Linking better shiftwork arrangements with safety and health management systems

OBJECTIVE: Various support measures useful for promoting joint change approaches to the improvement of both shiftworking arrangements and safety and health management systems were reviewed. A particular focus was placed on enterprise-level risk reduction measures linking working hours and management systems. METHODS: Voluntary industry-based guidelines on night and shift work for department stores and the chemical, automobile and electrical equipment industries were examined. Survey results that had led to the compilation of practicable measures to be included in these guidelines were also examined. The common support measures were then compared with ergonomic checkpoints for plant maintenance work involving irregular nightshifts. On the basis of this analysis, a new night and shift work checklist was designed. RESULTS: Both the guidelines and the plant maintenance work checkpoints were found to commonly cover multiple issues including work schedules and various job-related risks. This close link between shiftwork arrangements and risk management was important as shiftworkers in these industries considered teamwork and welfare services to be essential for managing risks associated with night and shift work. Four areas found suitable for participatory improvement by managers and workers were work schedules, ergonomic work tasks, work environment and training. The checklist designed to facilitate participatory change processes covered all these areas. CONCLUSIONS: The checklist developed to describe feasible workplace actions was suitable for integration with comprehensive safety and health management systems and offered valuable opportunities for improving working time arrangements and job content together.

Safety and efficacy of fenproporex for obesity treatment: a systematic review

ABSTRACT OBJECTIVE To evaluate clinical evidence on the safety and efficacy of fenproporex for treating obesity. METHODS MEDLINE, LILACS and Cochrane Controlled Trials Register were searched as well as references cited by articles and relevant documents. Two authors independently assessed the studies for inclusion and regarding risk of bias, collected data, and accuracy. Eligible studies were all those placebo-controlled that provided data on the efficacy and safety of Fenproporex to treat obesity. RESULTS Only four controlled studies met the inclusion criteria. One randomized, placebo-controlled trial on Fenproporex was found on electronic databases. Three placebo-controlled studies (in non-indexed journals) were identified by hand-searching. Patients with cardiovascular and other comorbidities were excluded in all studies. Trials lasted from 40 to 364 days and doses ranged from 20 to 33.6 mg/d. All controlled studies found that weight loss among Fenproporex-treated patients was greater than that produced by the placebo, but drug effect was modest. Fenproporex produced additional weight reductions of 4.7 kg (one year), 3.8 kg (six months) and 1.55 kg (two months) in average, in relation to diet and exercise only (three trials). Insomnia, irritability, and anxiety were the most frequently reported side effects in the four studies. CONCLUSIONS There is a paucity of randomized, placebo-controlled trials on Fenproporex and those identified here present major methodological flaws. These studies suggest that Fenproporex is modestly effective in promoting weight loss. Nonetheless, they failed to provide evidence that it reduces obesity-associated morbidity and mortality. Data from these studies are insufficient to determine the risk-benefit profile of Fenproporex. Abuse potential and amphetamine-like adverse effects are causes for concern.

Safety and immunogenicity of hepatitis B vaccine ButaNG in adults

Recombinant yeast-derived hepatitis B vaccine manufactured by Instituto Butantan was administered in two groups of adult volunteers (I, II) following two different schedules of immunization. In the first trial (10 mg doses and 0, 1, 3 months vaccination schedule) 106 individuals completed the full immunization program. The results of seroconversion by age group varied from 70 to 100% and the GMT from 46.5 to 124.9 mIU mL-1. In the second trial with 68 individuals (for dosage comparison and 0, 1, 6 months vaccination schedule) indicated that the vaccine formulated in 20 mg was more effective than in 10 mg. The adverse reactions observed in the vaccinees were less frequent than the ones previously found since the introduction of similar vaccines.

Proposal of abolition of the skin sensitivity test before equine rabies immune globulin application

An epizootic outbreak of rabies occurred in 1995 in Ribeirão Preto, SP, with 58 cases of animal rabies (54 dogs, 3 cats and 1 bat) confirmed by the Pasteur Institute of São Paulo, and one human death. The need to provide care to a large number of people for the application of equine rabies immune globulin (ERIG) prevented the execution of the skin sensitivity test (SST) and often also the execution of desensitization, procedures routinely used up to that time at the Emergency Unit of the University Hospital of the Faculty of Medicine of Ribeirão Preto, University of São Paulo (EU-UHFMRP-USP), a reference hospital for the application of heterologous sera. In view of our positive experience of several years with the abolition of SST and of the use of premedication before the application of antivenom sera, we used a similar schedule for ERIG application. Of the 1489 victims of animal bites, 1054 (71%) received ERIG; no patient was submitted to SST and all received intravenously anti-histamines (anti-H1 + anti-H2) and corticosteroids before the procedure. The patients were kept under observation for 60 to 180 minutes and no adverse reaction was observed. On the basis of these results, since December 1995 ERIG application has been decentralized in Ribeirão Preto and has become the responsibility of the Emergency Unit of the University Hospital and the Central Basic Health Unit, where the same routine is used. Since then, 4216 patients have received ERIG (1818 at the Basic Health Unit and 2398 at the EU-UHFMRP), with no problems. The ideal would be the routine use of human rabies immune globulin (HRIG) in public health programs, but this is problematic, because of their high cost. However, while this does not occur, the use of SST is no longer justified at the time of application of ERIG, in view of the clinical evidence of low predictive value and low sensitivity of SST involving the application of heterologous sera. It is very important to point out that a negative SST result may lead the health team to a feeling of false safety that no adverse reaction will occur, but this is not true for the anaphylactoid reactions. The decision to use premedication, which is based on knowledge about anaphylaxis and on the pharmacology of the medication used, is left to the judgment of health professionals, who should always be prepared for eventual untoward events.

Safety and skin delayed-type hypersensitivity response in vervet monkeys immunized with Leishmania donovani sonicate antigen delivered with adjuvants

In this study, we report on the safety and skin delayed-type hypersensitivity (DTH), responses of the Leishmania donovani whole cell sonicate antigen delivered in conjunction with alum-BCG (AlBCG), Montanide ISA 720 (MISA) or Monophosphoryl lipid A (MPLA) in groups of vervet monkeys. Following three intradermal injections of the inoculums on days 0, 28 and 42, safety and DTH responses were assessed. Preliminary tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels were also measured and these were compared with DTH. Only those animals immunized with alum-BCG reacted adversely to the inoculum by producing ulcerative erythematous skin indurations. Non-parametric analysis of variance followed by a post-test showed significantly higher DTH responses in the MISA+Ag group compared with other immunized groups (p < 0.001). The MPLA+Ag group indicated significantly lower DTH responses to the sonicate antigen compared with the AlBCG+Ag group. There was a significant correlation between the DTH and cytokine responses (p < 0.0001). Based on this study we conclude that Leishmania donovani sonicate antigen containing MISA 720 is safe and is associated with a strong DTH reaction following immunization.

Safety evaluation of SPF66 malaria vaccine in Brazil

The frequency and description of side effects secondaiy to the subcutaneous application of SPf66 malaria vaccine and placebo are reported for each dose of application in the participants of the vaccine efficacy trial in Brazil. Side effects evaluated two hours after each application were detected in 8.0%, 30.2% and 8.8%, for the Is', and 3"' dose, respectively, in the SPf66group, and in 7.0%, 8.5% and 2.9% in the placebo group. Local reactions such as mild inflammation, nodule and pain or erythema frequently accompanied by pruritus were the most common reactions detected in both groups (3-8%, 29.1% and 8.5% in the SPf66 group and 4.0%, 7.6% and 2.5% in the placebo group). Among vaccinees, local side effects after the 2nd dose were more frequent in females. Systemic side effects were expressed mainly through general symptoms referred by the participants and were most frequent after the 1st dose in both groups (4.3% in the SPf66 group and 3-0% in the placebo group). Muscle aches and fever were refewred by few participants. No severe adverse reactions were detected for either dose of application or group.

Feasibility study of the immunogenicity and safety of a novel DTPw/Hib (PRP-T) Brazilian combination compared to a licensed vaccine in healthy children at 2, 4, and 6 months of age

Vaccination of infants with conjugated Haemophilus influenzae type b (Hib) vaccines has been proven to reduce Hib meningitis by 95% and pneumoniae by 20%. The routine use of Hib vaccine is facilitated by the introduction of combination vaccines into the EPI (Expanded Plan of Immunization). The objective of this study was to compare the immunogenicity and reactogenicity of an extemporaneously mixed DTPw/Hib (diphtheria-tetanus-whole cell pertussis) combination, using the technology of two Brazilian manufacturers, against a licensed DTPw/Hib European combination in 108 infants vaccinated at 2, 4 and 6 months according to the local national schedule. The Brazilian combination was highly immunogenic with Hib seroprotection rates (anti-PRP > 0.15 mg /ml of 98% after 2 doses and 100% after 3). Also for tetanus and pertussis the new Brazilian combination was as immunogenic as the European counterpart, except the diphtheria seroprotection rates and titers were lower. There was also no clinically relevant difference in reactogenicity. If these feasibility results are confirmed, the Brazilian DTPw/Hib combination should help to boost the uptake of Hib vaccination in Brazil.

Curare - Botany, Chemistry, and Pharmacology

Some aspects of curare research carried out over the last 25 years are discussed. Accepting a pharmacological rather than purely ethnological definition means, that curares are not limited to South America but that they are also known from Central Africa and South-EastAsia. Among the criteria that have been suggested for classifying South American curares: type of container, geographical origin, botanical sourcesof the active, constituent!, and chemical composition. A combination of botanical and geographical criteria leads to much the same regional ;groupings a combination of criteria involving the type of container and the chemical composition. The active principles in curares may derive from members of thr Loganiaceae (Strychnos) and/or Menispermaceae mainly Chondrodendron and Curarea, but also Abuta,Anomospermum, Cissampelos, Sciadotenia, and Telitoxicum). Certain of the Strychnos dimeric indole alkaloids can undergo a variety of cleavages, oxidations, and isomerizations; hence., some of the compounds obtained by normal isolation procedures one almost certainly artefacts. The different genera of, Menispermaceae a wide range of bisbenzyl and other types of isoquinoline alkaloids. Many of the plant additives also contain a variety of isoquinoline bases, and this has to be taken into account in assessing the contribution these ingredients may make to the ovzJuxll activity of, curare. Loganiaceae-bated curares with toxiferinzas major alkaloid tend to be the most toxic. In the case of Menispermaceae-based products, there-is evidence that the process by which they are made may lead to a considerable increase in the toxicity of the finished poisons as compared with the original plant materials. The mechanism of action of the alkaloids it, outlined, and the role of curare alkaloids in the development of, present-day muscle-relaxant drugs used in surgery is indicated. Attention lb drawn to reported medicinal uses of some of the alkaloid-bearing plants incorporated into curares, suggesting that further evaluation of these plants may be of interest.

Myocardial perfusion by contrast echocardiography. Establishment of normal pattern of intracoronary injection and safety in humans

OBJECTIVE: To establish the normal pattern and safety of echocardiographic contrast in patients with no significant obstruction of epicardial coronary arteries. METHODS: 67 patients with normal coronary arteries or obstructions < 50% were selected from 277 patients who underwent coronary angiography (CA). Mean age was 56 ± 11years and 36 were males. At the end CA, echocardiographic contrast was selectively injected into each coronary artery. The parasternal short axis of the left ventricle (LV) was divided into six segments: anterior (A), antero-lateral (AL), postero-lateral (PL), posterior (P), infero-septal (IS) and antero-septal (AS). Anterolateral (ALPM) and posteromedial papillary muscles (PMPM) were also considered. The pattern and intensity of the appearance of the myocardial contrast was visually analyzed. RESULTS: The right coronary artery (RCA) was dominant in 60 patients. Contrast appearance was sudden and simultaneous in the 3 muscle layers. All segments could be contrasted after the injection in both coronary arteries. 100% of the AS, A and AL segments, 97% of the PL and 98% of the ALPM were perfused by the left coronary artery (LCA). P and IS segments were perfused by the RCA in 85% and 82%, respectively, and by a dominant LCA in 71% of the cases. The PMPM was perfused by a dominant RCA in 77% and by a dominant LCA in 86%. There were no symptoms. CONCLUSION: Intracoronary injection of the sonicated solution is a safe procedure that allows for an excellent opacification of the myocardium and can potentially be used during routine CA.

Safety and efficacy of coronary stent implantation. Acute and six month outcomes of 1,126 consecutive patients treated in 1996 and 1997

PURPOSE: The authors analyzed the 30-day and 6-month outcomes of 1,126 consecutive patients who underwent coronary stent implantation in 1996 and 1997. METHODS: The 30-day results and 6-month angiographic follow-up were analyzed in patients treated with coronary stents in 1996 and 1997. All patients underwent coronary stenting with high-pressure implantation (>12 atm) and antiplatelet drug regimen (aspirin plus ticlopidine). RESULTS: During the study period, 1,390 coronary stents were implanted in 1,200 vessels of 1,126 patients; 477 patients were treated in the year 1996 and 649 in 1997. The number of percutaneous procedures performed using stents increased significantly in 1997 compared to 1996 (64 % vs 48%, p=0.0001). The 30-day results were similar in both years; the success and stent thrombosis rates were equal (97% and 0.8%, respectively). The occurrence of new Q wave MI (1.3% vs 1.1%, 1996 vs 1997, p=NS), emergency coronary bypass surgery (1% vs 0.6%, 1996 vs 1997, p=NS) and 30-day death rates (0.2% vs 0.5%, 1996 vs 1997, p=NS) were similar. The 6-month restenosis rate was 25% in 1996 and 27% in 1997 (p= NS); the target vessel revascularization rate was 15% in 1996 and 16% in 1997 (p = NS). CONCLUSIONS: Intracoronary stenting showed a high success rate and a low incidence of 30-day occurrence of new major coronary events in both periods, despite the greater angiographic complexity of the patients treated with in 1997. These adverse variables did not have a negative influence at the 6-month clinical and angiographic follow-up, with similar rates of restenosis and ischemia-driven target lesion revascularization rates.

Safety and efficacy of angioplasty with intracoronary stenting in patients with unstable coronary syndromes. Comparison with stable coronary syndromes

OBJECTIVE: To assess safety and efficacy of coronary angioplasty with stent implantation in unstable coronary syndromes. METHODS: Retrospective analysis of in-hospital and late evolution of 74 patients with unstable coronary syndromes (unstable angina or infarction without elevation of the ST segment) undergoing coronary angioplasty with stent placement. These 74 patients were compared with 31 patients with stable coronary syndromes (stable angina or stable silent ischemia) undergoing the same procedure. RESULTS: No death and no need for revascularization of the culprit artery occurred in the in-hospital phase. The incidences of acute non-Q-wave myocardial infarction were 1.4% and 3.2% (p=0.6) in the unstable and stable coronary syndrome groups, respectively. In the late follow-up (11.2±7.5 months), the incidences of these events combined were 5.7% in the unstable coronary syndrome group and 6.9% (p=0.8) in the stable coronary syndrome group. In the multivariate analysis, the only variable with a tendency to significance as an event predictor was diabetes mellitus (p=0.07; OR=5.2; 95% CI=0.9-29.9). CONCLUSION: The in-hospital and late evolutions of patients with unstable coronary syndrome undergoing angioplasty with intracoronary stent implantation are similar to those of the stable coronary syndrome group, suggesting that this procedure is safe and efficacious when performed in unstable coronary syndrome patients.

A multicenter, open-label study of the efficacy and safety of telmisartan in mild to moderate hypertensive patients

OBJECTIVE: To evaluate the efficacy and tolerability of telmisartan, given once a day to patients with mild to moderate hypertension, as well as to assess the 24-hour blood pressure profile with ABPM. METHODS: Initially, 163 patients over 18 were selected, regardless of sex, with blood pressure levels >140/90mmHg at visit 1, which was confirmed at visit 2. One hundred thirty-four patients completed the study. After a 4-week placebo run-in phase, telmisartan 40mg/daily was given for 6 weeks. In those patients whose blood pressure (BP) levels were lower than 140/90mmHg, the same dosage was kept for an additional period of 6 weeks. For those who had BP higher than 140/90mmHg, the dosage was increased to 80mg/daily. Sixty-two patients were included in a subgroup that underwent ABPM 3 different times during the study. RESULTS: In the overall group, blood pressure reduction ranged from 162.3±14.5/101.3±5.75 mmHg (baseline) to 147.3±20.1/90.8±10.9 mmHg (week 12) (p<0.05). Mean blood pressure decreases were 14.4mmHg for systolic BP and 10.3mmHg for diastolic BP, after 12 weeks of active treatment. A subanalysis showed that 47 (35%) patients took telmisartan 40mg throughout the study and 81 (65%) had the dosage increased to 80mg daily. Using ABPM, an 8-mmHg reduction in systolic BP as well as a 5-mmHg reduction in diastolic BP were observed, when compared with baseline values in the final 6 hours (18-24 hours after the last dose of study medication). CONCLUSION: Our results confirm that telmisartan given once a day is effective in reducing blood pressure levels in mild to moderate hypertensive patients. This reduction occurs in a sustained and gradual manner during a 24-hour period confirmed by ABPM.

Safety, feasibility, and results of exercise testing for stratifying patients with chest pain in the emergency room

OBJECTIVE: To assess safety, feasibility, and the results of early exercise testing in patients with chest pain admitted to the emergency room of the chest pain unit, in whom acute myocardial infarction and high-risk unstable angina had been ruled out. METHODS: A study including 1060 consecutive patients with chest pain admitted to the emergency room of the chest pain unit was carried out. Of them, 677 (64%) patients were eligible for exercise testing, but only 268 (40%) underwent the test. RESULTS: The mean age of the patients studied was 51.7±12.1 years, and 188 (70%) were males. Twenty-eight (10%) patients had a previous history of coronary artery disease, 244 (91%) had a normal or unspecific electrocardiogram, and 150 (56%) underwent exercise testing within a 12-hour interval. The results of the exercise test in the latter group were as follows: 34 (13%) were positive, 191 (71%) were negative, and 43 (16%) were inconclusive. In the group of patients with a positive exercise test, 21 (62%) underwent coronary angiography, 11 underwent angioplasty, and 2 underwent myocardial revascularization. In a univariate analysis, type A/B chest pain (definitely/probably anginal) (p<0.0001), previous coronary artery disease (p<0.0001), and route 2 (patients at higher risk) correlated with a positive or inconclusive test (p<0.0001). CONCLUSION: In patients with chest pain and in whom acute myocardial infarction and high-risk unstable angina had been ruled out, the exercise test proved to be feasible, safe, and well tolerated.