Citations

Abstract Objectives We aimed to identify migraine treatment features preferred by patients and treatment outcomes most valued by patients. Background The values and preferences of people living with migraine are critical for both the choice of acute therapy and management approach of migraine. Methods We conducted a qualitative evidence synthesis. Two reviewers independently selected studies, appraised methodological quality, and undertook a framework synthesis. We developed summary of findings tables following the approach of Grading of Recommendations, Assessment, Development and Evaluations Confidence in the Evidence from Reviews of Qualitative Research to assess confidence in the findings. Results Of 1691 candidate references, we included 19 studies (21 publications) involving 459 patients. The studies mostly recruited White women from North America (11 studies) and Europe (8 studies). We identified eight themes encompassing features preferred by patients in a migraine treatment process. Themes described a treatment process that included shared decision‐making, a tailored approach, trust in health‐care professionals, sharing of knowledge and diversity of treatment options, a holistic approach that does not just address the headache, ease of communication especially for complex treatments, a non‐undermining approach, and reciprocity with mutual respect between patient and provider. In terms of the treatment itself, seven themes emerged including patients’ preferences for nonpharmacologic treatment, high effectiveness, rapidity of action, long‐lasting effect, lower cost and more accessibility, self‐management/self‐delivery option that increases autonomy, and a mixed preference for abortive versus prophylactic treatments. The treatment outcomes that have high value to patients included maintaining or improving function; avoiding side effects, potential for addiction to medications, and pain reoccurrence; and avoiding non‐headache symptoms such as nausea, vomiting, and sensitivity to light or sounds. Conclusion Patient values and preferences were individually constructed, varied widely, and could be at odds with conventional medical perspectives and evidence of treatment effects. Considering the availability of numerous treatments for acute migraine, it is necessary that decision‐making incorporates patient values and preferences identified in qualitative research. The findings of this qualitative synthesis can be used to facilitate an individually tailored approach, strengthen the patient–health‐care system relationship, and guide choices and decisions in the context of a clinical encounter or a clinical practice guideline.

Various pharmacotherapies exist for heart failure with preserved ejection fraction (HFpEF), but with unclear comparative efficacy. We searched EMBASE, Medline, and Cochrane Library from inception through August 2021 for all randomized clinical trials in HFpEF (EF >40%) that evaluated beta-blockers, mineralocorticoid receptor antagonist (MRA), angiotensin-converting enzyme inhibitors (ACE), angiotensin receptor blockers (ARB), angiotensin receptor-neprilysin inhibitor (ARNI), and sodium-glucose cotransporter-2 inhibitors (SGLT2i). Outcomes assessed were cardiovascular mortality, all-cause mortality, and HF hospitalization. A frequentist network meta-analysis was performed with a random-effects model. We included 22 randomized clinical trials (30,673 participants; mean age = 71.7 ± 4.2 years; females = 49.3 ± 7.7%; median follow-up = 24.4 ± 11.1 months). Compared with placebo, there was no statistically significant difference in cardiovascular mortality [beta-blockers; odds ratio (OR) 0.79 (0.46–1.34), MRA; OR 0.90 (0.70–1.14), ACE OR 0.95 (0.59–1.53), ARB; OR 1.02 (0.87–1.19), ARNI; OR 0.97 (0.74–1.26) and SGLT2i; OR 1.00 (0.84–1.18)] or all-cause mortality [beta blockers; OR 0.75 (0.54–1.04), MRA; OR 0.90 (0.75–1.08) ACE; OR 1.05 (0.71–1.54), ARB; OR 1.03 (0.91–1.15), ARNI; OR 0.99 (0.82–1.20) and SGLT2i; OR 1.00 (0.89–1.13)]. The certainty in these estimates was low or very low. There was a significantly reduction in HF hospitalization with the use of SGLT2i [OR 0.71 (0.62–0.82), moderate certainty], ARNI [OR 0.77 (0.63–0.94), low certainty], and MRA [OR 0.81 (0.66–0.98), moderate certainty]; with corresponding P scores of 0.84, 0.68, and 0.58, respectively. In HFpEF, the use of beta-blockers, MRA, ACE/ARB/ARNI, or SGLT2i was not associated with improved cardiovascular or all-cause mortality. SGLT2i, ARNI, and MRA reduced the risk of HF hospitalizations.

AbstractBackgroundIntegrating shared decision making between patients and physicians and incorporating their values and preferences in the development of clinical practice guidelines (CPGs) is of critical importance to optimize CPG implementation and treatment adherence. This applies to many debilitating diseases, including hypercalcemia of malignancy (HCM).ObjectiveEvaluate patient and physician values, preferences, and attitudes to better inform CPGs to treat HCM in adults.MethodsWe followed a mixed-methods approach. We conducted a systematic review using 5 databases to identify studies reporting on patient and physician values, costs and resources, feasibility, acceptability, and equity regarding HCM treatment. We also gathered data from different countries on the cost of multiple treatment modalities. We collected data on outcome prioritization from the CPG Working Group. Similarly, we collected data from patients with HCM regarding outcome prioritization and administered a questionnaire to evaluate their attitudes and perceptions toward treatment as well as treatment acceptability and feasibility.ResultsIn the systematic review, we included 2 cross-sectional surveys conducted on the same population of physicians who agreed that treating HCM alleviates symptoms and improves quality of life; however, harms and benefits should be thoroughly considered when deciding on the duration of treatment. We also included 2 studies on cost showing that intravenous (IV) bisphosphonate is more cost-effective than a combination of IV bisphosphonate and calcitonin and administration of IV zoledronic acid at home is more cost-effective than other IV bisphosphonates. The cost of zoledronic acid, denosumab, and cinacalcet varied widely among countries and types (brand vs generic). Both the CPG Working Group and patients with HCM agreed that the most important outcomes when deciding on treatment were survival and resolution of HCM, but there was some variability in the ratings for other outcomes.ConclusionUsing mixed methods, CPG developers can obtain meaningful information regarding evidence to decision criteria. In the case of HCM CPGs, this approach has provided the required contextual information and supported the development of evidence-based recommendations.

AbstractContextHypercalcemia is a common complication of malignancy that is associated with high morbidity and mortality.ObjectiveTo support development of the Endocrine Society Clinical Practice Guideline for the treatment of hypercalcemia of malignancy in adults.MethodsWe searched multiple databases for studies that addressed 8 clinical questions prioritized by a guideline panel from the Endocrine Society. Quantitative and qualitative synthesis was performed. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess certainty of evidence.ResultsWe reviewed 1949 citations, from which we included 21 studies. The risk of bias for most of the included studies was moderate. A higher proportion of patients who received bisphosphonate achieved resolution of hypercalcemia when compared to placebo. The incidence rate of adverse events was significantly higher in the bisphosphonate group. Comparing denosumab to bisphosphonate, there was no significant difference in the rate of patients who achieved resolution of hypercalcemia. Two-thirds of patients with refractory/recurrent hypercalcemia of malignancy who received denosumab following bisphosphonate therapy achieved resolution of hypercalcemia. Addition of calcitonin to bisphosphonate therapy did not affect the resolution of hypercalcemia, time to normocalcemia, or hypocalcemia. Only indirect evidence was available to address questions on the management of hypercalcemia in tumors associated with high calcitriol levels, refractory/recurrent hypercalcemia of malignancy following the use of bisphosphonates, and the use of calcimimetics in the treatment of hypercalcemia associated with parathyroid carcinoma. The certainty of the evidence to address all 8 clinical questions was low to very low.ConclusionThe evidence summarized in this systematic review addresses the benefits and harms of treatments of hypercalcemia of malignancy. Additional information about patients’ values and preferences, and other important decisional and contextual factors is needed to facilitate the development of clinical recommendations.

Abstract Background Hypercalcemia of malignancy (HCM) is the most common metabolic complication of malignancies, but its incidence may be declining due to potent chemotherapeutic agents. The high mortality associated with HCM has declined markedly due to the introduction of increasingly effective chemotherapeutic drugs. Despite the widespread availability of efficacious medications to treat HCM, evidence-based recommendations to manage this debilitating condition are lacking. Objective To develop guidelines for the treatment of adults with HCM. Methods A multidisciplinary panel of clinical experts, together with experts in systematic literature review, identified and prioritized 8 clinical questions related to the treatment of HCM in adult patients. The systematic reviews (SRs) queried electronic databases for studies relevant to the selected questions. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make recommendations. An independent SR was conducted in parallel to assess patients' and physicians' values and preferences, costs, resources needed, acceptability, feasibility, equity, and other domains relevant to the Evidence-to-Decision framework as well as to enable judgements and recommendations. Results The panel recommends (strong recommendation) in adults with HCM treatment with denosumab (Dmab) or an intravenous (IV) bisphosphonate (BP). The following recommendations were based on low certainty of the evidence. The panel suggests (conditional recommendation) (1) in adults with HCM, the use of Dmab rather than an IV BP; (2) in adults with severe HCM, a combination of calcitonin and an IV BP or Dmab therapy as initial treatment; and (3) in adults with refractory/recurrent HCM despite treatment with BP, the use of Dmab. The panel suggests (conditional recommendation) the addition of an IV BP or Dmab in adult patients with hypercalcemia due to tumors associated with high calcitriol levels who are already receiving glucocorticoid therapy but continue to have severe or symptomatic HCM. The panel suggests (conditional recommendation) in adult patients with hypercalcemia due to parathyroid carcinoma, treatment with either a calcimimetic or an antiresorptive (IV BP or Dmab). The panel judges the treatments as probably accessible and feasible for most recommendations but noted variability in costs, resources required, and their impact on equity. Conclusions The panel's recommendations are based on currently available evidence considering the most important outcomes in HCM to patients and key stakeholders. Treatment of the primary malignancy is instrumental for controlling hypercalcemia and preventing its recurrence. The recommendations provide a framework for the medical management of adults with HCM and incorporate important decisional and contextual factors. The guidelines underscore current knowledge gaps that can be used to establish future research agendas.

Abstract Context Interventions targeting hypoglycemia in people with diabetes are important for improving quality of life and reducing morbidity and mortality. Objective To support development of the Endocrine Society Clinical Practice Guideline for management of individuals with diabetes at high risk for hypoglycemia. Methods We searched several databases for studies addressing 10 questions provided by a guideline panel from the Endocrine Society. Meta-analysis was conducted when feasible. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess certainty of evidence. Results We included 149 studies reporting on 43 344 patients. Continuous glucose monitoring (CGM) reduced episodes of severe hypoglycemia in patients with type 1 diabetes (T1D) and reduced the proportion of patients with hypoglycemia (blood glucose [BG] levels <54 mg/dL). There were no data on use of real-time CGM with algorithm-driven insulin pumps vs multiple daily injections with BG testing in people with T1D. CGM in outpatients with type 2 diabetes taking insulin and/or sulfonylureas reduced time spent with BG levels under 70 mg/dL. Initiation of CGM in hospitalized patients at high risk for hypoglycemia reduced episodes of hypoglycemia with BG levels lower than 54 mg/dL and time spent under 54 mg/dL. The proportion of patients with hypoglycemia with BG levels lower than 70 mg/dL and lower than 54 mg/dL detected by CGM was significantly higher than point-of-care BG testing. We found no data evaluating continuation of personal CGM in the hospital. Use of an inpatient computerized glycemic management program utilizing electronic health record data was associated with fewer patients with and episodes of hypoglycemia with BG levels lower than 70 mg/dL and fewer patients with severe hypoglycemia compared with standard care. Long-acting basal insulin analogs were associated with less hypoglycemia. Rapid-acting insulin analogs were associated with reduced severe hypoglycemia, though there were more patients with mild to moderate hypoglycemia. Structured diabetes education programs reduced episodes of severe hypoglycemia and time below 54 mg/dL in outpatients taking insulin. Glucagon formulations not requiring reconstitution were associated with longer times to recovery from hypoglycemia, although the proportion of patients who recovered completely from hypoglycemia was not different between the 2 groups. Conclusion This systematic review summarized the best available evidence about several interventions addressing hypoglycemia in people with diabetes. This evidence base will facilitate development of clinical practice guidelines by the Endocrine Society.

Abstract Context Hypoglycemia in people with diabetes is common, especially in those taking medications such as insulin and sulfonylureas (SU) that place them at higher risk. Hypoglycemia is associated with distress in those with diabetes and their families, medication nonadherence, and disruption of life and work, and it leads to costly emergency department visits and hospitalizations, morbidity, and mortality. Objective To review and update the diabetes-specific parts of the 2009 Evaluation and Management of Adult Hypoglycemic Disorders: Endocrine Society Clinical Practice Guideline and to address developing issues surrounding hypoglycemia in both adults and children living with diabetes. The overriding objectives are to reduce and prevent hypoglycemia. Methods A multidisciplinary panel of clinician experts, together with a patient representative, and methodologists with expertise in evidence synthesis and guideline development, identified and prioritized 10 clinical questions related to hypoglycemia in people living with diabetes. Systematic reviews were conducted to address all the questions. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make recommendations. Results The panel agreed on 10 questions specific to hypoglycemia risk and prevention in people with diabetes for which 10 recommendations were made. The guideline includes conditional recommendations for use of real-time continuous glucose monitoring (CGM) and algorithm-driven insulin pumps in people with type 1 diabetes (T1D), use of CGM for outpatients with type 2 diabetes at high risk for hypoglycemia, use of long-acting and rapid-acting insulin analogs, and initiation of and continuation of CGM for select inpatient populations at high risk for hypoglycemia. Strong recommendations were made for structured diabetes education programs for those at high risk for hypoglycemia, use of glucagon preparations that do not require reconstitution vs those that do for managing severe outpatient hypoglycemia for adults and children, use of real-time CGM for individuals with T1D receiving multiple daily injections, and the use of inpatient glycemic management programs leveraging electronic health record data to reduce the risk of hypoglycemia. Conclusion The recommendations are based on the consideration of critical outcomes as well as implementation factors such as feasibility and values and preferences of people with diabetes. These recommendations can be used to inform clinical practice and health care system improvement for this important complication for people living with diabetes.

AbstractBackgroundHistory and physical examination are key features to narrow the differential diagnosis of central versus peripheral causes in patients presenting with acute vertigo. We conducted a systematic review and meta‐analysis of the diagnostic test accuracy of physical examination findings.MethodsThis study involved a patient–intervention–control–outcome (PICO) question: (P) adult ED patients with vertigo/dizziness; (I) presence/absence of specific physical examination findings; and (O) central (ischemic stroke, hemorrhage, others) versus peripheral etiology. Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) was assessed.ResultsFrom 6309 titles, 460 articles were retrieved, and 43 met the inclusion criteria: general neurologic examination—five studies, 869 patients, pooled sensitivity 46.8% (95% confidence interval [CI] 32.3%–61.9%, moderate certainty) and specificity 92.8% (95% CI 75.7%–98.1%, low certainty); limb weakness/hemiparesis—four studies, 893 patients, sensitivity 11.4% (95% CI 5.1%–23.6%, high) and specificity 98.5% (95% CI 97.1%–99.2%, high); truncal/gait ataxia—10 studies, 1810 patients (increasing severity of truncal ataxia had an increasing sensitivity for central etiology, sensitivity 69.7% [43.3%–87.9%, low] and specificity 83.7% [95% CI 52.1%–96.0%, low]); dysmetria signs—four studies, 1135 patients, sensitivity 24.6% (95% CI 15.6%–36.5%, high) and specificity 97.8% (94.4%–99.2%, high); head impulse test (HIT)—17 studies, 1366 patients, sensitivity 76.8% (64.4%–85.8%, low) and specificity 89.1% (95% CI 75.8%–95.6%, moderate); spontaneous nystagmus—six studies, 621 patients, sensitivity 52.3% (29.8%–74.0%, moderate) and specificity 42.0% (95% CI 15.5%–74.1%, moderate); nystagmus type—16 studies, 1366 patients (bidirectional, vertical, direction changing, or pure torsional nystagmus are consistent with a central cause of vertigo, sensitivity 50.7% [95% CI 41.1%–60.2%, moderate] and specificity 98.5% [95% CI 91.7%–99.7%, moderate]); test of skew—15 studies, 1150 patients (skew deviation is abnormal and consistent with central etiology, sensitivity was 23.7% [95% CI 15%–35.4%, moderate] and specificity 97.6% [95% CI 96%–98.6%, moderate]); HINTS (head impulse, nystagmus, test of skew)—14 studies, 1781 patients, sensitivity 92.9% (95% CI 79.1%–97.9%, high) and specificity 83.4% (95% CI 69.6%–91.7%, moderate); and HINTS+ (HINTS with hearing component)—five studies, 342 patients, sensitivity 99.0% (95% CI 73.6%–100%, high) and specificity 84.8% (95% CI 70.1%–93.0%, high).ConclusionsMost neurologic examination findings have low sensitivity and high specificity for a central cause in patients with acute vertigo or dizziness. In acute vestibular syndrome (monophasic, continuous, persistent dizziness), HINTS and HINTS+ have high sensitivity when performed by trained clinicians.