Pharmacogenetic testing among patients with depression in a US managed care population.

Actionable drug-gene pairs relevant to depression treatment include CYP2D6 and CYP2C19 with specific antidepressants. While clinical use of pharmacogenetic testing is growing, little is known about pharmacogenetic testing for depression treatment in managed care. We determined the incidence of single-gene CYP2D6 and CYP2C19 testing following a new depression episode among US managed care patients, and described characteristics and antidepressant use of patients receiving tests. We used paid medical and pharmacy claims for patients from commercial health plans in the US. For adult patients with a new depression episode from January 1, 2013 to June 30, 2018, we identified covered claims for single-gene CYP2D6 and CYP2C19 pharmacogenetic tests and antidepressant fills. Fewer than 1% (n = 1795) of the depressed cohort (n = 438,534) received a single-gene CYP2D6 or CYP2C19 test through their insurance within 365 days of their earliest depression episode. The percentage of patients who received a test nearly tripled from 0.2% in 2013 to 0.5% in 2014 before plateauing at 0.4% from 2014 to 2017. Among the patients who received a single-gene CYP2D6 or CYP2C19 test and filled an antidepressant within 365 days of their depression diagnosis, up to 30% may have had their initial antidepressant informed by the test result. Our findings describe the use of antidepressants before and after pharmacogenetic testing, which is clinically relevant as pharmacogenomic testing becomes more common in clinical practice. Our study also emphasizes the need for procedure and billing codes that capture multiple-gene panel tests to be more widely implemented in administrative databases.

Treatments to slow progression of autosomal dominant polycystic kidney disease: systematic review and meta-analysis of randomized trials.

AIM: Autosomal dominant polycystic kidney disease (ADPKD) is a monogenetic disorder that leads to kidney failure. Our aim was to undertake a meta-analysis of randomized trials of interventions that have been hypothesized to reduce the progression of total kidney volume (TKV) and renal function in ADPKD. METHODS: Relevant trials were identified, and outcomes were: change in TKV, total cyst volume (TCV), renal function and adverse events. Meta-analysis used random effects, with results expressed as mean difference and risk ratio both with 95% confidence intervals (CI). RESULTS: Eleven trials (2262 patients) were included. Compared with placebo, Target of Rapamycin complex 1 (TORC1) inhibitors (5 trials, n = 619), showed no significant change in TKV (P = 0.21), TCV (P = 0.06) or eGFR (P = 0.22). Somatostatin analogues (3 trials, n = 157) reduced TKV by 9% (95% CI -10.33 to -7.58%) but did not alter eGFR. The vasopressin receptor antagonist (n = 1455) attenuated TKV increase to 3%/year (95% CI -3.48 to -2.52) and slowed kidney function decline over a 3-year period. A single trial (n = 41) of eicosapentaenoic acid did not alter the progression of either TKV (P = 0.9) or renal dysfunction (P = 0.78). Adverse events were significant for interventions in all trials compared with placebo. CONCLUSION: These data suggest that somatostatin analogues and vasopressin receptor antagonists attenuate TKV increase. The neutral effects of TORC1 inhibitors on TKV could be true, or due to heterogeneity in study population, drug efficacy and follow-up duration. In the future, further well-designed and powered trials of longer duration using new biomarkers or therapeutic agents with better tolerance are required.

Health-related quality of life of patients awaiting kidney and simultaneous pancreas-kidney transplants.

AIM: Patients undergoing kidney and simultaneous pancreas-kidney (SPK) transplants are younger and fitter than the general dialysis population. Intuitively these patients might have better quality of life (QOL) than the general dialysis population, but their QOL scores are not well characterized. The aim of this study was to compare QOL of patients about to undergo kidney or SPK transplants with Australian dialysis outcomes and practice patterns (DOPPS) data and multiple comorbidity and age-adjusted general population data. METHODS: Patients attending Westmead Hospital for transplants from August 2009 to December 2011 were invited to complete the Kidney Disease QOL-SF(™) 1.3 (KDQOL-SF(™) 1.3) questionnaire regarding their immediate pretransplant QOL. This QOL instrument is predictive of hospitalizations and mortality. The questionnaire was completed within 4 weeks of transplantation. RESULTS: Of 180 patients seen within 4 weeks of transplantation 95 (53%) responded, with no differences from non-responders in age, sex, comorbidities or perioperative complications. Compared with DOPPS, these patients had better physical function and less pain, but significantly lower scores for role physical (CI: -19 to -4, P=0.004) and role emotional (CI: -17 to -2, P=0.018). Patients undergoing SPK transplants reported even poorer general health, energy, social support and function. Patients had lower emotional and social function than people with multiple comorbidities, with whom they shared poor general and mental health and vitality. Scores were markedly lower than the general population except for bodily pain (female). CONCLUSION: Younger, fitter patients are more vulnerable to effects of their illness on social, emotional and physical interactions and may benefit from targeted support.

Relationship of breast-feeding and hand-washing with dehydration in infants with diarrhoea due to Escherichia coli.

This prospective cohort study was carried out in the neonatal unit of the Yangon Children Hospital, Myanmar, to gather more information on the types of feedings and hand-washing practices of mothers as the determinant of severe dehydration in infants with acute diarrhoea due to Escherichia coli. The study subjects included 100 infants with diarrhoea, aged less than 4 months, admitted to the hospital from June 1997 to May 1998. Data on isolation of E. coli from rectal swab samples, types of feedings, hand-washing practices, and dehydration status were collected. Of the 100 cases, E. coli was isolated from rectal swab samples of 48 infants. Of these 48 cases, 28 had some dehydration and 20 had severe dehydration. Exclusive breast-feeding was observed only in the age group < 1 and > 1-2 month(s). The association of the severity of dehydration with other types of feedings compared to exclusive breast-feeding was not statistically significant. In this study, most mothers washed their hands with water only after cleansing their children's defaecation, and before and after feeding their children. The severity of dehydration was statistically significant in hand-washing practices when compared to washing with water only and washing with soap and water. This study has shown the association between types of feedings and hand-washing practices with dehydration in infants with acute diarrhoea due to E. coli. The results of the study suggest that there is a need for appropriate intervention programmes to promote exclusive breast-feeding and hand-washing practices with soap and water after cleansing children's defaecation, and before and after feeding children.

Vibrio cholerae non-O1 as a causal pathogen in cholera patients in Yangon, Myanmar.

Vibrio cholerae non-O1 was studied in patients with rice watery diarrhoea admitted to the Infectious Diseases Hospital, Yangon. The study was conducted during 1993-1994 to determine the association of the pathogen with the disease. Altogether 771 rectal swabs were collected and examined. V. cholerae were isolated by the standard methods. The seasonal, age and sex distribution, serotyping and susceptibility of these isolates to antibiotics were investigated, V. cholerae were isolated from 233 (3O.2%) samples. Among them, V. cholerae O1 were isolated from 117 (5O%) samples and V. cholerae non-O1 from 116 (5O%) samples. The seasonal, age and sex distribution was identical in both V. cholerae O1 and V. cholerae non-O1 groups. V. cholerae O139 was isolated during February 1994. Thus V. cholerae non-O1 was also one of the causal pathogens of cholera, like V. cholerae O1 in this community.

Serotype distribution and antimicrobial susceptibility of Shigellae isolated from diarrhoeal patients in Yangon, Myanmar.

In Myanmar there is a changing pattern in the prevalence of Shigella strains with an increasing antimicrobial resistance, and, thus the serotype prevalence and antibiotic sensitivity pattern of Shigellae were studied in 1993. Dysenteric stool samples were collected from the laboratory of Infectious Diseases Hospital, Yangon during January-June 1993. The Shigella isolates were identified by the standard bacteriologic procedures. Four hundred and sixty stool samples containing blood and mucous were collected in this study, and Shigella spp. were isolated from the 108 (23.5%) samples. The increasing antimicrobial resistance of shigellosis from 1980 to 1993 in this community was also discussed.

Maternal influences on low birth weight.

PIP: To identify the maternal risk factors associated with low birth weight in Malaysia, the records of the 2613 infants delivered at North Okkalapa General Hospital from January to September 1990 were reviewed. The incidence of low birth weight during the 9-month study period was 21.1%; 18.1% of these cases were attributable to intrauterine growth retardation and 3% were associated with preterm births. Univariate analysis identified the following risk factors as significant: age under 20 years (.001), parity 1 (.001), maternal height of 145 cm or under (.01), maternal cigarette smoking (.01), maternal education of 8 years or less (.001), parity 5 or above (.05), and maternal age of 35 years and above (.05). A last birth interval of 1 year or less and more than 3 years was associated with an odds ratio exceeding 1, but the correlation with low birth weight was not significant. These risk factors should be used to design maternal health programs aimed at reducing the incidence of low birth weight.^ieng

Effectiveness of potash alum in decontaminating household water.

To evaluate the effectiveness of potash alum in purifying household water, this study was carried out in a suburban community in Yangon, Myanmar. It was designed to test whether the application of potash alum (0.05%) regularly into household water storage vessels during water replenishment was capable of decontaminating household water in homes using shallow well water. It was conducted in 100 households (50 each in intervention and control groups). After alum (0.05%) was added, the contamination level of water decreased on the 2nd and 3rd days. The alum-treated water was well tolerated by the users; only one member complained of a metallic taste. We conclude that potash alum was effective and acceptable in this community in decontaminating household water.