The Role of Marital Status in the Association between Benzodiazepines,Psychotropics and Injurious Road Traffic Crashes: A Register-Based Nationwide Study of Senior Drivers in Sweden

Background

Among senior drivers, benzodiazepines (BZDs) have a documented effect on the risk of road traffic crashes (RTCs). It remains unclear however if BZDs play the same role when considering marital status. Therefore, we aimed to investigate the role of marital status in the association between BZD use and injurious RTCs among senior drivers.

Methods

Matched case-control study based on five national Swedish registers (n = 154 225). Cases comprised the first non-alcohol-related injurious RTC sustained by drivers aged 50–80 years from July 2005 to December 2009 and controls included registered residents with a valid license who did not crash during that period. Four controls were matched to each case by sex, age and place of residence. Conditional logistic regression analysis for injurious RTC was performed with adjustment for occupation and number of medications. The main exposure was dispensation of BZDs, alone or in combination with other psychotropic medications, 1–30 days prior to the crash date stratified by marital status.

Results

BZD use, alone or in combination with other psychotropic medications, increased the risk of being involved in an RTC (BZD only: adjusted OR: 1.26, 95% CI: 1.17–1.36; BZDs and other psychotropics: adjusted OR: 1.25, 95% CI: 1.12–1.41). Compared to married drivers, those divorced (1.48, 1.43–1.53) and widowed (1.54; 1.45–1.63) had higher adjusted ORs. Marital status modified the association between BZDs and RTCs, particularly among younger male drivers.

Conclusions

Both BZDs and marital status independently affect the risk for senior drivers to be involved in an RTC. However, marital status plays a role in the association between BZD use and RTCs and this may have implications for targeting risk populations for RTCs among senior drivers.     

The Increased Risk of Road Crashes in Attention Deficit Hyperactivity Disorder (ADHD) Adult Drivers: Driven by Distraction? Results from a Responsibility Case-Control Study

Background and Objective

Both distractions (external and internal) and attention-deficit/hyperactivity disorder (ADHD) are serious risk factors for traffic crashes and injuries. However, it is still unknown if ADHD (a chronic condition) modifies the effect of distractions (irregular hazards) on traffic crashes. The objective of this study was to assess the effects of distractions and ADHD on traffic crash responsibility.

Methods

A responsibility case-control study was conducted in the adult emergency department of Bordeaux University Hospital, France. Subjects were recruited among drivers injured in a motor vehicle crash between April 2010 and August 2011. Responsibility levels were estimated using a standardized method. Frequencies of exposures were compared between drivers responsible and drivers not responsible for the crash. Independent risk factors were identified using a multivariate logistic regression including test interactions between distractions and ADHD.

Results

A total of 777 subjects were included in the analysis. Factors associated with responsibility were distraction induced by an external event (adjusted OR (aOR)  = 1.47; 95% confidence interval (CI) [1.06–2.05]), distraction induced by an internal thought (aOR = 2.38; CI: [1.50–3.77]) and ADHD (aOR = 2.18 CI: [1.22–3.88]). The combined effect of ADHD and external distractions was strongly associated with responsibility for the crash (aOR = 5.79 CI: [2.06–16.32]). Interaction assessment showed that the attributable proportion due to the interaction among participants with both exposures was 68%.

Discussion

Adults with ADHD are a population at higher risk of being responsible for a road traffic crash when exposed to external distractions. This result reinforces the need to diagnose adult ADHD and to include road safety awareness messages delivered by the physician. Developing advanced driver assistance systems devoted to the management of attention lapses is also increasingly relevant for these drivers.     

What Influences the Association between Previous and Future Crashes among Cyclists? A Propensity Score Analysis

Background

It is known that experience of a previous crash is related to incidence of future crashes in a cohort of New Zealand cyclists. This paper investigated if the strength of such association differed by crash involvement propensity and by the need for medical care in the previous crash.

Methods

The Taupo Bicycle Study involved 2590 adult cyclists recruited in 2006 and followed over a median period of 4.6 years through linkage to four national databases. The crash involvement propensity was estimated using propensity scores based on the participants'' demographic, cycling and residential characteristics. Cox regression modelling for repeated events was performed with multivariate and propensity score adjustments. Analyses were then stratified by quintiles of the propensity score.

Results

A total of 801 (31.0%) participants reported having experienced at least one bicycle crash in the twelve months prior to the baseline survey. They had a higher risk of experiencing crash events during follow-up (hazard ratio (HR): 1.43; 95% CI: 1.28, 1.60) but in the stratified analysis, this association was significant only in the highest two quintiles of the propensity score where the likelihood of having experienced a crash was more than 33%. The association was stronger for previous crashes that had received medical care (HR 1.63; 95% CI: 1.41, 1.88) compared to those that had not (HR 1.30; 95% CI: 1.14, 1.49).

Conclusions

Previous crash experience increased the risk of future crash involvement in high-risk cyclists and the association was stronger for previous crashes attended medically. What distinguishes the high risk group warrants closer investigation, and the findings indicate also that health service providers could play an important role in prevention of bicycle crash injuries.     

Complaints of Poor Sleep and Risk of Traffic Accidents: A Population-Based Case-Control Study

Introduction

This study aimed to determine the sleepiness-related factors associated with road traffic accidents.

Methods

A population based case-control study was conducted in 2 French agglomerations. 272 road accident cases hospitalized in emergency units and 272 control drivers matched by time of day and randomly stopped by police forces were included in the study. Odds ratios were calculated for the risk of road traffic accidents.

Results

As expected, the main predictive factor for road traffic accidents was having a sleep episode at the wheel just before the accident (OR 9.97, CI 95%: 1.57–63.50, p<0.05). The increased risk of traffic accidents was 3.35 times higher in subjects who reported very poor quality sleep during the last 3 months (CI 95%: 1.30–8.63, p<0.05), 1.69 times higher in subjects reporting sleeping 6 hours or fewer per night during the last 3 months (CI 95%: 1.00–2.85, p<0.05), 2.02 times higher in subjects reporting symptoms of anxiety or nervousness in the previous day (CI 95%: 1.03–3.97, p<0.05), and 3.29 times higher in subjects reporting taking more than 2 medications in the last 24 h (CI 95%: 1.14–9.44, p<0.05). Chronic daytime sleepiness measured by the Epworth Sleepiness Scale, expressed heavy snoring and nocturnal leg movements did not explain traffic accidents.

Conclusion

Physicians should be attentive to complaints of poor sleep quality and quantity, symptoms of anxiety-nervousness and/or drug consumption in regular car drivers.     

Brain activation during processing of angry facial expressions in patients with alcohol dependency

Background

Alcoholism is associated with abnormal anger processing. The purpose of this study was to investigate brain regions involved in the evaluation of angry facial expressions in patients with alcohol dependency.

Methods

Brain blood-oxygenation-level-dependent (BOLD) responses to angry faces were measured and compared between patients with alcohol dependency and controls.

Results

During intensity ratings of angry faces, significant differences in BOLD were observed between patients with alcohol dependency and controls. That is, patients who were alcohol-dependent showed significantly greater activation in several brain regions, including the dorsal anterior cingulate cortex (dACC) and medial prefrontal cortex (MPFC).

Conclusions

Following exposure to angry faces, abnormalities in dACC and MPFC activation in patients with alcohol dependency indicated possible inefficiencies or hypersensitivities in social cognitive processing.     

Prevalence and Factors Associated with Road Traffic Crash among Taxi Drivers in Mekelle Town,Northern Ethiopia, 2014: A Cross Sectional Study

Objectives

The 2013 World Health Organization Status Report on Road Safety estimated that approximately 1.24 million deaths occur annually due to road traffic crashes with most of the burden falling on low- and middle-income countries. The objective of this research is to study the prevalence of road traffic crashes in Mekelle, Tigray, Northern Ethiopia and to identify risk factors with the ultimate goal of informing prevention activities and policies.

Methods

This study used a cross-sectional design to measure the prevalence and factors associated with road traffic crashes among 4-wheeled minibus (n = 130) and 3-wheeled Bajaj (n = 582) taxi drivers in Mekelle, Ethiopia. Bivariate and multivariate logistic regression were used to evaluate the association between risk factors and drivers’ involvement in a road traffic crash within the 3 years prior to the survey.

Findings

Among the 712 taxi drivers, 26.4% (n = 188) of them reported involvement in a road traffic crash within the past 3 years. Drivers who listened to mass media had decreased likelihood of road traffic crash involvement (AOR = 0.51, 0.33–0.78), while speedy driving (AOR = 4.57, 3.05–7.44), receipt of a prior traffic punishment (AOR = 4.57, 2.67–7.85), and driving a mechanically faulty taxi (AOR = 4.91, 2.81–8.61) were strongly associated with road traffic crash involvement. Receiving mobile phone calls while driving (AOR = 1.91, 1.24–2.92) and history of alcohol use (AOR = 1.51, 1.00–2.28) were also associated with higher odds of road traffic crash involvement.

Conclusion

The results of this study show that taxi drivers in Mekelle habitually place themselves at increased risk of road traffic crashes by violating traffic laws, especially related to speedy driving, mobile phone use, and taxi maintenance. This research can be used to support re-evaluation of the type, severity, and enforcement of traffic violation penalties.     

Alcohol Intake in Pregnancy Increases the Child's Risk of Atopic Dermatitis. The COPSAC Prospective Birth Cohort Study of a High Risk Population

Background

Atopic dermatitis has increased four-fold over the recent decades in developed countries, indicating that changes in environmental factors associated with lifestyle may play an important role in this epidemic. It has been proposed that alcohol consumption may be one contributing risk factor in this development.

Objective

To analyze the impact of alcohol intake during pregnancy on the development of atopic dermatitis during the first 7 years of life.

Method

The COPSAC cohort is a prospective, longitudinal, birth cohort study of 411 children born to mothers with a history of asthma, followed up for 7 years with scheduled visits every 6 months as well as visits for acute exacerbations of atopic dermatitis. Risk of atopic dermatitis from any alcohol consumption during pregnancy was analyzed as time-to-diagnosis and adjusted for known risk factors.

Results

177 of 411 children developed atopic dermatitis before age 7 years. We found a significant effect of alcohol intake during pregnancy on atopic dermatitis development (HR 1.44, 95% CI 1.05–1.99 p = 0.024). This conclusion was unaffected after adjustment for smoking, mother''s education and mother''s atopic dermatitis.

Limitations

The selection of a high-risk cohort, with all mothers suffering from asthma, and all children having a gestational age above 35 weeks with no congenital abnormality, systemic illness, or history of mechanical ventilation or lower airway infection.

Conclusion

Alcohol intake by pregnant women with a history of asthma, is significantly associated with an increased risk for the child for developing atopic dermatitis during the first 7 years of life.     

Alcohol Consumption and Breast Cancer Risk among Women in Three Sub-Saharan African Countries

Background

Alcohol drinking is linked to the development of breast cancer. However, there is little knowledge about the impact of alcohol consumption on breast cancer risk among African women.

Methods

We conducted a case-control study among 2,138 women with invasive breast cancer and 2,589 controls in Nigeria, Cameroon, and Uganda from 1998 to 2013. A structured questionnaire was used to collect information on alcohol consumption, defined as consuming alcoholic beverages at least once a week for six months or more. Logistic regression was used to estimate adjusted odds ratio (aOR) and 95% confidence interval (CI).

Results

Among healthy controls, the overall alcohol consumption prevalence was 10.4%, and the prevalence in Nigeria, Cameroon, and Uganda were 5.0%, 34.6%, and 50.0%, respectively. Cases were more likely to have consumed alcohol (aOR = 1.62, 95% CI: 1.33–1.97). Both past (aOR = 1.54; 95% CI: 1.19–2.00) and current drinking (aOR = 1.71; 95% CI: 1.30–2.23) were associated with breast cancer risk. A dose-response relationship was observed for duration of alcohol drinking (P-trend <0.001), with 10-year increase of drinking associated with a 54% increased risk (95% CI: 1.29–1.84).

Conclusion

We found a positive relationship between alcohol consumption and breast cancer risk, suggesting that this modifiable risk factor should be addressed in breast cancer prevention programs in Africa.     

Driving following Kava Use and Road Traffic Injuries: A Population-Based Case-Control Study in Fiji (TRIP 14)

Objective

To investigate the association between kava use and the risk of four-wheeled motor vehicle crashes in Fiji. Kava is a traditional beverage commonly consumed in many Pacific Island Countries. Herbal anxiolytics containing smaller doses of kava are more widely available.

Methods

Data for this population-based case-control study were collected from drivers of ‘case’ vehicles involved in serious injury-involved crashes (where at least one road user was killed or admitted to hospital for 12 hours or more) and ‘control’ vehicles representative of ‘driving time’ in the study base. Structured interviewer administered questionnaires collected self-reported participant data on demographic characteristics and a range of risk factors including kava use and potential confounders. Unconditional logistic regression models estimated odds ratios relating to the association between kava use and injury-involved crash risk.

Findings

Overall, 23% and 4% of drivers of case and control vehicles, respectively, reported consuming kava in the 12 hours prior to the crash or road survey. After controlling for assessed confounders, driving following kava use was associated with a four-fold increase in the odds of crash involvement (Odds ratio: 4.70; 95% CI: 1.90–11.63). The related population attributable risk was 18.37% (95% CI: 13.77–22.72). Acknowledging limited statistical power, we did not find a significant interaction in this association with concurrent alcohol use.

Conclusion

In this study conducted in a setting where recreational kava consumption is common, driving following the use of kava was associated with a significant excess of serious-injury involved road crashes. The precautionary principle would suggest road safety strategies should explicitly recommend avoiding driving following kava use, particularly in communities where recreational use is common.     

Pediatric and Youth Traffic-Collision Injuries in Al Ain,United Arab Emirates: A Prospective Study

Aim

To study the mechanism of road traffic collisions (RTC), use of safety devices, and outcome of hospitalized pediatric and youth RTC injured patients so as to give recommendations regarding prevention of pediatric RTC injuries.

Methods

All RTC injured children and youth (0–19-year-olds) who were admitted to Al Ain City’s two major trauma centers or who died after arrival to these centers were prospectively studied from April 2006 to October 2007. Demography of patients, road-user and vehicle types, crash mechanism, usage of safety devices, injured body regions, injury severity, Revised Trauma Score, Glasgow Coma Scale, intensive care unit admissions, hospital stay and mortality were analyzed.

Results

245 patients were studied, 69% were vehicle occupants, 15% pedestrians, 9% motorcyclists and 5% bicyclists. 79% were males and 67% UAE citizens. The most common mechanism of RTC was rollover of vehicle (37%) followed by front impact collision (32%). 32 (13%) of vehicle occupants were ejected from car. 63% of ejected occupants and 70% of motorcyclists sustained head injuries. Only 2% (3/170) vehicle passengers used seatbelts and 13% (3/23) motorcyclists a helmet.

Conclusions

Male drivers and UAE nationals were at high risk of RTC as drivers and as motorcyclists. Ejection rate was high because safety restraint use was extremely low in our community. More education and law enforcement focusing especially on car/booster seat use is needed.     

Alcohol Consumption,One-Carbon Metabolites,Liver Cancer and Liver Disease Mortality

Background

Excess alcohol consumption adversely affects one-carbon metabolism and increases the risk of liver disease and liver cancer. Conversely, higher folate levels have been inversely associated with liver damage. The current study investigated the effects of alcohol and one-carbon metabolite intake on liver cancer incidence and liver disease mortality within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study.

Methods

Cox proportional hazards modeling was used to calculate hazard ratios and 95% confidence intervals (CIs) in a population of 27,086 Finnish males with 194 incident liver cancers and 213 liver disease deaths. In a nested case-control subset (95 liver cancers, 103 controls), logistic regression was used to calculate odds ratios and 95% CIs for serum one-carbon metabolites in relation to liver cancer risk.

Results

Daily alcohol consumption of more than 20.44 g was associated with an increased risk of both liver cancer incidence (Hazard Ratio (HR) 1.52, 95%CI 1.06–2.18) and liver disease mortality (HR 6.68, 95%CI 4.16–10.71). These risks were unaffected by one-carbon metabolite intake. Similarly, in the case-control study, none of the serum one-carbon metabolites were associated with liver cancer.

Conclusions

The current study provided no convincing evidence for a protective association of one-carbon metabolite intake or serum level on the risk of liver cancer or liver disease mortality.     

Motor Vehicle Crashes in Diabetic Patients with Tight Glycemic Control: A Population-based Case Control Analysis

Background

Complications from diabetes mellitus can compromise a driver''s ability to safely operate a motor vehicle, yet little is known about whether euglycemia predicts normal driving risks among adults with diabetes. We studied the association between glycosylated hemoglobin (HbA1c) and the risk of a motor vehicle crash using a population-based case control analysis.

Methods and Findings

We identified consecutive drivers reported to vehicle licensing authorities between January 1, 2005 to January 1, 2007 who had a diagnosis of diabetes mellitus and a HbA1c documented. The risk of a crash was calculated taking into account potential confounders including blood glucose monitoring, complications, and treatments. A total of 57 patients were involved in a crash and 738 were not involved in a crash. The mean HbA1c was lower for those in a crash than controls (7.4% versus 7.9%, unpaired t-test, p = 0.019), equal to a 26% increase in the relative risk of a crash for each 1% reduction in HbA1c (odds ratio = 1.26, 95% confidence interval 1.03–1.54). The trend was evident across the range of HbA1c values and persisted after adjustment for measured confounders (odds ratio = 1.25, 95% confidence interval 1.02–1.55). The two other significant risk factors for a crash were a history of severe hypoglycemia requiring outside assistance (odds ratio = 4.07, 95% confidence interval 2.35–7.04) and later age at diabetes diagnosis (odds ratio per decade = 1.29, 95% confidence interval 1.07–1.57).

Conclusions

In this selected population, tighter glycemic control, as measured by the HbA1c, is associated with an increased risk of a motor vehicle crash. Please see later in the article for the Editors'' Summary     

Condom Negotiation,HIV Testing,and HIV Risks among Women from Alcohol Serving Venues in Cape Town,South Africa

Background

Women in South Africa are at particularly high-risk for HIV infection and are dependent on their male partners'' use of condoms for sexual risk reduction. However, many women are afraid to discuss condoms with male partners, placing them at higher risk of HIV infection.

Purpose

To examine the association between fear of condom negotiation with HIV testing and transmission risk behaviors, including alcohol use and sexual risks among South African women.

Method

Women (N = 1333) residing in a primarily Xhosa-speaking African township in Cape Town and attending informal alcohol-serving venues (shebeens) completed anonymous surveys. Logistic regression was used to test the hypothesis that fear of condom negotiation would be associated with increased risk for HIV.

Results

Compared to women who did not fear condom negotiation, those who did were significantly less likely to have been tested for HIV, were more likely to have experienced relationship abuse, and to report more alcohol use and more unprotected sex.

Conclusions

For women in South Africa, fear of condom negotiation is related to higher risk of HIV. HIV prevention efforts, including targeted HIV counseling and testing, must directly address gender issues.     

The disappearing seasonality of autism conceptions in california

Background

Autism incidence and prevalence have increased dramatically in the last two decades. The autism caseload in California increased 600% between 1992 and 2006, yet there is little consensus as to the cause. Studying the seasonality of conceptions of children later diagnosed with autism may yield clues to potential etiological drivers.

Objective

To assess if the conceptions of children later diagnosed with autism cluster temporally in a systematic manner and whether any pattern of temporal clustering persists over time.

Method

We searched for seasonality in conceptions of children later diagnosed with autism by applying a one-dimensional scan statistic with adaptive temporal windows on case and control population data from California for 1992 through 2000. We tested for potential confounding effects from known risk factors using logistic regression models.

Results

There is a consistent but decreasing seasonal pattern in the risk of conceiving a child later diagnosed with autism in November for the first half of the study period. Temporal clustering of autism conceptions is not an artifact of composition with respect to known risk factors for autism such as socio-economic status.

Conclusion

There is some evidence of seasonality in the risk of conceiving a child later diagnosed with autism. Searches for environmental factors related to autism should allow for the possibility of risk factors or etiological drivers that are seasonally patterned and that appear and remain salient for a discrete number of years.     

Butyrylcholinesterase Genetic Variants: Association with Cocaine Dependence and Related Phenotypes

Objective

The search for genetic vulnerability factors in cocaine dependence has focused on the role that neuroplasticity plays in addiction. However, like many other drugs, the ability of an individual to metabolize cocaine can also influence susceptibility to dependence. Butyrylcholinesterase (BChE) metabolizes cocaine, and genetic variants of the BChE gene (BCHE) alter its catalytic activity. Therefore, we hypothesize that cocaine users with polymorphisms in BCHE can show diverse addictive behaviors due to differences in effective plasma concentrations of cocaine. Those polymorphisms might also influence users to prefer one of the two main preparations (crack or powder cocaine), despite having equal access to both. The present work investigates polymorphisms in BCHE and if those genetic variants constitute risk factors for cocaine dependence and for crack cocaine use.

Methods

A total of 1,436 individuals (698 cocaine-dependent patients and 738 controls) were genotyped for three single nucleotide polymorphisms (SNPs) in BCHE: rs1803274, rs4263329, and rs4680662.

Results

For rs4263329, a nominal difference was found between cases and controls. For rs1803274 (the functional SNP), a statistically significant difference was found between patients who used crack cocaine exclusively and those who used only powder cocaine (P = 0.027; OR = 4.36; 95% CI = 1.18–16.04). Allele frequencies and genotypes related to other markers did not differ between cases and controls or between the two cocaine subgroups.

Conclusions

Our findings suggest that the AA genotype of rs1803274 is a risk factor for crack cocaine use, which is more addictive than powder cocaine use. Further studies are needed in order to confirm this preliminary result and clarify the role of BCHE and its variants in cocaine dependence.     

Trouble with bleeding: risk factors for acute hepatitis C among HIV-positive gay men from Germany--a case-control study

Objectives

To identify risk factors for hepatitis C among HIV-positive men who have sex with men (MSM), focusing on potential sexual, nosocomial, and other non-sexual determinants.

Background

Outbreaks of hepatitis C virus (HCV) infections among HIV-positive MSM have been reported by clinicians in post-industrialized countries since 2000. The sexual acquisition of HCV by gay men who are HIV positive is not, however, fully understood.

Methods

Between 2006 and 2008, a case-control study was embedded into a behavioural survey of MSM in Germany. Cases were HIV-positive and acutely HCV-co-infected, with no history of injection drug use. HIV-positive MSM without known HCV infection, matched for age group, served as controls. The HCV-serostatus of controls was assessed by serological testing of dried blood specimens. Univariable and multivariable regression analyses were used to identify factors independently associated with HCV-co-infection.

Results

34 cases and 67 controls were included. Sex-associated rectal bleeding, receptive fisting and snorting cocaine/amphetamines, combined with group sex, were independently associated with case status. Among cases, surgical interventions overlapped with sex-associated rectal bleeding.

Conclusions

Sexual practices leading to rectal bleeding, and snorting drugs in settings of increased HCV-prevalence are risk factors for acute hepatitis C. We suggest that sharing snorting equipment as well as sharing sexual partners might be modes of sexual transmission. Condoms and gloves may not provide adequate protection if they are contaminated with blood. Public health interventions for HIV-positive gay men should address the role of blood in sexual risk behaviour. Further research is needed into the interplay of proctosurgery and sex-associated rectal bleeding.     

Respiratory paradoxical adverse drug reactions associated with acetylcysteine and carbocysteine systemic use in paediatric patients: a national survey

Objective

To report pediatric cases of paradoxical respiratory adverse drug reactions (ADRs) after exposure to oral mucolytic drugs (carbocysteine, acetylcysteine) that led to the withdrawal of licenses for these drugs for infants in France and then Italy.

Design

The study followed the recommendations of the European guidelines of pharmacovigilance for medicines used in the paediatric population.

Setting

Cases voluntarily reported by physicians from 1989 to 2008 were identified in the national French pharmacovigilance public database and in drug company databases.

Patients

The definition of paradoxical respiratory ADRs was based on the literature. Exposure to mucolytic drugs was arbitrarily defined as having received mucolytic drugs for at least 2 days (>200 mg) and at least until the day before the first signs of the suspected ADR.

Results

The non-exclusive paradoxical respiratory ADRs reported in 59 paediatric patients (median age 5 months, range 3 weeks to 34 months, 98% younger than 2 years old) were increased bronchorrhea or mucus vomiting (n = 27), worsening of respiratory distress during respiratory tract infection (n = 35), dyspnoea (n = 18), cough aggravation or prolongation (n = 11), and bronchospasm (n = 1). Fifty-one (86%) children required hospitalization or extended hospitalization because of the ADR; one patient died of pulmonary oedema after mucus vomiting.

Conclusion

Parents, physicians, pharmacists, and drug regulatory agencies should know that the benefit risk ratio of mucolytic drugs is at least null and most probably negative in infants according to available evidence.     

Risk of Severe Upper Gastrointestinal Complications among Oral Bisphosphonate Users

Background

Oral bisphosphonates (BPs) are the primary agents for the treatment of osteoporosis. Although BPs are generally well tolerated, serious gastrointestinal adverse events have been observed.

Aim

To assess the risk of severe upper gastrointestinal complications (UGIC) among BP users by means of a large study based on a network of Italian healthcare utilization databases.

Methods

A nested case-control study was carried out by including 110,220 patients aged 45 years or older who, from 2003 until 2005, were treated with oral BPs. Cases were the 862 patients who experienced the outcome (hospitalization for UGIC) until 2007. Up to 20 controls were randomly selected for each case. Conditional logistic regression model was used to estimate odds ratio (OR) associated with current use of BPs after adjusting for several covariates. A set of sensitivity analyses was performed in order to account for sources of systematic uncertainty.

Results

The adjusted OR for current use of BPs with respect to past use was 0.94 (95% CI 0.81 to 1.08). There was no evidence that this risk changed either with BP type and regimen, or concurrent use of other drugs or previous hospitalizations.

Conclusions

No evidence was found that current use of BPs increases the risk of severe upper gastrointestinal complications compared to past use.     

Selective serotonin reuptake inhibitors and gastrointestinal bleeding: a case-control study

Background

Selective serotonin reuptake inhibitors (SSRIs) have been associated with upper gastrointestinal (GI) bleeding. Given their worldwide use, even small risks account for a large number of cases. This study has been conducted with carefully collected information to further investigate the relationship between SSRIs and upper GI bleeding.

Methods

We conducted a case-control study in hospitals in Spain and in Italy. Cases were patients aged ≥18 years with a primary diagnosis of acute upper GI bleeding diagnosed by endoscopy; three controls were matched by sex, age, date of admission (within 3 months) and hospital among patients who were admitted for elective surgery for non-painful disorders. Exposures to SSRIs, other antidepressants and other drugs were defined as any use of these drugs in the 7 days before the day on which upper gastrointestinal bleeding started (index day).

Results

581 cases of upper GI bleeding and 1358 controls were considered eligible for the study; no differences in age or sex distribution were observed between cases and controls after matching. Overall, 4.0% of the cases and 3.3% of controls used an SSRI antidepressant in the week before the index day. No significant risk of upper GI bleeding was encountered for SSRI antidepressants (adjusted odds ratio, 1.06, 95% CI, 0.57–1.96) or for whichever other grouping of antidepressants.

Conclusions

The results of this case-control study showed no significant increase in upper GI bleeding with SSRIs and provide good evidence that the magnitude of any increase in risk is not greater than 2.