Publications

OBJECTIVES

To evaluate the risk and predictors of thiazide-induced adverse events (AEs) in multimorbid older adults in real-world clinical settings.

DESIGN

Observational cohort study.

SETTING

National Veterans Affairs data from 2007 to 2008.

PARTICIPANTS

Veterans aged 65 and older newly prescribed a thiazide (N = 1,060) compared with propensity-matched nonusers of antihypertensive medications (N = 1,060).

MEASUREMENTS

The primary outcome was a composite of metabolic AEs defined as sodium less than 135 mEq/L, potassium less than 3.5 mEq/L, or a decrease in the estimated glomerular filtration rate (eGFR) of more than 25% from the baseline rate. Secondary outcomes included sev-ere AEs (sodium <130 mEq/L, potassium <3.0 mEq/L, or a decrease in eGFR of more than 50%).

RESULTS

Over 9 months of follow-up, 14.3% of new thiazide users developed an AE, compared with 6.0% of nonusers (number needed to harm (NNH) 12, 95% confidence interval (CI) = 9-17, P < .001); 1.8% of new users developed a severe AE, compared with 0.6% of nonusers (NNH = 82, P = .008), and 3.8% of new users had an emergency department visit or hospitalization with an AE, compared with 2.0% of nonusers (NNH = 56, P = .02). Risk of AEs did not vary according to age, but having five or more comorbidities was associated with 3.0 times the odds (95% CI = 1.4-6.2) of developing an AE as having one comorbidity (hypertension). Low-normal and unmeasured baseline sodium and potassium values were among the strongest predictors of hyponatremia and hypokalemia, respectively. Only 42% of thiazide users had laboratory monitoring within 90 days after initiation.

CONCLUSION

Thiazide-induced AEs are common in older adults. Greater attention should be paid to potential complications in prescribing thiazides to older adults, including closer laboratory monitoring before and after initiation of thiazides.

BACKGROUND

Artemisinin-based combination therapy (ACT) has become the standard of care for the treatment of uncomplicated Plasmodium falciparum malaria. Although several ACT regimens are approved, data guiding optimal choices of ACTs are limited. We compared short- and long-term outcomes in a cohort of young Ugandan children randomized to 2 leading ACTs.

METHODS

Overall, 312 children were randomized to artemether-lumefantrine or dihydroartemisinin-piperaquine (DP) at the time of the first episode of uncomplicated malaria (median age, 10.5 months). The same treatment was given for all subsequent episodes of uncomplicated malaria and children were followed until they reached 5 years of age. The cohort included a subgroup that was human immunodeficiency virus (HIV) infected (n = 44) or HIV exposed (n = 175) and prescribed trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis. Outcomes included time to recurrent malaria following individual treatments and the overall incidences of treatments for malaria, complicated malaria, and hospitalizations.

RESULTS

Among children not prescribed TMP-SMX prophylaxis, 4443 treatments for malaria were given over 790 person-years following randomization. Treatment with DP was associated with a lower hazard of recurrent malaria over the 84 days after treatment (hazard ratio, 0.66; 95% confidence interval [CI], .61-.70; P < .001). Children randomized to DP had a lower incidence of all treatments for malaria (incidence rate ratio [IRR], 0.85; 95% CI, .75-.96; P = .01), complicated malaria (IRR, 0.12; 95% CI, .04-.39; P < .001), and hospitalizations (IRR, 0.31; 95% CI, .13-.77; P = .01). Among children prescribed TMP-SMX prophylaxis, there were no significant differences in longitudinal outcomes.

CONCLUSIONS

Compared to artemether-lumefantrine, the use of DP to treat uncomplicated malaria delayed the time to recurrent malaria and reduced the incidences of treatments for malaria, complicated malaria, and hospitalizations.

CLINICAL TRIALS REGISTRATION

NCT00527800.

Asthma is a complex disease with sex-specific differences in prevalence. Candidate gene studies have suggested that genotype-by-sex interaction effects on asthma risk exist, but this has not yet been explored at a genome-wide level. We aimed to identify sex-specific asthma risk alleles by performing a genome-wide scan for genotype-by-sex interactions in the ethnically diverse participants in the EVE Asthma Genetics Consortium. We performed male- and female-specific genome-wide association studies in 2653 male asthma cases, 2566 female asthma cases and 3830 non-asthma controls from European American, African American, African Caribbean and Latino populations. Association tests were conducted in each study sample, and the results were combined in ancestry-specific and cross-ancestry meta-analyses. Six sex-specific asthma risk loci had P-values < 1 × 10(-6), of which two were male specific and four were female specific; all were ancestry specific. The most significant sex-specific association in European Americans was at the interferon regulatory factor 1 (IRF1) locus on 5q31.1. We also identify a Latino female-specific association in RAP1GAP2. Both of these loci included single-nucleotide polymorphisms that are known expression quantitative trait loci and have been associated with asthma in independent studies. The IRF1 locus is a strong candidate region for male-specific asthma susceptibility due to the association and validation we demonstrate here, the known role of IRF1 in asthma-relevant immune pathways and prior reports of sex-specific differences in interferon responses.

BACKGROUND

Childhood tuberculosis causes significant morbidity and mortality in Southeast Asia, yet little is known about the epidemiology and clinical characteristics of this disease in Viet Nam.

OBJECTIVES

To determine the demographics, clinical presentations, radiographic and microbiologic findings, treatment regimens, and outcomes of children admitted with tuberculosis (TB) to a national referral hospital in Viet Nam.

METHODS

We conducted a retrospective case series study of children ≤ 15 years old with bacteriologically confirmed or clinically diagnosed TB admitted to a national referral hospital in Ha Noi, Viet Nam from January through December 2007.

RESULTS

One hundred three children were identified: median age 5 years (IQR 2-10), 44% female, 99% Kinh ethnicity, 27% residing in Ha Noi, 88% with BCG vaccination, 27% with known TB contact, and 38% malnourished. Intrathoracic TB was present in 62%, extrathoracic in 52%, both intra and extrathoracic in 19%, and undetermined site in 5%. The most common extrathoracic manifestation was peripheral lymphadenitis, and children under 5 were more likely to have miliary TB or both intra and extrathoracic TB. Fever and failure to thrive were common presenting symptoms among all participants (65% and 56%, respectively), 66% of those with intrathoracic TB presented with cough, and 92% of those with TB meningitis presented with severe neurologic impairment. Acid-fast bacilli smears and mycobacterial cultures were positive in 18% and 21% of children tested, and histopathology was positive in 88% of those biopsied. There were no adverse drug reactions necessitating change in therapy, and no inpatient mortality.

CONCLUSIONS

Extrathoracic TB was common, treatment well tolerated and clinical outcomes excellent. Culture confirmation rates were low and emphasize the need for improved diagnostics.