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Air pollution and human health: a review and reanalysis.

Since 1970, Lave and Seskin have published a series of articles dealing with the question, "Does air pollution shorten lives?" Their recent book reports revised and extended analyses of their previous studies emphasizing policy implications. We have undertaken a review of Lave and Seskin's book to evaluate the methodology used and hence gain some insight into the strength of the conclusions reached. This review concentrates on methodology and its application to establishing and quantifying the association between air quality and health. Beyond simply reviewing the analyses reported in Lave and Seskin's book, we have duplicated and expanded two of the reported analyses. Our detailed reanalysis is presented both to verify reported results, and to illustrate the difficulties encountered in such an analysis. Our overall conclusion is that Lave and Seskin have done a thorouth job of reporting and interpreting the various analyses that they performed. Lave and Seskin have made a pioneering effort in showing an association between mortality rates and air pollution. We do not disagree with the conclusion of the existence of an association but have some reservations about their methods of estimating its magnitude. We were particularly concerned that Lave and Seskin did not fully investigate how well their models fit these data. Our reanalysis results in estimated effects which differ considerably from the values reported by Lave and Seskin. Thus, we conclude that the regression coefficients are quite unstable and so must be used with care. Assessing the relative costs and benefits of reducing air pollution without extensive sensitivity analysis could, therefore, be misleading.

Air Pollution↗

European Pharmacopoeia (EP), USDA and MAFF standards--will they ever be harmonised under the VICH umbrella?

Harmonisation of standards can have benefits for both users and manufacturers of vaccines. It also helps regulatory authorities when products are assessed to have a uniform standard in different regions. The first priority for harmonisation has to be the elimination of duplicate testing for the same purpose, for example tests for safety, immunogenicity and batch potency. A further priority is to harmonise batch-testing requirements first, since duplication of testing affects production batches. Fish vaccines present particularities as far as harmonisation between regions is concerned because of geographical, climatic and other factors. A commitment from regulatory authorities and manufacturers is a precondition for harmonisation. The different parties should commit themselves to harmonisation within a reasonable time and to implementing their decisions promptly. When there is a commitment on the part of all participants to work together in developing common science-based regulatory standards, then the optimal conditions exist. Harmonisation is time-consuming and costly but in the end the benefits can no doubt exceed the investment. Harmonisation also needs a forum since the present terms of reference of regulatory and standardisation bodies do not cover this. The only forum at present is the International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Products (VICH), which is a tripartite activity involving the European Union, Japan and the U.S.A. Before deciding to propose inclusion in the VICH programme, a preliminary study should be carried out to assess the benefits expected, the obstacles to harmonisation and the feasibility of achieving a satisfactory result. In the framework of VICH, there have been some successful harmonisation projects for veterinary vaccines: residual formaldehyde determination, and residual moisture determination. A harmonised proposal for mycoplasma testing is now available for public comment. Work on extraneous agents testing for avian and mammalian viral vaccines is well advanced.

Animals↗

Reflection on the history, coordination, and funding trends for U.S. public meat research: information to enhance resource allocation.

A study was conducted to analyze resource allocation for public meat research in the United States and characterize the portfolio of meat research investments. Trends in the amount of public resources provided for meat research (beef, pork, lamb, and poultry) were analyzed for fiscal years 1980, 1985, 1990, 1995, and 1997. An in-depth analysis was conducted for data from fiscal year 1998 to characterize the profile of the research portfolio. Funding levels and scientist-year equivalents were aggregated to represent the measures of resource allocation for three mutually exclusive research categories: 1) meat quality, 2) food safety, and 3) product development and processing. Data for the 1998 profile analysis were derived from a computer search based on the combination of key words and research classification codes to avoid duplication and cluster research projects. Individual research projects were individually reviewed and a percentage was assigned to four mutually exclusive research categories: 1) meat quality, 2) food safety, 3) product development and processing, and 4) marketing. As meat research evolved over the past century, considerable efforts were expended by researchers and administrators to ensure the coordination of research and program relevance. This is demonstrated by the establishment of numerous multistate research committees. Total funding for meat science increased only modestly when adjusted for inflation during the two decades of this study; however, notable changes occurred in the distribution of resources in the portfolio. Funding for meat quality and product development and processing remained virtually unchanged when adjusted for inflation, whereas funding for food safety increased considerably. The total number of scientists conducting meat research remained virtually unchanged during the period, but the proportion allocated to food safety research increased substantially. The federal portion of total funding decreased from 61.3% to 51.6% between 1980 and 1997, whereas the percentage from both state appropriations and private sources increased. Modifications in research emphasis were influenced by industry problems such as meat quality, public perceptions about food safety, the availability of research funding, scientific advances occurring in molecular biology and genetic manipulation, and the changing meat industry. The information in this paper provides administrators and researchers the opportunity to make better informed decisions about resource allocation for meat research.

Advertising↗

Pulp treatment for extensive decay in primary teeth.

BACKGROUND: Dental decay in primary teeth remains a considerable health problem. Where decay extends to involve the dental pulp, pulp treatment techniques are often used to manage both symptomatic and symptom free teeth. OBJECTIVES: To assess the relative effectiveness of: various pulp treatment techniques in retaining primary molar teeth with decay involving the pulp for at least 12 months; pulp treatment techniques and extractions in avoiding long term sequelae. SEARCH STRATEGY: We searched the Cochrane Oral Health Group's Trials Register (August 2002); the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2002); MEDLINE (January 1966 to August 2002); EMBASE (1980 to August 2002); Science Citation Index Expanded (1981 to August 2002); Social Science Citation Index (1981 to August 2002); Index to Scientific and Technical Proceedings (1982 to August 2002); System for Information on Grey Literature in Europe (August 2002). Key journals were handsearched. There was no restriction on language of publication. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials (RCTs) comparing different pulp treatment techniques (with each other, with extraction or with no treatment) for extensive decay in primary molar teeth. Primary outcomes were extractions following pulp treatment and long term effects. DATA COLLECTION AND ANALYSIS: Data extraction and quality assessment were carried out independently and in duplicate. Authors were contacted for additional information where necessary. MAIN RESULTS: Eighty-two studies were identified but only three were suitable for inclusion. Nine studies meeting the inclusion criteria but with inappropriate study design or analysis are also described. Included trials investigated formocresol pulpotomy, ferric sulphate pulpotomy, electrosurgical pulpotomy or zinc oxide eugenol pulpectomy in symptom free, cariously exposed teeth. Data were unavailable on long term effects. Data on extraction following pulp treatment was available in all three studies and in two studies there was no statistically significant difference between the treatments. The difference seen in the other study, where more teeth treated by ferric sulphate pulpotomy were extracted compared to zinc oxide eugenol pulpectomy, must be viewed with caution. REVIEWER'S CONCLUSIONS: Based on the available RCTs, there is no reliable evidence supporting the superiority of one type of treatment for pulpally involved primary molars. No conclusions can be made as to the optimum treatment or techniques for pulpally involved primary molar teeth due to the scarcity of reliable scientific research. High quality RCTs, with appropriate unit of randomisation and analysis are needed.

Controlled Clinical Trials as Topic↗

Total parenteral nutrition in the critically ill patient: a meta-analysis.

CONTEXT: Nutritional support has become a standard of care for hospitalized patients, but whether total parenteral nutrition (TPN) affects morbidity and mortality is unclear. OBJECTIVE: To examine the relationship between TPN and complication and mortality rates in critically ill patients. DATA SOURCES: Computerized search of published research on MEDLINE from 1980 to 1998, personal files, and review of relevant reference lists. STUDY SELECTION: We reviewed 210 titles, abstracts, and papers. Primary studies were included if they were randomized clinical trials of critically ill or surgical patients that evaluated the effect of TPN (compared with standard care) on complication and mortality rates. We excluded studies comparing TPN with enteral nutrition. DATA EXTRACTION: Relevant data were abstracted on the methodology and outcomes of primary studies. Data were abstracted in duplicate, independently. DATA SYNTHESIS: There were 26 randomized trials of 2211 patients comparing the use of TPN with standard care (usual oral diet plus intravenous dextrose) in surgical and critically ill patients. When the results of these trials were aggregated, TPN had no effect on mortality (risk ratio [RR], 1.03; 95% confidence interval [CI], 0.81-1.31). Patients who received TPN tended to have a lower complication rate, but this result was not statistically significant (RR, 0.84; 95% CI, 0.64-1.09). We examined several a priori hypotheses and found that studies including only malnourished patients were associated with lower complication rates but no difference in mortality when compared with studies of nonmalnourished patients. Studies published since 1989 and studies with a higher methods score showed no treatment effect, while studies published in 1988 or before and studies with a lower methods score demonstrated a significant treatment effect. Complication rates were lower in studies that did not use lipids; however, there was no difference in mortality rates between studies that did not use lipids and those studies that did. Studies limited to critically ill patients demonstrated a significant increase in complication and mortality rates compared with studies of surgical patients. CONCLUSIONS: Total parenteral nutrition does not influence the overall mortality rate of surgical or critically ill patients. It may reduce the complication rate, especially in malnourished patients, but study results are influenced by patient population, use of lipids, methodological quality, and year of publication.

Critical Care↗

The nature and quality of periodontal related patient information on the world-wide web.

BACKGROUND: The internet provides a potentially invaluable source of health education material for members of the public. OBJECTIVES: This study aimed to investigate the nature and quality of periodontal-related patient information on the world-wide web. METHODS: The search term ' "gum disease" AND "patient information" ' was entered into three common internet search engines. The top 50 sites identified by each search engine were downloaded and assessed for authorship, content, accord with accepted dental practice, currency, and references to peer reviewed data. RESULTS: The search term returned in excess of 3,615 hits across the three search engines. Of the top 150 identified, 68 were deemed relevant to patients seeking information on periodontal disease. Of these, 17 were duplicated either within or between search engines, therefore the following analysis is based on the remaining 51 sites. The majority of sites (25) were authored by individual dental practitioners, with sites originating in the USA predominating (80%). Information on the aetiology, signs and symptoms, and treatment options for periodontal disease was provided by 38, 38, and 29 sites respectively. This information was deemed in accordance with conventional periodontal practice in 27, 33, and 23 cases respectively. Only seven sites indicated the currency of the information and five provided peer-reviewed references for further reading. The rank order identified by the search engines meant that sites providing comprehensive and authoritative information, were not readily differentiable from sites whose primary objective was promoting attendance at specific dental practices. CONCLUSIONS: Judicious and active support from professionals is required to aid patients' interpretation of the information identified and to direct them to the most instructive sites.

Dentist-Patient Relations↗

Misrepresentation and responsibility in medical research.

Early in 1985, after being questioned about duplicate data in two of his papers, Robert A. Slutsky, M.D., resigned his appointments as a radiology resident (trainee) and nonsalaried associate clinical professor in the Department of Radiology at the University of California, San Diego. During the following year, faculty committees investigated Slutsky's entire bibliography of 137 articles published in seven years; 77 (including reviews) were classified as valid, 48 were judged questionable, and 12 were deemed fraudulent. The majority of these papers were published while Slutsky was a research or clinical trainee in cardiology, nuclear medicine, and then radiology. Our analysis of this case leads us to conclude that research fraud, although probably rare, in view of the size of the research establishment, may evade detection, and that there are scientists prepared to run the appreciable risk of submitting inaccurate statements for publication. Sophisticated dishonesty can escape detection by peer review and replication. The emphasis on competition and the pressure to produce, while intended to advance the discovery of truth, may foster a conflict between personal career goals and the intellectual motivation of scientists to seek the truth. The scientific community needs to address the issues raised by recent reports of fraud. Each institution and granting agency must have procedures for investigating suspected fraud or unethical practices, procedures that protect both the person who reports such practices and the accused person from premature disclosure. As we heighten awareness, we must avoid a "witch hunt." Deterrence of research fraud is clearly needed, but institution of practices that might stifle originality or discourage cooperative research would be counterproductive.

Authorship↗

Inositol for respiratory distress syndrome in preterm infants.

BACKGROUND: Inositol is an essential nutrient required by human cells in culture for growth and survival. Inositol promotes maturation of several components of surfactant and may play a critical role in fetal and early neonatal life. OBJECTIVES: To assess the effectiveness/safety of supplementary inositol in preterm infants with RDS in reducing adverse neonatal outcomes. SEARCH STRATEGY: Medline, Embase, and Reference Update Databases were searched in August 1997 using key words: inositol and infant-newborn and random allocation or controlled trial or randomized trial (RCT). The reference lists of identified RCTs, personal files and Science Citation Index were searched. Unpublished additional information was obtained from the authors of one RCT published in abstract form. SELECTION CRITERIA: All randomized controlled trials of inositol supplementation to preterm infants with a control group that received a placebo or no intervention were included. Outcomes of interest were bronchopulmonary dysplasia (BPD), death, BPD or death, retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and sepsis. DATA COLLECTION AND ANALYSIS: Data on neonatal outcomes were abstracted independently by the two researchers and any discrepancy was resolved through consensus. Revman was used for analysis of the data. MAIN RESULTS: Four reports of three RCTs were identified. One report was a duplicate publication. The outcome of death or bronchopulmonary dysplasia was reported in two trials, and was found to be significantly reduced (RR 0.56, 95% CI 0.42, 0.77; RD -0.215, 95% CI -0.323, -0.107). The outcome of death was reported in two trials and was found to be significantly reduced (RR 0.48, 95% CI 0.28, 0.80; RD -0.131, 95% CI -0.218, -0.043). Retinopathy of prematurity, stage 4 or needing therapy, was reported in two trials, and was found to be significantly reduced (RR 0.09, 95% CI 0.01, 0.67; RD -0.078, 95% CI -0.128, -0.027). Intraventricular hemorrhage, grade III-IV, was significantly decreased (RR 0.55, 95% CI 0.32, 0.95; RD -0.090, 95% CI -0.170, -0.010). Neither sepsis nor necrotizing enterocolitis outcomes were increased. When a secondary analysis was done excluding a study published in abstract form, the results differed only in that there was a significant reduction in retinopathy of prematurity, any stage (RR 0.53, 95% CI 0.29, 0.97; RD -0.082, 95% CI -0.159,-0.005). REVIEWER'S CONCLUSIONS: Inositol supplementation results in statistically significant and clinically important reductions in important short-term adverse neonatal outcomes. A multi-center RCT of appropriate size is justified to confirm these findings.

Dietary Supplements↗

Granulopoiesis-stimulating factors in the prevention for adverse effects in the therapeutic treatment of malignant lymphoma.

BACKGROUND: Granulopoiesis-stimulating factors (G-CSF and GM-CSF) are being used to prevent febrile neutropenia and infections in the treatment of patients with malignant lymphoma. The question whether G-CSF and GM-CSF improve dose-intensity, tumour response and overall survival in this patient population has not been answered yet. Since the results from single studies are inconclusive a systematic review was required. OBJECTIVES: To undertake a systematic review in patients with malignant lymphoma to determine the effectiveness of G-CSF and GM-CSF to prevent neutropenia, febrile neutropenia, infection, improve quality of life, adherence to the treatment protocol, tumour response, freedom from treatment failure (FFTF), overall survival (OS) and to assess adverse events of G-CSF and GM-CSF. SEARCH STRATEGY: Medline, Embase, CancerLit, the Cochrane Library and smaller databases, Internet-databases of ongoing trials, conference proceedings of the American Society of Clinical Oncology and the American Society of Hematology were searched. We included full-text and abstract publications as well as unpublished data. SELECTION CRITERIA: Randomised controlled trials comparing prophylaxis with G-CSF or GM-CSF versus placebo/no prophylaxis in adult patients with malignant lymphoma undergoing chemotherapy were included in this review. Both study arms had to receive identical chemotherapy and supportive care. DATA COLLECTION AND ANALYSIS: Eligibility and quality assessment, data extraction and analysis were done in duplicate. All authors were contacted to obtain missing data. MAIN RESULTS: We included 11 eligible studies with 1434 randomised patients. Compared with no prophylaxis, G-/GM-CSF significantly reduced the relative risk for severe neutropenia (RR 0.64 [95% CI 0.55-0.75]), febrile neutropenia (RR 0.74 [95% CI 0.62-0.89]) and infection (RR 0.74 [95% CI 0.64-0.85]). There was no evidence for G-/GM-CSF to decrease the number of patients who required iv antibiotics (RR 0.82 [95%CI 0.57-1.18]), to reduce infection related mortality (RR 2.07 [95% CI 0.81-5.34]), or to improve complete tumour response (RR 1.06 [95% CI 0.96-1.16]), FFTF (HR 1.22 [95% CI 0.83-1.80]) and OS (HR 0.98 [95% CI 0.81-1.18]). None of the studies evaluated quality of life parameters. REVIEWER'S CONCLUSIONS: G-CSF and GM-CSF, when given prophylactically in patients with malignant lymphoma undergoing conventional chemotherapy, reduce the risk of neutropenia, febrile neutropenia and infection. However, based on the currently available randomised trials in this clinical setting, there is no evidence for G-/GM-CSF to provide a significant advantage in terms of complete tumour response, FFTF and OS.

Antineoplastic Agents↗

Total parenteral nutrition in the surgical patient: a meta-analysis.

OBJECTIVE: To examine the relationship between total parenteral nutrition(TPN) and complication and death rates in surgical patients. DATA SOURCES: A computer search of published research on MEDLINE, personal files and a review of relevant reference lists. STUDY SELECTION: A review of 237 titles, abstracts or papers. Primary studies were included if they were randomized clinical trials of surgical patients that evaluated the effect of TPN (compared to no TPN or standard care) on complication and death rates. Studies comparing TPN to enteral nutrition (EN) were excluded. DATA EXTRACTION: Relevant data were abstracted on the methodology and outcomes of primary studies. Data were independently abstracted in duplicate. DATA SYNTHESIS: There were 27 randomized trials in surgical patients that compared the use of TPN to standard care (usual oral diet plus intravenous dextrose). When the results of these trials were aggregated, there was no effect on mortality (risk ratio = 0.97, 95% confidence intervals, 0.76 to 1.24). There were fewer major complications in patients who received TPN, although there was significant heterogeneity in the overall estimate (risk ratio = 0.81, 95% CI, 0.65 to 1.01). Because of this significant heterogeneity, several a priori hypotheses were examined. Studies that included only malnourished patients demonstrated a trend to a reduction in complication rates but no difference in death rate when compared with studies of patients who were not malnourished. Studies published in 1988 or earlier and studies with a lower methods score were associated with a significant reduction in complication rates and a trend to a reduction in death rate when compared with studies published after 1988 and studies with a higher methods score. There was no difference in studies that provided lipids as a component of TPN when compared with studies that did not. Studies that initiated TPN preoperatively demonstrated a trend to a reduction in complication rates but no difference in death rate when compared with studies that initiated TPN postoperatively. CONCLUSIONS: TPN does not influence the death rate of surgical patients. It may reduce the complication rate, especially in malnourished patients, but study results are influenced by methodologic quality and year of publication.

Enteral Nutrition↗

Granulopoiesis-stimulating factors to prevent adverse effects in the treatment of malignant lymphoma.

BACKGROUND: Granulopoiesis-stimulating factors (G-CSF and GM-CSF) are being used to prevent febrile neutropenia and infections in the treatment of patients with malignant lymphoma. The question whether G-CSF and GM-CSF improve dose-intensity, tumour response and overall survival in this patient population has not been answered yet. Since the results from single studies are inconclusive a systematic review was required. OBJECTIVES: To undertake a systematic review in patients with malignant lymphoma to determine the effectiveness of G-CSF and GM-CSF to prevent neutropenia, febrile neutropenia, infection, improve quality of life, adherence to the treatment protocol, tumour response, freedom from treatment failure (FFTF), overall survival (OS) and to assess adverse events of G-CSF and GM-CSF. SEARCH STRATEGY: Medline, Embase, CancerLit, the Cochrane Library and smaller databases, Internet-databases of ongoing trials, conference proceedings of the American Society of Clinical Oncology and the American Society of Hematology were searched. We included full-text and abstract publications as well as unpublished data. SELECTION CRITERIA: Randomised controlled trials comparing prophylaxis with G-CSF or GM-CSF versus placebo/no prophylaxis in adult patients with malignant lymphoma undergoing chemotherapy were included in this review. Both study arms had to receive identical chemotherapy and supportive care. DATA COLLECTION AND ANALYSIS: Eligibility and quality assessment, data extraction and analysis were done in duplicate. Authors were contacted to obtain missing data. MAIN RESULTS: We included 12 eligible studies with 1.823 randomised patients. Compared with no prophylaxis, G-/GM-CSF significantly reduced the relative risk for severe neutropenia (RR 0.67 [95% CI 0.60-0.73]), febrile neutropenia (RR 0.74 [95% CI 0.62-0.89]) and infection (RR 0.74 [95% CI 0.64-0.85]). There was no evidence for G-/GM-CSF to decrease the number of patients who required iv antibiotics (RR 0.82 [95%CI 0.57-1.18]), to reduce infection related mortality (RR 1.37 [95% CI 0.66-2.82]), or to improve complete tumour response (RR 1.02 [95% CI 0.94-1.11]), FFTF (HR 1.11 [95% CI 0.91-1.35]) and OS (HR 1.00 [95% CI 0.86-1.16]). One study evaluated quality of life parameters and did not find differences between the groups. REVIEWER'S CONCLUSIONS: G-CSF and GM-CSF, when given prophylactically in patients with malignant lymphoma undergoing conventional chemotherapy, reduce the risk of neutropenia, febrile neutropenia and infection. However, based on the currently available randomised trials in this clinical setting, there is no evidence for G-/GM-CSF to provide a significant advantage in terms of complete tumour response, FFTF and OS.

Antineoplastic Agents↗

Exploring the dose-response relationship between prenatal exercise and postpartum depression: A systematic review and meta-analysis of randomized controlled trials.

IMPORTANCE: Postpartum depression (PPD) is a hidden and widespread global public health crisis affecting millions of mothers and infants annually. Prenatal exercise is a potentially accessible nonpharmacological strategy for PPD prevention, but its optimal dose remains uncertain. OBJECTIVE: To explore the dose-response relationship between prenatal exercise and the incidence of PPD through meta-analysis of randomized controlled trials (RCTs). DATA SOURCES: Systematic searches were conducted in PubMed, Embase, Web of Science, and Cochrane Library using MeSH terms and keywords related to "pregnant women," "prenatal exercise," and "postpartum depression," up to June 23, 2025. STUDY SELECTION: RCTs included examined prenatal exercise interventions in pregnant women without a history of depression, with PPD incidence reported using validated depression scales (such as EPDS, CES-D). Non-RCT studies, duplicate publications, and studies with insufficient data were excluded. DATA EXTRACTION AND SYNTHESIS: Two researchers independently extracted data according to the PRISMA guidelines. A random-effects model was used to pool odds ratios (OR) and their 95% confidence intervals (CI). Linear and nonlinear dose-response models were employed to analyze and evaluate the relationship between exercise dose (measured in METs-min/week) and the incidence of PPD. MAIN OUTCOME(S) AND MEASURE(S): The primary outcome is the incidence of PPD, analyzing its relationship with prenatal exercise dose. RESULTS: Eight RCTs involving 2231 pregnant women were included. The pooled analysis showed that prenatal exercise was associated with a potential reduction in PPD incidence, although the overall effect did not reach statistical significance (OR=0.58, 95% CI [0.33, 1.02]). In dose-stratified analysis, exercise doses ≥500 METs-min/week were associated with significantly lower PPD incidence (OR=0.44, 95% CI [0.24, 0.78]). Subgroup analyses suggested trends toward greater benefits among women aged ≥30 years and those initiating exercise between 14 and 28 weeks of gestation; however, subgroup differences did not reach statistical significance. The linear dose-response trend did not reach statistical significance (p = 0.0533), and neither the overall spline association (p = 0.1704) nor the test for nonlinearity (p = 0.6361) was statistically significant. CONCLUSIONS AND RELEVANCE: Prenatal exercise may be associated with a lower risk of PPD, but the overall pooled effect did not reach statistical significance. Findings concerning ≥500 METs-min/week and the apparent flattening of the dose-response curve should be considered exploratory and require confirmation in larger trials.

Humans↗

A population-based evaluation of an intervention to improve advanced stage cancer pain management.

The purpose of this study was to evaluate the effect of a community-oriented intervention in one part of the Free Town of Bremen, northern Germany (population 541,000) on the prescription prevalence of World Health Organization (WHO) class III opioids for cancer patients in their final year of life. A community-oriented, multimodal intervention included information, teaching, and training modules tailored to physicians, pharmacists, nursing staff, and patients and their relatives, and the public. Prescription prevalences were calculated for the intervention region (Bremen-Nord) and a control region (Bremen-Mitte) before and after the intervention. Specifically, a population-based, controlled, quantitative assessment of opioid prescriptions for patients with cancer during their final year of life was undertaken for two time periods, prior to 1992-1993 and after 1995-1996, respectively. Prescription ascertainment was based on duplicates kept in the pharmacies. Patients comprised two anonymized complete 4-month samples who died in 1993 and 1996, respectively, with cancer as the primary or a contributory cause of death on their death certificates. A total of 1282 prescriptions were abstracted from duplicates in 109 of 119 pharmacies in Bremen-Mitte and all 31 pharmacies in Bremen-Nord (overall pharmacy participation proportion 93%) and individually matched to 856 patients with cancer in their final year of life. In 1993, 16.3% of all terminal cancer patients in Bremen-Mitte and 19.1% in Bremen-Nord had received at least one prescription for a WHO class III opioid. Corresponding numbers after the intervention were 20% and 21%, respectively. The total amount of class III opioids, however, increased 20% in Bremen-Mitte and 210% in Bremen-Nord after the intervention. In 1996, the spectrum of prescribed opioids had changed markedly toward the WHO recommendations. The proportion of prescribing physicians remained constant. These data suggest that a community-oriented intervention in one part of Bremen had a limited impact on cancer pain therapy on the population level. A measurable change of prescription practice seemed to be restricted to the minority of physicians, who had prior experience with prescribing WHO class III opioids.

Analgesics, Opioid↗

Feeding interventions for growth and development in infants with cleft lip, cleft palate or cleft lip and palate.

BACKGROUND: Cleft lip and cleft palate are common birth defects, affecting about one baby of every 700 born. Feeding these babies is an immediate concern and there is evidence of delay in growth of children with a cleft as compared to those without clefting. In an effort to combat reduced weight for height, a variety of advice and devices are recommended to aid feeding of babies with clefts. OBJECTIVES: This review aims to assess the effects of these feeding interventions in babies with cleft lip and/or palate on growth, development and parental satisfaction. SEARCH STRATEGY: We searched the Cochrane Oral Health Group's Trials register (June 2001), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2, 2004), MEDLINE (1966 to May 24th 2004), EMBASE (1980 to August 7th 2002), CINAHL (1982 to August 7th 2002), PsychINFO (1967 to August 13th 2002), AMED (1985 to August 13th 2002). Attempts were made to identify both unpublished and ongoing studies. There was no restriction with regard to language of publication. SELECTION CRITERIA: Studies were included if they were randomised controlled trials (RCTs) of feeding interventions for babies born with cleft lip, cleft palate or cleft lip and palate up to the age of 6 months (from term). DATA COLLECTION AND ANALYSIS: Studies were assessed for relevance independently and in duplicate. All studies meeting the inclusion criteria were data extracted and assessed for validity independently by each member of the review team. Authors were contacted for clarification or missing information whenever possible. MAIN RESULTS: Four RCTs with a total of 232 babies, were included in the review. Comparisons made within the RCTs were squeezable versus rigid feeding bottles (two studies), breastfeeding versus spoon-feeding (one study) and maxillary plate versus no plate (one study). No statistically significant differences were shown for any of the primary outcomes when comparing bottle types, although squeezable bottles were less likely to require modification. No statistically significant difference was shown for infants fitted with a maxillary plate compared to no plate. A statistically significant difference in weight (kg) at 6 weeks post-surgery was shown in favour of breastfeeding when compared to spoon-feeding (mean difference 0.47; 95% CI: 0.20, 0.74). REVIEWERS' CONCLUSIONS: Squeezable bottles appear easier to use than rigid feeding bottles for babies born with clefts of the lip and/or palate, however, there is no evidence of a difference in growth outcomes between the bottle types. There is weak evidence that babies should be breastfed rather than spoon-fed following surgery for cleft lip. No evidence was found to assess the use of any types of maternal advice and/or support for these babies.

Cleft Lip↗

A strategic action plan for achieving uncompromising "treat to target" in individuals with insulin-dependent diabetes: a report by the Center for Insulin-Dependent Diabetes Access' Blue Ribbon Panel.

The Center for Insulin-Dependent Diabetes Access, created by the Juvenile Diabetes Research Foundation International and funded by an unrestricted grant from The Medtronic Foundation, convened a Blue Ribbon Panel (the Panel) to identify barriers to achieving universal treatment-to-target in patients with insulin-dependent diabetes and to recommend solutions for addressing those barriers. The Panel was comprised of experts in diabetes care and included providers, academicians, researchers, payers, patient advocates, and policymakers. After reviewing the latest research on diabetes care, the Panel made six overall findings that identify barriers to achieving optimal diabetes care and made recommendations to address those barriers that are intended to achieve the goal of universal, uncompromising "Treat to Target" in insulin-dependent patients. The Panel's findings were: Finding 1: Improving care of patients with insulin-dependent diabetes depends on the public availability and ongoing collection of data that document patient characteristics, processes of care, health outcomes, the benefits and costs of new technologies, and the benefits and costs of different care models. Finding 2: Availability of new technologies and information systems for monitoring and treating insulin-dependent diabetes is critical to achieving recommended hemoglobin A1c levels. Finding 3: Increased reimbursement for new technologies and services provided by the "team" approach to medical management, such as coordinated non-face-to-face care and Internet communications, is imperative to achieving optimal diabetes care. Finding 4: Improving access to endocrinologists, certified diabetes educators, and adopting a chronic care or "team" approach to treating insulin-dependent diabetes are critical to achieving a "Treat to Target" objective. Finding 5: Primary care providers and individuals with insulin-dependent diabetes need to better understand the importance and impact of intensive insulin management and the "team" approach for treating diabetes in improving quality of life and reducing the incidence of long-term diabetes-related complications. Finding 6: Demographic characteristics of individuals with insulin-dependent diabetes require innovative approaches to patient education, outreach, and patient-centric care in order to achieve a "Treat to Target" objective. In the detailed report that follows, each finding is accompanied by a series of recommended action items intended to address the barriers that the Panel identified. A number of entities and organizations have ongoing and planned activities intended to improve diabetes care, particularly for individuals with insulin-dependent diabetes. The Panel recommended that the diabetes community work to coordinate those efforts in order to avoid duplication and ensure more effective program management of those activities.

Diabetes Mellitus, Type 1↗

Granulopoiesis-stimulating factors to prevent adverse effects in the treatment of malignant lymphoma.

BACKGROUND: Granulopoiesis-stimulating factors, such as granulocyte-colony-stimulating factor (G-CSF) and granulocyte-macrophage-colony-stimulating factor (GM-CSF), are being used to prevent febrile neutropenia and infection in patients undergoing treatment for malignant lymphoma. The question of whether G-CSF and GM-CSF improve dose intensity, tumour response, and overall survival in this patient population has not been answered yet. Since the results from single studies are inconclusive, a systematic review was undertaken. OBJECTIVES: To determine the effectiveness of G-CSF and GM-CSF in patients with malignant lymphoma with respect to preventing neutropenia, febrile neutropenia and infection; improving quality of life, adherence to treatment protocol, tumour response, freedom from treatment failure (FFTF) and overall survival (OS); and adverse effects. SEARCH STRATEGY: We searched The Cochrane Library, MEDLINE, EMBASE, CancerLit, and other relevant literature databases; internet databases of ongoing trials; and conference proceedings of the American Society of Clinical Oncology and the American Society of Hematology (1980 - 2003). We included full-text and abstract publications as well as unpublished data. SELECTION CRITERIA: Randomised controlled trials comparing prophylaxis with G-CSF or GM-CSF versus placebo/no prophylaxis in adult patients with malignant lymphoma undergoing chemotherapy were included for review. Both study arms had to receive identical chemotherapy and supportive care. DATA COLLECTION AND ANALYSIS: Trial eligibility and quality assessment, data extraction and analysis were done in duplicate. Authors were contacted to obtain missing data. MAIN RESULTS: We included 12 eligible randomised controlled trials with 1823 patients. Compared with no prophylaxis, both G-CSF and GM-CSF significantly reduced the relative risk (RR) for severe neutropenia (RR 0.67; 95% confidence interval (CI) 0.60 to 0.73), febrile neutropenia (RR 0.74; 95% CI 0.62 to 0.89) and infection (RR 0.74; 95% CI 0.64 to 0.85). There was no evidence that either G-CSF or GM-CSF reduced the number of patients requiring intravenous antibiotics (RR 0.82; 95%CI 0.57 to 1.18); lowered infection related mortality (RR 1.37; 95% CI 0.66 to 2.82); or improved complete tumour response (RR 1.02; 95% CI 0.94 to 1.11), FFTF (hazard ratio 1.11; 95% CI 0.91 to 1.35) and OS (hazard ratio 1.00; 95% CI 0.86 to 1.16). One study evaluated quality of life parameters and found no differences between the treatment groups. REVIEWERS' CONCLUSIONS: G-CSF and GM-CSF, when used as a prophylaxis in patients with malignant lymphoma undergoing conventional chemotherapy, reduce the risk of neutropenia, febrile neutropenia and infection. However, based on the randomised trials currently available, there is no evidence that either G-CSF or GM-CSF provide a significant advantage in terms of complete tumour response, FFTF or OS.

Antineoplastic Agents↗

Manual versus powered toothbrushes: a summary of the Cochrane Oral Health Group's Systematic Review. Part II.

PURPOSE: A systematic review examining the clinical effectiveness of power versus manual toothbrushes was conducted by the Cochrane Collaborations Oral Health Group. Their review examined clinical trials conducted through 2001 and used international standards to identify, access, evaluate, analyze, and report the data. Part I of this series discussed distinguishing characteristics of evidence-based publications, such as systematic reviews, whereas this report provides a summary of the Cochrane Review, its importance to the profession, and discusses the strengths and limitations of systematic reviews. METHODS: Search strategies to identify published clinical trials on power toothbrushes were developed, and manufacturers were contacted for additional published and unpublished information. Trials were selected based on pre-established criteria; including whether they compared power versus manual toothbrushes used a randomized research design tested products in the general population without disabilities, provided data on plaque and gingivitis, and were at least 28 days in length. Six reviewers independently extracted information in duplicate. Indices for plaque and gingivitis levels were expressed as standardized mean differences for data distillation. Data distillation was accomplished using a meta-analysis, with a mean difference between power and manual toothbrushes as the measure of effectiveness. RESULTS: Searches identified 354 trials, of which 29 met inclusion criteria. These trials involved 2.547 participants who provided data for meta-analysis. Results indicated that for both plaque and gingivitis, all types of power toothbrushes worked as well as manual toothbrushes, however only the rotating oscillating toothbrush consistently provided a statistically significant though modest benefit over manual toothbrushes in reducing plaque (7%) and gingivitis (17%). None of the battery powered toothbrush studies met the inclusion criteria. CONCLUSION: The Cochrane systematic review used international standards to examine more than 30 years of published studies. A concern is that only one type of electric toothbrush, the rotating oscillating toothbrush consistently demonstrated a statistically significant benefit over manual toothbrushes, and the majority of studies did not meet the standards for inclusion in moving forward it will be important to conduct methodologically sound studies demonstrating the ability of power toothbrushes to reduce the incidence and prevalence of caries and periodontal disease.

Decision Making↗

Purine antagonists for chronic lymphocytic leukaemia.

BACKGROUND: Recent trials suggest improved response rates for purine antagonists compared to alkylator-based regimens in the treatment of B-CLL. However, none was able to show a survival advantage. OBJECTIVES: To determine if there is any advantage of purine antagonists compared to alkylating agents (alone or in combination) in the treatment of patients with previously untreated B-CLL. SEARCH STRATEGY: Medical databases (Cochrane Library, MEDLINE, EMBASE), conference proceedings and internet-based trial registers were searched electronically and/or by hand (1990-2003). All references were checked for further trial information. We also contacted experts in the field and pharmaceutical companies. SELECTION CRITERIA: Randomised controlled trials comparing purine antagonists as single agents with alkylator-based regimens in patients with previously untreated B-CLL were included. We included full-text and abstract publications as well as unpublished data. DATA COLLECTION AND ANALYSIS: Data extraction and quality assessment were done in duplicate by two independent reviewers. Missing data were obtained from original authors. Endpoints included overall survival, overall response rate, rate of complete remissions, progression-free survival, treatment-related morbidity and mortality. MAIN RESULTS: Five trials with 1838 randomised patients were included. There is some evidence for improved overall survival after treatment with purine antagonists compared to alkylators, but statistical significance was not reached (HR 0.89 [95% CI 0.78-1.01], 4 trials, n=1638). However, the relative risk for achieving an overall response (RR 1.22 [95% CI 1.13-1.31], 5 trials, n=1751) and complete remission (RR 1.94 [95% CI 1.65-2.28], 5 trials, n=1751) was significantly higher, resulting in a longer progression-free survival (HR 0.70 [95% CI 0.61-0.82], 4 trials, n=1638). Incidence of grade III/IV infections was significantly higher in patients receiving treatment with purine antagonists (RR 1.83 [95% 1.30-2.58], 4 trials, n=1620). There was no significant difference concerning the relative risk for grade III/IV neutropenia (RR 1.14 [95% CI 0.98-1.34], 4 trials, n=1620) and therapy-related mortality (RR 0.94 [95% CI 0.45-1.95]). Overall incidence of hemolytic anemia was low, but significantly increased in the purine antagonist group (RR 3.36 [95% CI 1.27-8.91], 3 trials, n=1258). AUTHORS' CONCLUSIONS: Despite significantly increased overall response and complete remission rates and longer progression-free survival with first-line treatment of B-CLL patients with single-agent purine antagonists, we were not able to detect a statistically significant improvement of overall survival compared to alkylator-based regimens. Furthermore, the use of purine antagonists also augments the risk for grade III/IV infections and hemolytic anemia.

Antineoplastic Agents↗