Michael R. Gionfriddo

The efficacy of resiliency training programs: a systematic review and meta-analysis of randomized trials.

Importance Poor mental health places a burden on individuals and populations. Resilient persons are able to adapt to life’s challenges and maintain high quality of life and function. Finding effective strategies to bolster resilience in individuals and populations is of interest to many stakeholders. Objectives To synthesize the evidence for resiliency training programs in improving mental health and capacity in 1) diverse adult populations and 2) persons with chronic diseases. Data Sources Electronic databases, clinical trial registries, and bibliographies. We also contacted study authors and field experts. Study Selection Randomized trials assessing the efficacy of any program intended to enhance resilience in adults and published after 1990. No restrictions were made based on outcome measured or comparator used. Data Extraction and Synthesis Reviewers worked independently and in duplicate to extract study characteristics and data. These were confirmed with authors. We conducted a random effects meta-analysis on available data and tested for interaction in planned subgroups. Main Outcomes The standardized mean difference (SMD) effect of resiliency training programs on 1) resilience/hardiness, 2) quality of life/well-being, 3) self-efficacy/activation, 4) depression, 5) stress, and 6) anxiety. Results We found 25 small trials at moderate to high risk of bias. Interventions varied in format and theoretical approach. Random effects meta-analysis showed a moderate effect of generalized stress-directed programs on enhancing resilience [pooled SMD 0.37 (95% CI 0.18, 0.57) p = .0002; I2 = 41%] within 3 months of follow up. Improvement in other outcomes was favorable to the interventions and reached statistical significance after removing two studies at high risk of bias. Trauma-induced stress-directed programs significantly improved stress [−0.53 (−1.04, −0.03) p = .03; I2 = 73%] and depression [−0.51 (−0.92, −0.10) p = .04; I2 = 61%]. Conclusions We found evidence warranting low confidence that resiliency training programs have a small to moderate effect at improving resilience and other mental health outcomes. Further study is needed to better define the resilience construct and to design interventions specific to it. Registration Number PROSPERO #CRD42014007185

Minimally Disruptive Medicine: A Pragmatically Comprehensive Model for Delivering Care to Patients with Multiple Chronic Conditions

An increasing proportion of healthcare resources in the United States are directed toward an expanding group of complex and multimorbid patients. Federal stakeholders have called for new models of care to meet the needs of these patients. Minimally Disruptive Medicine (MDM) is a theory-based, patient-centered, and context-sensitive approach to care that focuses on achieving patient goals for life and health while imposing the smallest possible treatment burden on patients’ lives. The MDM Care Model is designed to be pragmatically comprehensive, meaning that it aims to address any and all factors that impact the implementation and effectiveness of care for patients with multiple chronic conditions. It comprises core activities that map to an underlying and testable theoretical framework. This encourages refinement and future study. Here, we present the conceptual rationale for and a practical approach to minimally disruptive care for patients with multiple chronic conditions. We introduce some of the specific tools and strategies that can be used to identify the right care for these patients and to put it into practice.

World Health Organization strong recommendations based on low-quality evidence (study quality) are frequent and often inconsistent with GRADE guidance

OBJECTIVES In 2007 the World Health Organization (WHO) adopted the GRADE system for development of public health guidelines. Previously we found that many strong recommendations issued by WHO are based on evidence for which there is only low or very low confidence in the estimates of effect (discordant recommendations). GRADE guidance indicates that such discordant recommendations are rarely appropriate but suggests five paradigmatic situations in which discordant recommendations may be warranted. We sought to provide insight into the many discordant recommendations in WHO guidelines. STUDY DESIGN AND SETTING We examined all guidelines that used the GRADE method and were approved by the WHO Guideline Review Committee between 2007 and 2012. Teams of reviewers independently abstracted data from eligible guidelines and classified recommendations either into one of the five paradigms for appropriately-formulated discordant recommendations or into three additional categories in which discordant recommendations were inconsistent with GRADE guidance: 1) the evidence warranted moderate or high confidence (a misclassification of evidence) rather than low or very low confidence; 2) good practice statements; or 3) uncertainty in the estimates of effect would best lead to a conditional (weak) recommendation. RESULTS The 33 eligible guidelines included 160 discordant recommendations, of which 98 (61.3%) addressed drug interventions and 132 (82.5%) provided some rationale (though not entirely explicit at times) for the strong recommendation. Of 160 discordant recommendations, 25 (15.6%) were judged consistent with one of the five paradigms for appropriate recommendations; 33 (21%) were based on evidence warranting moderate or high confidence in the estimates of effect; 29 (18%) were good practice statements; and 73 (46%) warranted a conditional, rather than a strong recommendation. CONCLUSION WHO discordant recommendations are often inconsistent with GRADE guidance, possibly threatening the integrity of the process. Further training in GRADE methods for WHO guideline development group members may be necessary, along with further research on what motivates the formulation of such recommendations.

Testing for germline mutations in sporadic pheochromocytoma/paraganglioma: a systematic review

The presence of germline mutations in sporadic pheochromocytomas and paragangliomas (SPPs) may change the clinical management of both index patients and their family members. However, the frequency of germline mutations in SPPs is unknown.

The psychometric properties of Observer OPTION5, an observer measure of shared decision making

OBJECTIVES Observer OPTION(5) was designed as a more efficient version of OPTION(12), the most commonly used measure of shared decision making (SDM). The current paper assesses the psychometric properties of OPTION(5). METHODS Two raters used OPTION(5) to rate recordings of clinical encounters from two previous patient decision aid (PDA) trials (n=201; n=110). A subsample was re-rated two weeks later. We assessed discriminative validity, inter-rater reliability, intra-rater reliability, and concurrent validity. RESULTS OPTION(5) demonstrated discriminative validity, with increases in SDM between usual care and PDA arms. OPTION(5) also demonstrated concurrent validity with OPTION(12), r=0.61 (95%CI 0.54, 0.68) and intra-rater reliability, r=0.93 (0.83, 0.97). The mean difference in rater score was 8.89 (95% Credibility Interval, 7.5, 10.3), with intraclass correlation (ICC) of 0.67 (95% Credibility Interval, 0.51, 0.91) for the accuracy of rater scores and 0.70 (95% Credibility Interval, 0.56, 0.94) for the consistency of rater scores across encounters, indicating good inter-rater reliability. Raters reported lower cognitive burden when using OPTION(5) compared to OPTION(12). CONCLUSIONS OPTION(5) is a brief, theoretically grounded observer measure of SDM with promising psychometric properties in this sample and low burden on raters. PRACTICE IMPLICATIONS OPTION(5) has potential to provide reliable, valid assessment of SDM in clinical encounters.

The efficacy of resilience training programs: a systematic review protocol

BackgroundResilience has been defined as the ability of individuals to manage and adapt to stress and life challenges. Training programs that develop and/or enhance resilience may have efficacy in improving health, well-being, and quality of life. Because patients with chronic conditions must reliably self-manage their health, strategies to bolster resilience in this population may be of particular value. The objectives of this systematic review are to synthesize the evidence of resilience training program efficacy in improving outcomes related to quality of life, self-efficacy and activation, and resilience and coping ability in: 1) diverse adult populations; and 2) patients with chronic conditions.Methods/DesignWe will conduct a systematic review of randomized controlled trials assessing the efficacy of any program designed to enhance resilience in adults that measure any outcome against any comparator. We will search multiple electronic databases, trial registries, bibliographies, and will contact authors and experts to identify studies. We will use systematic review software to independently and in duplicate screen reports and extract data. We will extract characteristics of the study populations, interventions, comparators, outcomes, and quality/risk of bias. Primary, patient reported outcomes will be categorized into domains of quality of life, self-efficacy, and resilience. Secondary outcomes will be considered based on findings of the review. We will attempt meta-analysis by pooling standardized mean differences and minimally important differences (MIDs), when possible. Planned trial subgroup analyses are: 1) studies of patients with chronic conditions; 2) studies with placebo controls; 3) studies with similar intervention characteristics; and 4) studies with common lengths of follow-up.DiscussionThis study is intended to accumulate the evidence for resilience training programs in improving quality of life, resilience, and self-efficacy for care management, particularly among adult patients with chronic conditions. Its findings will be valuable to policy-makers, funding agencies, clinicians, and patients seeking innovative and effective ways to achieve patient-centered care.Trial registrationPROSPERO registration number: CRD42014007185.

Patient capacity and constraints in the experience of chronic disease: A qualitative systematic review and thematic synthesis

BackgroundLife and healthcare demand work from patients, more so from patients living with multimorbidity. Patients must respond by mobilizing available abilities and resources, their so-called capacity. We sought to summarize accounts of challenges that reduce patient capacity to access or use healthcare or to enact self-care while carrying out their lives.MethodsWe conducted a systematic review and synthesis of the qualitative literature published since 2000 identifying from MEDLINE, EMBASE, Psychinfo, and CINAHL and retrieving selected abstracts for full text assessment for inclusion. After assessing their methodological rigor, we coded their results using a thematic synthesis approach.ResultsThe 110 reports selected, when synthesized, showed that patient capacity is an accomplishment of interaction with (1) the process of rewriting their biographies and making meaningful lives in the face of chronic condition(s); (2) the mobilization of resources; (3) healthcare and self-care tasks, particularly, the cognitive, emotional, and experiential results of accomplishing these tasks despite competing priorities; (4) their social networks; and (5) their environment, particularly when they encountered kindness or empathy about their condition and a feasible treatment plan.ConclusionPatient capacity is a complex and dynamic construct that exceeds “resources” alone. Additional work needs to translate this emerging theory into useful practice for which we propose a clinical mnemonic (BREWS) and the ICAN Discussion Aid.

A number of factors explain why WHO guideline developers make strong recommendations inconsistent with GRADE guidance

OBJECTIVE Many strong recommendations issued by the World Health Organization (WHO) are based on low- or very low-quality (low certainty) evidence (discordant recommendations). Many such discordant recommendations are inconsistent with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance. We sought to understand why WHO makes discordant recommendations inconsistent with GRADE guidance. STUDY DESIGN AND SETTING We interviewed panel members involved in guidelines approved by WHO (2007-2012) that included discordant recommendations. Interviews, recorded and transcribed, focused on use of GRADE including the reasoning underlying, and factors contributing to, discordant recommendations. RESULTS Four themes emerged: strengths of GRADE, challenges and barriers to GRADE, strategies to improve GRADE application, and explanations for discordant recommendations. Reasons for discordant recommendations included skepticism about the value of making conditional recommendations; political considerations; high certainty in benefits (sometimes warranted, sometimes not) despite assessing evidence as low certainty; and concerns that conditional recommendations will be ignored. CONCLUSION WHO panelists make discordant recommendations inconsistent with GRADE guidance for reasons that include limitations in their understanding of GRADE. Ensuring optimal application of GRADE at WHO and elsewhere likely requires selecting panelists who have a commitment to GRADE principles, additional training of panelists, and formal processes to maximize adherence to GRADE principles.

Organic Anion Transporter 3 Interacts Selectively with Lipophilic β-Lactam Antibiotics

Transporters are major determinants of the disposition of xenobiotics and endogenous chemicals in the body. Organic anion transporter 3 (Oat3) functions in the kidney and brain to remove metabolic waste, toxins, and drugs, and thus transports diverse chemicals. Some β-lactam antibiotics interact with Oat3, and penicillin G exhibits a strong dependence on Oat3 for renal elimination. However, over 80 β-lactams exist, and many have not been assessed for an interaction with Oat3. Moreover, β-lactams continue to receive U.S. Food and Drug Administration approval. This study identified new β-lactam–Oat3 interactions, provided a head-to-head comparison with Oat1, and characterized the physicochemical determinants of affinity for Oat3. Cells expressing mouse Oat3 (mOat3) and Oat1 (mOat1), and human OAT3 (hOAT3) were used to test inhibitors, and high-performance liquid chromatography (HPLC) was used to measure transport. Of 26 β-lactams tested, 12 were clear inhibitors of Oat3, and 14 exhibited poor interactions. Inhibitors exhibited a nearly identical rank-order of potency against mOat3 and hOAT3. Oat1 demonstrated a poor interaction with most β-lactams. The majority of Oat3 inhibitors were substrates, and there were clear physicochemical differences between inhibitors and noninhibitors. That is, inhibitors had nearly 40% fewer hydrogen bond donors (P < 0.001), a lower total polar surface area (P < 0.05), and greater lipophilicity (LogP of inhibitors, +1.41; noninhibitors, −1.54; P < 0.001). Pharmacophore mapping revealed a prohibitive hydrogen bond donor group in noninhibitors adjacent to a hydrophobic moiety that was important for binding to Oat3. These findings indicate that Oat3 recognizes lipophilic β-lactams more readily. Moreover, this study has potential implications for designing β-lactams to avoid renal accumulation or brain efflux via Oat3.

Shared decision-making in the care of individuals with diabetes

People with diabetes often live with other chronic conditions and lead complicated lives. Determining what is the best management decision for a patient requires consideration of each individuals personal, social and biomedical context, what he or she values, the reasons he or she has to value the available options, and the relative contribution of each option in terms of benefits, harms, costs and inconveniences. Empathic conversations between patients and clinicians to diagnose the patient situation that necessitates action and the range of evidence‐based actions that best address the situation, so‐called shared decision‐making, are essential to the personalized care of people with diabetes. The aim of the present review was to present key elements of shared decision‐making and propose three different approaches for its application. The first approach focuses on transferring information to patients so that they can make decisions. The second approach, choice, focuses on cultivating the individuals ability to give voice to which choice is best for them. The third approach, conversation, establishes an empathic conversational environment through which the individual with diabetes and their clinician think and talk through how to address the problems of living with diabetes and related illnesses. These approaches are manifest in the design of evidence‐based decision aids created to support shared decision‐making. In randomized trials, decision aids can efficiently improve patients knowledge, satisfaction, risk awareness, decisional conflict and involvement. Further research, however, is needed to better understand when and how to promote the empathic conversations, patient, clinician and service and policy contexts necessary to routinely implement shared decision‐making in different at scale healthcare systems. In the interim, sufficient evidence and tools exist for persons with diabetes and their clinicians to gain expertise in making decisions together.