The STARRT trial: a cost comparison of optimal vs sub-optimal initiation of dialysis in Canada.

BACKGROUND: Sub-optimal transitioning of patients from chronic kidney disease (CKD) to end stage renal disease (ESRD) may result in poor clinical outcomes and increased healthcare costs. The objectives of this study were to estimate the average total cost per patient who requires initiation of renal replacement therapy (RRT) stratified by status at initiation; optimal (RRT initiation as an outpatient with an arterio-venous [AV] Fistula, Graft or Peritoneal Dialysis [PD] catheter), and sub-optimal (RRT initiation as an inpatient and/or via central venous catheter [CVC]). METHODS: Data from the Study To Assess Renal Replacement Therapy (STARRT), a Canadian, multi-centre, 6 month retrolective study (n = 339), were used for this analysis. Unit costs for resources were obtained from participating hospitals, the literature, and/or standard costing sources. The analysis was performed from the perspective of healthcare payors and reported in 2011 Canadian Dollars (CAD). A propensity score technique was applied to control for potential confounders between the two groups. RESULTS: Two hundred of the eligible patients for analysis (61.9%) were sub-optimally and 123 (38.1%) were optimally prepared. For this analysis, 106 "matched" pairs were used. The average total cost per patient was estimated to be $63,225 (with a 95% CI ranging from $58,663-$67,958) for the sub-optimally initiated patients, and $39,260 (with a 95% CI ranging from $35,683-$43,007) for the optimally initiated patients (p < 0.001). LIMITATIONS: Costs were calculated utilizing a conservative approach, using the cheapest available prices for medications and other resources. Assumptions had to be made for the costing of dialyses. CONCLUSION: The results of this study indicate, after adjusting for potential confounders, that optimally initiated patients for RRT have significantly lower healthcare-associated costs compared to sub-optimally initiated patients.

Renin-angiotensin blockade is associated with increased mortality after vascular surgery.

PURPOSE: The outcome of patients with preoperative renin-angiotensin system (RAS) blockade, achieved either by angiotensin converting enzyme inhibitors or angiotensin receptor blocking agents, was assessed using 30-day mortality as a primary end point. METHODS: An observational cohort study of 883 consecutive patients undergoing elective open abdominal aortic aneurysm repair (AAA) was undertaken and analyzed using a propensity score matched study. The data collected included medical history, anesthetic techniques, and postoperative outcomes. Logistic regression analysis identified predictors of RAS blockade: hypertension, stroke, congestive heart failure, diabetes, and heart disease. A propensity score for RAS blockade was calculated for each subject using several factors: age, sex, serum creatinine, hypertension, heart disease, congestive heart failure, stroke, diabetes, and exposure to cardiovascular medications. Subjects and controls were matched using the calculated propensity score. RESULTS: The overall 30-day mortality rate was 3.5% (31/883 patients). The crude mortality rate in RAS blocked patients was 5.8% (21/359) vs 1.9% (10/524) in unexposed patients (odds ratio 3.2, with 95% confidence intervals [CI(95)] 1.5-6.7; P < 0.001). Analysis of 261 propensity score matched pairs showed a 30-day mortality rate of 6.1% (16/261) in the RAS blocked group vs 1.5% (4/261) in unblocked patients (P = 0.008). The estimated odds ratio for 30-day mortality associated with RAS blockade was 5.0 (CI(95) 1.4-27). CONCLUSIONS: Examination of 883 cases of AAA repair showed increased mortality associated with preoperative RAS blockade. A better understanding of perioperative pharmacology and physiology of RAS blockade is needed as well as future studies to identify causality.

Determinants of aciclovir-induced nephrotoxicity in children.

BACKGROUND: Aciclovir is the drug of choice for severe systemic herpes virus infections. Nephrotoxicity is one of the clinically significant adverse effects of this drug, but studies examining nephrotoxicity in children are scarce. OBJECTIVE: To identify risk factors for aciclovir-associated nephrotoxicity in the pediatric population. PATIENTS AND METHODS: A retrospective review was conducted on all children (mean age 81 months; n = 126 [74 boys]) who were treated with aciclovir in a tertiary center between July 2005 and January 2006 and who met our inclusion criteria. Glomerular filtration rate (GFR) was calculated on the first day of treatment and at the peak measured creatinine level while on therapy, using Schwartz's method. RESULTS: Aciclovir therapy was associated with a significant increase in serum creatinine levels and a parallel decrease in GFR (n = 93; both p

The weekly cost of nausea and vomiting of pregnancy for women calling the Toronto Motherisk Program.

BACKGROUND: Nausea with or without vomiting of pregnancy (NVP) is the most common medical condition in pregnancy. NVP, even with mild symptoms, is associated with costs to society, patients, and the health care system. OBJECTIVE: The main objective of this study was to estimate the total direct and indirect costs per woman-week associated with the onset of NVP in Canada from the perspective of society. METHODS: A cost of illness study was performed to estimate the cost per woman-week associated with the onset of NVP in Canada, stratified according to the severity of NVP. Data were collected from 139 pregnant women, who called the Motherisk Program at the Hospital for Sick Children in Toronto. Results are reported in 2005 Canadian dollars. RESULTS: From the perspective of society, the total cost per woman-week was $132 ($114 indirect and $18 direct costs), $355 ($271 indirect and $84 direct costs), and $653 ($494 indirect and $159 direct costs) for women with mild, moderate, and severe NVP, respectively. Costs increased with increasing severity of NVP. CONCLUSIONS: Nausea and vomiting of pregnancy imposes an economic burden, particularly with respect to productivity losses. Limitations of the study could be potential recall bias, the unavailability of household income and follow-up interviews.

Child neurodevelopmental outcome and maternal occupational exposure to solvents.

BACKGROUND: Many women of reproductive age are employed in industries involving exposure to organic solvents. Animal toxicological studies and human case reports demonstrate that high exposure to solvents causes neurodevelopmental toxicity in exposed offspring. Data from occupationally exposed women and their children are few. OBJECTIVE: To compare the cognitive, language, and motor performance and the behavioral achievements of children whose mothers were exposed occupationally to organic solvents during pregnancy with those of a matched unexposed control group. PARTICIPANTS: Thirty-two pregnant women occupationally exposed to organic solvents were recruited during pregnancy and followed up. Their offspring (age range, 3-9 years) were tested for cognitive functioning (IQ), language, visual-motor functioning, and behavioral functioning and were compared with a matched unexposed control group that was recruited and tested in a similar manner. Examiners were blinded to the exposure status. RESULTS: Mothers occupationally exposed to organic solvents did not differ significantly from matched controls in demographic variables. After controlling for potential confounding because of maternal IQ and maternal education, children exposed in utero to organic solvents obtained lower scores on subtests of intellectual, language, motor, and neurobehavioral functioning. CONCLUSIONS: In utero exposure to organic solvents is associated with poorer performance on some specific subtle measures of neurocognitive function, language, and behavior. Reducing exposure in pregnancy is merited until more refined risk assessment is possible. Further studies that address exposure to specific solvents, dose, and gestational timing of exposure are needed.

Recall bias of the symptoms of nausea and vomiting of pregnancy.

OBJECTIVE: Nausea and vomiting of pregnancy is the most common medical condition in pregnancy. Relatively little research has been conducted on this condition, and much of it is based on women's reports. Determinants that affect women's reports of their nausea and vomiting of pregnancy symptoms have not been elucidated. The purpose of this study was to assess the accuracy of recall by women of their symptoms of nausea and vomiting of pregnancy. STUDY DESIGN: Two hundred women who called the Motherisk nausea and vomiting of pregnancy counseling line in Toronto were asked about the severity of their nausea and vomiting of pregnancy symptoms with the use of the pregnancy unique quantification of emesis and nausea system (PUQE). The patients were asked the same questions again during a follow-up call, which took place up to 16 weeks later. RESULTS: There was a recall (or reporting) bias for nausea and vomiting, with women reporting significantly more severe symptoms during their follow-up call than they had reported originally. Multivariate analysis revealed that the severity of the symptoms affected the accuracy of recall positively, whereas the time that has elapsed affected it negatively. CONCLUSION: Retrospective evaluation of nausea and vomiting of pregnancy symptoms may produce a recall bias, which may distort the evaluation of the therapeutic effectiveness of antiemetics.

Diclectin therapy for nausea and vomiting of pregnancy: effects of optimal dosing.

OBJECTIVES: (1) To quantify rates of suboptimal use of pyridoxine hydrochloride-doxylamine (Diclectin); and (2) to study responses to optimal doses of Diclectin in women previously taking a suboptimal dose. METHODS: Women who called the Motherisk NVP helpline, and were taking only Diclectin (vitamin B6 10 mg and doxylamine 10 mg), were enrolled in the study and assessed for the severity of nausea and vomiting of pregnancy (NVP) with the Motherisk-PUQE (pregnancy-unique quantification of emesis and nausea) scoring system. Their Diclectin doses were subsequently increased according to body weight and individual symptoms. A follow-up phone call occurred within 1 to 3 weeks after the intervention, at which time the overall PUQE score was repeated, along with individual scoring of symptoms of nausea, vomiting, and retching. RESULTS: Sixty-eight women were enrolled and completed the study. Despite moderate to severe NVP, defined by the validated PUQE scoring system, most women (50/68) were receiving 2 tablets a day of Diclectin instead of the recommended dose of 4 tablets a day. Following a mean doubling of the dose to 4 tablets a day, there was a significant decrease in length of nausea (from 4 to 3 hours, P < 0.001), frequency of vomiting (from mean 1.6 to 1.3 a day, P = 0.02), and overall PUQE score (from mean 7.5 to 6.1, P < 0.001). CONCLUSION: Women suffering from NVP are often given subtherapeutic doses of Diclectin. Women should receive a dosage according to their body weight and severity of their symptoms.

Child development following exposure to tricyclic antidepressants or fluoxetine throughout fetal life: a prospective, controlled study.

OBJECTIVE: Previous work suggested that first-trimester exposure to tricyclic antidepressants or fluoxetine does not affect adversely child IQ and language development. However, many women need antidepressants throughout pregnancy to avoid morbidity and suicide attempts. Little is known about the fetal safety of tricyclic antidepressants and fluoxetine when taken throughout pregnancy. The goal of this study was to assess the effects of tricyclic antidepressants and fluoxetine used throughout gestation on child IQ, language, and behavior. METHOD: In a prospective study, mother-child pairs exposed throughout gestation to tricyclic antidepressants (N=46) or fluoxetine (N=40) and an unexposed, not depressed comparison group (N=36) were blindly assessed. The three groups were compared in terms of the children's IQ, language, behavior, and temperament between ages 15 and 71 months. The authors adjusted for independent variables such as duration and severity of maternal depression, duration of pharmacological treatment, number of depression episodes after delivery, maternal IQ, socioeconomic status, cigarette smoking, and alcohol use. RESULTS: Neither tricyclic antidepressants nor fluoxetine adversely affected the child's global IQ, language development, or behavior. IQ was significantly and negatively associated with duration of depression, whereas language was negatively associated with number of depression episodes after delivery. CONCLUSIONS: Exposure to tricyclic antidepressants or fluoxetine throughout gestation does not appear to adversely affect cognition, language development, or the temperament of preschool and early-school children. In contrast, mothers' depression is associated with less cognitive and language achievement by their children. When needed, adequate antidepressant therapy should be instituted and maintained during pregnancy and postpartum.