Odile Sheehy

Osteoporosis among patients with type 1 and type 2 diabetes.

Both diabetes and fractures are prevalent in adults. The relationship between diabetes and osteoporosis is complex and, although it has been investigated extensively, the subject remains controversial. While low bone mineral density (BMD) is consistently observed in type 1 diabetes, the relationship is less clear in type 2 diabetes, with some studies reporting modestly increased or unchanged BMD. Both type 1 and type 2 diabetes have been associated with a higher risk of fractures. Despite discrepancies between BMD and fracture rates, clinical trials uniformly support the fact that new bone formation and bone microarchitecture and, thus, bone quality, are altered in both types of diabetes. Although a causal association between diabetes and osteoporosis cannot be established on the basis of existing data, it is possible to conclude from many studies and from a better understanding of the physiopathology of diabetes that it can increase the risk of fractures through skeletal (decreased BMD and bone quality) and extraskeletal (increased risk of falls) factors. Even though osteoporosis screening or prophylactic treatment in all patients with type 1 and type 2 diabetes is not being recommended at present, such patient populations should be given general guidelines regarding calcium and vitamin D intakes, exercise and the avoidance of potential risk factors for osteoporosis. The extent of diagnostic and therapeutic interventions should be based on the individuals risk profile for fractures.

Clinical consequences of generic substitution of lamotrigine for patients with epilepsy

CLINICAL CONSEQUENCES OF GENERIC SUBSTITUTION OF LAMOTRIGINE FOR PATIENTS WITH EPILEPSY To the Editor: LeLorier et al.1 studied the risks associated with patients switching to and from generic antiepileptic drugs (AEDs) in Quebec. The authors did not consider that such changes could be attributed to promotionally driven doctor and patient preferences. Industry representatives vigorously promote the idea that generics are less potent (“up to 20% less effective”) than their brand name equivalents despite Food and Drug Administration (FDA) assertions to the contrary.2 Study patients taking generics underwent dose escalations. The authors suggest that dose escalations were in response to increased side effects, but this is counterintuitive. More plausibly, anxietyinduced dose escalations contributed to side effects and, in turn, switch-backs. The unspoken hypothesis that switches to generic led to more seizures is unaddressed by the presented data, which blur psychiatric and neurologic indications for lamotrigine (LTG). LTG is used heavily in psychiatry and most recent growth in sales is driven by the psychiatric market.3 A single claim submitted with a code for epilepsy is considered sufficient evidence that LTG is being prescribed as an AED, but this is unlikely. The leading outpatient diagnostic code as well as four of five diagnostic codes for outpatient visits and two of three diagnostic codes for inpatient hospitalizations were not for epilepsy. By contrast, all comparator non-AED drugs in this study lent themselves to readily available objective efficacy assessment (blood pressure and lipid levels). There is no such equivalent for any LTG indication. FDA standards for generic bioequivalence are the same standards applied to branded medication for between-batch variability.2 Bioequivalence is complex.4 For example, the area under the curve and maximum concentration but not time to maximum (tmax) concentration are used by the FDA in determining bioequivalence. Manufacturer disclosures of bioequivalence data indicate that branded LTG tmax varies from half an hour to 6 hours for various formulations of the 100 mg tablets.5 Clinical relevance of FDA-permitted variance within a brand or between brand and generic medication is unclear. Millions of doses of generic medications have been dispensed with no well-documented instances of therapeutic failures for medications produced in accordance with existing FDA standards.4 It is clear that promotional activity influences prescribing behavior. Furthermore, under experimental conditions, expensive placebos are more effective.6 Not only patients but neurologists are anxious about generic medications encouraged in this regard by controversial American Academy of Neurology (AAN) policies on generic substitution of AEDs.7 The authors should compare switches to and from generics by specialty of the prescriber (neurologist, psychiatrist, primary care) and by first indication for which the medication was prescribed, stratifying by promotional dollars spent per indication and specialty.

Use of nonaspirin nonsteroidal anti-inflammatory drugs during pregnancy and the risk of spontaneous abortion

Background: The association between the use of nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) during pregnancy and the risk of spontaneous abortion remains unclear because of inconsistent research results and the lack of evidence for an effect due to specific types or dosages of nonaspirin NSAIDs. We aimed to quantify the association between having a spontaneous abortion and types and dosages of nonaspirin NSAIDs in a cohort of pregnant women. Methods: Using a nested case–control design, we obtained data from the Quebec Pregnancy Registry for 4705 women who had a spontaneous abortion. For each instance, we randomly selected 10 controls from the remaining women in the registry who were matched by index date (date of the spontaneous abortion) and gestational age. Use of nonaspirin NSAIDs (identified by filled prescriptions) and nonuse were compared. We also looked for associations between different types and dosages of nonaspirin NSAIDs and having a spontaneous abortion. Analyses of associations and adjustment for confounding were done using conditional logistic regression. Results: We identified 4705 cases of spontaneous abortion (352 exposed [7.5%]); 47 050 controls (1213 exposed [2.6%]). Adjusting for potential confounders, the use of nonaspirin NSAIDs during pregnancy was significantly associated with the risk of spontaneous abortion (odds ratio [OR] 2.43, 95% confidence interval [CI] 2.12–2.79). Specifically, use of diclofenac (OR 3.09, 95% CI 1.96–4.87), naproxen (OR 2.64, 95% CI 2.13–3.28), celecoxib (OR 2.21, 95% CI 1.42–3.45), ibuprofen (OR 2.19, 95% CI 1.61–2.96) and rofecoxib (OR 1.83, 95% CI 1.24–2.70) alone, and combinations thereof (OR 2.64, 95% CI 1.59–4.39), were all associated with increased risk of spontaneous abortion. No dose–response effect was seen. Interpretation: Gestational exposure to any type or dosage of nonaspirin NSAIDs may increase the risk of spontaneous abortion. These drugs should be used with caution during pregnancy

Reliability and validity of the 4‐item perceived stress scale among pregnant women: Results from the OTIS antidepressants study

We aimed to estimate the reliability of the 4-item Perceived Stress Scale (PSS) and its validity in predicting maternal depression and quality of life (QoL). Data regarding stress, depression and QoL were collected during pregnancy among a sub-sample from the Organization of Teratology Information Specialists Antidepressants in Pregnancy Cohort. The 4-item PSS demonstrated acceptable internal consistency (Cronbachs alpha coefficient = .79), alternate forms stability reliability with the 10-item PSS (Pearson correlation coefficient r = .63; p < .001), convergent validity with the Edinburgh Postnatal Depression Scale (r = .67; p < .001), and concurrent validity with the mental health component of the Short-Form-12 (r = -.62; p < .001) as a measure of QoL. The 4-item PSS is a valid and useful tool for assessing maternal stress during pregnancy.

The Quebec Pregnancy Cohort – Prevalence of Medication Use during Gestation and Pregnancy Outcomes

Purpose We evaluated the potential and the validity of the Quebec Pregnancy Cohort (QPC) as a research tool in perinatal pharmacoepidemiology. Methods The QPC was built by linking four administrative databases: RAMQ (medical and pharmaceutical data), Med-Echo (hospitalizations), ISQ (births/deaths), and MELS (Ministry of Education data). A self-administered questionnaire was sent to a random sample of women to collect lifestyle information. The QPC includes data on all pregnancies of women covered by the Quebec provincial prescription drug insurance between 1998 and 2008. Date of entry in the QPC is the first day of pregnancy, and women are followed during and after pregnancy; children are followed after birth up until 2009. The prevalence of prescribed medications before, during and after pregnancy was compared between time-window. Pregnancy outcomes were also estimated among pregnancies ending with a live born infant. Results The QPC included 289,688 pregnancies of 186,165 women. Among them, 167,398 ended with a delivery representing 19.4% of all deliveries occurring in the Province of Quebec between 1998–2009. The total frequency of abortions was 35.9% in the QPC comparable to the 36.4% observed in the Province of Quebec. The prevalence of prescribed medication use was 74.6%, 59.0%, and 79.6% before, during and after pregnancy, respectively. Although there was a statistically significant decrease in the proportion of use once the pregnancy was diagnosed (p<.01), post-pregnancy prescribed medication use returned above the pre-pregnancy level. The prevalence of pregnancy outcomes found in the QPC were similar to those observed in the Province of Quebec. Conclusion The QPC is an excellent tool for the study of the risk and benefit of drug use during the perinatal period. This cohort has the advantage of including a validated date of beginning of pregnancy giving the possibility of assigning the exact gestational age at the time of maternal exposure.

Economic impact of generic substitution of lamotrigine: projected costs in the US using findings in a Canadian setting.

ABSTRACT Background: Generic substitution may not always save health care costs for antiepileptic drugs (AED). Objective: (1) To examine the economic impacts of generic substitution of lamotrigine in Canada; and (2) to convert observed Canadian costs to a United States (US) setting. Methods: Health claims from Québecs health plan (RAMQ) between 08/2002 and 07/2006 were analyzed. Patients with ≥ 1 epilepsy claim and treated with branded lamotrigine (Lamictal*) before generic entry were selected. Health care costs (

Sertraline use during pregnancy and the risk of major malformations

/person-year) were compared during periods of branded and generic use of lamotrigine. Two cost-conversion methods were employed; one using purchasing power parities, US/Canada service use ratios, and exchange rate, and another employing Canadian health care utilization and US unit costs. Results: 671 patients were observed during 1650.9 and 291.2 person-years of branded and generic use of lamotrigine, respectively. The generic-use period was associated with an increase in overall costs (2006 constant Canadian dollars) relative to brand use (C

Antiepileptic drug use during pregnancy: perinatal outcomes.

7902 vs. C

Risk of Spontaneous Intracranial Hemorrhage in HIV-infected Individuals: A Population-based Cohort Study

6419/person-year; cost ratio (CR) = 1.22; p = 0.05), despite the lower cost of generic lamotrigine. Non-lamotrigine costs were 33% higher in the generic period ( p = 0.013). Both conversion methods yielded increases in total projected health care costs excluding lamotrigine (2006 constant US dollars) during the generic period (Method 1: cost difference: US

Savings in direct medical costs from the use of tobramycin solution for inhalation in patients with cystic fibrosis.

1758/person-year, CR = 1.33, p = 0.01); Method 2: cost difference: US