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Biomedical subjects

R Thomas

Publications and source records attributed to R Thomas.

At least 19 recordsLinked to original sources
PubMed2006

Weekly cisplatin, epirubicin, and paclitaxel with granulocyte colony-stimulating factor support vs triweekly epirubicin and paclitaxel in locally advanced breast cancer: final analysis of a sicog phase III study.

The present study aimed at evaluating whether a weekly cisplatin, epirubicin, and paclitaxel (PET) regimen could increase the pathological complete response (pCR) rate in comparison with a tri-weekly epirubicin and paclitaxel administration in locally advanced breast cancer (LABC) patients. Patients with stage IIIB disease were randomised to receive either 12 weekly cycles of cisplatin 30 mg m(-2), epirubicin 50 mg m(-2), and paclitaxel 120 mg m(-2) (PET) plus granulocyte-colony stimulating factor support, or four cycles of epirubicin 90 mg m(-2)+paclitaxel 175 mg m(-2) (ET) every 3 weeks. Overall, 200 patients (PET/ET=100/100) were included in this study. A pCR in both breast and axilla occurred in 16 (16%) PET patients and in six (6%) ET patients (P=0.02). The higher activity of PET was evident only in ER negative (27.5 vs 5.4%; P=0.026), and in HER/neu positive (31 vs 5%; P=0.037) tumours. The two arms yielded similar pCR rate in ER positive (PET/ET=7.5/7.1%) and HER/neu negative (PET/ET=10/6%) patients. At a 39 months median follow-up, 70 patients showed a progression or relapses (PET, 32 vs ET, 38). Anaemia, mucositis, peripheral neuropathy, and gastrointestinal toxicity were substantially more frequent in the PET arm. The PET weekly regimen is superior to ET in terms of pCR rate in LABC patients with ER negative and/or HER2 positive tumours Mature data in terms of disease-free and overall survival are needed to ascertain whether this approach could improve the prognosis of these subsets of LABC patients.

Adult↗
PubMed2006

Maternal smoking is associated with impaired neonatal toll-like-receptor-mediated immune responses.

Infants of smokers have much higher rates of respiratory infection, asthma and airway disease. The current study assessed the effects of maternal smoking in pregnancy on neonatal toll-like-receptor (TLR)-mediated immune responses as a possible contributing factor to the elevated rates of respiratory illness. In a prospective birth cohort, the cord blood immune responses of neonates of smoking and nonsmoking mothers were compared. Maternal and cord serum cotinine were measured to confirm the level of cigarette smoke exposure. Neonatal cytokine responses were assessed to optimal doses of TLR2, TLR3, TLR4 and TLR9 ligands. Cotinine levels confirmed maternal reporting of cigarette smoking in pregnancy, with significantly higher cotinine levels in maternal and cord blood compared with the nonsmoking group. Infants of smoking mothers showed significantly attenuated innate TLR-mediated responses compared with infants of nonsmokers. The current findings indicate that in addition to effects on developing airways, maternal smoking also has significant immunological effects in pregnancy, which could contribute to the well recognised, subsequent increased risk of respiratory infections and asthma. These effects appear to be mediated through effects on toll-like receptor-mediated innate response pathways, which also promote regulatory pathways in the inhibition of allergic immune responses in the postnatal period, suggesting that other environmental interactions are highly relevant to the "hygiene hypothesis".

Adult↗
PubMed2006

School-based programmes for preventing smoking.

BACKGROUND: Smoking rates in adolescents are rising in some countries. Helping young people to avoid starting smoking is a widely endorsed goal of public health, but there is uncertainty about how to do this. Schools provide a route for communicating with a large proportion of young people, and school-based programmes for smoking prevention have been widely developed and evaluated. OBJECTIVES: To review all randomized controlled trials of behavioural interventions in schools to prevent children (aged 5 to12) and adolescents (aged 13 to18) starting smoking. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Tobacco Addiction Group's Specialized Register, MEDLINE, EMBASE, PsyclNFO, ERIC, CINAHL, Health Star, Dissertation Abstracts and studies identified in the bibliographies of articles. Individual MEDLINE searches were made for 133 authors who had undertaken randomized controlled trials in this area. SELECTION CRITERIA: Types of studies: those in which individual students, classes, schools, or school districts were randomized to the intervention or control groups and followed for at least six months. TYPES OF PARTICIPANTS: Children (aged 5 to12) or adolescents (aged 13 to18) in school settings. Types of interventions: Classroom programmes or curricula, including those with associated family and community interventions, intended to deter use of tobacco. We included programmes or curricula that provided information, those that used social influences approaches, those that taught generic social competence, and those that included interventions beyond the school into the community. We included programmes with a drug or alcohol focus if outcomes for tobacco use were reported. Types of outcome measures: Prevalence of non-smoking at follow up among those not smoking at baseline. We did not require biochemical validation of self-reported tobacco use for study inclusion. DATA COLLECTION AND ANALYSIS: We assessed whether identified citations were randomized controlled trials. We assessed the quality of design and execution, and abstracted outcome data. Because of the marked heterogeneity of design and outcomes, we computed pooled estimates only for those trials that could be analyzed together and for which statistical data were available. We predominantly synthesized the data using narrative systematic review. We grouped studies by intervention method (information; social competence; social influences; combined social influences/social competence; multi-modal programmes). Within each group, we placed them into three categories (low, medium and high risk of bias) according to validity using quality criteria for reported study design. MAIN RESULTS: Of the 94 randomized controlled trials identified, we classified 23 as category one (most valid). There was one category one study of information-giving and two of teaching social comeptence. There were thirteen category one studies of social influences interventions. Of these, nine found some positive effect of intervention on smoking prevalence, and four failed to detect an effect on smoking prevalence. The largest and most rigorous study, the Hutchinson Smoking Prevention Project, found no long-term effect of an intensive eight-year programme on smoking behaviour. There were three category one RCTs of combined social influences and social competence interventions: one provided significant results and one only for instruction by health educators compared to self-instruction. There was a lack of high quality evidence about the effectiveness of combinations of social influences and social competence approaches. There was one category one study providing data on social influences compared with information giving. There were four category one studies of multi-modal approaches but they provided limited evidence about the effectiveness of multi-modal approaches including community initiatives. AUTHORS' CONCLUSIONS: There is one rigorous test of the effects of information-giving about smoking. There are well-conducted randomized controlled trials to test the effects of social influences interventions: in half of the group of best quality studies those in the intervention group smoke less than those in the control, but many studies failed to detect an effect of the intervention. There are only three high quality RCTs which test the effectiveness of combinations of social influences and social competence interventions, and four which test multi-modal interventions; half showed significant positive results.

Adolescent↗
PubMed2006

Vaccines for preventing influenza in the elderly.

BACKGROUND: Influenza vaccination of elderly individuals is recommended worldwide and has been targeted toward the elderly and those at serious risk of complications. OBJECTIVES: Our aim was to review the evidence of efficacy, effectiveness and safety of influenza vaccines in individuals aged 65 years or older. SEARCH STRATEGY: We searched the following databases on The Cochrane Library, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effectiveness (Issue 1, 2006); MEDLINE (January 1966 to March Week 3 2006); EMBASE (Dialog 1974 to 1979; SilverPlatter 1980 to December 2005); Biological Abstracts (SilverPlatter 1969 to December 2004); and Science Citation Index (Web of Science 1974 to December 2004). SELECTION CRITERIA: We considered randomised, quasi-randomised, cohort and case-control studies assessing efficacy against influenza (laboratory-confirmed cases) or effectiveness against influenza-like illness (ILI) or safety. Any influenza vaccine given independently, in any dose, preparation or time schedule, compared with placebo or with no intervention was considered. DATA COLLECTION AND ANALYSIS: We grouped reports first according to the setting of the study (community or long-term care facilities) and then by level of viral circulation and vaccine matching. We further stratified by co-administration of pneumococcal polysaccharide vaccine (PPV) and by different types of influenza vaccines. We analysed the following outcomes: influenza, influenza-like illness, hospital admissions, complications and deaths. MAIN RESULTS: Sixty-four studies were included in the efficacy / effectiveness assessment, resulting in 96 data sets. In homes for elderly individuals (with good vaccine match and high viral circulation) the effectiveness of vaccines against ILI was 23% (6% to 36%) and non-significant against influenza (RR 1.04: 95% CI 0.43 to 2.51). We found no correlation between vaccine coverage and ILI attack rate. Well matched vaccines prevented pneumonia (VE 46%; 30% to 58%), hospital admission (VE 45%; 16% to 64%) and deaths from influenza or pneumonia (VE 42%, 17% to 59%). In elderly individuals living in the community, vaccines were not significantly effective against influenza (RR 0.19; 95% CI 0.02 to 2.01), ILI (RR 1.05: 95% CI 0.58 to 1.89), or pneumonia (RR 0.88; 95% CI 0.64 to 1.20). Well matched vaccines prevented hospital admission for influenza and pneumonia (VE 26%; 12% to 38%) and all-cause mortality (VE 42%; 24% to 55%). After adjustment for confounders, vaccine performance was improved for admissions to hospital for influenza or pneumonia (VE* 27%; 21% to 33%), respiratory diseases (VE* 22%; 15% to 28%) and cardiac disease (VE* 24%; 18% to 30%); and for all-cause mortality (VE* 47%; 39% to 54%). The public health safety profiles of the vaccines appear to be acceptable. AUTHORS' CONCLUSIONS: In long-term care facilities, where vaccination is most effective against complications, the aims of the vaccination campaign are fulfilled, at least in part. However, according to reliable evidence the usefulness of vaccines in the community is modest. The apparent high effectiveness of the vaccines in preventing death from all causes may reflect a baseline imbalance in health status and other systematic differences in the two groups of participants.

Aged↗
PubMed2006

The central issue? Visceral fat mass is a good marker of insulin resistance and metabolic disturbance in women with polycystic ovary syndrome.

OBJECTIVE: To establish whether visceral fat mass is the most significant variable correlating with insulin resistance and other metabolic parameters in women with polycystic ovary syndrome (PCOS). DESIGN: Prospective cross-sectional trial. SETTING: Reproductive medicine clinic. POPULATION: Forty women with anovulatory PCOS. METHODS: Measurements were taken at recruitment, and analysis was performed to define correlations between the outcome measures and the explanatory variables. MAIN OUTCOME MEASURES: Visceral and subcutaneous fat by computed tomography scan, insulin resistance, anthropometric measures, markers of the metabolic syndrome and androgens. RESULTS: Strong linear correlation of visceral fat to insulin resistance (r = 0.68, P < 0.001) was observed. There were also statistically significant correlations with fasting insulin (r = 0.73, P < 0.001), homeostasis model assessment beta-cell function (r = 0.50, P = 0.007), triglycerides (r = 0.45, P = 0.003), high-density lipoprotein cholesterol (r = -0.42, P = 0.007), urate (r = 0.47, P = 0.002), Sex hormone binding globulin (r = -0.39, P = 0.01) and luteinising hormone (r = -0.32, P = 0.02). There were no significant correlations of testosterone with fat distribution or metabolic parameters. Insulin resistance showed closest correlation to visceral fat mass (r = 0.68, P < 0.001), then to waist circumference (r = 0.62, P < 0.001), with the weakest correlation being waist:hip ratio (r = 0.36, P = 0.01). The best regression model for predicting insulin resistance is with visceral fat mass and triglycerides as the explanatory variables (r = 0.72, P < 0.001). CONCLUSIONS: Visceral fat is the most significant variable correlating with metabolic dysfunction in women with PCOS. Our data support the hypothesis that visceral fat either causes insulin resistance or is a very early effect of it. It also implies that reducing visceral fat should reduce insulin resistance which may account for the observations that exercise and weight loss appear to be more effective interventions than pharmacological treatments. The best anthropometric measure of insulin resistance is waist circumference.

Adult↗
PubMed2006

Effects of Helicobacter pylori on the cadherin-catenin complex.

BACKGROUND: The cadherin-catenin complex is the key component of the adherens junction in epithelial cells, and changes in this complex are implicated in gastric adenocarcinoma. Germline mutations in E-cadherin have been described in diffuse-type gastric adenocarcinoma. Helicobacter pylori infection is the first stage in gastric carcinogenesis. AIMS: To determine whether H pylori was associated with changes in the complex, and whether this was affected by virulence of the strain. METHODS: Epithelial cell lines were cultured with H pylori using the wild-type pathogenic and non-pathogenic strains and CagE null and VacA null isogenic mutants. Gastric biopsy specimens at endoscopy were obtained from patients with (n = 17) and without (n = 15) H pylori infection, and E-cadherin and beta-catenin expression was assessed by immunohistochemistry. H pylori was typed by polymerase chain reaction from these patients for CagE and VacA. RESULTS: In vitro studies showed that coculture with a pathogenic strain of H pylori led to disruption of epithelial junctional beta-catenin expression, but without evidence of nuclear translocation or signalling. This effect was independent of a functional Cag pathogenicity island and vacuolating activity, but dependent on live bacteria. No marked differences in beta-catenin or E-cadherin expression were seen in gastric biopsy specimens in patients with and without H pylori infection. CONCLUSION: Acute H pylori infection disrupts junctional beta-catenin in vitro, but chronic infection by H pylori has no effect on E-cadherin and beta-catenin expression, as seen in gastric biopsy specimens at the initial gastritis stage of the proposed Correa pathway of gastric carcinogenesis. A later effect at the later stages of atrophy or intestinal metaplasia cannot be ruled out.

Biopsy↗
PubMed2006

Shortcomings of protein removal prior to high performance liquid chromatographic analysis-A case study using method development for BAY 11-7082.

During the analytical method development for BAY 11-7082 ((E)-3-[4-methylphenylsulfonyl]-2-propenenitrile), using HPLC-MS-MS and HPLC-UV, we observed that the protein removal process (both ultrafiltration and precipitation method using organic solvents) prior to HPLC brought about a significant reduction in the concentration of this compound. The use of a structurally similar internal standard, BAY 11-7085 ((E)-3-[4-t-butylphenylsulfonyl]-2-propenenitrile), was not effective in compensating for the loss of analyte as the extent of reduction was different to that of the analyte. We present here a systematic investigation of this problem and a new validated method for the determination of BAY 11-7082.

Chromatography, High Pressure Liquid↗
PubMed2006

Helminth infections in British troops following an operation in Sierra Leone.

One hundred and fifty-three British soldiers and 86 Royal Air Force (RAF) personnel were deployed on a hostage rescue operation in Sierra Leone. For 3 days they were exposed to various infection risks and 6 weeks later some of the soldiers presented with gastrointestinal complaints. Both groups were screened with structured questionnaires, blood investigations and (where indicated) faecal microscopy and charcoal culture for helminths. Definite and probable cases of helminth infection were treated with albendazole and all soldiers were screened again after 3 months. Among the soldiers investigated, 73/145 (50%) reported gastrointestinal symptoms and 70/139 (50%) had eosinophilia. Among these, 17/66 (26%) had hookworm infection, 6/66 (9%) had Strongyloides stercoralis infection and 1/66 (2%) had Giardia lamblia infection. Eosinophilia was most strongly associated with entering the enemy camp and being in the platoon that attacked the area around the camp latrines. Among RAF personnel, who were not involved in activities on the ground, 3/86 (3%) had borderline eosinophilia. Treatment of 105/153 (69%) soldiers with albendazole was well tolerated and, on follow-up screening 3 months later, 23/124 soldiers (19%) had gastrointestinal symptoms and 18/121 (15%) had eosinophilia. Faecal investigations and schistosomiasis serology tests were all negative at this stage.

Albendazole↗
PubMed2006

Effects of drug resistance on viral load in patients failing antiretroviral therapy.

Previous studies on patients who develop drug resistant HIV-1 variants have shown that continued use of failing regimens might provide clinical benefit. However, the effect of long-term exposure to drug resistant variants may lead to emergence of compensatory mutations that may jeopardize this effect. In this study, we assess associations among type and number of drug resistant mutations, viral load and disease progression in patients with long-term follow up. Patients with genotypic testing performed at the time of treatment failure were enrolled. Comparison of viral load and CD4 cell count between different resistance groups was performed using analysis of variance. Multiple linear regression analysis was performed to assess the simultaneous effects of the presence of particular mutations and their accumulation on viral load. Data from 475 patients who were followed for a median of 43 months from October 1999 to July 2005 were studied. A "V shape" relationship was observed between the number of mutations and viral load. Specifically, in patients harboring up to five mutations, viral load was reduced by 0.8 log/copies when compared to wild-type variants. However, with more than six mutations viral load progressively increased. Certain reverse transcriptase mutations such as M184V/I, K70R, V108I, and protease mutations such as L33FIV, M84V, and M36I were associated with reduced viral load. Together, these findings suggest that long-term maintenance of a sub-optimal antiretroviral regimen may have deleterious consequences for the patient.

Adult↗
PubMed2006

Circular causality.

The problem of disentangling complex dynamic systems is addressed, especially with a view to identifying those variables that take part in the essential qualitative behaviour of systems. The author presents a series of reflections about the methods of formalisation together with the principles that govern the global operation of systems. In particular, a section on circuits, nuclei, and circular causality and a rather detailed description of the analytic use of the generalised asynchronous logical description, together with a brief description of its synthetic use (OreverseO logic). Some basic rules are recalled, such as the fact that a positive circuit is a necessary condition of multistationarity. Also, the interest of considering as a model, rather than a well-defined set of differential equations, a variety of systems that differ from each other only by the values of constant terms is emphasised. All these systems have a common Jacobian matrix and for all of them phase space has exactly the same structure. It means that all can be partitioned in the same way as regards the signs of the eigenvalues and thus as regards the precise nature of any steady states that might be present. Which steady states are actually present, depends on the values of terms of order zero in the ordinary differential equations (ODEs), and it is easy to find for which values of these terms a given point in phase space is steady. Models can be synthesised first at the level of the circuits involved in the Jacobian matrix (that determines which types and numbers of steady states are consistent with the model), then only at the level of terms of order zero in the ODE's (that determines which of the steady states actually exist), hence the title 'Circular casuality'.

Adaptation, Physiological↗
PubMed2006

A crypto-Dravidian origin for the nontribal communities of South India based on human leukocyte antigen class I diversity.

The Dravidian communities are considered to be the original inhabitants of India, now restricted to South India. The southern most state, Kerala, is socio-culturally stratified into Hindus, Muslims and Christians on the basis of religion. The origin of these religious communities in Kerala is considered to be unique in comparison with that in other parts of the country. These communities were later influenced by the hierarchical caste structure established by the Hindu Brahmins. In the present study, we compared six nontribal (Namboothiri, Nair, Ezhava, Pulaya, Malabar Muslim and Syrian Christian) communities belonging to the major religious groups in Kerala (Hindu, Muslim and Christian) based on the human leukocyte antigen (HLA)-A, -B and -C diversity. Our aim was to understand the genomic substructuring associated with the changing social scenario in various caste and religious groups and compare it with the Dravidian tribal and other world populations. The present study reveals that the HLA diversity of the Dravidian communities is very distinct from that in the other world populations. It is obvious that the nontribal communities of Kerala display a greater Dravidian influence, but traces of genetic admixture with the Mediterranean, western European, central Asian and East Asian populations can be observed. This characterizes the crypto-Dravidian features of the nontribal communities of Kerala. Demic diffusion of the local progressive communities with the migrant communities may have given rise to crypto-Dravidian features among the nontribal communities of Kerala.

Alleles↗
PubMed2006

Adults with spontaneous aerobic Gram-negative bacillary meningitis admitted to the intensive care unit.

The characteristics of spontaneous aerobic Gram-negative bacillary meningitis (AGNBM) were determined in 40 adults requiring admission to an intensive care unit (ICU) during a 16-year period in ten French ICUs. Eight infections were hospital-acquired and most patients had predisposing factors, mainly chronic alcoholism and an immunocompromised status. Three immunosuppressed patients had disseminated strongyloidiasis. Gram's stain, cerebrospinal fluid and blood cultures were positive for 85%, 98% and 80% of cases, respectively. Escherichia coli (57%) and Klebsiella pneumoniae (17%) were the most frequent pathogens. In-ICU mortality was 38%. Spontaneous AGNBM is a rare complication of bacteraemia in adults. The severity of predisposing underlying diseases might explain the poor prognosis despite appropriate antimicrobial therapy.

Adult↗
PubMed2006

The effect of metformin on fat distribution and the metabolic syndrome in women with polycystic ovary syndrome--a randomised, double-blind, placebo-controlled trial.

OBJECTIVE: To establish whether metformin has a significant action in reducing visceral fat and improving other metabolic parameters in women with polycystic ovary syndrome (PCOS). DESIGN: Randomised, double-blind, placebo-controlled trial. SETTING: Reproductive medicine clinic. POPULATION: Forty women with anovulatory PCOS. METHODS: Participants were randomised into receiving metformin 500 mg three times a day or placebo for 3 months. MAIN OUTCOME MEASURES: Fat distribution was measured by computed tomography scan. Secondary outcome measures included serum indices of the metabolic syndrome and evidence of ovulation. RESULTS: We found no significant differences in any of the measures of fat distribution between the placebo and metformin groups. The metformin group had significantly lower total cholesterol (P= 0.02), low-density lipoprotein cholesterol (P= 0.02) and cholesterol:high-density lipoprotein cholesterol ratio (P= 0.05), but there was no statistically significant treatment effect on androgens, insulin, insulin resistance, triglycerides, ovulation or pregnancy. CONCLUSIONS: Metformin has no clinically significant effect in reducing visceral fat mass, although it does have a beneficial effect on lipids. This trial lends support to the growing evidence that metformin is not a weight loss drug. Metformin might therefore be used as an adjunct to lifestyle modification in women with PCOS, but not as a substitute for it.

Adult↗
PubMed2006

Multiple cavitating masses in an immunocompromised host with rheumatoid arthritis-related interstitial lung disease: an unusual expression of cytomegalovirus pneumonitis.

Cytomegalovirus is a known opportunistic infection in immunocompromised individuals. We document multiple cavitating lung masses caused by cytomegalovirus in a patient with rheumatoid arthritis-induced interstitial lung disease on immunosuppressant medication, an unusual expression of CMV pneumonitis. With increasing use of immunosuppressive therapy and increase in AIDS, pulmonary cytomegalovirus infection is expected to be a more frequently encountered disease and familiarity with its uncommon radiological manifestations will be advantageous.

Aged↗
PubMed2005

Evidence for in-medium changes of four-quark condensates.

Utilizing the QCD sum rule approach to the behavior of the omega meson in nuclear matter we derive evidence for in-medium changes of particular four-quark condensates from the recent CB-TAPS experiment for the reaction gamma + A --> A' + omega(--> pi0gamma) with A = Nb and LH2.

Journal Article↗
PubMed2005

The impact of past alcohol use on treatment response rates in patients with chronic hepatitis C.

BACKGROUND: Studies have shown that past alcohol consumption reduces response rates in patients with chronic hepatitis C treated with interferon monotherapy. AIM: To clarify the importance of alcohol consumption on response rates in patients undergoing treatment with pegylated interferon and ribavirin. METHODS: In a single centre, prospective study, median daily alcohol consumption (determined by previously validated method) and quartiles of alcohol consumption were calculated. Univariate and binary logistic regression analyses were performed using treatment response status as the dependent variable. RESULTS: Overall, in an intention-to-treat analysis, 34 of 115 patients (30%) responded to treatment. In univariate analysis, black patients, especially those with hepatitis C virus genotype 1, high viral load and low alanine aminotransferase were significantly less likely to respond. Predictors of response by regression analysis included alcohol <30 g/day (OR=3.02, 95% CI: 1.02-8.93; P=0.04), non-genotype 1 status (OR=1.98, 95% CI: 1.03-3.80; P=0.04) and non-black race (OR=2.79, 95% CI: 1.33-5.85; P=0.006). CONCLUSIONS: Median daily alcohol use >30 g/day is associated with failure to respond to pegylated interferon and ribavirin for treatment of hepatitis C. Past alcohol use should be evaluated when considering treatment for hepatitis C.

Adult↗
PubMed2005

Interventions to improve outpatient referrals from primary care to secondary care.

BACKGROUND: The primary care specialist interface is a key organisational feature of many health care systems. Patients are referred to specialist care when investigation or therapeutic options are exhausted in primary care and more specialised care is needed. Referral has considerable implications for patients, the health care system and health care costs. There is considerable evidence that the referral processes can be improved. OBJECTIVES: To estimate the effectiveness and efficiency of interventions to change outpatient referral rates or improve outpatient referral appropriateness. SEARCH STRATEGY: We conducted electronic searches of the Cochrane Effective Practice and Organisation of Care (EPOC) group specialised register (developed through extensive searches of MEDLINE, EMBASE, Healthstar and the Cochrane Library) (February 2002) and the National Research Register. SELECTION CRITERIA: Randomised controlled trials, controlled clinical trials, controlled before and after studies and interrupted time series of interventions to change or improve outpatient referrals. Participants were primary care physicians. The outcomes were objectively measured provider performance or health outcomes. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. MAIN RESULTS: Seventeen studies involving 23 separate comparisons were included. Nine studies (14 comparisons) evaluated professional educational interventions. Ineffective strategies included: passive dissemination of local referral guidelines (two studies), feedback of referral rates (one study) and discussion with an independent medical adviser (one study). Generally effective strategies included dissemination of guidelines with structured referral sheets (four out of five studies) and involvement of consultants in educational activities (two out of three studies). Three studies evaluated organisational interventions (patient management by family physicians compared to general internists, attachment of a physiotherapist to general practices and requiring a second 'in-house' opinion prior to referral), all of which were effective. Five studies (six comparisons) evaluated financial interventions. Two studies evaluating change from a capitation based to mixed capitation and fee-for-service system and from a fee-for-service to a capitation based system (with an element of risk sharing for secondary care services) observed a reduction in referral rates. Modest reductions in referral rates of uncertain significance were observed following the introduction of the general practice fundholding scheme in the United Kingdom (UK). One study evaluating the effect of providing access to private specialists demonstrated an increase in the proportion of patients referred to specialist services but no overall effect on referral rates. AUTHORS' CONCLUSIONS: There are a limited number of rigorous evaluations to base policy on. Active local educational interventions involving secondary care specialists and structured referral sheets are the only interventions shown to impact on referral rates based on current evidence. The effects of 'in-house' second opinion and other intermediate primary care based alternatives to outpatient referral appear promising.

Family Practice↗