Tarek A. Hammad

Risk of suicidality in clinical trials of antidepressants in adults: analysis of proprietary data submitted to US Food and Drug Administration

Objective To examine the risk of suicidal behaviour within clinical trials of antidepressants in adults. Design Meta-analysis of 372 double blind randomised placebo controlled trials. Setting Drug development programmes for any indication in adults. Participants 99 231 adults assigned to antidepressants or placebo. Median age was 42 and 63.1% were women. Indications for treatment were major depression (45.6%), other depression (4.6%), other psychiatric disorders (27.6%), and non-psychiatric disorders (22.2%). Main outcome measures Suicidal behaviour (completed suicide, attempted suicide, or preparatory acts) and ideation. Results For participants with non-psychiatric indications, suicidal behaviour and ideation were extremely rare. For those with psychiatric indications, risk was associated with age. For suicidal behaviour or ideation and for suicidal behaviour only, the respective odds ratios were 1.62 (95% confidence interval 0.97 to 2.71) and 2.30 (1.04 to 5.09) for participants aged <25, 0.79 (0.64 to 0.98) and 0.87 (0.58 to 1.29) for those aged 25-64, and 0.37 (0.18 to 0.76) and 0.06 (0.01 to 0.58) for those aged ≥65. When age was modelled as a continuous variable, the odds ratio for suicidal behaviour or ideation declined at a rate of 2.6% per year of age (−3.9% to −1.3%, P=0.0001) and the odds ratio for suicidal behaviour declined at a rate of 4.6% per year of age (−7.4% to −1.8%, P=0.001). Conclusions Risk of suicidality associated with use of antidepressants is strongly age dependent. Compared with placebo, the increased risk for suicidality and suicidal behaviour among adults under 25 approaches that seen in children and adolescents. The net effect seems to be neutral on suicidal behaviour but possibly protective for suicidal ideation in adults aged 25-64 and to reduce the risk of both suicidality and suicidal behaviour in those aged ≥65.

Relationship between blood lead and dietary iron intake in preschool children: A cross-sectional study☆

The relationship between dietary iron intake and blood lead levels in urban preschool children was investigated in a cross-sectional study of 299 children from 9 months to 5 years old. Mothers of children attending the University of Maryland Pediatric Ambulatory Clinic volunteered for the children and themselves to join the study. The data collected included nutritional status, socioeconomic status, medical history, and potential sources of lead exposure. Blood samples from all participants were evaluated for levels of blood lead, serum iron (ferritin), free erythrocyte protoporphyrin, calcium, and hematocrit. The average blood lead level (standard deviation) in the studied population was 11.4 (7.3) micrograms/dL. With multiple linear and logistic regression analyses to adjust for covariates, a negative association (P = 0.03) between blood lead and dietary iron intake was found. This finding is consistent with similar results from experimental studies. It is concluded that there is evidence that higher dietary iron intake is associated with lower blood lead among urban preschool children in the studied population.

Cancer recording and mortality in the General Practice Research Database and linked cancer registries

Large electronic datasets are increasingly being used to evaluate healthcare delivery. The aim of this study was to compare information held by cancer registries with that of the General Practice Research Database (GPRD).

Hallucinations and Other Psychotic Symptoms Associated With the Use of Attention-Deficit/Hyperactivity Disorder Drugs in Children

OBJECTIVES. To gain a better understanding of the capacity of psychostimulant medications to induce adverse psychiatric reactions and determine the frequency of such reactions, we analyzed postmarketing surveillance data and clinical trial data for drugs, either approved or under development, for the treatment of attention-deficit/hyperactivity disorder. METHODS. The US Food and Drug Administration requested manufacturers of drugs approved for attention-deficit/hyperactivity disorder or with active clinical development programs for that indication to search their electronic clinical trial databases for cases of psychosis or mania using prespecified search terms. The manufacturers supplied descriptions of clinical trials, numbers of patients exposed to study drug, and duration of exposure to permit calculations of incidence rates. Independently, cases of psychosis or mania in children and adults for drugs used to treat attention-deficit/hyperactivity disorder from the Food and Drug Administration Adverse Event Reporting System safety database were analyzed. Manufacturers were asked to conduct similar analyses of their postmarketing surveillance databases. RESULTS. We analyzed data from 49 randomized, controlled clinical trials in the pediatric development programs for these products. A total of 11 psychosis/mania adverse events occurred during 743 person-years of double-blind treatment with these drugs, and no comparable adverse events occurred in a total of 420 person-years of placebo exposure in the same trials. The rate per 100 person-years in the pooled active drug group was 1.48. The analysis of spontaneous postmarketing reports yielded >800 reports of adverse events related to psychosis or mania. In ∼90% of the cases, there was no reported history of a similar psychiatric condition. Hallucinations involving visual and/or tactile sensations of insects, snakes, or worms were common in cases in children. CONCLUSIONS. Patients and physicians should be aware that psychosis or mania arising during drug treatment of attention-deficit/hyperactivity disorder may represent adverse drug reactions.

Determining the predictive value of Read/OXMIS codes to identify incident acute myocardial infarction in the General Practice Research Database

To determine (1) the positive predictive value (PPV) of multiple Read/OXMIS codes to identify incident acute myocardial infarction (AMI) cases in General Practice Research Database (GPRD); (2) the ability to capture the correct timing of the clinical event.

Validity of health plan and birth certificate data for pregnancy research

To evaluate the validity of health plan and birth certificate data for pregnancy research.

Massage with kinesthetic stimulation improves weight gain in preterm infants

Objective:The aim of this study was to evaluate the effects of massage with or without kinesthetic stimulation on weight gain and length of hospital stay in the preterm infant.Study Design:A prospective randomized clinical trial was conducted evaluating the effects of massage with or without kinesthetic stimulation (KS) on weight gain and length of stay (LOS) in medically stable premature (<1500 g and/or ⩽32 weeks gestational age) neonates. Infants were randomized either to receive no intervention (control), massage therapy alone (massage), or massage therapy with KS (M/KS). Linear regression analysis was performed to evaluate differences in the primary outcomes between the groups after controlling for covariates. Post hoc analysis with stratification by birthweight (BW> and <1000 g) was also performed.Result:A total of 60 premature infants were recruited for this study; 20 infants in each group. Average daily weight gain and LOS were similar between the groups after controlling for covariates. For infants with BW>1000 g, average daily weight gain was increased in the intervention groups compared to control. This effect was mainly attributable to the M/KS group.Conclusion:Massage with KS is a relatively simple and inexpensive intervention that can improve weight gain in selected preterm infants. Length of hospital stay is not impacted by massage with or without KS. Further studies are needed to evaluate the effect of massage in the extremely low BW(<1000 g) infant.

Trends in the use of antiepileptic drugs among pregnant women in the US, 2001-2007: a medication exposure in pregnancy risk evaluation program study

BACKGROUND Little is known about the extent of antiepileptic drug (AED) use in pregnancy, particularly for newer agents. Our objective was to assess whether AED use has increased among pregnant women in the US, 2001-2007. METHODS   We analysed data from the Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP) database, 1 January 2001 to 31 December 2007. We identified liveborn deliveries among women, aged 15-45 years on delivery date, who were members of MEPREP health plans (n=585615 deliveries). Pregnancy exposure to AEDs, determined through outpatient pharmacy dispensing files. Older AEDs were available for clinical use before 1993; other agents were considered newer AEDs. Information on sociodemographic and medical/reproductive factors was obtained from linked birth certificate files. Maternal diagnoses were identified based on ICD-9 codes. RESULTS   Prevalence of AED use during pregnancy increased between 2001 (15.7 per 1000 deliveries) and 2007 (21.9 per 1000 deliveries), driven primarily by a fivefold increase in the use of newer AEDs. Thirteen per cent of AED-exposed deliveries involved a combination of two or more AEDs. Psychiatric disorders were the most prevalent diagnoses, followed by epileptic and pain disorders, among AED users regardless of AED type, year of conception or gestational period. CONCLUSIONS   AED use during pregnancy increased between 2001 and 2007, driven by a fivefold increase in the use of newer AEDs. Nearly one in eight AED-exposed deliveries involved the concomitant use of more than one AED. Additional investigations of the reproductive safety of newer AEDs may be needed.

Description of hypersensitivity adverse events following administration of heparin that was potentially contaminated with oversulfated chondroitin sulfate in early 2008

To characterize the nature of a heparin contaminants clinical effects in cases reported to the Adverse Event Reporting System (AERS). The FDA received reports of heparin‐associated adverse events (AEs) starting in late 2007–early 2008 during a national investigation of allergic‐type events. The investigation identified Baxter Healthcare‐brand heparin product due to its strongest association with the events. Later, oversulfated chondroitin sulfate (OSCS), a heparin‐like contaminant, was discovered.

The identification of pregnancies within the general practice research database

The United States is moving toward active drug safety surveillance using sources such as administrative claims and electronic medical records, but use of these data for studying teratogenicity has been challenging, as they typically do not allow for the easy identification of pregnancies. Our goal was to develop and validate an algorithm for the identification of pregnancies in the general practice research database (GPRD) that could be used to study pregnancy outcomes.