Patient and physician perspectives and experiences of basal insulin titration in type 2 diabetes in the United States: Cross-sectional surveys.

AIM: Patient- and physician-associated barriers impact the effectiveness of basal insulin (BI) titration in the management of type 2 diabetes (T2D). We evaluated the experiences of patients with T2D and physicians with BI titration education. MATERIALS AND METHODS: In this observational, cross-sectional study, patients with T2D and physicians treating patients with T2D were identified by claims in the Optum Research Database and were invited to complete a survey. Eligible patients had 12 months of continuous health-plan enrolment with medical and pharmacy benefits during the baseline period, and recent initiation of BI therapy. Eligible physicians had initiated BI for ≥1 eligible patient with T2D during the past 6 months. RESULTS: In total, 416 patients and 386 physicians completed the survey. Ninety per cent of physicians reported treating ≥50 patients with T2D; 66% treated ≥25% of patients with BI. Whereas 74% of patients reported that BI titration was explained to them by a physician, 96% of physicians reported doing so. Furthermore, 20% of patients stated they were offered educational materials whereas 56% of physicians reported having provided materials. Physicians had higher expectations of glycaemic target achievement than were seen in the patient survey; their main concern was the patients' ability to titrate accurately (79%). CONCLUSIONS: There is a marked difference in patients' and physicians' experiences of BI titration education. Novel tools and strategies are required to enable effective BI titration, with more educational resources at the outset, and ongoing access to tools that provide clear, simple direction for self-titration with less reliance on physicians/health care providers.

Validation of an Algorithm to Identify Venous Thromboembolism in Health Insurance Claims Data Among Patients with Rheumatoid Arthritis.

Purpose: Health insurance claims databases provide an opportunity to study uncommon events, such as venous thromboembolism (VTE), in large patient populations. This study evaluated case definitions for identifying VTE among patients treated for rheumatoid arthritis (RA) using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes in claims data. Patients and Methods: Study participants were insured adults who received treatment for and had a diagnosis of RA between 2016 and 2020. After a 6-month covariate assessment window, patients were observed for ≥1 month until health plan disenrollment, occurrence of a presumptive VTE, or end of the study (12/31/2020). Presumptive VTEs were identified using predefined algorithms based on ICD-10-CM diagnosis codes, anticoagulant use, and care setting. Medical charts were abstracted to confirm the VTE diagnosis. Performance of primary and secondary (less stringent) algorithms was assessed by calculating the positive predictive value (PPV; primary and secondary objectives). Additionally, a linked electronic health record (EHR) claims database and abstracted provider notes were used as a novel alternative source to validate claims-based outcome definitions (exploratory objective). Results: A total of 155 charts identified with the primary VTE algorithm were abstracted. The majority of patients were female (73.5%), with mean (standard deviation) age 66.4 (10.7) years and Medicare insurance (80.6%). Obesity (46.8%), ever smoking (55.8%), and prior evidence of VTE (28.4%) were commonly reported in medical charts. The PPV for the primary VTE algorithm was 75.5% (117/155; 95% confidence interval [CI], 68.7%, 82.3%). A less stringent secondary algorithm had a PPV of 52.6% (40/76; 95% CI, 41.4%, 63.9%). Using an alternative EHR-linked claims database, the primary VTE algorithm PPV was lower, potentially due to the unavailability of relevant records for validation. Conclusion: Administrative claims data can be used to identify VTE among patients with RA in observational studies.

Thrombopoietin receptor agonist discontinuation rates and reasons among patients with immune thrombocytopenia: a study of administrative claims linked with medical chart review.

Administrative claims provide a rich data source for retrospective studies of real-world clinical practice, yet some important data may be inconsistent or unavailable. This study explored factors influencing discontinuation of thrombopoietin receptor agonists (TPO-RAs) among patients with immune thrombocytopenia (ITP), by adding medical chart abstraction for additional details. Adult (≥ 18 years) patients with continuous commercial or Medicare Advantage with Part D health insurance coverage were included. Inclusion criteria were ≥ 1 claim for eltrombopag or romiplostim and ≥ 2 diagnoses of ITP between December 31, 2017, and January 1, 2020. Providers were asked to provide access to medical charts for abstraction. The analyses included only patients who discontinued TPO-RA and described patient characteristics, treatment patterns, platelet values, and reasons for discontinuation. Among 207 ITP patients treated with a TPO-RA, 137 (66%) discontinued treatment during the observation period. The mean TPO-RA treatment duration was 185 days. Mean platelet count at the time of discontinuation was 197 × 109/L. The most common reason for discontinuation was improvement of the patient's condition (42%). Other reasons included worsening of ITP/lack of response (12%), adverse events (12%), and cost-related or social reasons (23%). No reason was reported for 10%. Notably 26% of patients who discontinued remained off all ITP therapy for the remainder of the study, with a mean treatment-free period of 262 days. These results emphasize that some patients with ITP are able to discontinue TPO-RA therapy and achieve durable treatment-free periods.

Adherence and usage patterns of inhaled corticosteroids-long-acting beta-agonists by using inhaler-monitoring technology.

Background: Results of previous research indicate that adherence to prescribed inhaled corticosteroid-long-acting beta2-agonist (ICS-LABA) asthma controller medications is suboptimal, yet actual daily-use patterns are unclear and may be influenced by regimen complexity or dosing frequency. Objective: To investigate real-world use of asthma medications by using inhaler sensors for the ICS-LABA controllers: twice-daily fluticasone propionate (FP) plus salmeterol (SAL) and once-daily fluticasone furoate (FF) plus vilanterol (VI); and albuterol rescue medication. Methods: This longitudinal, two-phase, observational study included adults with asthma-prescribed FP-SAL (phase I) or FF-VI (phase II), and albuterol metered-dose inhalers. The participants completed baseline and follow-up surveys, and used clip-on inhaler sensors to monitor real-time inhaler use over the 6-month study period. Pharmacy claims data for the 6-month follow-up period were used to assess refills of ICS-LABA and albuterol inhalers. Results: Patients who used twice-daily FP-SAL received a sufficient dose (≥2 actuations/day) approximately one third of the time, those on once-daily FF-VI received a sufficient dose (≥1 actuation/day) ∼60% of the time. Patients who used once-daily FF-VI were more likely to take their medication as prescribed versus those who used twice-daily FP-SAL. There were no significant differences in the percentage of albuterol-free days (FP-SAL, 68.06% [n = 241]; FF-VI, 72.67% [n = 127]; p = 0.230). Exploratory outcomes are reported in this article's Online Supplemental Material. Claims-based measures of adherence were higher than sensor-based measures, hence claims data may have overestimated adherence, whereas sensors may have more accurately measured patients' medication use. Conclusion: These data supported the use of inhaler sensors as tools to directly and accurately measure ICS-LABA adherence and rescue medication use, and the adherence benefits of once-daily versus twice-daily ICS-LABA regimens.

Characterizing female patients with haemophilia A: Administrative claims analysis and medical chart review.

AIM: Haemophilia A (HA) is a male-predominant disorder, yet women and girls can have factor VIII (FVIII) deficiency with bleeding events requiring treatment. This study aimed to identify and characterize female patients with HA. METHODS: Administrative claims dated 01 January 2012-31 July 2016 were accessed for patients with 18 months' coverage by commercial or Medicare Advantage with Part D insurance. Patients were included by HA diagnoses or treatments and/or bleeding-related diagnoses or procedures, and excluded by haemophilia B or qualitative platelet disorder diagnoses. A sample of charts was examined for bleeding history, HA therapies and bleeding treatments. All-cause healthcare utilization and costs were also described. RESULTS: Among 353 patients meeting initial inclusion criteria, 86 charts were procured, with 8 patients identified as having HA. Their mean age was 60 ± 17 years and most were Medicare-insured. The mean Charlson Comorbidity Index score was 2.50 ± 2.56; the most prevalent comorbid conditions involved coagulation/haemorrhage, fluid/electrolyte balance and non-traumatic joint disorders. Over 18 months, a mean of 54 ambulatory visits and 120 pharmacy fills were observed; mean medical costs were $86 694 and pharmacy costs were $25 396. CONCLUSIONS: Identifying females with HA is challenging using healthcare claims, because diagnostic nomenclature is unclear for female patients treated for bleeding events. Although chart abstraction enhanced claims data, very few female patients were identified with HA. Nevertheless, even in a small sample, sizeable burden in comorbidity and healthcare use was observed. Improved nomenclature and coding for HA diagnoses for women and girls is key to improving research and treatment.

Assessment of the COPD Assessment Test Within U.S. Primary Care.

RATIONALE: Uptake of the COPD Assessment Test (CATTM) is not yet widespread in patients with chronic obstructive pulmonary disease (COPD) within U.S. primary care and its alignment with other assessments has not been evaluated in U.S. clinical practice. OBJECTIVES: To assess the alignment of the CAT with other standard measures of COPD severity and its usability in a U.S. primary care population. METHODS: This was a multicenter, prospective, observational, longitudinal study of patients with COPD and their primary care physicians. Patients with spirometry-confirmed airflow restriction completed a daily electronic diary (eDiary) over 12 weeks; surveys were also administered at baseline and at 6- and 12-week follow-up. MEASUREMENTS AND MAIN RESULTS: In the study population (n=178), statistically significant differences (P<0.05) were found across 4 CAT impact score groups where at all time points patients in the Low Impact CAT score group had superior lung function and physical/mental health status than patients in the Medium, High, and Very High Impact groups. Numerical, though lesser, differences were also found across these latter 3 groups. Furthermore, the average total EXAcerbations of COPD Tool (EXACT®) score was significantly worse in patients in the highest CAT score group over the first 7 days. CONCLUSIONS: COPD severity; respiratory symptoms; frequency, severity, and duration of pulmonary exacerbations; and overall physical and mental health status are linked concurrently and prospectively to CAT impact score categories. The stratification of patients according to CAT impact scores, and application of clinical and functional health status information to these categories, enhances the usability of the CAT in practice settings for COPD management.

Patient-reported outcomes of dual bronchodilator fixed-dose combination versus bronchodilator monotherapy in individuals with COPD.

Background: This study compared real-world patient-reported outcomes (PROs) measured by the Clinical COPD Questionnaire (CCQ), the London Chest Activities of Daily Living (LCADL) scale, and the Work Productivity and Activity Impairment (WPAI) questionnaire between individuals with COPD initiating LAMA/LABA fixed-dose combination (FDC) dual therapy versus either long-acting muscarinic antagonist (LAMA) or long-acting beta2-agonist (LABA) monotherapy. Methods: Individuals with COPD aged ≥40 years initiating a LAMA/LABA FDC dual therapy or a LAMA or LABA monotherapy (index date = first prescription date) between January 1, 2016 and December 31, 2016 were identified from a large US administrative claims database. Individuals were excluded if they were prescribed an inhaled corticosteroid (ICS) or ICS/LABA two months prior to the index date or were diagnosed with cystic fibrosis, idiopathic pulmonary fibrosis, or asthma. The cohorts were propensity score matched (PSM) 1:1 for COPD severity using baseline measures. Each participant completed a survey. Results: Surveys were completed by 399 participants in the dual therapy cohort, and 718 participants in the monotherapy cohort. Following PSM, 379 participants remained in each cohort for analysis (monotherapy: 369 LAMA and 10 LABA). The dual therapy cohort reported fewer COPD-related symptoms (CCQ symptom score 2.75 vs 2.97, respectively, P=0.023), and, fewer limitations in leisure activities (LCADL leisure score 4.78 vs 5.17, respectively, P=0.021) versus the monotherapy cohort. No significant differences were found in the WPAI. A greater percentage of participants in the dual therapy cohort stayed on index therapy (63.1%) when compared with the monotherapy cohort (30.3%, P<0.0001). Conclusions: Only 30% of the participants prescribed monotherapy, usually with a LAMA, remained on index therapy alone at the time of survey administration. In the dual therapy cohort, 63% of the participants remained on the index medication and had fewer COPD-related symptoms and fewer limitations in leisure activities compared with participants in the monotherapy cohort.

A Retrospective Claims Analysis of Dual Bronchodilator Fixed-Dose Combination Versus Bronchodilator Monotherapy in Patients with Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) increasingly receive combination bronchodilator therapies. Real world evidence for the benefits of combination therapy compared to monotherapy is lacking. METHODS: COPD patients aged ≥ 40 years initiating monotherapy (MT) with either a long-acting muscarinic antagonist (LAMA) or long-acting beta2-agonist (LABA) or dual therapy (DT) with a LAMA/LABA fixed dose combination (FDC) between January 1, 2016 and December 31, 2016 were identified from a large U.S. administrative claims database. Patients diagnosed with cystic fibrosis, idiopathic pulmonary fibrosis, or asthma were excluded. Cohorts were propensity score matched 1:1 using baseline measures (e.g., exacerbations, hospitalizations) as proxies for COPD severity to create balanced cohorts. RESULTS: Following propensity score matching (PSM), 1286 patients remained in each cohort for analysis. Patients were followed for approximately 1 year. Patients in the DT versus MT cohort had lower rates of exacerbations leading to hospitalization (incidence rate ratio 0.7886; p=0.019), lower mean COPD-related pharmacy costs per patient per month (PPPM) ($300 versus $379, respectively; p<0.001) and total costs PPPM ($990 versus $1203, respectively; p=0.003). This occurred despite lower mean COPD-related pharmacy fills PPPM in the DT versus MT cohorts (1.41 versus 1.51, respectively; p=0.038). Patients in the DT cohort had lower rates of switching (p<0.001) and augmentation (p<0.001), and higher rates of non-persistence (p<0.001) versus the MT cohort. Rates of discontinuation were similar. CONCLUSIONS: Patients in the DT cohort had lower rates of exacerbations leading to hospitalization, lower COPD-related pharmacy and total costs PPPM, and lower rates of switching and augmentation compared to patients in the MT cohort.

Pharmacologic Treatment of Insomnia Disorder: An Evidence Report for a Clinical Practice Guideline by the American College of Physicians.

BACKGROUND: Pharmacologic interventions are often prescribed for insomnia disorder. PURPOSE: To assess the benefits, harms, and comparative effectiveness of pharmacologic treatments for adults with insomnia disorder. DATA SOURCES: Several electronic databases (2004-September 2015), reference lists, and U.S. Food and Drug Administration (FDA) documents. STUDY SELECTION: 35 randomized, controlled trials of at least 4 weeks' duration that evaluated pharmacotherapies available in the United States and that reported global or sleep outcomes; 11 long-term observational studies that reported harm information; FDA review data for nonbenzodiazepine hypnotics and orexin receptor antagonists; and product labels for all agents. DATA EXTRACTION: Data extraction by single investigator confirmed by a second reviewer; dual-investigator assessment of risk of bias; consensus determination of strength of evidence. DATA SYNTHESIS: Eszopiclone, zolpidem, and suvorexant improved short-term global and sleep outcomes compared with placebo, although absolute effect sizes were small (low- to moderate-strength evidence). Evidence for benzodiazepine hypnotics, melatonin agonists, and antidepressants, and for most pharmacologic interventions in older adults, was insufficient or low strength. Evidence was also insufficient to compare efficacy within or across pharmacotherapy classes or versus behavioral therapy. Harms evidence reported in trials was judged insufficient or low strength; observational studies suggested that use of hypnotics for insomnia was associated with increased risk for dementia, fractures, and major injury. The FDA documents reported that most pharmacotherapies had risks for cognitive and behavioral changes, including driving impairment, and other adverse effects, and they advised dose reduction in women and in older adults. LIMITATIONS: Most trials were small and short term and enrolled individuals meeting stringent criteria. Minimum important differences in outcomes were often not established or reported. Data were scant for many treatments. CONCLUSION: Eszopiclone, zolpidem, and suvorexant may improve short-term global and sleep outcomes for adults with insomnia disorder, but the comparative effectiveness and long-term efficacy of pharmacotherapies for insomnia are not known. Pharmacotherapies for insomnia may cause cognitive and behavioral changes and may be associated with infrequent but serious harms. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. ( PROSPERO: CRD42014009908).

Psychological and Behavioral Interventions for Managing Insomnia Disorder: An Evidence Report for a Clinical Practice Guideline by the American College of Physicians.

BACKGROUND: Psychological and behavioral interventions are frequently used for insomnia disorder. PURPOSE: To assess benefits and harms of psychological and behavioral interventions for insomnia disorder in adults. DATA SOURCES: Ovid MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and PsycINFO through September 2015, supplemented with hand-searching. STUDY SELECTION: Randomized, controlled trials of psychological or behavioral interventions that were published in English and enrolled adults with insomnia disorder lasting 4 or more weeks. DATA EXTRACTION: Data extraction by single investigator confirmed by a second reviewer; dual investigator assessment of risk of bias; consensus determination of strength of evidence. DATA SYNTHESIS: Sixty trials with low to moderate risk of bias compared psychological and behavioral interventions with inactive controls or other psychological and behavioral interventions. Cognitive behavioral therapy for insomnia (CBT-I) improved posttreatment global and most sleep outcomes, often compared with information or waitlist controls (moderate-strength evidence). Use of CBT-I improved several sleep outcomes in older adults (low- to moderate-strength evidence). Multicomponent behavioral therapy improved several sleep outcomes in older adults (low- to moderate-strength evidence). Stimulus control improved 1 or 2 sleep outcomes (low-strength evidence). Evidence for other comparisons and for harms was insufficient to permit conclusions. LIMITATIONS: A wide variety of comparisons limited the ability to pool data. Trials did not always report global outcomes and infrequently conducted remitter or responder analysis. Comparisons were often information or waitlist groups, and publication bias was possible. CONCLUSION: Use of CBT-I improves most outcomes compared with inactive controls. Multicomponent behavioral therapy and stimulus control may improve some sleep outcomes. Evidence on other outcomes, comparisons, and long-term efficacy were limited. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. ( PROSPERO: CRD42014009908).

Long-term Outcomes of Living Kidney Donation.

BACKGROUND: In an effort to improve outcomes associated with living kidney donation, the Kidney Diseases Improving Global Outcomes (KDIGO) assembled a Work Group to develop comprehensive guidelines addressing the evaluation and care of living kidney donors. We conducted this systematic review to inform guideline development. METHODS: We searched Ovid Medline, Ovid Embase, and the Cochrane Library to identify systematic reviews, randomized controlled trials, and observational studies published through September of 2014 and consulted the KDIGO Expert Work Group. We extracted data from systematic reviews and observational studies with sample size over 100 and mean follow-up time of at least 5 years. Studies had to have an adequate comparison group that excludes subjects with contraindications to kidney donation. RESULTS: For the long-term donor outcomes, we extracted 5 systematic reviews and 40 observational studies. Moderate grade evidence reveals an association between living kidney donation and greater risk of end-stage renal disease. This association is true for donors of all races with African American donors sustaining the greatest increase in absolute risk. We found very low grade evidence that kidney donation is associated with lower kidney function, proteinuria, hypertension, and psychosocial outcomes. Consistent evidence from 3 studies reveals that donors are at higher risk for preeclampsia and gestational hypertension with postdonation pregnancies and compared with healthy matched nondonors. CONCLUSIONS: Living kidney donation appears to be associated with a small absolute increase in risk of end-stage renal disease, hypertension, and pregnancy complications, such as preeclampsia and gestational hypertension.

Intermediate- and Long-Term Cognitive Outcomes After Cardiovascular Procedures in Older Adults: A Systematic Review.

BACKGROUND: Risks for intermediate- and long-term cognitive impairment after cardiovascular procedures in older adults are poorly understood. PURPOSE: To summarize evidence about cognitive outcomes in adults aged 65 years or older at least 3 months after coronary or carotid revascularization, cardiac valve procedures, or ablation for atrial fibrillation. DATA SOURCES: MEDLINE, Cochrane, and Scopus databases from 1990 to January 2015; ClinicalTrials.gov; and bibliographies of reviews and eligible studies. STUDY SELECTION: English-language trials and prospective cohort studies. DATA EXTRACTION: One reviewer extracted data, a second checked accuracy, and 2 independently rated quality and strength of evidence (SOE). DATA SYNTHESIS: 17 trials and 4 cohort studies were included; 80% of patients were men, and mean age was 68 years. Cognitive function did not differ after the procedure between on- and off-pump coronary artery bypass grafting (CABG) (n = 6; low SOE), hypothermic and normothermic CABG (n = 3; moderate to low SOE), or CABG and medical management (n = 1; insufficient SOE). One trial reported lower risk for incident cognitive impairment with minimal versus conventional extracorporeal CABG (risk ratio, 0.34 [95% CI, 0.16 to 0.73]; low SOE). Two trials found no difference between surgical carotid revascularization and carotid stenting or angioplasty (low and insufficient SOE, respectively). One cohort study reported increased cognitive decline after transcatheter versus surgical aortic valve replacement but had large selection and outcome measurement biases (insufficient SOE). LIMITATIONS: Mostly low to insufficient SOE; no pertinent data for ablation; limited generalizability to the most elderly patients, women, and persons with substantial baseline cognitive impairment; and possible selective reporting and publication bias. CONCLUSION: Intermediate- and long-term cognitive impairment in older adults attributable to the studied cardiovascular procedures may be uncommon. Nevertheless, clinicians counseling patients before these procedures should discuss the uncertainty in their risk for adverse cognitive outcomes. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Effectiveness of Caregiver Interventions on Patient Outcomes in Adults With Dementia or Alzheimer's Disease: A Systematic Review.

Objective: We conducted a systematic review to evaluate whether caregiver-involved interventions improve patient outcomes among adults with dementia or Alzheimer's disease. Method: We identified and summarized data from randomized controlled trials enrolling adults with dementia or Alzheimer's disease by searching MEDLINE, PsycINFO, and other sources. Patient outcomes included global quality of life, physical and cognitive functioning, depression/anxiety, symptom control and management, and health care utilization. Results: We identified 31 trials; 20 compared a caregiver intervention with usual care or usual care with promise of intervention at completion of study period. Fifteen compared one caregiver intervention with another individual or caregiver intervention (active control). Compared with usual care or active controls, caregiver-involved interventions had low to insufficient strength of evidence and did not consistently improve patient outcomes. Discussion: Evidence is insufficient to endorse use of most caregiver interventions to improve outcomes for patients with dementia or Alzheimer's disease.

Ascertaining cause of death among men in the prostate cancer intervention versus observation trial.

BACKGROUND: The Prostate Cancer Intervention Versus Observation Trial (PIVOT) randomized 731 men with localized prostate cancer to radical prostatectomy or observation. PURPOSE: We describe the methods and results for cause-of-death assignments in PIVOT, and compare them to alternative strategies for ascertaining prostate cancer-specific mortality, as well as to the methods and results in the similar Scandinavian Prostate Cancer Group Study 4 (SPCG-4) trial. METHODS: Three PIVOT Endpoints Committee members, blinded to randomized treatment assignments, reviewed medical records and death certificates when available to assign a cause of death using a primary and a secondary adjudication question. Initial disagreements were resolved through discussion. The level of initial agreement among committee members was examined, as well as guesses at randomized treatment assignments for a convenience sample of cases. Final cause of death determinations were compared to death certificates. RESULTS: Complete agreement on cause of death by all three committee members before any discussion was achieved in 200/354 (56%) cases on the primary and 209/354 (59%) cases on the secondary. However, complete agreement on the primary rose to 306/354 (86%) when 'definite' and 'probably' categories were collapsed, as planned a priori. The three committee members' proportions of correct guesses of randomized treatment assignment were 82/121 (68%), 113/148 (76%), and 99/134 (74%). Using the committee's final adjudications as a gold standard, death certificates had suboptimal sensitivities, specificities, or predictive values depending on how they were used to determine cause of death. LIMITATIONS: There was no separate 'gold standard' by which to judge the accuracy of the final endpoints committee adjudications, and useful death certificates could not be obtained on about a third of PIVOT participants who died. CONCLUSIONS: The low level of initial agreement on cause of death among endpoint committee members and the potential for biased determinations due to partial unblinding to treatment assignment raise methodologic concerns about using prostate cancer mortality as an endpoint in clinical trials like PIVOT.

Couple and family involvement in adult mental health treatment: a systematic review.

We reviewed randomized controlled trials conducted in the United States from January, 1996 through December, 2011 that examined family interventions for adult mental health conditions. We identified 51 articles (39 trials) evaluating 21 different family interventions. Findings for behavioral couple or family therapy (BCT/BFT) and community reinforcement and training (CRAFT) for substance use disorders were each pooled separately for examination in meta-analyses. Findings suggest BCT/BFT reduced substance use (small-to-moderate effects) and improved relationship adjustment (large effects) compared to individually-oriented treatments. CRAFT increased treatment initiation three-fold but did not improve substance use or family functioning over alternative family interventions. Family focused therapy for bipolar disorder improved symptoms over less intensive treatments with mixed findings when compared to equally intensive treatments. For both bipolar disorder and schizophrenia spectrum disorders, the few trials meeting our search criteria and heterogeneity among trials precluded generating broader conclusions regarding which family interventions are most effective for US populations. Overall, trials were limited in their methodological quality, and many interventions were evaluated in one trial. Future research is needed to replicate findings for these single trials, examine relationship distress as a moderator of outcome, and examine BCT/BFT among dual substance using couples and outside the research group frequently represented.