Clinical research monitoring: scenarios and challenges

Clinical research is essential for the development of new drugs, diagnostic tests and new devices. Clinical monitoring is implemented to improve the quality of research and attain high ethical and scientific standards. This review discusses the role of clinical monitors, taking into account the variety of scenarios in which medical research is developed, and highlights the challenges faced by research teams to ensure that patients rights are respected and that the social role of scientific research is preserved. Specific emphasis is given to the ethical dilemmas related to the multiple roles which clinical monitors play in the research framework, mainly those involving the delicate equilibrium between the loyalty to the sponsor and to the research subjects. The essential role of clinical monitoring for research developed in poor healthcare scenarios is highlighted as an approach to get the local infrastructure strengthening needed to achieve an adequate level of good clinical practices.

Revisiting the concept of hepatosplenic schistosomiasis and its challenges using traditional and new tools

Different aspects of hepatosplenic schistosomiasis are revisited here. Manson's schistosomiasis causes periportal fibrosis and portal hypertension in approximately 6% of infected subjects, usually with preservation of their hepatic function. The assessment of liver involvement is of major importance in determining the prognosis and risk of complications from schistosomiasis, such as upper digestive bleeding secondary to variceal rupture. For many years, the diagnosis of hepatosplenic schistosomiasis and liver fibrosis was made by abdominal palpation and the finding of liver and/or spleen enlargement. However, there is no consensus regarding the clinical parameters of the liver and spleen to be considered in this physical evaluation. For the last three decades, abdominal ultrasound (US) has become the best imaging technique to evaluate liver fibrosis caused by schistosomiasis mansoni. However, US is a subjective procedure and is therefore examiner-dependent. Magnetic resonance imaging (MRI) findings have provided valuable information in addition to ultrasound and clinical examination. The combination of a comprehensive history and physical examination, basic laboratory tests (a stool examination for Schistosoma mansoni eggs and a blood cell count), biomarkers for liver fibrosis/portal hypertension and imaging methods seem to offer the best approach for evaluating patients with this disease. In situations where research is involved or in patients with severe disease, MRI may be considered.

Two decades of tuberculosis in a city in Northeastern Brazil: advances and challenges in time and space

Abstract: INTRODUCTION This study presents two decades of epidemiological data on tuberculosis (TB), in order to understanding the disease profile and its spatiotemporal dynamics. METHODS This descriptive study was performed in the City of Olinda/Pernambuco, Brazil, from 1991-2010, and it analyzed new patients with TB living in the city. We used the χ²-test with a p-value <0.05 to identify differences in trends. Incidence and cluster distribution were identified using spatial scan statistics. RESULTS In total, 6202 new cases were recorded during the two decades. The highest incidence occurred in 1995 (110 cases/100,000 inhabitants), and the lowest occurred in 2009 (65 cases/100,000 inhabitants) (β=-1.44; R²=0.43; p=0.0018). The highest mortality occurred in 1998 (16 deaths/100,000 inhabitants), and the lowest occurred in 2008 (5 deaths/100,000 inhabitants) (β=-0.19; R²=0.17; p=0.07). There was a male predominance (65%), and ages ranged from 20-49 years (65%). There was a substantial increase in the number of patients that were cured after treatment (60% to 67%; p<0.001) as well as those tested for HIV (1.9% to 58.5%; p<0.001). During the first decade, clusters with p-values <0.05 included 29% of the total notified cases, and in the second decade, that percentage was 12%. CONCLUSIONS We observed a decreasing trend in incidence, which was significant, and mortality rates, which was not significant. The increased number of laboratory tests performed reflects advances in surveillance, and a reduction in the proportion of cases in primary clusters suggests, among other things, that the disease is spreading across the region.

Effects of continuous versus bolus infusion of enteral nutrition in critical patients

PURPOSE: Enteral alimentation is the preferred modality of support in critical patients who have acceptable digestive function and are unable to eat orally, but the advantages of continuous versus intermittent administration are surrounded by controversy. With the purpose of identifying the benefits and complications of each technique, a prospective controlled study with matched subjects was conducted. PATIENTS AND METHODS: Twenty-eight consecutive candidates for enteral feeding were divided into 2 groups (n = 14 each) that were matched for diagnosis and APACHE II score. A commercial immune-stimulating polymeric diet was administered via nasogastric tube by electronic pump in the proportion of 25 kcal/kg/day, either as a 1-hour bolus every 3 hours (Group I), or continuously for 24 hours (Group II), over a 3-day period. Anthropometrics, biochemical measurements, recording of administered drugs and other therapies, thorax X-ray, measurement of abdominal circumference, monitoring of gastric residue, and clinical and nutritional assessments were performed at least once daily. The principal measured outcomes of this protocol were frequency of abdominal distention and pulmonary aspiration, and efficacy in supplying the desired amount of nutrients. RESULTS: Nearly half of the total population (46.4%) exhibited high gastric residues on at least 1 occasion, but only 1 confirmed episode of pulmonary aspiration occurred (3.6%). Both groups displayed a moderate number of complications, without differences. Food input during the first day was greater in Group II (approximately 20% difference), but by the third day, both groups displayed similarly small deficits in total furnished volume of about 10%, when compared with the prescribed diet. CONCLUSIONS: Both administration modalities permitted practical and effective administration of the diet with frequent registered abnormalities but few clinically significant problems. The two groups were similar in this regard, without statistical differences, probably because of meticulous technique, careful monitoring, strict patient matching, and conservative amounts of diet employed in both situations. Further studies with additional populations, diagnostic groups, and dietetic prescriptions should be performed in order to elucidate the differences between these commonly used feeding modalities.

Critical analysis of the allocation policy for liver transplantation in Brazil

Liver transplantation is now the standard treatment for end-stage liver disease. Given the shortage of liver donors and the progressively higher number of patients waiting for transplantation, improvements in patient selection and optimization of timing for transplantation are needed. Several solutions have been suggested, including increasing the donor pool; a fair policy for allocation, not permitting variables such as age, gender, and race, or third-party payer status to play any role; and knowledge of the natural history of each liver disease for which transplantation is offered. To observe ethical rules and distributive justice (guarantee to every citizen the same opportunity to get an organ), the "sickest first" policy must be used. Studies have demonstrated that death has no relationship with waiting time, but rather with the severity of liver disease at the time of inclusion. Thus, waiting time is no longer part of the United Network for Organ Sharing distribution criteria. Waiting time only differentiates between equally severely diseased patients. The authors have analyzed the waiting list mortality and 1-year survival for patients of the State of São Paulo, from July 1997 through January 2001. Only the chronological criterion was used. According to "Secretaria de Estado da Saúde de São Paulo" data, among all waiting list deaths, 82.2% occurred within the first year, and 37.6% within the first 3 months following inclusion. The allocation of livers based on waiting time is neither fair nor ethical, impairs distributive justice and human rights, and does not occur in any other part of the world.

Critical analysis of old and new vaccines against N. meningitidis serogroup C, considering the meningococcal disease epidemiology in Brazil

Worldwide, the impact of meningococcal disease is substantial, and the potential for the introduction and spread of more virulent strains of N. meningitidis or strains with increased resistance to current antibiotics causes concern, making prevention essential. OBJECTIVES: Review the indications for meningococcal disease vaccines, considering the epidemiological status in Brazil. METHODS: A critical literature review on this issue using the Medline and Lilacs databases. RESULTS: In Brazil, MenB and MenC were the most important serogroups identified in the 1990s. Polysaccharide vaccines available against those serogroups can offer only limited protection for infants, the group at highest risk for meningococcal disease. Additionally, polysaccharide vaccines may induce a hypo-responsive state to MenC. New meningococcal C conjugate vaccines could partially solve these problems, but it is unlikely that in the next few years a vaccine against MenB that can promote good protection against multiple strains of MenB responsible for endemic and epidemic diseases will become available. CONCLUSIONS: In order to make the best decision about recommendations on immunization practices, better quality surveillance data are required. In Brazil, MenC was responsible for about 2,000 cases per year during the last 10 years. New conjugate vaccines against MenC are very effective and immunogenic, and they should be recommended, especially for children less than 5 years old. Polysaccharide vaccines should be indicated only in epidemic situations and for high-risk groups. Until new vaccines against MenC and MenB are available for routine immunization programs, the most important measure for controlling meningococcal disease is early diagnosis of these infections in order to treat patients and to offer chemoprophylaxis to contacts.

A critical review of the possible benefits associated with homeopathic medicine

OBJECTIVE: To evaluate the recent scientific research progress on homeopathy. METHODOLOGY: Homeopathy was evaluated in terms of its clinical research; in vitro research, and physical foundations. The Medline database was the main reference source for the present research, concerning data of approximately the last 10 years. Secondary references (not available in this database) were obtained by means of direct requests to authors listed in the primary references. RESULTS: Clinical studies and in vitro research indicate the inefficacy of homeopathy. Some few studies with positive results are questionable because of problems with the quality and lack of appropriate experimental controls in these studies. The most recent meta-analyses on the topic yielded negative results. One of the few previous meta-analyses with positive results had serious publication bias problems, and its results were later substantially reconsidered by the main authors. The sparse in vitro homeopathic research with positive results has not been replicated by independent researchers, had serious methodological flaws, or when replicated, did not confirm the initial positive results. A plausible mechanism for homeopathic action is still nonexistent, and its formulation, by now, seems highly unlikely. CONCLUSIONS: As a result of the recent scientific research on homeopathy, it can be concluded that ample evidence exists to show that the homeopathic therapy is not scientifically justifiable.

Proton magnetic resonance spectroscopy of the frontal lobe in schizophrenics: a critical review of the methodology

Schizophrenic patients undergoing proton magnetic resonance spectroscopy show alterations in N-acetyl aspartate levels in several brain regions, indicating neuronal dysfunction. The present review focuses on the main proton magnetic resonance spectroscopy studies in the frontal lobe of schizophrenics. A MEDLINE search, from 1991 to March 2004, was carried out using the key-words spectroscopy and schizophrenia and proton and frontal. In addition, articles cited in the reference list of the studies obtained through MEDLINE were included. As a result, 27 articles were selected. The results were inconsistent, 19 papers reporting changes in the N-acetyl aspartate levels, while 8 reported no change. Methodological analysis led to the conclusion that the discrepancy may be due the following factors: (i) number of participants; (ii) variation in the clinical and demographic characteristics of the groups; (iii) little standardization of the acquisition parameters of spectroscopy. Overall, studies that fulfill strict methodological criteria show N-acetyl aspartate decrease in the frontal lobe of male schizophrenics.

Cyperaceae of Tropical America: some new or critical species III

Discussed are the taxonomy of the Scleria arundinacea-latifoliacomplex, S. mitis, and S. myricocarpa, all controversial and widespread taxa in tropical America. Scleria cerradicola is described as new in the section Hymenolytrum and a range extension of a rare species, Scleria neogranatensis, is noted.

NOMENCLATURAL AND CRITICAL NOTES ON SOME BRAZILIAN SPECIES OF Paspalum (POACEAE: PANICEAE)

A critical analysis of the type collections of 39 species names of Paspalum L. (Poaceae: Paniceae) from Brazil described by Swallen is presented along with comments based on more recent gatherings of the species. Eighteen new synonyms are proposed.

Critical aortic stenosis in the neonate. Clinical assessment and surgical outcome in 18 patients

OBJECTIVE - To assess neonates with aortic stenosis with early decompensation operated upon. (LCO) (CHF). METHODS - A and retrospective study analyzing 6 neonates with LCO, group I (GI), and 12 neonates with CHF, group II (GII). Clinical radiographic, electrocardiographic and echocardiographic findings also provided comparative bases for the study, as did surgical and evolutional findings. RESULTS - The mean ages at hospitalization and surgery (p = 0.0031) were 14.3 and 14.8 days in GI and 35.4 and 42.8 days in GII, respectively. Cardiac murmurs were more intense in GII (p = 0.0220). The aortic ring was smaller in GI (8.0 ± 2.5mm) as compared to GII (11.4±1.4mm) (p = 0.2882). Ventricular function was reduced to 18±5.5% and 33.3±7.6% in GI and GII, respectively (p = 0.0162). Aortic atresia, however, was present only in 2 neonates in GI. Five of 6 patients in GI died but all patients in GII survived (p=0.0007). In the latter group, 84.6% of the patients were in functional class I (FC-I) in the long-term follow-up, with moderate residual lesions in 6 neonates, discrete residual lesions in 4, and reoperation in 2. CONCLUSION - Aortic stenosis is a severe anomaly of the neonate, whose immediate evolution depends on the pre-operative anatomic and functional findings, and the late evolution essentially depends on the anatomic features of the valve.