Effectiveness of the 10-valent pneumococcal conjugate vaccine among girls, boys, preterm and low-birth-weight infants - Results from a randomized, double-blind vaccine trial.

BACKGROUND: Several studies have shown differences in susceptibility to infections and immune response to vaccines by sex. Prematurely born infants are at higher risk for pneumococcal diseases, with lower effectiveness for some vaccines compared to term infants. We have reported the effectiveness of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) on several endpoints in the Finnish Invasive Pneumococcal disease (FinIP) vaccine trial. Now, we present the results of a post-hoc analysis evaluating PHiD-CV10 effectiveness in subgroups by sex, gestational age, and birth weight. METHODS: The FinIP trial was a phase III/IV cluster-randomized, double-blind trial. Infants enrolled < 7 months of age received PHiD-CV10 in two thirds of clusters (3 + 1 or 2 + 1 schedule) and hepatitis B vaccine as control in remaining third. Outcome data included invasive pneumococcal disease, pneumonia, tympanostomy tube placements, and antimicrobial purchases collected through national, routinely used health registers. Negative binomial model was used in the incidence and vaccine effectiveness estimation, and differences in incidences between subgroups were tested among control children. RESULTS: Of the 30,527 infants enrolled 51% were boys. The incidences of hospital-diagnosed pneumonia and otitis-related outcomes were higher among boys in control groups. There were no significant sex differences in the vaccine effectiveness estimates. Altogether, 1519 (5%) infants were born before 37th gestational week. The incidences of pneumonia outcomes were higher among premature infants when compared to term infants. The vaccine effectiveness estimates among preterm infants were not statistically significant except for antimicrobial purchases, but all point estimates were at the same level among preterm infants as among term infants. There was no significant difference between 2 + 1 and 3 + 1 schedules in any of the subgroups analysed. CONCLUSION: PHiD-CV10 had a similar effectiveness in both sexes, and seemed to be protective in preterm infants. TRIAL REGISTRATION: ClinicalTrials.gov NCT00861380 and NCT00839254.

Presumption of consent in the echr practice and legal systems: legal models for organ removal for transplantation.

OBJECTIVE: Introduction: Post-mortem organ donation is widely used and poses a problem for transplant specialists and lawyers, whose task is to provide legal support for the removal of organs of the deceased. The aim: of the article is the scientific search for the optimal legal model of organ removal for transplantation. PATIENTS AND METHODS: Materials and methods: The theoretical base of the research consists of the works of Bonnie F., Dakhno I.N., Erin C., Evans R., Kevorkian J.A., Price D., Richardson R., Reriht A.A. The empirical base includes the results of the opinion poll and the analysis of the ECHR practice. Formal-logical (dogmatic) method, comparative legal method, logical-semantic method, generalization and modelling techniques are used. CONCLUSION: Conclusions: To improve the legal regulation of transplantation it is necessary to improve the legal literacy; create effective mechanisms to protect the patients' and doctors' rights; increase the information and scientific support of transplantation.

Effectiveness of pneumococcal Haemophilus influenzae protein D conjugate vaccine against pneumonia in children: A cluster-randomised trial.

BACKGROUND: Pneumococcal conjugate vaccines have potential to prevent significant proportion of childhood pneumonia. Finnish Invasive Pneumococcal disease vaccine trial was designed to assess the vaccine effectiveness (VE) of the 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against several outcomes. We now report results for pneumonia. METHODS: In this nationwide, cluster-randomised, double-blind trial, children younger than 19 months received PHiD-CV10 in 52 clusters or hepatitis vaccines as control in 26 clusters. Infants younger than 7 months at the first vaccination received either 3+1 or 2+1 vaccination schedule, children aged 7-11 months received 2+1, and those 12-18 months of age two-dose schedule. All hospitalizations and outpatient visits to hospital associated with ICD-10 codes compatible with pneumonia were identified through the National Care Register and 1-3 frontal chest X-ray images per event were collected. External readers who were unaware of the patients' vaccination status retrospectively interpreted the images. The evaluated outcomes were hospital-diagnosed, hospital-treated pneumonia as primary diagnosis, and radiologically confirmed pneumonia during the blinded, intention-to-treat follow-up period from the first vaccination to the end of 2011. Total VE was calculated as 1 minus rate ratio of all pneumonia episodes. RESULTS: 47 366 children were enrolled from February 2009, to October 2010. VE against all episodes of hospital-diagnosed pneumonia was 27% (95% confidence interval [CI]: 14%, 38%), 32% (95% CI: 3%, 52%), and 23% (95% CI: -5%, 44%) in subjects enrolled at age <7, 7-11, and 12-18 months, respectively. Corresponding rate reductions were 3.4, 4.7, and 2.5 per 1000 person-years. VE estimates against pneumonia with alveolar consolidation or pleural effusion (WHO criteria) in the three cohorts were 45% (95% CI: 26%, 60%), 56% (95% CI: 14%, 77%), and 48% (95% CI: 2%, 73%), respectively. CONCLUSION: PHiD-CV10 vaccination remarkably reduced disease burden due to pneumonia in infants and young children. CLINICAL TRIAL REGISTRATION: Main trial NCT00861380, nested carriage and otitis media trial NCT00839254 (ClinicalTrials.gov).

The role of interventions in the cancer evolution-an evolutionary games approach.

We propose to endow evolutionary gamemodels with changes of the phenotypes adjustment during the transient generations performed by the parameters in the payoff matrix which determine the fitness resulting from different interactions between players. These changes represent an alteration of access to external resources which, in turn, may reflect anticancer treatment. In the case of spatial games, these functions are represented by an additional lattice where another and parallel game based on cellular automata is performed. The main assumption of the spatial games is that each cell on the lattice is represented by a player following only one strategy. We propose to consider cells on the spatial lattice as heterogeneous (instead of homogeneous), so that each particular player may contain mixed phenotypes. Spatial games of the type, proposed by us, are called multidimensional spatial evolutionary games (MSEG). It may happen that within the population, all of the players have diverse phenotypes (which probably better describes biological phenomena). The additional lattice representing the evolution of resources increases only the dimension of the lattice in the MSEG.

Immunogenicity, safety and reactogenicity of the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in 2-17-year-old children with asplenia or splenic dysfunction: A phase 3 study.

BACKGROUND: Immunization with pneumococcal vaccines is an important prophylactic strategy for children with asplenia or splenic dysfunction, who are at high risk of bacterial infections (including S. pneumoniae). This study aimed to assess immunogenicity and safety of pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, GSK) in this at-risk population. METHODS: This phase III, multi-centre, open-label, controlled study, in which at-risk children with asplenia or splenic dysfunction were enrolled (age strata: 2-4, 5-10 and 11-17years), was conducted in Poland and the Russian Federation. For the 2-4years at-risk group, healthy age-matched children were enrolled as control. Unprimed children (not previously vaccinated with any pneumococcal vaccine) received 2 PHiD-CV doses (≥2months apart) and pneumococcal vaccine-primed children received 1 dose. Immune responses were assessed pre-vaccination and one month post-each dose. Solicited and unsolicited adverse events (AEs) were recorded for 4 and 31days post-vaccination, respectively, and serious AEs (SAEs) throughout the study. RESULTS: Of 52 vaccinated children (18 at-risk primed, 28 at-risk unprimed and 6 control unprimed), 45 (18, 23 and 4, respectively) were included in the according-to-protocol cohort for immunogenicity. Post-vaccination (post-dose 1 in primed and post-dose 2 in unprimed children), for each vaccine pneumococcal serotype and vaccine-related serotype 6A all at-risk children had antibody concentrations ≥0.2µg/mL, and for vaccine-related serotype 19A at least 94.4%. Increases in antibody geometric mean concentrations were observed. For most serotypes, all at-risk children had post-vaccination opsonophagocytic activity (OPA) titers ≥8 and increases in OPA geometric mean titers were observed. No safety concerns were raised. One non-fatal SAE (respiratory tract infection, considered not vaccine-related) was reported by one at-risk unprimed child. CONCLUSION: PHiD-CV was immunogenic and well tolerated in 2-17-year-old children with asplenia or splenic dysfunction. Clinical Trial Registry: www.clinicaltrials.gov, NCT01746108.

Reactogenicity, safety and immunogenicity of a protein-based pneumococcal vaccine in Gambian children aged 2-4 years: A phase II randomized study.

Pneumococcal conjugate vaccines (PCVs) have been successful in preventing invasive pneumococcal disease but effectiveness has been challenged by replacement of vaccine serotypes with non-vaccine serotypes. Vaccines targeting common pneumococcal protein(s) found in most/all pneumococci may overcome this limitation. This phase II study assessed safety and immunogenicity of a new protein-based pneumococcal vaccine containing polysaccharide conjugates of 10 pneumococcal serotypes combined with pneumolysin toxoid(dPly) and pneumococcal histidine triad protein D(PhtD) (PHiD-CV/dPly/PhtD-30) in African children. 120 Gambian children (2-4 years, not previously vaccinated against Streptococcus pneumoniae) randomized (1:1) received a single dose of PHiD-CV/dPly/PhtD-30 or PCV13. Adverse events occurring over 4 d post-vaccination were reported, and blood samples obtained pre- and 1-month post-vaccination. Serious adverse events were reported for 6 months post-vaccination. Solicited local and systemic adverse events were reported at similar frequency in each group. One child (PHiD-CV/dPly/PhtD-30 group) reported a grade 3 local reaction to vaccination. Haematological and biochemical parameters seemed similar pre- and 1-month post-vaccination in each group. High pre-vaccination Ply and PhtD antibody concentrations were observed in each group, but only increased in PHiD-CV/dPly/PhtD-30 vaccinees one month post-vaccination. One month post-vaccination, for each vaccine serotype ≥96.2% of PHiD-CV/dPly/PhtD-30 vaccinees had serotype-specific polysaccharide antibody concentrations ≥0.20µg/mL except serotypes 6B (80.8%) and 23F (65.4%), and ≥94.1% had OPA titres of ≥8 except serotypes 1 (51.9%), 5 (38.5%) and 6B (78.0%), within ranges seen in PCV13-vaccinated children. A single dose of PHiD-CV/dPly/PhtD-30 vaccine, administered to Gambian children aged 2-4 y not previously vaccinated with a pneumococcal vaccine, was well-tolerated and immunogenic.

Vaccine effectiveness of the pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) against clinically suspected invasive pneumococcal disease: a cluster-randomised trial.

BACKGROUND: Vaccine effectiveness of pneumococcal conjugate vaccines against culture-confirmed invasive pneumococcal disease has been well documented. In the Finnish Invasive Pneumococcal disease (FinIP) trial, we reported vaccine effectiveness and absolute rate reduction against laboratory-confirmed invasive pneumococcal disease (confirmation by culture or antigen or DNA detection irrespective of serotype). Here, we assessed vaccine effectiveness of PHiD-CV10 against clinically suspected invasive pneumococcal disease in children by use of diagnoses coded in hospital discharge registers. METHODS: For this phase 3/4 cluster-randomised, double-blind trial, undertaken between Feb 18, 2009, and Dec 31, 2011, in municipal health-care centres and the Tampere University Vaccine Research Centre (Finland), we randomly assigned (2:2:1:1) 78 clusters into PHiD-CV10 three plus one, PHiD-CV10 two plus one, control three plus one, control two plus one groups (26:26:13:13 clusters) to give PHiD-CV10 in either three plus one or two plus one schedule (if enrolled before 7 months of age; infant schedules), two plus one (if enrolled between 7 and 11 months; catch-up schedules), and two doses at least 6 months apart (if enrolled between 12 and 18 months; catch-up schedules). Children were eligible if they had not received and were not anticipated to receive any of the study vaccines and had no general contraindications to vaccinations. We collected all inpatient and outpatient discharge notifications from the national hospital discharge register with International Classification of Diseases (ICD) 10 diagnoses compatible with invasive pneumococcal disease or unspecified sepsis, and verified data with patient files. We excluded invasive pneumococcal disease cases confirmed by positive culture or DNA/RNA detection from normally sterile body fluid. The primary objective was to estimate vaccine effectiveness against all register-based non-laboratory-confirmed invasive pneumococcal disease or unspecified sepsis and patient-file verified non-laboratory-confirmed invasive pneumococcal disease in infants younger than 7 months at enrolment. Masked follow-up lasted from the date of the first vaccination to Dec 31, 2011. Vaccine effectiveness was calculated against all episodes. This trial is registered with ClinicalTrials.gov, numbers NCT00861380 and NCT00839254. FINDINGS: We enrolled 47,366 children. On the basis of ICD-10 diagnoses, we recorded 264 episodes of register-based non-laboratory-confirmed invasive pneumococcal disease or unspecified sepsis, of which 102 were patient-file verified non-laboratory-confirmed invasive pneumococcal disease. The vaccine effectiveness was 50% (95% CI 32-63) in the 30,527 infants with three plus one and two plus one schedules combined and the absolute incidence rate reduction was 207 episodes per 100,000 person-years (95% CI 127-286). The vaccine effectiveness against the patient-file verified non-laboratory-confirmed invasive pneumococcal disease was 71% (95% CI 52-83) in infant three plus one and two plus one schedules combined. The absolute rate reduction was 142 episodes per 100,000 person-years (95% CI 91-191) in infant cohorts. INTERPRETATION: This vaccine-probe analysis is the first report showing the effect of pneumococcal conjugate vaccines on clinically suspected invasive pneumococcal disease. The absolute rate reduction was markedly higher compared with laboratory-confirmed invasive pneumococcal disease, which implies low sensitivity of the laboratory-based case definitions and subsequently higher public health effect of pneumococcal conjugate vaccines against invasive pneumococcal disease than previously estimated. FUNDING: GlaxoSmithKline Biologicals SA and National Institute for Health and Welfare (THL), Finland.

Immunogenicity, safety and reactogenicity of the 10-valent pneumococcal non-typeable haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Nigerian Infants: a randomised trial.

AIMS AND OBJECTIVES: The immunogenicity, reactogenicity and safety of the 10- valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) were evaluated in a cohort of Nigerian infants included in a study conducted in Mali and Nigeria (ClinicalTrials.gov identifier: NCT00678301). SUBJECTS AND METHODS: In this open, randomised, controlled study, 119 healthy infants received combined diphtheria-tetanus-whole-cell pertussis-hepatitis B/ Haemophilus influenzae type b vaccine (DTPw-HBV/Hib) and oral poliovirus vaccine (OPV) co-administered with PHiD-CV (PHiD-CV group) or without PHiD-CV (control group) at 6-10-14 weeks of age. Pneumococcal antibody responses and opsonophagocytic activity were measured and adverse events were recorded. RESULTS: One month post-dose 3, for each of the vaccine pneumococcal serotypes, e"90.1% of PHiD-CV recipients had an antibody concentration e"0.2 ug/mL compared to < 9 % (except for serotypes 14 [32.4%] and 19F [27.8%]) in the control group. For each of the vaccine pneumococcal serotypes, e"90.6% of infants in the PHiD-CV group had an OPA titre e"8, compared to % 18% (except for serotype 7F [60.0%]) in the control group. Anti-protein D antibody geometric mean antibody concentrations were 2949.7 EL.U/mL in the PHiD-CV group and 68.9 EL.U/mL in the control group. For each DTPw-HBV/Hib antigen antibody seroprotection/seropositivity rates were e"94.4%. Tolerability was generally comparable between the PHiD-CV and control vaccination groups. CONCLUSIONS: PHiD-CV co-administered with routine vaccines was immunogenic for all vaccine pneumococcal serotypes and protein D in Nigerian infants. Vaccine tolerability was generally comparable between the PHiD-CV and control groups. These results suggest PHiD-CV can be co-administered with other vaccines included in the National Programme on Immunisation.

Trends in the incidence of the free wall cardiac rupture in acute myocardial infarction. observational study: experience of a single center.

PURPOSE: Free wall cardiac rupture (CR) is one of the most common cause of in-hospital death in acute myocardial infarction (AMI). The early diagnosis of CR and selection of the patients predisposed to CR become an important clinical tool. AIM: assessing the occurrence of CR in patients with AMI, to determine the factors which could help to identify the patients threatened with CR. MATERIAL AND METHODS: 2320 consecutive patients with AMI. CR was proved by autopsy or by echocardiography performed during cardio-pulmonary resuscitation (CPR). RESULTS: In-hospital mortality was 11% (254 patients). 50 patients (2%) died from CR. CR was the cause of 20% of total in-hospital death. Patients with CR were older than survivors (72 vs 60 years, p<0.0001). Women prevailed in CR group: (62% in CR group vs 27% in the survivors, p<0.01). 29% of patients were treated with thrombolytics (Th+). Out of 58 patients from Th (+) group who died, 17 (29.31%) died because of CR. CR occurred in 33 (16.8%) patients out of 196 died in Th (-) group. In the logistic regression analysis only age and sex remained as predictors of CR. 16 patients died from CR during first 24 h from admission (ECR). In 34 patients CR occurred >24 h (LCR). In ECR group were no prevalence of women, while in LCR women constituted 68%. In ECR group all but one patient had no previous history of MI (p=0.06). Frequency of thrombolythic therapy was equal. CONCLUSIONS: Advanced age patients, particularly women with first AMI are at risk of CR. Decision of thrombolytic treatment in this group of patients must be very cautious.

Somatic mutation screening: identification of individuals harboring K-ras mutations with the use of plasma DNA.

BACKGROUND: Many cancers are attributed to somatic mutation of DNA. We investigated whether it is feasible to detect cancer-associated somatic mutations in patients with neoplasms by using plasma DNA. METHODS: Plasma samples were prospectively collected from 240 patients undergoing colonoscopy. Colorectal biopsies were performed as clinically indicated in 135 patients, and risk factor information was available from 232 patients. DNA was extracted from plasma and colorectal tissue and was amplified by use of a polymerase chain reaction method that enriches for mutations in codon 12 of the K-ras oncogene. Molecular, histologic, and clinical data were compared by use of two-sided Fisher's exact test. RESULTS: Mutations in the K-ras gene detected in the plasma of 64 (28%) of 232 patients were statistically significantly associated with colorectal cancer risk factors (P =.0002). Of those patients having tissue available for comparison (n = 135), mutations in the K-ras gene were found in the tissues of 35 patients, and 29 (83%) of these 35 showed mutations in plasma samples. In contrast, the plasma assay was negative in 93 of the 100 patients whose tissue K-ras was wild-type. Among patients without biopsies (n = 105), 28 had mutated K-ras in their plasma DNA, despite the absence of remarkable colonoscopy findings; 24 of these 28 patients had risk factors for colorectal cancer. Overall, 25 (39%) of 64 patients showing mutations in plasma DNA had colorectal neoplasms with K-ras mutations compared with five (3%) of 176 patients without K-ras mutations in plasma DNA. CONCLUSION: Plasma DNA assays for the detection of mutations in K-ras codon 12 may provide a feasible method to screen populations for somatic mutations frequently found in neoplasms. The clinical utility of using this test in screening populations requires further study.

A retrospective analysis of 96 "asp" (Megalopyge opercularis) envenomations in Central Texas during 1996.

BACKGROUND: The most frequently reported caterpillar envenomation in Central Texas is by the puss caterpillar or "asp," Megalopyge opercularis. This caterpillar is described by patients and physicians as inflicting intense radiating pain. The intensity of symptoms may be underestimated leading to undertreatment. Adequate treatment protocols have been lacking and those in use are not very successful. We present a retrospective study of patients who were stung and contacted the Central Texas Poison Center. METHODS: All human exposures to asp stings reported to the Central Texas Poison Center during 1996 were included. Inclusion criteria consisted of all cases documented as an asp envenomation by the specialists in poison information. Characterization of symptoms and treatment used were evaluated. RESULTS: There were 96 exposures to asps reported. Ninety-five of the patients experienced local pain with 26 of these reporting intense radiating pain. Forty developed erythema, 27 described edema, and 9 complained of welts/hives. Other symptoms reported included white spots (4), pruritus (3), red streak (2), numbness (2), and individual accounts of chest pain, rash, ecchymosis, tingling, blister, and muscle spasm. There was no treatment modality that promptly relieved pain. DISCUSSION: Although asp envenomations appear to be very common, clinical cases have rarely been documented. This may be due to physicians not recognizing the etiological agent. Pain may be very intense and standard pain management appears to be unsuccessful. CONCLUSION: This study suggests that further examination of treatment modalities may be beneficial in addressing the morbidity of Megalopyge opercularis envenomations.

Assessing cross-media impacts: a comparative risk approach.

The Oregon Department of Environmental Quality has developed a Cross-Media Comparative Risk Assessment model to address certain regulatory concerns. The model generates a Human and Ecological Risk Index for a facility releasing toxins into the environment. The risk indices are based on chemical fate and transport predictions, toxicity, population density, and ecological sensitive areas. The model can be used to rank facilities for inspection or as a tool to assess the progress of pollution prevention programs. Regulatory permitting departments can use the model to address the cross-media transfer of pollutants from one environmental compartment to another. The versatility of the model allows adaptation to each specific users needs.

Five-year multicenter retrospective review of cyclobenzaprine toxicity.

Cyclobenzaprine (CBP) has a cyclic structure similar to amitriptyline. In overdose, CBP has been suggested to produce the cardiovascular and neurologic toxicity found with the cyclic antidepressants. To examine this possibility, a retrospective chart review of all cases of CBP exposure reported to five regional poison centers was performed for the years 1989-93. There were a total of 750 charts identified for CBP exposure, of which 523 had data sufficient for evaluation. There were 121 polydrug ingestions leaving 402 pure CBP ingestions. Ages ranged from 7 mo to 77 yrs, with a mean of 20 yrs; 26% were 6 yrs or less. Females comprised 63% of the patient group. No deaths occurred. Dysrhythmias beyond sinus tachycardia were infrequent, and none were life-threatening. No seizures occurred. Common effects were lethargy, sinus tachycardia, and agitation, and both hypertension and hypotension were seen. All symptomatic cases with a known time of ingestion were symptomatic within 4 h of ingestion. Doses ingested ranged from 5-1000 mg, with a mean of 133 mg. Asymptomatic and symptomatic patients had a mean dose ingested of 45 mg and 183 mg, respectively. Treatment was primarily gastrointestinal (GI) decontamination and supportive care. Other therapies required were mechanical ventilation, dopamine, fluid bolus, sedation, and foley catheter. Symptoms requiring treatment beyond GI decontamination did not occur with ingestions less than 100 mg. In conclusion, cyclobenzaprine does not appear to produce the life-threatening cardiovascular or neurologic effects of the cyclic antidepressants in doses less than 1 g. Lethargy and anticholinergic effects are prominent, though serious toxicity is infrequent.

Unintentional albuterol ingestion in children.

This study was designed to determine the threshold dose for toxicity, the potential for serious medical complications, and the medical care required after unintentional albuterol ingestion in children. This study was prospective and descriptive. Data were obtained on pediatric albuterol ingestions evaluated emergently as reported to three regional poison control centers. Data elements included dose ingested, physical findings, medical treatment, and outcome. During 18 months, 78 patients who ingested albuterol and who received urgent medical evaluation were identified. Mean age was 2.8 years. The amount ingested ranged from 0.2 to 8.8 mg/kg. The most commonly reported signs of toxicity were tachycardia (57%, 44/78), widened pulse pressure (50%, 27/54), hyperglycemia (50%, 12/24), agitation (45%, 35/78), low serum carbon dioxide (42%, 10/24), vomiting (26%, 20/78), and hypokalemia (26%, 9/35). We found a threshold dose o 1 mg/kg for three or more signs of toxicity (P < 0.01). No patient required any specific treatment for toxicity. Seventy-two percent of patients were discharged from medical care within six hours of ingestion. Albuterol overdose in children causes a variety of cardiovascular, neuromuscular, and metabolic effects that are usually benign. The threshold dose for the development of three or more signs of toxicity is 1 mg/kg or three to 10 times the recommended daily dose. Toxicity is short-lived and does not require specific therapy or hospital admission in most cases.

Bupropion overdose: a 3-year multi-center retrospective analysis.

Bupropion (Wellbutrin; Burroughs Welcome Co, Research Triangle Park, NC) is a unique monocyclic antidepressant about which there is limited overdose information. A retrospective analysis of all bupropion ingestions reported to five regional poison control centers from 1989 through 1991 was conducted. There were 58 cases of bupropion ingestion and nine cases of combined bupropion and benzodiazepine ingestion. Sinus tachycardia was the only toxic cardiovascular effect noted, except for one case of hypotension in the bupropioin and benzodiazepine group. Neurological toxicity was commonly encountered and included lethargy, tremors, and seizures. Both benzodiazepines and phenytoin were efficacious in controlling seizures. Five cases of pure bupropion overdose had electrolytes reported. Serum potassium ranged from 2.6 to 4.2 mEq/L (mean, 3.3 mEq/L). In overdose, bupropion seems to lack major cardiovascular toxicity; however, it does manifest significant neurological toxicity.

A one-year evaluation of calcium channel blocker overdoses: toxicity and treatment.

STUDY OBJECTIVE: To examine the cardiovascular toxicity of calcium channel blockers and the efficacy of various treatments. DESIGN: Case series collected prospectively over one year. SETTING: Three regional poison control centers. TYPE OF PARTICIPANTS: One hundred thirty-nine hospitalized patients who had ingested a calcium channel blocker. INTERVENTIONS: Calcium, dopamine, atropine, isoproterenol, glucagon, and pacemakers. MAIN RESULTS: Hypotension, sinus node suppression, and dysrhythmias often occur with calcium channel blocker overdoses, but atrioventricular nodal block occurs more often with verapamil (chi 2 test, P < .025). Calcium was administered to 23 patients and was efficacious in reversing depression of cardiac conduction and increasing blood pressure. Dopamine was administered to ten patients and was efficacious in increasing blood pressure. Atropine was administered to eight patients, but only two had a positive response. CONCLUSION: Atrioventricular nodal depression is more common with verapamil overdoses. Calcium and dopamine are useful in treating toxicity from calcium channel blocker overdose, whereas atropine is sometimes useful.

Acute fluoxetine overdose: a report of 234 cases.

Limited toxicity information is available in the medical literature on the antidepressant fluoxetine (Prozac, Dista Products Co, Indianapolis, IN). The goal of this prospective multicenter study was to develop a toxicity profile of initial signs and symptoms observed in an acute fluoxetine overdose. A prospective study was made of patients reported to one of four American Association of Poison Control Centers' regional poison control centers after ingesting an acute overdose of fluoxetine. A standard data collection form was used on all patients ingesting fluoxetine. Information obtained included age, current medications, dose, coingested drugs, presenting symptoms, vital signs, electrocardiogram abnormalities, outcome, and fluoxetine levels. The authors collected 272 cases; 234 cases met the criteria of the study. Fluoxetine was ingested alone in 87 cases and with ethanol or other drugs in the remaining 147 cases. Of the 87 cases where fluoxetine was ingested alone, 67 patients were adults and 20 were children. Symptoms that were seen in the adult group included: tachycardia (15/67), drowsiness (14/67), tremor (five/67), vomiting (four/67), or nausea (four/67). Thirty patients did not develop symptoms. Twelve of the adult overdose patients had total fluoxetine levels ranging from 232 to 1390 ng/mL. The authors conclude that symptoms that develop after an acute overdose of fluoxetine appear minor and of short duration. Aggressive supportive care is the only intervention necessary.

The effects of fluoxetine in the overdose patient.

Fluoxetine (Prozac) is a new antidepressant, first marketed in the United States in January 1988. Only limited toxicologic information during a fluoxetine overdose is available. The goal of this prospective multi-center study was to develop a toxicity profile of initial signs and symptoms observed in fluoxetine overdose. A standardized data collection form was used on all patients ingesting fluoxetine as reported to four poison centers. Information obtained included age, dose, co-ingested drugs, presenting symptoms, vital signs, EKG abnormalities and lab values. Of the 127 cases of acute fluoxetine overdose collected, 106 cases met the criteria of the study. Of these, 69/106 ingested other drugs, including ethanol and 37/106 ingested fluoxetine alone. Of the latter group, the amounts ingested ranged from 20 to 1500 mg. It was observed that 48.6% (18/37) remained asymptomatic, 16.2% (7/37) were sleepy, 24.3% (9/37) had a sinus tachycardia (of 100 beats per minute or greater), and 8.1% (3/37) had a diastolic pressure over 100 mm Hg. Data collection is ongoing. Based upon our initial experience, fluoxetine in overdose appears to be relatively benign.