4 (SD, 13.6) years, and the majority of participants were women (62.2%). Participants with transportation trouble were more likely to report being disabled/unable to work (63.6%) and annual household income <$15 000 (45.5%). Mean TTR was significantly lower for participants with transportation trouble compared to those without (53.8% [SD, 24.7%] vs 64.7% [SD, 25.0%]; P = .03). Participants reporting transportation trouble or at least one transportation barrier were 1.60 (95% CI, 1.07-2.39) and 1.68 (95% CI, 1.01-2.80) times more likely, respectively, to have suboptimal AC compared to those without. CONCLUSION: Inner-city, low-income individuals with transportation barriers were more likely to have suboptimal AC. Further research is warranted to evaluate the impact of alleviating patient-specific transportation barriers on anticoagulation outcomes.

Trimethoprim-Sulfamethoxazole Associated Drug-Induced Liver Injury in Pediatrics: A Systematic Review.

BACKGROUND: Drug-induced liver injury (DILI) is a rare but known adverse event associated with trimethoprim-sulfamethoxazole (TMP-SMX) in adults. No studies to date have looked at the risk of this association in children. We systematically reviewed the evidence for a potential association between TMP-SMX and DILI in the pediatric population. METHODS: PubMed, Medline, Embase, Cochrane Database of Systematic Reviews, Scopus and Web of Science was searched using a combination of terms to identify reports of TMP-SMX exposure, liver injury and pediatrics (≤18 years old). We included any studies with hepatic adverse events occurring after exposure to TMP-SMX. Bibliographies were reviewed for additional relevant references. The Narajno scale was used to assess causality in case studies. RESULTS: A total of 22 studies were identified: 3 randomized trials, 1 prospective observational study, 8 retrospective observational studies and 10 case reports. Among the randomized trials and prospective studies, only mild, transient hepatic function abnormalities were reported. Retrospective observational studies reported 1 fatal DILI and statistically significant increased odds of DILI with TMP-SMX use compared with nonuse. Among the 10 case reports, severe liver outcomes and mild hepatic function abnormalities were both reported. Naranjo scores suggested reported hepatic adverse events were probably because of exposure in 5, possible in 4, and doubtful in 1 case report. CONCLUSIONS: Evidence regarding DILI associated with TMP-SMX exposure in pediatrics is limited. Observational population studies show mild hepatic abnormalities. Case reports suggest more severe manifestations of DILI. Additional studies may reveal the association between TMP-SMX and DILI in pediatrics.

Barriers and Facilitators of Using Sensored Medication Adherence Devices in a Diverse Sample of Patients With Multiple Myeloma: Qualitative Study.

BACKGROUND: Many recently approved medications to manage multiple myeloma (MM) are oral, require supportive medications to prevent adverse effects, and are taken under complex schedules. Medication adherence is a concern; however, little attention has been directed toward understanding adherence in MM or associated barriers and facilitators. Advanced sensored medication devices (SMDs) offer opportunities to intervene; however, acceptability among patients with MM, particularly African American patients, is untested. OBJECTIVE: This study aimed to explore patients' (1) perceptions of their health before MM including experiences with chronic medications, (2) perceptions of adherence barriers and facilitators, and (3) attitudes toward using SMDs. METHODS: An in-person, semistructured, qualitative interview was conducted with a convenience sample of patients being treated for MM. Patients were recruited from within an urban, minority-serving, academic medical center that had an established cancer center. A standardized interview guide included questions targeting medication use, attitudes, adherence, barriers, and facilitators. Demographics included the use of cell phone technology. Patients were shown 2 different pill bottles with sensor technology-Medication Event Monitoring System and the SMRxT bottle. After receiving information on the transmission ability of the bottles, patients were asked to discuss their reactions and concerns with the idea of using such a device. Medical records were reviewed to capture information on medication and diagnoses. The interviews were audio-recorded and transcribed. Interviews were independently coded by 2 members of the team with a third member providing guidance. RESULTS: A total of 20 patients with a mean age of 56 years (median=59 years; range=29-71 years) participated in this study and 80% (16/20) were African American. In addition, 18 (90%, 18/20) owned a smartphone and 85% (17/20) were comfortable using the internet, text messaging, and cell phone apps. The average number of medications reported per patient was 13 medications (median=10; range=3-24). Moreover, 14 (70%, 14/20) patients reported missed doses for a range of reasons such as fatigue, feeling ill, a busy schedule, forgetting, or side effects. Interest in using an SMD ranged from great interest to complete lack of interest. Examples of concerns related to the SMDs included privacy issues, potential added cost, and the size of the bottle (ie, too large). Despite the concerns, 60% (12/20) of the patients expressed interest in trying a bottle in the future. CONCLUSIONS: Results identified numerous patient-reported barriers and facilitators to missed doses of oral anticancer therapy. Many appear to be potentially mutable if uncovered and addressed. SMDs may allow for capture of these data. Although patients expressed concerns with SMDs, most remained willing to use one. A feasibility trial with SMDs is planned.