Effect of collaborative dementia care on potentially inappropriate medication use: Outcomes from the Care Ecosystem randomized clinical trial.

INTRODUCTION: Potentially inappropriate medications (PIMs) cause adverse events and death. We evaluate the Care Ecosystem (CE) collaborative dementia care program on medication use among community-dwelling persons living with dementia (PLWD). METHODS: Secondary analysis of a randomized clinical trial (RCT) comparing CE to usual care (UC) on changes in PIMs, over 12 months between March 2015 and May 2020. Secondary outcomes included change in number of medications, clinically relevant PIMs, and anti-dementia medications. RESULTS: Of 804 PLWD, N = 490 had complete medication data. The CE resulted in significantly fewer PIMs compared to UC (-0.35; 95% CI, -0.49 to -0.20; P < 0.0001). Number needed to prevent an increase in 1 PIM was 3. Total medications, PIMs for dementia or cognitive impairment, CNS-active PIMs, anticholinergics, benzodiazepines, and opioids were also fewer. Anti-dementia medication regimens were modified more frequently. CONCLUSION: The CE medication review intervention embedded in collaborative dementia care optimized medication use among PLWD. HIGHLIGHTS: Compared to usual care (UC), the Care Ecosystem (CE) medication review intervention prevented increases in potentially inappropriate medications (PIMs). Use of anticholinergics, benzodiazepines, and opioids were significantly reduced, with a trend for antipsychotics. Anti-dementia medications were adjusted more frequently. The CE medication review intervention embedded in collaborative dementia care optimized medication use.

Integrative genomic analysis in African American children with asthma finds three novel loci associated with lung function.

Bronchodilator (BD) drugs are commonly prescribed for treatment and management of obstructive lung function present with diseases such as asthma. Administration of BD medication can partially or fully restore lung function as measured by pulmonary function tests. The genetics of baseline lung function measures taken before BD medication have been extensively studied, and the genetics of the BD response itself have received some attention. However, few studies have focused on the genetics of post-BD lung function. To address this gap, we analyzed lung function phenotypes in 1103 subjects from the Study of African Americans, Asthma, Genes, and Environment, a pediatric asthma case-control cohort, using an integrative genomic analysis approach that combined genotype, locus-specific genetic ancestry, and functional annotation information. We integrated genome-wide association study (GWAS) results with an admixture mapping scan of three pulmonary function tests (forced expiratory volume in 1 s [FEV1 ], forced vital capacity [FVC], and FEV1 /FVC) taken before and after albuterol BD administration on the same subjects, yielding six traits. We identified 18 GWAS loci, and five additional loci from admixture mapping, spanning several known and novel lung function candidate genes. Most loci identified via admixture mapping exhibited wide variation in minor allele frequency across genotyped global populations. Functional fine-mapping revealed an enrichment of epigenetic annotations from peripheral blood mononuclear cells, fetal lung tissue, and lung fibroblasts. Our results point to three novel potential genetic drivers of pre- and post-BD lung function: ADAMTS1, RAD54B, and EGLN3.

Identification of CFTR variants in Latino patients with cystic fibrosis from the Dominican Republic and Puerto Rico.

BACKGROUND: In cystic fibrosis (CF), the spectrum and frequency of CFTR variants differ by geography and race/ethnicity. CFTR variants in White patients are well-described compared with Latino patients. No studies of CFTR variants have been done in patients with CF in the Dominican Republic or Puerto Rico. METHODS: CFTR was sequenced in 61 Dominican Republican patients and 21 Puerto Rican patients with CF and greater than ​​​​60 mmol/L sweat chloride. The spectrum of CFTR variants was identified and the proportion of patients with 0, 1, or 2 CFTR variants identified was determined. The functional effects of identified CFTR variants were investigated using clinical annotation databases and computational prediction tools. RESULTS: Our study found 10% of Dominican patients had two CFTR variants identified compared with 81% of Puerto Rican patients. No CFTR variants were identified in 69% of Dominican patients and 10% of Puerto Rican patients. In Dominican patients, there were 19 identified CFTR variants, accounting for 25 out of 122 disease alleles (20%). In Puerto Rican patients, there were 16 identified CFTR variants, accounting for 36 out of 42 disease alleles (86%) in Puerto Rican patients. Thirty CFTR variants were identified overall. The most frequent variants for Dominican patients were p.Phe508del and p.Ala559Thr and for Puerto Rican patients were p.Phe508del, p.Arg1066Cys, p.Arg334Trp, and p.I507del. CONCLUSIONS: In this first description of the CFTR variants in patients with CF from the Dominican Republic and Puerto Rico, there was a low detection rate of two CFTR variants after full sequencing with the majority of patients from the Dominican Republic without identified variants.