Sleep and mood changes in advanced age after blue-blocking (yellow) intra ocular lens (IOLs) implantation during cataract surgical treatment: a randomized controlled trial.

OBJECTIVES: Both advanced age and depression are characterized by changes in sleep patterns. Light exposure is one of the main synchronizers of circadian cycles and influences sleep by inhibiting melatonin secretion, which is mostly sensitive to light of low wavelengths (blue). Blue-blocking (yellow) intraocular lenses (IOLs) have supplanted the usual UV-blocking (clear) IOLs during cataract surgery to prevent age-related macular degeneration, however, the impact of yellow IOLs on sleep and mood is unclear. The purpose of this study was to compare the effects of yellow and clear IOLs on sleep and mood in aged patients undergoing bilateral cataract surgery. METHODS: A randomized controlled superiority study was conducted within three ophthalmic surgical wards in France. A total of 204 subjects (mean age 76.2 ± 7.5 years) were randomized into yellow or clear IOLs groups. Patients completed a sleep diary, the pictorial sleepiness scale and the Beck Depression Inventory (BDI) one week before and eight weeks after the last surgical procedure. RESULTS: According to an Intent To Treat (ITT) analysis, no significant difference was found between yellow and clear IOLs groups regarding sleep time, sleep latency, total sleep duration, quality of sleep and BDI scores. The rate of patients whose BDI score increased at the cutoff score of ≥5 after surgery was significantly higher in the yellow IOL group (n = 11, 13.1%) compared with the clear IOL group (n = 4; 4.7%); p = 0.02. CONCLUSIONS: Using yellow IOLs for cataract surgery doesn't significantly impact sleep but may induce mood changes in aging.

[Hydroxychloroquine during pregnancy: a review of retinal toxicity in the newborns]. / Toxicité rétinienne de l'hydroxychloroquine chez le nouveau-né exposé in utero.

OBJECTIVE: The objective of this study is to review the published data on ocular toxicity in newborns after in utero exposure to hydroxychloroquine. METHODS: All publications related ophthalmologic follow-up of newborns or infants who were exposed to hydroxychloroquine during pregnancy were selected. RESULTS: Nine studies were analyzed, concerning 246 infants for which an ophthalmological examination was available. None of the infants had signs of ocular toxicity at the clinical stage. Among the 31 infants having electrophysiologics explorations, 4 had suggestive signs of retinal toxicity at the preclinical stage. This could probably be explained by a low cumulative dose, the immaturity of the fetal retina and the low light stimulation in utero. However, without a remote monitoring of infants, it is difficult to conclude to the absence of functional impairment. CONCLUSION: Data are not for a major risk of retinal toxicity associated with exposure in utero to hydroxychloroquine.

[Neonatal risks of drugs exposure at the end of pregnancy]. / Risque néonatal des médicaments pris à la fin de la grossesse.

Foetal drugs exposure consequences depend according to the drug involved and to the length of the exposure which in the sum of length of treatment and of drug elimination (5 half life). Decisions are based upon risk evaluation and are a compromise between a risk banalisation and an excess of carefully. We described risks management for drugs used for a disease due to the pregnancy (glucocorticoïdes, antibiotics) then for drugs used for a chronic disease often preceding the pregnancy (non steroidal anti-inflammatory, serotonin recapture inhibitors, benzodiazepines, antiepileptics, conversion enzyme inhibitors/renine angiotensine antagonists, betabloquants). We also present the elements to take in account for the best drug choice at the end of pregnancy and/or for an adapted advice if the drug has been already taken: the drug itself (pharmacological effects, kinetics in neonate, toxicity marker, risk detection tool), drug amount possibly received by the neonate and literature data about neonatal manifestations due to the drug.

Heptavalent pneumococcal conjugate vaccine (PCV7): French survey of serious adverse reactions.

PURPOSE: Previous study did not reveal any particular heptavalent pneumococcal conjugate vaccine (PCV7) related risk. However, french drugs agency (Afssaps) requested the continuation of its surveillance. METHODS: All serious PCV7-related adverse drug reactions spontaneously reported between October 1, 2004 and December 31, 2007 to the French pharmacovigilance centers or to Wyeth Pharmaceutical France were included. Vaccine failure was defined as an invasive pneumococcal infection due to vaccine serotype which occurs at least 15 days after the third dose of vaccine. Incidence rates were estimated according to the doses number except for vaccine failure estimated according to the vaccinated children number. RESULTS: During the 39-month follow-up period, 154 serious adverse drug reactions were spontaneously reported: convulsions (17%), fever (13%), hypotonia (10%), sudden death (7%) and thrombopenic purpura (6%). Evolution was recovery in 72% of cases. PCV7 was the only suspect medication in 28% of cases. The median age was 4 months (range 1-108), and the children's sex was male in 53%. The adverse drug reaction recurred after a subsequent injection in six cases. Among the 24 pneumococcal infections PCV7 failure was certain in 4 cases. The incidences of serious adverse drug reactions did not differ from our previous survey, except the incidence of thrombopenic purpura and of PCV7 failure which seems to be increasing. CONCLUSIONS: This new study confirms the risk of vascular purpura, raises the thrombopenic purpura issue, and the emergence of PCV7 failures which will need a strict monitoring of the future 13 valences vaccine.

Clinical features and risk factors for upper gastrointestinal bleeding in children: a case-crossover study.

OBJECTIVE: This population-based survey was conducted to provide a formal description of upper gastrointestinal bleeding (UGIB) in children on a nationwide basis and assess the contribution of risk factors, principally nonsteroidal anti-inflammatory drugs (NSAID). METHODS: A case-crossover study of UGIB patients aged between 2 months and 16 years was conducted in France. Medical data were collected by physicians, and personal risk factors and exposure to drugs during the month preceding the onset of the bleeding was ascertained by a standardised telephone interview with parents. The odds ratios for UGIB and NSAID was assessed by comparing exposure during the 7 days preceding the date of hospitalisation and the 21st to the 28th days before that date. RESULTS: A total of 177 children with UGIB were included over 2 years. Eighty-three children had taken at least one NSAID before the index date, among which 58 were ibuprofen, 26 aspirin and nine others. The adjusted odds ratio (OR) of exposure was 8.2 [95% confidence interval (CI) 2.6-26.0] for NSAIDs altogether, and this was 10.0 (95% CI 2.0-51.0) for ibuprofen and 7.3 (95% CI 0.9-59.4) for aspirin. There was no increased risk associated with NSAIDS for oesophageal lesion [OR = 1.0 [(5% CI:0.2-7.2)]. CONCLUSION: The study confirms that UGIB is rare but that some cases may be avoided, as one third of the cases was attributable to exposure to NSAID at doses used for analgesic or antipyretic purposes, which may be attained with alternative therapy. The findings from this study call for more caution in prescribing NSAIDS to children.

Drug dependence associated with triptans and ergot derivatives: a case/non-case study.

INTRODUCTION: The aim of this case/non-case study was to assess and compare the risk of drug dependence associated with different migraine-specific drugs, i.e., ergot derivatives and triptans, using the French pharmacovigilance database. METHODS: Reports on drug side effects recorded in this database between January 1985 and June 2007 were analyzed, and triptans (almotriptan, eletriptan, naratriptan, sumatriptan, and zolmitriptan) as well as ergot derivatives used in acute migraine were examined. For all reports, cases were defined as those reports corresponding to "drug abuse," "physical or mental drug dependence," and "pharmacodependence," whereas "non-cases" were defined as all the remaining SED reports. The method's reliability was assessed by calculating the risk associated with a negative (amoxicillin) and a positive (benzodiazepines) control. The risk of dependence associated with each drug and control was evaluated by calculating the odds ratio (OR) with a confidence interval of 95%. RESULTS: Among the 309,178 reports recorded in the database, drug dependence accounted for 0.8% (2,489) of the reports, with 10.9% (449) involving a triptan, and 9.33% (332) an ergot derivative. The risk of dependence was similar for triptans and ergot derivatives and did not differ from that of benzodiazepines. In the triptan group, the risk (odds ratio [95% CI]) ranged from 10.3 [4.8-22.3] for sumatriptan to 21.5 for eletriptan [10.1-45.6], while in the ergot derivative group, it ranged from 12 [8-17.9] for ergotamine to 20.6 [8-53] for dihydroergotamine. CONCLUSIONS: These findings confirm the hypothesis that triptans and ergot derivatives are associated with an increased risk of drug dependence.

[Adverse reactions of atazanavir, fosamprenavir and tipranavir in "real life"]. / Effets indésirables de l'atazanavir, du fosamprénavir et du tipranavir en situation réelle d'emploi.

OBJECTIVE: To precise adverse effects of atazanavir, fosamprenavir and tipranavir "in real life". METHOD: Descriptive study of 3 protease inhibitor adverse effects stored in the French Bank of Pharmacovigilance. RESULTS: Nineteen adverse effects having at least possible links with antiretroviral drugs studied were reported. It was essentially hepatobiliary (atazanavir: 29/59, tipranavir: 4/6) and skin (fosamprenavir: 10/20) adverse reactions. These reactions, relatively "serious" (35.1%) led to the interruption of the person (or persons) medication (s) suspected (s) in 69 folds (82.1%) and evolved to healing without sequelae in 68 folds (81%). CONCLUSION: The drug side effects were for the most expected. However, their frequency and their seriously underline the interest of a post-AMM monitoring to reassess the drugs risk-benefit report.

Avoidability of adverse drug reactions spontaneously reported to a French regional drug monitoring centre.

BACKGROUND: Adverse drug reactions (ADRs) are now recognized as a major category of iatrogenic illness in terms of morbidity and mortality. OBJECTIVE: To describe the type and frequency of avoidable ADRs spontaneously reported to a regional drug monitoring centre following inappropriate prescribing, as a basis for preventive actions. METHODS: A prospective, observational study of ADRs reported to the Regional Drug Monitoring Centre of Tours, France, between 26 November 2002 and 28 November 2003. The outcome measure was ADRs secondary to inappropriate prescribing that were defined as entirely or partly avoidable, i.e. at least one of the recommendations in various sections of the summary of product characteristics (SPC; indication, route of administration, dose, duration of treatment, dose adaptation, precautions for use, monitoring of treatment, absolute contraindications and contraindicated interactions) had not been respected. The link between the lack of conformity of the drug prescription with the SPC and occurrence of the ADR was evaluated by a working group using two criteria: (i) is nonconformity of the prescription of this drug a known and validated risk factor for this ADR?; and (ii) are there other aetiologies or other risk factors for this ADR? RESULTS: Three hundred and sixty ADRs in 294 adults and 66 children were analysed. The prescription was considered inappropriate for 213 of the 659 (32%) drugs implicated in ADRs, corresponding to 161 patients (45%). The ADR was adjudged entirely avoidable for 32 (9%) patients, partly avoidable for 28 (8%) patients and unavoidable for 300 (83%) patients. Not taking into account a history of allergy or altered renal function and not respecting the recommended dose were the most frequent causes of entirely avoidable ADRs. Allopurinol and lamotrigine were the drugs most frequently involved in serious avoidable ADRs. CONCLUSIONS: Preventive actions should focus on more systematic allergy checks when prescribing drugs and on dose adaptation in cases of altered renal function.

A multicentre case-control study of nonsteroidal anti-inflammatory drugs as a risk factor for severe sepsis and septic shock.

INTRODUCTION: We aimed to establish whether the use of nonsteroidal anti-inflammatory drugs (NSAIDs) during evolving bacterial community-acquired infection in adults is associated with severe sepsis or septic shock. METHODS: We conducted a multicentre case-control study in eight intensive care units. Cases were all adult patients admitted for severe sepsis or septic shock due to a bacterial community-acquired infection. Control individuals were patients hospitalized with a mild community-acquired infection. Each case was matched to one control for age, presence of diabetes and site of infection. RESULTS: The main outcome measures were the proportions of cases and controls exposed to NSAIDs or aspirin during the period of observation. In all, 152 matched pairs were analyzed. The use of NSAIDs or aspirin during the observation period did not differ between cases and controls (27% versus 28; odds ratio = 0.93, 95% confidence interval [CI] = 0.52 to 1.64). If aspirin was not considered or if a distinction was made between acute and chronic drug treatment, there remained no difference between groups. However, the median time to prescription of effective antibiotic therapy was longer for NSAID users (6 days, 95% CI = 3 to 7 days) than for nonusers (3 days, 95% CI = 2 to 3 days; P = 0.02). CONCLUSIONS: In this study, the use of NSAIDs or aspirin during evolving bacterial infection was frequent and occurred in one-quarter of the patients with such infection. Although the use of NSAIDs by patients with severe sepsis or septic shock did not differ from their use by those with mild infection at the same infected site, we observed a longer median time to prescription of effective antibiotic therapy in NSAID users.

Lack of association between rifampicin plasma concentration and treatment-related side effects in osteoarticular infections.

The aim of this study was to assess the frequency of gastrointestinal side effects (GSE) and hepatotoxicity in patients treated with rifampicin for an osteoarticular infection and to determine if there is an association between rifampicin plasma concentrations and side effects. Rifampicin plasma concentrations were prospectively measured before (trough concentration, C(0)) and 2 +/- 0.5 h (peak concentration, C(2)) after drug intake. The presence of GSE, the alanine transferase (ALT) value, and concomitantly administered medications were recorded on the day rifampicin concentrations were measured. C(0) and C(2) were compared for differences regarding the presence or absence of side effects. Multivariate analysis was performed, with associated medications being taken into account. Seventy C(0) and 57 C(2) values were measured in 46 adults after a median treatment of 8 days (range, 1-179). Wide inter-individual variability was observed for C(0) and C(2). Thirteen (28%) patients reported GSE at least once. When GSE occurred, C(0) (median, 1 mg L(-1); range, 0.1-9.9 mg L(-1)) and C(2) (median, 10.3 mg L(-1); range, 1.8-40.3 mg L(-1)) were similar to C(0) (median, 0.6 mg L(-1); range, 0.1-10.3 mg L(-1)) and C(2) (median, 10.9 mg L(-1); range, 2.9-29.0 mg L(-1)) without GSE. The ALT value was more than normal in only three patients (6.5%) after rifampicin treatment began. The patients received no different associated medications whether or not GSE were present. Multivariate analysis showed no association between rifampicin plasma concentrations and GSE. GSE occur frequently in patients receiving rifampicin for osteoarticular infection but without an association with rifampicin plasma concentrations. Thus, therapeutic drug monitoring of rifampicin is irrelevant in the management of GSE.

Upper gastrointestinal complications associated with NSAIDs in children.

OBJECTIVE: To analyse serious upper gastrointestinal (UGI) complications associated with non-salicylate non-steroidal anti-inflammatory drugs (NSAIDs) in children. METHODS: All serious UGI complications associated with non-salicylate NSAIDs approved in France to treat moderate pain or fever in children, spontaneously reported to the French Pharmacovigilance system or to the companies, between the launching of each study drug in France to December 31, 2000. RESULTS: Serious UGI complications were reported in 61 children aged from 11 months to 15 years during treatment with niflumic acid (27), ibuprofen (23) and tiaprofenic acid (11). No case was reported with ketoprofen. UGI manifestations were UGI bleeding (15) and 46 gastrointestinal symptoms with endoscopic lesions i.e. gastritis (18), gastric ulcer (13), duodenal ulcer (7), duodenitis (4) and oesophageal ulcer (4). NSAID was combined with a salicylate in 36% of cases, given by the parents in self medication in 6.6% of cases and used outside its product licence in 33.8% of cases. CONCLUSION: NSAIDs used in children for fever or moderate pain are associated with a risk of serious UGI complications which increases with length, dose and association with a salicylate.

[Chemical submission: a literature review]. / La soumission chimique: une revue de la littérature.

The aim of this review is to describe the present knowledge about chemical submission. The number of scientific publications on this phenomenon has increased over the last 10 years. Perpetrators choose drugs which act rapidly, produce desinhibition, sedation, and anterograde amnesia during the abuse. Ethanol and benzodiazepines are the most frequently used. A few drugs, including flunitrazepam and gamma-hydroxybutyric acid (GHB), have received widespread media coverage. Toxicological investigations on blood, urine or hair samples allow to detect the substance used. Every effort should be made to collect appropriate specimens as quickly as possible. Gas chromatography-mass spectrometry is at present the most appropriate analytical method to detect these drugs in a biological specimen.

A general overview of the use of ibuprofen in paediatrics.

Ibuprofen is prescribed for children for the treatment of acute pain and fever, and for juvenile idiopathic arthritis. The pharmacokinetic characteristics of ibuprofen in children are similar to those in adults and the relationship between dose and response is linear over the range 5-10 mg/kg. Clinical trials of ibuprofen have shown the effective dose range to be 7.5-10 mg/kg. The maximum reduction in temperature occurs 3-4 hours after administration. In comparative clinical trials, ibuprofen has been shown to be equally as effective as or more effective than paracetamol as an analgesic and antipyretic and to have a longer duration of action; it is also as effective as aspirin. The adverse effects of ibuprofen are similar to those of other non-steroidal anti-inflammatory drugs but clinical experience suggests that ibuprofen is better tolerated by children than adults and it is safer in overdose than paracetamol and aspirin.

[Vaccines pharmacovigilance]. / Pharmacovigilance des vaccins.

The pharmacovigilance of vaccines has the particularity of concerning medications with a preventative target, used in healthy subjects, who are often young. Their individual benefit is deferred and unknown, whereas their risk is immediate. Certain undesirable effects are linked to the antigen of live attenuated vaccines (post-MMR lymphocytic meningitis). Other non-specific effects are linked to other different components of the vaccines (macrophage and aluminium myofasciitis). Undesirable events susceptible to being due to the vaccination are identified and managed according to standardised procedures of pharmacovigilance, that is to say, based on "spontaneous notification", generation of an alert, confirmed or not by studies of pharmaco-epidemiology. The studies of pharmaco-epidemiology: have made evident oedematous reactions with cyanosis or purpura, with the vaccines containing the Haemophilus b valence, and the absence of an association with sudden death of the newborn; have excluded the existence of an elevated risk of demyelinisation or auto-immune disease associated with vaccination against hepatitis B, without being able to exclude a slight risk; go against the finding of an association between Crohn's disease and/or autisim and the MMR vaccination. Only their frequently encountered undesirable effects are well identified at the moment of commercialisation. Post-marketing surveillance of vaccines (declaration to the regional pharmacovigilance centres) allow the detection of possible rare and serious effects and the evaluation of the real vaccination risk. Thus it must be intensive and systematic.