Guideline-based Pharmacotherapy Research Articles

Reverse Remodeling of Methamphetamine-Associated Cardiomyopathy: An Update on Mechanisms for Recovery

Methamphetamine (MA) use continues to rise worldwide. The adverse effects of MA on the cardiovascular system include cardiomyopathy, dysrhythmias, coronary arterial vasospasm, and atherosclerosis. Methamphetamine-associated cardiomyopathy (MACM) affects predominantly younger male patients and is responsible for an increasing proportion of heart failure emergency department visits, hospital admissions/readmissions, morbidity, and mortality. Reverse remodeling of MACM and full cardiac recovery is achievable in patients who cease using MA and remain abstinent with self-direction, cognitive behavioral therapy, brief interventions, contingency management, motivational interviewing, and residential rehabilitation. Recovery is further enhanced by the addition of an exercise program and guideline-based pharmacotherapy for heart failure, which includes β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or angiotensin receptor-neprilysin inhibitors, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors. Alternative heart failure treatment with isosorbide dinitrate plus hydralazine, ivabradine, vericiguat, and omecamtiv mecarbil represent further adjuncts which may promote reverse remodeling. Antioxidant compounds such as coenzyme-Q10, omega-3 polyunsaturated fatty acids, resveratrol, and cannabidiol may aid in cardiac restoration. Diet changes, metformin and glucose control, stem cell therapy, melatonin, and sleep quality improvement are further steps on the road to recovery. In this article we review the cardiotoxicity of MA, pathogenesis of MACM, and evidence behind pharmacologic and lifestyle interventions to reverse its progression.

Primary care utilisation, adherence to guideline-based pharmacotherapy and continuity of care in primary care patients with chronic diseases and multimorbidity – a cross-sectional study

Abstract Background To understand how to improve care for patients with chronic diseases and multimorbidity we wanted to describe the prevalence of different chronic diseases and the pattern of multimorbidity and to analyse the associations between occurrence of diseases and primary care utilization, adherence to guideline-based pharmacotherapy, and continuity of care. Methods Retrospective cross-sectional study of routine care data of the general population in region Jönköping in Sweden (345 916 inhabitants using primary care services) covering 4.3 years. Participants Patients fulfilling the inclusion criteria of having ≥ 1 of 10 common chronic diseases and ≥ 3 visits to primary care between 2011 and 2015. Primary outcome measures In order to determine diseases and multimorbidity, primary care utilisation, adherence to guideline-based pharmacotherapy, frequencies and percentages, interval and ratio scaled variables were described using means, standard deviations, and various percentiles in the population. Two continuity indices were used (MMCI, COC) to describe continuity. Results Of the general population, 25 829 patients fulfilled the inclusion criteria (7.5% of the population). Number of diseases increased with increasing age, and multimorbidity was much more common than single diseases (mean 2.0 per patient). There was a slight positive correlation (0.29) between number of diseases and visits, but visits did not increase proportionally to the number of diseases. Patients with physical diseases combined with anxiety and/or depression made more visits than others. The number of diseases per patient was negatively associated with the adherence to pharmacotherapy guidelines. There was no association between continuity and healthcare utilisation or adherence to pharmacotherapy guidelines. Conclusions Multimorbid patients are common in primary care and for many chronic diseases it is more common to have other simultaneous diseases than having only one disease. This can make adherence to pharmacotherapy guidelines a questionable measure for aged multimorbid patients. Existing continuity indices also revealed limitations. Holistic and patient-centred measures should be used for quality assessment of care for multimorbid patients in primary care.

Multimorbidity in Difficult Asthma: The Need for Personalised and Non-Pharmacological Approaches to Address a Difficult Breathing Syndrome.

Three to ten percent of people living with asthma have difficult-to-treat asthma that remains poorly controlled despite maximum levels of guideline-based pharmacotherapy. This may result from a combination of multiple adverse health issues including aggravating comorbidities, inadequate treatment, suboptimal inhaler technique and/or poor adherence that may individually or collectively contribute to poor asthma control. Many of these are potentially “treatable traits” that can be pulmonary, extrapulmonary, behavioural or environmental factors. Whilst evidence-based guidelines lead clinicians in pharmacological treatment of pulmonary and many extrapulmonary traits, multiple comorbidities increase the burden of polypharmacy for the patient with asthma. Many of the treatable traits can be addressed with non-pharmacological approaches. In the current healthcare model, these are delivered by separate and often disjointed specialist services. This leaves the patients feeling lost in a fragmented healthcare system where clinical outcomes remain suboptimal even with the best current practice applied in each discipline. Our review aims to address this challenge calling for a paradigm change to conceptualise difficult-to-treat asthma as a multimorbid condition of a “Difficult Breathing Syndrome” that consequently needs a holistic personalised care attitude by combining pharmacotherapy with the non-pharmacological approaches. Therefore, we propose a roadmap for an evidence-based multi-disciplinary stepped care model to deliver this.

Developing a novel tool to assess the ability to self-administer medication in non-demented in-hospital patients: ABLYMED study protocol

BackgroundOlder people often suffer from multimorbidity resulting in polypharmacy. The correct administration of medication is a crucial factor influencing treatment efficacy. However, tools for evaluating the ability to self-administer different dosage forms of medications are lacking. The objectives of the ABLYMED study are to 1) assess the ability to self-administer different dosage forms of medication in older non-demented in-hospital patients who report autonomous management of medication, 2) identify factors influencing the ability to self-administer medication, and 3) develop a standardized tool to validly assess the ability to self-administer different dosage forms of medications based on the final study results.MethodsOne hundred in-patients from the department of orthopedics and trauma surgery of the University Hospital Düsseldorf ≥ 70 years of age and regularly taking ≥ 5 different drugs autonomously will be prospectively recruited into the observational cross-sectional single-center ABLYMED study. Patients undergo an interview addressing demographic and clinical information, medication history (which medications are taken since when, in which dose and dosage form, and subjective proficiency of taking these medications), medication adherence, and factors possibly influencing adherence including personality traits and perceived quality of the medication regimen. Quality of the medication regimen is also rated by clinicians according to validated lists. Further, patients receive a comprehensive geriatric assessment including measures of cognition, mobility, and functional status. The ability to self-administer medication is assessed by having patients perform different tasks related to medication self-administration, which are video recorded and rated by different experts. The patients’ self-reported ability will be correlated with the observed performance in the self-administration tasks. Further, factors correlating with the reported and observed ability to self-administer medication will be evaluated using correlation and regression models. Based on the final study results, a novel tool to assess the ability of older patients to self-administer medication will be developed.DiscussionIn addition to guideline-based pharmacotherapy, correct intake of prescribed medication is crucial for optimal therapy of multimorbidity in older people. Tools to validly assess the ability of older patients to self-administer different dosage forms of medications are lacking, but should be included in comprehensive geriatric assessments to secure functional health.Trial registrationDevelopment of an assessment instrument to evaluate the ability to manage various dosage forms, DRKS-ID: DRKS00025788, (date of registration: 07/09/2021).

Disparities in the Use of Guideline-Based Pharmacotherapy Exist for Atherosclerotic Cardiovascular Disease and Heart Failure Patients Who Have Intellectual/Developmental Disabilities in a Commercially Insured Database.

Patients who have intellectual/developmental disabilities (IDDs) develop atherosclerotic cardiovascular disease (ASCVD) or heart failure (HF) at rates similar to or higher than the general population. They also face disparities accessing and using health care services. To determine if disparities exist in the use of guideline-based pharmacotherapy (GBP) for ASCVD or HF for adults with IDD. Using the 2014 Clinformatics Data Mart Database, adults with ASCVD or HF were divided into IDD or non-IDD groups. Patients with contraindications for GBP medications were excluded. Use of GBP between IDD and non-IDD groups was examined. Subgroup analysis included comparisons between IDD groups. For HF, 1011 patients with IDD and 236,638 non-IDD patients were identified. For ASCVD, 2190 IDD and 790,343 non-IDD patients were identified. We found that 47.9%, 35.8%, and 13.1% of IDD and 58.7%, 48.4%, and 18.9% of non-IDD patients had pharmacy claims for statins (P < 0.001), β-blockers (P < 0.001), or antiplatelet therapy (P < 0.001), respectively. For HF, 46.8% and 50.3% of IDD and 59.8% and 55.4% of non-IDD patients had pharmacy claims for β-blockers (P < 0.001) and angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs; P = 0.003), respectively. In all but one multivariate regression models patients with IDD were less likely to use GBP than patients in the non-IDD group. Subgroup analysis revealed that patients who had Down syndrome had lower GBP use in 4 of the 5 measures. Disparities exist in the use of GBP for patients with IDD with ASCVD or HF. Patients who have an IDD should be examined by clinicians to ensure appropriate access to and use of GBP.

A Randomized Comparison of Two Psychosocial Interventions on Family Functioning in Adolescents with Bipolar Disorder

Impairments in family functioning are associated with more severe depressive and manic symptoms, earlier recurrences, and more suicidal behaviors in early-onset bipolar disorder. This study examined whether family-focused treatment for adolescents (FFT-A) with BD I or II disorder led to greater increases in family cohesion and adaptability and decreases in conflict over 2years compared to a briefer psychoeducational treatment (enhanced care, EC). Participants were 144 adolescents (mean age: 15.6±1.4years) with BD I or II with a mood episode in the previous 3months. Adolescents and parents were randomized to either FFT-A (21 sessions) or EC (three sessions). Patients received guideline-based pharmacotherapy throughout the 2-year study. Trajectories of adolescent- and parent-rated family cohesion, adaptability, and conflict were analyzed over 2years. FFT-A had greater effects on adolescent-rated family cohesion compared to EC over 2years. Participants in FFT-A and EC reported similar improvements in family conflict across the 2years. In the FFT-A group, low-conflict families had greater adolescent-rated family cohesion throughout the study compared to high-conflict families. High-conflict families in both treatment groups tended to show larger reductions in conflict over 2years than low-conflict families. Family psychoeducation and skills training may improve family cohesion in the early stages of BD. Measuring levels of family conflict at the start of treatment may inform treatment responsiveness among those receiving FFT-A.

Association between Physicians' Adherence to a Pharmacotherapy Guideline and Continuity of Care for Patients with Depression and/or Anxiety Disorder.

The aim of the paper is to investigate the association between physicians' adherence to a pharmacotherapy guideline and continuity of care for patients with depressive and/or anxiety disorders in a collaborative care program. This retrospective observational study was conducted using medical records of subjects suffering from depression and/or anxiety disorder visited by 26 general practitioners (GP) working with Community Mental Health Center (CMHC), who run a collaborative care program in Tehran, Iran. All patients were visited by a general practitioner in private offices from November 2010 to May 2013. A scoring system was utilized to assess physicians' adherence to the pharmacotherapy guideline using medical records. Patients' continuity of care was calculated based on the number of days of being in the collaborative care program. To investigate the association between physicians' adherence to the guideline and the patients' continuity of care, univariate logistic regression analysis, multiple logistic regression analysis and parametric survival analysis were performed using Stata version 11. A total of 3,338 patients were studied. Their mean age was 37 years and 81.6% were female. Being treated by a particular GP was an important factor in patients with depressive and/or anxiety diagnosis as well as having both diagnoses. Furthermore, higher score of adherence to the guideline was associated with less continuity of care in depressive patients. Being treated by certain GPs is an effective way of retention of patients in the treatment. The results demonstrate that patients with guideline-based pharmacotherapy need to be told about continuity of care in community mental health program.

Real-life study showing better control of allergic rhinitis by immunotherapy than regular pharmacotherapy

Treatment for allergic rhinitis (AR) aims at reducing the burden of allergic inflammation, either by suppression of the nasal inflammation with pharmacotherapy or by inducing tolerance via immunotherapy (IT). At present, we lack information on the comparison between the degree of symptom control in AR patients treated with IT and those on pharmacotherapy. An observational study was conducted evaluating the degree of symptom control, the total and individual nasal symptom severity and current medication use at 3 years after starting either pharmacotherapy or subcutaneous immunotherapy (SCIT) for AR. A total number of 800 patients diagnosed with AR between October 2007 and February 2010 at the Ear, Nose and Throat Unit and Allergology Clinical Department of the University Hospitals of KU Leuven, Belgium, were included. Among these patients, 120 had been started on IT at the time of their initial visit, and 680 were prescribed guideline-based pharmacotherapy. In 2013, patients were sent a questionnaire asking for the current severity of nasal symptoms using a visual analogue scale (VAS) score, duration of nasal symptoms and presence or absence of abnormal sleep, impairment of daily activities, sport, leisure, impaired functioning at work/school, troublesome symptoms, and current medication use. A VAS score for total nasal symptoms (TNS) was used to distinguish between controlled and uncontrolled AR. An overall response rate of 54%. At 3 years after the initiation of the treatment, the IT group showed lower VAS scores for TNS than the pharmacotherapy group, with lower percentages of patients having a VAS score of equal or higher than 5. The IT group consisted of more patients with mild AR than the pharmacotherapy group despite the higher percentage of polysensitization at the onset of treatment in the IT group. 18% of the IT patients met the criteria of persistent AR whereas this was 51% amongst non-IT patients. Interestingly, 70% of IT patients did not use any medical treatment for AR anymore, whereas 61% of pharmacotherapy patients were still on medical treatment. This observational study demonstrates that IT is associated with higher control of AR, reduced symptom severity and reduced medication use at 3 years after the onset of treatment. Therefore, this real-life study reinforces the clinical value of immunotherapy in allergic rhinitis.

Telephone-Delivered Stepped Collaborative Care for Treating Anxiety in Primary Care: A Randomized Controlled Trial.

Collaborative care for depression is more effective in improving treatment outcomes than primary care physicians' (PCPs) usual care (UC). However, few trials of collaborative care have targeted anxiety. To examine the impact and 12-month durability of a centralized, telephone-delivered, stepped collaborative care intervention (CC) for treating anxiety disorders across a network of primary care practices. Randomized controlled trial with blinded outcome assessments. A total of 329 patients aged 18-64 referred by their PCPs in response to an electronic medical record (EMR) prompt. They include 250 highly anxious patients randomized to either CC or to UC, and 79 moderately anxious patients who were triaged to a watchful waiting (WW) cohort and later randomized if their conditions clinically deteriorated. Twelve months of telephone-delivered CC involving non-mental health professionals who provided patients with basic psycho-education, assessed preferences for guideline-based pharmacotherapy, monitored treatment responses, and informed PCPs of their patients' care preferences and progress via the EMR. Mental health-related quality of life ([HRQoL]; SF-36 MCS); secondary outcomes: anxiety (Hamilton Anxiety Rating Scale [SIGH-A], Panic Disorder Severity Scale) and mood (PHQ-9). At 12-month follow-up, highly anxious patients randomized to CC reported improved mental HRQoL (effect size [ES]: 0.38 [95% CI: 0.13-0.63]; P = 0.003), anxiety (SIGH-A ES: 0.30 [0.05-0.55]; P = 0.02), and mood (ES: 0.45 [0.19-0.71] P = 0.001) versus UC. These improvements were sustained for 12months among African-Americans (ES: 0.70-1.14) and men (ES: 0.43-0.93). Of the 79 WW patients, 29% met severity criteria for randomization, and regardless of treatment assignment, WW patients reported fewer anxiety and mood symptoms and better mental HRQoL over the full 24-month follow-up period than highly anxious patients who were randomized at baseline. Telephone-delivered, centralized, stepped CC improves mental HRQoL, anxiety and mood symptoms. These improvements were durable and particularly evident among those most anxious at baseline, and among African-Americans and men.

Rehabilitation in Heart Failure

Heart failure patients (HF-rEF, HF-pEF or in combination) represent a relevant proportion of patients in cardiological rehabilitation facilities. They require a multimodal therapy concept due to the impaired systolic and/or diastolic ventricular function, the risk of malignant arrhythmias and the cardiac implantable electrical devices (CIED). In addition to guideline-based pharmacotherapy, individualized training therapy and psychosocial support play a key role in the rehabilitation of heart failure patients. Professional reintegration is determined by hemodynamic stability, cognitive performance, job requirements and job security, especially for CIED carriers. The suitability for driving is mainly determined in individual decisions and depends, among other things, on the left ventricular ejection fraction, the hemodynamic stability and the arrhythmia-free interval.

Agitation in Nursing Home Residents With Dementia (VIDEANT Trial): Effects of a Cluster-Randomized, Controlled, Guideline Implementation Trial

To test the effect of a complex guideline-based intervention on agitation and psychotropic prescriptions. Cluster randomized controlled trial (VIDEANT) with blinded assessment of outcome in 18 nursing homes in Berlin, Germany, comprising 304 dementia patients. Training, support, and activity therapy intervention, delivered at the level of each nursing home, focusing on the management of agitation in dementia. Control group nursing homes received treatment as usual. Levels of agitated and disruptive behavior (Cohen-Mansfield agitation inventory [CMAI]) as the primary outcome. Number of neuroleptics, antidepressants, and cholinesterase inhibitors (ChEIs) prescribed in defined daily dosages (DDDs). Of 326 patients screened, 304 (93.3%) were eligible and cluster-randomized to 9 intervention (n= 163) and 9 control (n= 141) nursing homes. Data were collected from 287 (94.4%) patients at 10 months. At 10 months, compared with controls, nursing home residents with dementia in the intervention group exhibited significantly less agitation as measured with the CMAI (adjusted mean difference, 6.24; 95% CI 2.03-14.14; P= .009; Cohen's d= 0.43), received fewer neuroleptics (P < .05), more ChEIs (P < .05), and more antidepressants (P < .05). Complex guideline-based interventions are effective in reducing agitated and disruptive behavior in nursing home residents with dementia. At the same time, increased prescription of ChEIs and antidepressants together with decreased neuroleptic prescription suggests an effect toward guideline-based pharmacotherapy.

Who Receives Guideline-Based Pharmacotherapy for Bipolar Depression?

Who Receives Guideline-Based Pharmacotherapy for Bipolar Depression?

Adherence With Once Daily Versus Twice Daily Carvedilol in Patients With Heart Failure: The Compliance and Quality of Life Study Comparing Once-Daily Controlled-Release Carvedilol CR and Twice-Daily Immediate-Release Carvedilol IR in Patients With Heart Failure (CASPER) Trial

Background Suboptimal compliance in taking guideline-based pharmacotherapy in patients with chronic heart failure (HF) potentially increases the burden of hospitalizations and diminishes quality of life. By simplifying the medical regimen, once-daily dosing can potentially improve compliance. The Compliance And Quality of Life Study Comparing Once-Daily Controlled-Release Carvedilol CR and Twice-Daily Immediate-Release Carvedilol IR in Patients with Heart Failure (CASPER) Trial was designed to measure differential compliance, satisfaction, and quality of life in chronic HF patients taking carvedilol immediate release (IR) twice daily versus the bioequivalent carvedilol controlled-release (CR) once daily. Methods and Results CASPER was a prospective multicenter, 3-arm, parallel-group, randomized clinical trial for a 5-month period. The primary objective of the study was to evaluate and compare compliance with carvedilol IR twice daily (BID) and carvedilol phosphate CR once daily (QD) in patients with chronic HF who were taking carvedilol IR. Secondary objectives included comparisons of quality of life (Kansas City Cardiomyopathy Questionnaire), satisfaction with medication, and brain natriuretic peptide levels between subjects taking the two formulations. A total of 405 patients with chronic HF and left ventricular dysfunction were randomized to: (A) carvedilol IR twice daily, given double blind; (B) carvedilol CR taken in the morning and placebo in the afternoon, given double blind; or (C) carvedilol CR once daily, open label. Compliance was measured using the medication event monitoring system that captures time of bottle opening. The primary end point was a comparison of taking compliance (doses taken divided by total number of prescribed doses over the actual duration of the study) between the double-blind carvedilol IR BID versus the open-label carvedilol CR QD groups. Sample size estimates were based on assumptions of 75% compliance with BID dosing and 90% compliance with QD dosing. Mean compliance with carvedilol IR BID was 89.3% compared with 88.2% for carvedilol CR QD, and differential mean compliance was 1.1% (95% CI –4.4%, 6.6%; ie, not significant). There were no statistically significant differences in compliance between any of the 3 groups, nor differences in quality of life, treatment satisfaction, or physiologic measures among the 3 study arms. There were also no significant differences in adverse events or side effects among patients switching from carvedilol IR to carvedilol CR in arms B or C over the 5-month study duration compared with patients remaining on carvedilol IR. Conclusions Compliance among chronic HF patients in the CASPER trial was high at baseline and unaffected by QD versus BID dosing. Over the 5-month follow-up period, there were no differences in adverse events among patients switching from carvedilol IR to CR.

Implementing Cardiac Risk-Factor Case Management

Case-management (CM) can positively influence chronic disease care by facilitating guideline-concordant interventions that improve outcomes through intensive, individualized, longitudinal care. Implementation of CM, however, is difficult. We have identified lessons learned from a cardiovascular risk reduction CM program that may aid future CM implementation. Heart to Heart is both a clinical trial and program dissemination project implementing CM for persons at elevated risk of coronary heart disease (CHD) events in a multiethnic, low-income population in a county health system. Patients were randomized to CM plus usual primary care (N = 212) or primary care alone (N = 207). CM patients received face-to-face nurse and dietitian visits (mean of 14 hours) over 17 months. Visits emphasized behavior change, risk-factor monitoring, and guideline-based pharmacotherapy. A total of 341 patients (81%) were available for follow-up. This CM model is currently transitioning to a County-run program. Findings demonstrated statistically significant reductions in mean Framingham Risk for CM versus usual primary care (1.56% absolute decrease in 10-year CHD risk, P = 0.007). Favorable changes were noted across most major CHD risk factors. Lessons learned are the need for the following: (1) Strategies for implementing CM in low-income, ethnically-diverse populations, (2) Methods for developing clinically more effective CM, and (3) Approaches to increase the efficiency of cardiovascular CM. CM for cardiac risk factors faces notable implementation barriers, particularly in County health systems. Specific implementation solutions recommended may help confront these barriers and improve diffusion of this evidence-based and patient centered model of care.

Critical Factors in Case Management: Practical Lessons from a Cardiac Case Management Program

Case management (CM) is an important strategy for chronic disease care. By utilizing non-physician providers for conditions requiring ongoing care and follow-up, CM can facilitate guideline-concordant care, patient empowerment, and improvement in quality of life. We identify a series of critical factors required for successful CM implementation. Heart to Heart is a clinical trial evaluating CM for coronary heart disease (CHD) risk reduction in a multiethnic, low-income population. Patients at elevated cardiac risk were randomized to CM plus primary care (212 patients) or to primary care alone (207). Over a mean follow-up of 17 months, patients received face-to-face nurse and dietitian visits. Mean contact time was 14 hours provided at an estimated cost of $1250 per patient for the 341 (81%) patients completing follow-up. Visits emphasized behavior change, risk-factor monitoring, self-management skills, and guideline-based pharmacotherapy. A statistically significant reduction in mean Framingham risk probability occurred in CM plus primary care relative to primary care alone (1.6% decrease in 10-year CHD risk, p = 0.007). Favorable changes were noted across individual risk factors. Our findings suggest that successful CM implementation relies on choosing appropriate case managers and investing in training, integrating CM into existing care systems, delineating the scope and appropriate levels of clinical decision making, using information systems, and monitoring outcomes and costs. While our population, setting, and intervention model are unique, these insights are broadly relevant. If implemented with attention to critical factors, CM has great potential to improve the process and outcomes of chronic disease care.

`Treat to Remission' Is Message of STEP-BD Study

`Treat to Remission' Is Message of STEP-BD Study