Use of Acid-Suppression Therapy and Odds of Migraine and Severe Headache in the National Health and Nutrition Examination Survey.

Background and Objectives: Headache is an adverse event associated with the use of proton pump inhibitors (PPIs). Recently, migraine has emerged more specifically as a potential adverse event with PPI use. The objectives of this work were to capitalize on existing data to evaluate the association between migraine and severe headache prevalence and use of acid-suppression therapy, including PPIs, H2 receptor antagonists (H2RAs), and generic antacids; to compare risk from PPIs vs H2RAs; and to assess for potential mitigation by a dietary factor affected by acid-suppression therapy. Methods: Data from adults in the 1999-2004 National Health and Nutrition Examination Survey were used for this cross-sectional analysis. Acid-suppression therapy use was identified from self-report confirmed by product packaging review. Respondents who endorsed migraine or severe headache in the past 3 months were classified in the migraine or severe headache group. Dietary intake of magnesium was determined using one 24-hour recall interview. Multivariable logistic regression models were generated to analyze the relationship between acid-suppression therapy use and migraine or severe headache, and an interaction test was conducted to evaluate whether migraine or severe headache prevalence differed in relation to nutritional magnesium intake across acid-suppression therapy users and nonusers. Results: In 11,818 US adults, the use of acid-suppression therapy was associated with higher odds of migraine or severe headache for all types of acid-suppression therapy and use of any type, as compared with those who did not use acid-suppression therapy: use of PPIs (70% higher), H2RAs (40% higher), and generic antacids (30% higher). Differences between acid-suppression therapy were not significant. An interaction was observed for H2RA use and magnesium intake (p = 0.024). Discussion: These observations in US adults agree with previous findings that migraine or severe headache is a potential adverse event of PPIs, the most efficacious and most frequently used type of acid suppressing medication, and further suggest that other classes of acid suppressing medications (H2RAs and generic antacids) may also be implicated for migraine and severe headache. Future prospective analyses are needed to investigate migraine risk associated with acid suppressing medications while current evidence is sufficient to evaluate patients with migraine in light of recent deprescribing advice for PPIs.

Changes in opioid prescribing in veterans with headache during the COVID-19 pandemic: A regression discontinuity in time analysis.

OBJECTIVE: To determine changes in opioid prescribing among veterans with headaches during the coronavirus disease of 2019 (COVID-19) pandemic by comparing the stay-at-home phase (March 15 to May 30, 2020) and the reopening phase (May 31 to December 31, 2020). BACKGROUND: Opioid prescribing for chronic pain has declined substantially since 2016; however, changes in opioid prescribing during the COVID-19 pandemic among veterans with headaches remain unknown. METHODS: This retrospective cohort study utilized regression discontinuity in time and difference-in-differences design to analyze veterans aged ≥18 years with a previous diagnosis of headache disorders and an outpatient visit to the Veterans Health Administration (VHA) during the study period. We measured the weekly number of opioid prescriptions, the number of days supplied, the daily dose in morphine milligram equivalents (MMEs), and the number of prescriptions with ≥50 morphine equivalent daily doses (MEDD). RESULTS: A total of 81,376 veterans were analyzed with 589,950 opioid prescriptions. The mean (SD) age was 51.6 (13.5) years, 57,242 (70.3%) were male, and 53,464 (65.7%) were White. During the pre-pandemic period, 323.6 opioid prescriptions (interquartile range 292.1-325.8) were dispensed weekly, with an median (IQR) of 24.1 (24.0-24.4) days supplied and 31.8 (31.2-32.5) MMEs. Transition to stay-at-home was associated with a 7.7% decrease in the number of prescriptions (incidence rate ratio [IRR] 1.077, 95% confidence interval [CI] 0.866-0.984) and a 9.8% increase in days supplied (IRR 1.098, 95% CI 1.078-1.119). Similar trends were observed during the reopening period. Subgroup analysis among veterans on long-term opioid therapy also revealed 1.7% and 1.4% increases in days supplied during the stay-at-home (IRR 1.017, 95% CI 1.009-1.025) and reopening phase (IRR 1.014, 95% CI 1.007-1.021); however, changes in the total number of prescriptions, MME/day, or the number of prescriptions >50 MEDD were insignificant. CONCLUSION: Prescription opioid access was maintained for veterans within VHA during the pandemic. The de-escalation of opioid prescribing observed prior to the pandemic was not seen in our study.

Trajectory of blood pressure after initiating anti-calcitonin gene-related peptide treatment of migraine: a target trial emulation from the veterans health administration.

BACKGROUND: Calcitonin gene-related peptide (CGRP) is involved in migraine pathophysiology and blood pressure regulation. Although clinical trials have established the cardio-cerebrovascular safety profile of anti-CGRP treatment, limited high-quality real-world evidence exists on its long-term effects on blood pressure (BP). To address this gap, we examined the safety of anti-CGRP treatment on BP in patients with migraine headache in the Veterans Health Administration (VHA). METHODS: We emulated a target trial of patients who initiated anti-CGRP treatment or topiramate for migraine prevention between May 17th, 2018 and February 28th, 2023. We calculated stabilized inverse probability weights to balance between groups and then used weighted linear mixed-effect models to estimate the systolic and diastolic BP changes over the study period. For patients without hypertension at baseline, we estimated the cumulative incidence of hypertension using Kaplan-Meier curve. We also used weight mixed-effect Poisson model to estimate the number of antihypertension medications for patients with hypertension at baseline. RESULTS: This analysis included 69,589 patients and 554,437 blood pressure readings. of these, 18,880 patients received anti-CGRP treatment, and they were more likely to be women, have a chronic migraine diagnosis and higher healthcare utilization than those received topiramate. Among patients without hypertension at baseline, we found no significant differences in systolic BP changes over the four-year follow-up between anti-CGRP (slope [standard error, SE] = 0.48[0.06]) and topiramate treated patients (slope[SE] = 0.39[0.04]). The incidence of hypertension was similar for anti-CGRP and topiramate group (4.4 vs 4.3 per 100 person-years). Among patients with hypertension at baseline who initiated anti-CGRP treatment, we found a small but persistent effect on exacerbating hypertension during the first four years of treatment, as evidenced by a significant annual 3.7% increase in the number of antihypertensive medications prescribed (RR = 1.037, 95%CI 1.025-1.048). CONCLUSIONS: Our findings suggest that anti-CGRP treatment is safe regarding blood pressure in patients without hypertension. However, for those with baseline hypertension, anti-CGRP treatment resulted in a small but persistent increase in the number of antihypertensives, indicating an exacerbation of hypertension. Future studies are needed to evaluate the cardio-cerebrovascular safety of anti-CGRP treatment beyond the first four years.

Evaluating the Effectiveness of Diabetes Shared Medical Appointments (SMAs) as Implemented in Five Veterans Affairs Health Systems: a Multi-site Cluster Randomized Pragmatic Trial.

OBJECTIVE: To examine whether diabetes shared medical appointments (SMAs) implemented as part of usual clinical practice in diverse health systems are more effective than usual care in improving and sustaining A1c improvements. RESEARCH DESIGN AND METHODS: A multi-site cluster randomized pragmatic trial examining implementation in clinical practice of diabetes SMAs in five Veterans Affairs (VA) health systems was conducted from 2016 to 2020 among 1537 adults with type 2 diabetes and elevated A1cs. Eligible patients were randomly assigned to either: (1) invitation to participate in a series of SMAs totaling 8-9 h; or (2) continuation of usual care. Relative change in A1c (primary outcome) and in systolic blood pressure, insulin starts, statin starts, and anti-hypertensive medication classes (secondary outcomes) were measured as part of usual clinical care at baseline, at 6 months and at 12 months (~7 months after conclusion of the final SMA in four of five sites). We examined outcomes in three samples of SMA participants: all those scheduled for a SMA, those attending at least one SMA, and those attending at least half of SMAs. RESULTS: Baseline mean A1c was 9.0%. Participants scheduled for an SMA achieved A1c reductions 0.35% points greater than the control group between baseline and 6-months follow up (p = .001). Those who attended at least one SMA achieved reductions 0.42 % points greater (p < .001), and those who attended at least half of scheduled SMAs achieved reductions 0.53 % points greater (p < .001) than the control group. At 12-month follow-up, the three SMA analysis samples achieved reductions from baseline ranging from 0.16 % points (p = 0.12) to 0.29 % points (p = .06) greater than the control group. CONCLUSIONS: Diabetes SMAs as implemented in real-life diverse clinical practices improve glycemic control more than usual care immediately after the SMAs, but relative gains are not maintained. Our findings suggest the need for further study of whether a longer term SMA model or other follow-up strategies would sustain relative clinical improvements associated with this intervention. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT02132676.

The Shared Health Appointments and Reciprocal Enhanced Support (SHARES) study: study protocol for a randomized trial.

BACKGROUND: Diabetes shared medical appointments (SMAs) and reciprocal peer support programs have been found in efficacy trials to help adults with diabetes improve their self-management and achieve short-term gains in clinical and patient-centered outcomes. In order to translate this evidence to system-level interventions, there is a need for large-scale, pragmatic trials that examine the effectiveness, implementation, and costs of SMAs and reciprocal peer support across diverse settings. METHODS: The Shared Health Appointments and Reciprocal Enhanced Support (SHARES) study is a multisite, cluster randomized trial that is evaluating the effectiveness and implementation of SMAs with and without an additional reciprocal Peer-to-Peer (P2P) support program, when compared to usual care. The P2P program comprises periodic peer support group sessions and telephone contact between SMA participant pairs to promote more effective diabetes self-management. We will examine outcomes across three different treatment groups: (1) SMAs, (2) SMAs plus P2P, and (3) usual care. We will collect and analyze data over a 2.5-year implementation period at five geographically diverse Veterans Affairs (VA) health systems. The primary outcome is the relative change in hemoglobin A1c over time. Secondary outcomes are changes in systolic blood pressure, antihypertensive medication use, statin use, and insulin initiation over the study period. The unit of analysis is the individual, adjusted by the individual's SMA group (the cluster). We will use mixed methods to rigorously evaluate processes and costs of implementing these programs in each of the clinic settings. DISCUSSION: We hypothesize that patients will experience improved outcomes immediately following participation in SMAs and that augmenting SMAs with reciprocal peer support will help to maintain these gains over time. The results of this study will be among the first to examine the effects of diabetes SMAs alone and in conjunction with P2P in a range of real-life clinical settings. In addition, the study will provide important information on contextual factors associated with successful program implementation. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02132676 . Registered on 21 August 2013.

Pharmacist-physician collaboration for diabetes care: the diabetes initiative program.

BACKGROUND: Multiple complications can arise secondary to poor control of glucose, blood pressure, and cholesterol in a patient with diabetes. OBJECTIVE: To evaluate the effect of a pharmacist-physician collaboration on attainment of diabetes-related measures of control. METHODS: This was a prospective, multicenter, cohort study. Patients were enrolled from 7 practice sites throughout Tennessee if they had been diagnosed with type 2 diabetes, were aged 18 years or older with a life expectancy greater than 1 year, and were English speaking. Pregnant women were excluded. Patients were followed for 12 months following enrollment by informed consent. The pharmacist-physician collaboration method was established prior to study initiation. Primary outcomes included hemoglobin A1c (A1C), number of patients with A1C less than 7%, and percentage of patients with A1C greater than 9%. RESULTS: Of the 206 patients enrolled, the mean age was 59.73 years, and most were male (59.71%) and white (66.02%). The A1C was reduced by an average of 1.16% (p < 0.0001). The proportion of patients with A1C less than 7% increased from 12.75% at baseline to 36.76% at study conclusion (p = 0.0002). The proportion of patients with A1C greater than 9% decreased from 34.15% to 16.50%, (p < 0.0001). CONCLUSIONS: Pharmacist-physician collaborative management at multiple practice locations and types of setting (eg, private, academic, Veterans Affairs medical center) has a positive impact on glycemic control and diabetes-related health maintenance. This was accomplished without increasing the total number of antihyperglycemic agents prescribed and without an increase in patient-reported episodes of hypoglycemia.

Smoking cessation: barriers to success and readiness to change.

BACKGROUND AND OBJECTIVES: Smoking cessation interventions should be individualized based on patient history and readiness for change. The objective of this study was to assess stages of change and key components of smoking and cessation history among a sample of primary care patients. METHODS: A telephone survey of current or recent smokers identified smoking status, stage of change, motivation, concerns, relapse history, pharmacotherapy, and social support. RESULTS: Of 150 participants, most were within precontemplation (22.7 percent) or contemplation (44.0 percent) stages of change; 14.0 percent were in preparation, 4.7 percent in action, and 14.7 percent in maintenance. The primary motivation for quitting was to improve general health (42.3 percent). The most common cessation-related concerns were: breaking the habit, stress, and weight gain. Pharmacotherapy was discontinued due to adverse events in 31.5 percent of users. Intratreatment social support was reported by 17.5 percent. The most common reasons for relapse were falling back into the habit (36 percent), stressful situations (27 percent), and being around other smokers (25 percent). CONCLUSIONS: Targeted interventions are needed for patients in either precontemplation or contemplation stages. Counseling should focus on helping patients resolve barriers to cessation and reasons for relapse, particularly stress and weight management. Pharmacotherapy should be utilized when patients are ready to quit. Increased intratreatment social support and counseling appear warranted to support behavior change and appropriate medication use.

Comparing team-based and mixed active-learning methods in an ambulatory care elective course.

OBJECTIVES: To assess students' performance and perceptions of team-based and mixed active-learning methods in 2 ambulatory care elective courses, and to describe faculty members' perceptions of team-based learning. METHODS: Using the 2 teaching methods, students' grades were compared. Students' perceptions were assessed through 2 anonymous course evaluation instruments. Faculty members who taught courses using the team-based learning method were surveyed regarding their impressions of team-based learning. RESULTS: The ambulatory care course was offered to 64 students using team-based learning (n = 37) and mixed active learning (n = 27) formats. The mean quality points earned were 3.7 (team-based learning) and 3.3 (mixed active learning), p < 0.001. Course evaluations for both courses were favorable. All faculty members who used the team-based learning method reported that they would consider using team-based learning in another course. CONCLUSIONS: Students were satisfied with both teaching methods; however, student grades were significantly higher in the team-based learning course. Faculty members recognized team-based learning as an effective teaching strategy for small-group active learning.

Probable drug interaction between warfarin and hormonal contraceptives.

OBJECTIVE: To report a single patient case that presented with a probable drug interaction between warfarin and 3 methods of hormonal contraceptives, as assessed by the Horn Interaction Probability Scale. CASE SUMMARY: A 33-year-old female patient required long-term anticoagulation following an aortic valve replacement. While taking warfarin (38.5 mg weekly), she transitioned from a monophasic combined oral contraceptive (ethinyl estradiol plus norethindrone) to an implantable progestin-only contraceptive (etonogestrel) on the advice of her cardiologist. Nineteen days following etonogestrel implant insertion, her international normalized ratio (INR) decreased to 1.8 and required a 55.8% warfarin dose increase (resulting dose of 60 mg weekly). Within 10 months, the patient elected to have the implant removed due to vaginal bleeding. Nine days following removal of etonogestrel, she experienced a transient INR increase to 6.5. Her INR returned to within goal range after her warfarin dose was decreased to 55.5 mg weekly. After using barrier methods of contraception for 48 days, she initiated an oral progestin-only contraceptive (norethindrone). Further warfarin dose adjustments were made, resulting in a weekly warfarin dose of 53.5 mg. Thirty-nine days after initiation of oral norethindrone, she elected to discontinue use due to vaginal bleeding and no longer uses hormonal contraceptive methods. No further adjustments to her warfarin dose were warranted. DISCUSSION: The increased warfarin requirement observed in this patient may have been a result of multiple factors. Based on a literature review, we hypothesize that the predominant mechanism of interaction was ethinyl estradiol inhibition of CYP1A2 and 2C19. CONCLUSIONS: We recommend that further in vivo studies be completed to definitively identify the mechanism of the interaction. It is necessary to intensify warfarin monitoring upon initiation or alteration of hormonal contraceptives.

Clinical outcomes and pharmacists' acceptance of a community hospital's anticoagulation management service utilizing decentralized clinical staff pharmacists.

BACKGROUND: In 2008, the Joint Commission released an updated National Patient Safety Goals document that requires institutions to implement practices that reduce the likelihood of patient harm associated with use of anticoagulation therapy. One of the expectations associated with this goal was that each organization would establish an anticoagulant management program. To our knowledge, few data exist to describe the implementation and assessment of anticoagulation programs in smaller, nonteaching community hospitals using decentralized pharmacists in an integrated practice model. OBJECTIVE: To compare the performance of a protocol-driven anticoagulation management service led by decentralized pharmacists in a nonteaching community hospital with that of usual medical care provided by hospitalist physicians before this program was implemented. Based on these results, as well as a pharmacist satisfaction survey, evaluate the service and identify barriers to expansion. METHODS: We conducted a retrospective cohort study comparing 50 consecutive patients who were starting warfarin for the first time beginning in November 2003 with 50 patients managed by hospitalist physicians prior to November 2002 (the time of program implementation). RESULTS: There were no significant differences between groups with regard to time in therapeutic range once therapeutic, length of stay, international normalized ratios (INRs) greater than 3.5, or INRs less than 2. Patients in the pharmacy management group had significantly fewer drug interactions with antimicrobials than did the usual medical care group. Although time to therapeutic range was longer in the pharmacy protocol group, there were fewer patients with INRs greater than 3.5, although this did not reach statistical significance. CONCLUSIONS: The efficacy of the pharmacist-led anticoagulation management service was no different from that of usual medical care. Patient safety appeared improved, in part due to more careful initial dose selection based on patient-specific factors. Although this program was accepted by pharmacists, time limitations were perceived to be a major barrier to quality care and expansion of the service.