A case of dysgraphia induced by sertraline and a review of official spontaneous adverse reaction databases.

WHAT IS KNOWN AND OBJECTIVES: The occurrence of dysgraphia after sertraline intake has never been reported. The objective was to describe a case of this adverse drug reaction and present a review of similar cases held in international databases with a discussion of the possible pharmacological mechanisms. CASE SUMMARY: We observed a 60-year-old man who experienced resting tremors, dyskinesia and dysgraphia 2 months after a stepwise increase in sertraline dosing from 50 to 200 mg/day. WHAT IS NEW AND CONCLUSION: Dysgraphia is a possible adverse drug reaction to sertraline, and we suggest that inhibition of extrapyramidal dopaminergic activity might be the pharmacological mechanism.

Throbbing headache associated with enoxaparin administration: a case report, a review of pharmacovigilance databases for similar cases and possible mechanisms.

WHAT IS KNOWN AND OBJECTIVES: To date, no case of headache has been reported with enoxaparin. We present the case of a 60-years-old man, who developed enoxaparin-induced throbbing headache and discuss the possible pharmacological mechanisms. We provide an analysis of enoxaparin-induced headache in three international databases. CASE SUMMARY: A few hours after the subcutaneous administration of this drug at therapeutic dose, the patient experienced throbbing headache. Rechallenge on two other separate occasions separated by several days produced the same effect although with reduced intensity when the dose was lowered. The Naranjo Algorithm indicated a 'certain' relationship. WHAT IS NEW AND CONCLUSION: We report a case of throbbing headache associated with the use of enoxaparin; with the increasing use of enoxaparin, physicians who prescribe this drug should be aware of this potential ADR. We suggest that it is a heparin class-effect, and therefore, a more general caution is also appropriate.

Prevalence of respiratory colonisations and related antibiotic resistances among paediatric tracheostomised patients of a long-term rehabilitation centre in Italy.

Patients with brain injury are prone to bacterial colonisations because of mechanical ventilation during intensive care and the long-term retention of tracheostomical tubes during rehabilitation. Reduced levels of isolation, typical of rehabilitation, could also contribute to propagate colonisations. We evaluated the presence of bacteria through different stages of healthcare, their antibiotic resistances and their clinical impact in a rehabilitation setting. This retrospective study included all tracheostomised patients referred to the paediatric brain injury unit of the Scientific Institute IRCCS E. Medea (Italy) over a six-year period. Data were collected from antibiograms regarding the presence of bacterial species and antibiotic resistances; clinical data were collected from medical records. Antibiograms revealed bacteria and antibiotic resistances typical of intensive care, while prevalence patterns were characteristic for each species (P. aeruginosa and S. aureus prevailing in the acute setting, K. pneumoniae, A. baumannii and others in rehabilitation). Despite very frequent antibiotic resistances, consistent with Italian averages, we observed a limited clinical impact for these colonisations. We analysed risk factors correlating to the development of respiratory symptoms and found a role for the acute clinical course after brain injury (having undergone neurosurgery; duration of intensive care stay) as well as for rehabilitation (duration of coma). Our data suggest that, in a long-term perspective, an appropriate balance is yet to be found between patient isolation and social interactions, to control respiratory colonisations and antibiotic resistances without compromising rehabilitation. They also suggest that regular containment measures should be complemented by thorough training to non-medic personnel and parents alike.

The first steps towards the era of personalised vaccinology: predicting adverse reactions.

Until now, the occurrence of adverse reactions among individuals inoculated with identical vaccines has been ascribed to unpredictable stochastic processes. Recent advances in pharmacogenomics indicate that some features of host response to immunisation are influenced by genetic traits, henceforth predictable. The ability to predict the adverse reaction to vaccination would represent an important step towards the development of personalised vaccinology and could enhance public confidence in the safety of vaccines. Herein, we have reviewed all the available information on the association between genetic variants and the risk for healthy subjects to develop adverse reactions.

Epidemiological analysis on two decades of hospitalisations for meningitis in the United States.

Bacterial meningitis is an important source of mortality and morbidity worldwide. Data exist on specific vaccines against Streptococcus pneumoniae and Neisseria meningitidis indicating that they reduce the incidence of meningitis, yet comprehensive information on the trend of bacterial meningitis is still lacking. We analysed the Kids' Inpatient Database and the National Inpatient Database considering all bacterial meningitides in the United States, excluding cases of tuberculosis and sexually transmitted diseases. We analysed the trend of meningitis incidence from 1993 to 2011 and in specific age groups before and after the introduction of the pneumococcal conjugate vaccine 7 (PCV-7) and the meningococcal conjugate vaccine 4 (MCV-4). Moreover, we analysed the prevalence of aetiological agents to assess their changes. We estimated 295,706 cases of meningitis having occurred in the United States and a reduction of the discharge rate of 21 %. We observed a significant reduction in cases of meningitis in children and elderly patients following the introduction of the PCV-7. We also found a reduction in subjects aged 10-14 years, an age span consistent with the introduction of MCV-4, although further analyses based on serotypes data are required to confirm this observation. By contrast, we observed an increased prevalence of cases of staphylococcal and streptococcal meningitides. The introduction of PCV-7 has reduced the incidence and changed significantly the aetiology of bacterial meningitis in the United States during the last two decades.

Neurological and psychiatric adverse events with prucalopride: case report and possible mechanisms.

WHAT IS KNOWN AND OBJECTIVE: Chronic constipation is very frequent in the general population. Although usually considered banal, this disorder has considerable personal, social and healthcare impact. Several studies have shown that the psychological impact exceeds that caused by rheumatoid arthritis or haemodialysis. Recently, prucalopride, a highly selective 5-HT4 receptor agonist has been shown to improve the symptoms of chronic constipation and to have a beneficial effect on social and healthcare impact. The drug was approved by the European Medicine Agency, in 2009 at a dose of 2 mg/day, 'for symptomatic treatment of chronic constipation in women in whom laxatives fail to provide adequate relief'. Neurological side effects or psychiatric disorders have not been reported previously with prucalopride. We present the case of a 61-year-old woman, who developed such adverse effects when given prucalopride for the treatment for chronic constipation. CASE SUMMARY: A few hours after oral administration of this drug at therapeutic dose (2 mg/day), the patient experienced life-threatening neurological effects that included visual hallucination, loss of balance and memory, disorientation, exhaustion and suicidal ideation. Analysis with the Naranjo algorithm indicated a 'possible' relationship between prucalopride and these disorders. WHAT IS NEW AND CONCLUSION: This is the first report of prucalopride-induced neurological side effects and psychiatric disorders with prucalopride. The absence of other similar reports suggests that prucalopride rarely causes these adverse effects.

Feeding a diet contaminated with ochratoxin A for broiler chickens at the maximum level recommended by the EU for poultry feeds (0.1 mg/kg). 2. Effects on meat quality, oxidative stress, residues and histological traits.

The European Commission Recommendation 2006/576/EC indicates that the maximum tolerable level of ochratoxin A (OTA) in poultry feeds is 0.1 mg OTA/kg. Thirty-six 1-day-old male broiler chicks were divided into two groups, a control (basal diet) and an OTA (basal diet + 0.1 mg OTA/kg) group. The OTA concentration was quantified in serum, liver, kidney, breast and thigh samples. The thiobarbituric acid reactive substances (TBARS) content were evaluated in the liver, kidney, breast and thigh samples. The glutathione (GSH) content, and catalase (CAT) and superoxide dismutase (SOD) activity were measured in the liver and kidney samples. Histopathological traits were evaluated for the spleen, bursa of Fabricius and liver samples. Moreover, the chemical composition of the meat was analysed in breast and thigh samples. In the OTA diet-fed animals, a serum OTA concentration of 1.15 ± 0.35 ng/ml was found, and OTA was also detected in kidney and liver at 3.58 ± 0.85 ng OTA/g f.w. and 1.92 ± 0.21 ng OTA/g f.w., respectively. The TBARS content was higher in the kidney of the ochratoxin A group (1.53 ± 0.18 nmol/mg protein vs. 0.91 ± 0.25 nmol/mg protein). Feeding OTA at 0.1 mg OTA/kg also resulted in degenerative lesions in the spleen, bursa of Fabricius and liver. The maximum tolerable level of 0.1 mg OTA/kg, established for poultry feeds by the EU, represents a safe limit for the final consumer, because no OTA residues were found in breast and thigh meat. Even though no clinical signs were noticed in the birds fed the OTA-contaminated diet, moderate histological lesions were observed in the liver, spleen and bursa of Fabricius.

A case of urinary incontinence by hydroxychloroquine in a geriatric patient.

WHAT IS KNOWN AND OBJECTIVE: Rheumatoid arthritis is an autoimmune disorder characterized by persistent synovitis and systemic inflammation. Genetic factors account for approximately 50% of cases of rheumatoid arthritis and environmental factors include smoking. Urinary incontinence may occur as a medication adverse effect. We present the first report of a case of hydroxychloroquine-induced urinary incontinence in rheumatoid arthritis. DETAILS OF THE CASE: A 71-year-old female with a history of rheumatoid arthritis developed urinary incontinence as an adverse drug reaction to hydroxychloroquine administered at therapeutic doses. Urinary incontinence remitted with drug withdrawal and reappeared on rechallenge. The Naranjo's algorithm indicated that hydroxychloroquine was a probable cause of this adverse drug reaction. The likely mechanism of this adverse drug is a direct action of the quinolone on the urinary system. WHAT IS NEW AND CONCLUSION: This is the first report of hydroxychloroquine-induced urinary incontinence. The absence of previous reports suggest that the drug rarely causes this adverse effect. Methotrexate is most often used as first-line treatment, and several other drugs are now available to act as Disease-Modifying Antirheumatic Drugs (DMARDs). These drugs may be used alone or combined with methotrexate, most often to increase efficacy and reduce toxicity. The introduction of new biological agents, such as abatacept, rituximab, tocilizumab and inhibitors of tumour necrosis factor, has opened new therapeutic perspectives but are restricted by high costs and risk of infections. Thus, antimalarial drugs, especially the quinolones chloroquine (CQ) and hydroxychloroquine (HCQ), are still in use, and the latter is very efficacious. An advantage of HCQ is its low toxicity compared with other antimalarial drugs. Common side-effects of HCQ and the other antimalarial drugs include gastrointestinal effects such as nausea and vomiting, as well as skin rashes and headache, whereas their most common and severe side-effect is retinopathy. No case of urinopathy has been reported previously with HCQ.

Type I autoimmune hepatitis: clinical course and outcome in an Italian multicentre study.

BACKGROUND: Many reports of autoimmune hepatitis (AIH) were written in the 'pre-Hepatitis C era' and data on the natural history are still incomplete. AIM: To evaluate the clinical presentation and the natural history of type I AIH. METHODS: Seventy-three consecutive patients with a regular follow-up of at least 2 years were prospectively included in the study. The mean follow-up was 91 +/- 61 months. RESULTS: Patients with 'acute' onset at presentation were significantly older than patients with 'chronic' onset (P < 0.05) and had significantly higher serum levels of transaminase, gamma-glutamyltransferase and bilirubin; Prothrombin time was significantly lower in the said group compared with AIH patients with 'chronic' onset. In 4 of 63 (6.3%) female patients, AIH had the onset during pregnancy; in all of them the outcome of pregnancy was favourable. The major events during the follow-up included oesophageal varices (n = 9) and ascites (n = 4), and 60 patients remained in remission while receiving immunosuppression. None of the patients died during the follow-up, but seven patients were transplanted. The cumulative transplant-free probability of survival was 73.5% at 280 months. CONCLUSIONS: Elderly patients have more frequently an acute onset at presentation. Survival in AIH is apparently good; with early diagnosis, and improved medical therapy, liver transplantation for AIH will become a rare event in future.

[Hemodynamic, immunologic and systemic stress response during surgery under total intravenous anesthesia with midazolam-ketamine-fentanyl or remifentanil-midazolam: a randomized clinical trial]. / Estudio comparativo de anestesia total intravenosa con midazolam- ketamina-fentanilo y remifentanilo-midazolam: evaluación de la respuesta hemodinámica, leucocitaria y de los marcadores sistémicos de estrés.

OBJECTIVE: To assess the effect of stress from surgery on hemodynamics, white cell count, and systemic markers during cholecystectomies performed under 2 intravenous anesthetic techniques. PATIENTS AND METHOD: Randomized clinical trial in patients classified ASA 1 or 2. The patients received 0.15 mg x kg(-1) of midazolam, 1 mg x kg(-1) x h(-1) of ketamine, and 2 microg x kg(-1) of fentanyl (MKF group) or 1 microg x kg(-1) x min of remifentanil and 0.15 mg x kg(-1) of midazolam (RM group). Hemodynamic parameters, white cell counts in circulating blood, and serum levels of cortisol, prolactin, and interleukin-6 were recorded before surgery, after intubation, and at the end of surgery. RESULTS: Thirty-two patients were enrolled. Hemodynamic stability was good in both groups. After intubation, mean (SD) heart rate (75 [14] beats x min(-1)) and systolic (96 [14] mm Hg) and diastolic (60 [7] mm Hg) blood pressures were lower in the RM group than in the MKF group (99 [17] beats x min(-1); 121 [29] mm Hg; and 79 [14] mm Hg, respectively, P<0.01). After surgery whi- te cell (10528 [6480] microL(-1)) and neutrophil (8155 [5657] microL(-1)) counts and cortisol concentration (225 [257] ng x mL(-1)) were significantly lower in the RM patients than in the MKF patients (white cell count, 14,002 [5927] cells x micromL(-1); neutrophil count, 11530 [5657] cells x microL(-1), and 788.8 [146] ng x mL(-1); P<0.01). CONCLUSIONS: The 2 intravenous anesthesia regimens compared differ slightly with regard to their effects on surgical stress. Anesthesia with remifentanil and midazolam contributes to reducing the inflammatory response through modulation of the neurohumoral response to stress.

Estudio comparativo de anestesia total intravenosa con midazolamketamina- fentanilo y remifentanilo-midazolam: evaluación de la respuesta hemodinámica, leucocitaria y de los marcadores sistémicos de estrés / Hemodynamic, immunologic and systemic stress response during surgery under total intravenous anesthesia with midazolamketamine-fentanyl or remifentanilmidazolam: a randomized clinical trial

OBJETIVO: Evaluar el estrés anestésico quirúrgico,durante colecistectomías realizadas con dos regímenesde anestesia intravenosa, observando la respuesta hemodinámica,leucocitaria y de los marcadores sistémicos deestrés.MATERIAL Y MÉTODO: Estudio clínico prospectivo randomizadoen pacientes ASA I-II. Los pacientes recibieronmidazolam 0,15 mg Kg-1, ketamina 1 mg Kg-1 h-1 y fentanilo2 µg Kg-1 (grupo MKF) o remifentanilo 1 µg Kg-1 miny midazolam 0,15 mg Kg-1 (grupo RM). Se evaluaronvariables hemodinámicas, recuentos leucocitarios en sangreperiférica y niveles séricos de cortisol, prolactina einterleucina-6, que fueron registrados antes de la cirugía,después de la intubación y al final de la cirugía.RESULTADOS: Se incluyeron treinta y dos pacientes.Ambos grupos mostraron buen control hemodinámico.Después de la intubación, en el grupo RM la frecuenciacardiaca (75±14 latidos min-1) y la presión arterial sistólica(96±14 mm Hg) y diastólica (60±7 mm Hg) fueroninferiores a las del grupo MKF (99±17 latidos min-1,121±29 mm Hg y 79±14 mm Hg, respectivamente,p<0,01). Al final de la cirugía se verificó un nivel de leucocitos(10528±6480 mL-1), neutrófilos (8155±5657 mL-1 )y de cortisol (225±257 ng mL-1) significativamente menoresen los pacientes RM, comparados con los pacientesMKF (14002±5927 leucocitos mL-1, 11530±5657 neutrófilosmL-1 y 788,8±146 ng mL-1, respectivamente, p<0,01).CONCLUSIONES: Los regímenes de anestesia intravenosaevaluados difieren escasamente en sus efectos sobre larespuesta de estrés a la cirugía. La anestesia con remifentanilo-midazolam contribuye a disminuir la respuestainflamatoria al modular la respuesta neurohumoral deestrés

OBJECTIVE: To assess the effect of stress from surgeryon hemodynamics, white cell count, and systemic markersduring cholecystectomies performed under 2 intravenousanesthetic techniques.PATIENTS AND METHOD: Randomized clinical trial inpatients classified ASA 1 or 2. The patients received 0.15mg·kg-1 of midazolam, 1 mg·kg-1·h-1 of ketamine, and 2µg·kg-1 of fentanyl (MKF group) or 1 µg·kg-1·min of remifentaniland 0.15 mg·kg-1 of midazolam (RM group).Hemodynamic parameters, white cell counts in circulatingblood, and serum levels of cortisol, prolactin, andinterleukin-6 were recorded before surgery, after intubation,and at the end of surgery.RESULTS: Thirty-two patients were enrolled. Hemodynamicstability was good in both groups. After intubation,mean (SD) heart rate (75 [14] beats·min-1) and systolic(96 [14] mm Hg) and diastolic (60 [7] mm Hg) bloodpressures were lower in the RM group than in theMKF group (99 [17] beats·min-1; 121 [29] mm Hg; and79 [14] mm Hg, respectively, P<0.01). After surgery whimistecell (10528 [6480] µL-1) and neutrophil (8155 [5657]µL-1 ) counts and cortisol concentration (225 [257]ng·mL-1) were significantly lower in the RM patientsthan in the MKF patients (white cell count, 14 002[5927] cells·µmL-1; neutrophil count, 11530 [5657]cells·µL-1, and 788.8 [146] ng·mL-1; P<0.01).CONCLUSIONS: The 2 intravenous anesthesia regimenscompared differ slightly with regard to their effects on surgicalstress. Anesthesia with remifentanil and midazolamcontributes to reducing the inflammatory response throughmodulation of the neurohumoral response to stress