PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (39)
 

Clipboard (0)
None
Journals
Year of Publication
Document Types
1.  Predicting long-term response to strong opioids in patients with low back pain: findings from a randomized, controlled trial of transdermal fentanyl and morphine 
BMC Medicine  2007;5:39.
Background
Some patients with long-standing low back pain will benefit from treatment with strong opioids. However, it would be helpful to predict which patients will have a good response. A fixed-term opioid trial has been recommended, but there is little evidence to suggest how long this trial should be. We assessed data from a large-scale randomized comparison of transdermal fentanyl (TDF) and sustained-release oral morphine (slow-release morphine; SRM) to determine characteristics of treatment responders.
Methods
This was a secondary analysis of a previously published 13-month randomized trial involving 680 patients with long-standing low back pain (median age 52 years, 61% women, median duration of back pain 87 months). Pain relief was recorded using visual analogue scales (VAS). Treatment response was defined as pain relief of at least 30% from baseline to any point during the trial. We used a step-wise logistic regression to identify variables that might predict response to treatment. Covariates included treatment group, sex, age, duration of pain, presence of neuropathic pain, baseline pain scores, educational/employment status, use of high doses of opioids, and social functioning (SF)-36 scores.
Results
Over half the patients in both groups (n = 370; 54% TDF, 55% SRM) were treatment responders. There were no differences between the TDF and SRM responders in terms of age, sex, type or duration of pain between responders and non-responders. The difference in response to treatment between responders and non-responders could be detected at 3 weeks. Lack of response after 1 month had a stronger negative predictive value (i.e., ability to detect non-responders) than the presence of response after 1 month. The most influential factors for predicting a response were employment status (χ2 = 11.06, p = 0.0259) and use of high doses of opioids (χ2 = 3.04, p = 0.0811).
Conclusion
No clear pattern of baseline pain (type or severity) or patient characteristics emerged that could be used to predict responders before the start of opioid treatment. However, a 1-month trial period appears sufficient to determine response and tolerability in most cases.
doi:10.1186/1741-7015-5-39
PMCID: PMC2242794  PMID: 18154644
2.  Knee arthroscopy and exercise versus exercise only for chronic patellofemoral pain syndrome: a randomized controlled trial 
BMC Medicine  2007;5:38.
Background
Arthroscopy is often used to treat patients with chronic patellofemoral pain syndrome (PFPS). As there is a lack of evidence, we conducted a randomized controlled trial to study the efficacy of arthroscopy in patients with chronic PFPS.
Methods
A total of 56 patients with chronic PFPS were randomized into two treatment groups: an arthroscopy group (N = 28), treated with knee arthroscopy and an 8-week home exercise program, and a control group (N = 28), treated with the 8-week home exercise program only. The arthroscopy included finding-specific surgical procedures according to current recommendations. The primary outcome was the Kujala score on patellofemoral pain and function at 9 months following randomization. Secondary outcomes were visual analog scales (VASs) to assess activity-related symptoms. We also estimated the direct healthcare costs.
Results
Both groups showed marked improvement during the follow-up. The mean improvement in the Kujala score was 12.9 (95% confidence interval (CI) 8.2–17.6) in the arthroscopy group and 11.4 (95% CI 6.9–15.8) in the control group. However, there was no difference between the groups in mean improvement in the Kujala score (group difference 1.1 (95% CI -7.4 - 5.2)) or in any of the VAS scores. Total direct healthcare costs in the arthroscopy group were estimated to exceed on average those of the control group by €901 per patient (p < 0.001).
Conclusion
In this controlled trial involving patients with chronic PFPS, the outcome when arthroscopy was used in addition to a home exercise program was no better than when the home exercise program was used alone.
Trial registration
Current Controlled Trials ISRCTN 41800323
doi:10.1186/1741-7015-5-38
PMCID: PMC2249589  PMID: 18078506
3.  Information for decision making from imperfect national data: tracking major changes in health care use in Kenya using geostatistics 
BMC Medicine  2007;5:37.
Background
Most Ministries of Health across Africa invest substantial resources in some form of health management information system (HMIS) to coordinate the routine acquisition and compilation of monthly treatment and attendance records from health facilities nationwide. Despite the expense of these systems, poor data coverage means they are rarely, if ever, used to generate reliable evidence for decision makers. One critical weakness across Africa is the current lack of capacity to effectively monitor patterns of service use through time so that the impacts of changes in policy or service delivery can be evaluated. Here, we present a new approach that, for the first time, allows national changes in health service use during a time of major health policy change to be tracked reliably using imperfect data from a national HMIS.
Methods
Monthly attendance records were obtained from the Kenyan HMIS for 1 271 government-run and 402 faith-based outpatient facilities nationwide between 1996 and 2004. A space-time geostatistical model was used to compensate for the large proportion of missing records caused by non-reporting health facilities, allowing robust estimation of monthly and annual use of services by outpatients during this period.
Results
We were able to reconstruct robust time series of mean levels of outpatient utilisation of health facilities at the national level and for all six major provinces in Kenya. These plots revealed reliably for the first time a period of steady nationwide decline in the use of health facilities in Kenya between 1996 and 2002, followed by a dramatic increase from 2003. This pattern was consistent across different causes of attendance and was observed independently in each province.
Conclusion
The methodological approach presented can compensate for missing records in health information systems to provide robust estimates of national patterns of outpatient service use. This represents the first such use of HMIS data and contributes to the resurrection of these hugely expensive but underused systems as national monitoring tools. Applying this approach to Kenya has yielded output with immediate potential to enhance the capacity of decision makers in monitoring nationwide patterns of service use and assessing the impact of changes in health policy and service delivery.
doi:10.1186/1741-7015-5-37
PMCID: PMC2225405  PMID: 18072976
4.  Clinical effectiveness of usual care with or without antidepressant medication for primary care patients with minor or mild-major depression: a randomized equivalence trial 
BMC Medicine  2007;5:36.
Background
Minor and mild-major depression are highly prevalent in primary care. There is insufficient evidence for the effectiveness of antidepressants in the treatment of minor and mild-major depression. We compared the effectiveness of usual primary care treatment, with or without antidepressants, in minor and mild-major depression.
Methods
A pragmatic patient-randomized equivalence trial with 52 weeks follow-up was conducted in The Netherlands. In total, 59 primary care physicians (PCPs) recruited and treated 181 adult patients with minor or mild-major depression. Patients were randomized to four consultations within 3 months of usual care plus antidepressants (UCandAD) or usual care alone (UCnoAD). The Montgomery Åsberg Depression Rating Scale (MADRS) was used to assess changes in severity of depressive symptoms. The predefined equivalence margin was set at five points. Multilevel analysis was used to analyze the data. Secondary outcome measures were the Short-Form 36 (SF-36), and the Client Satisfaction Questionnaire (CSQ-8).
Results
Patients received on average 3.0 (SD 1.4) 15-min consultations within 3 months with (n = 85) or without paroxetine (n = 96). Equivalence of UCandAD and UCnoAD was demonstrated in the intention-to-treat analyses as well as the per-protocol analysis after 6 weeks, but not at 13, 26 and 52 weeks follow-up. No statistical differences in effectiveness between treatment groups were found in the intention-to-treat analysis. No differences in the physical and mental functioning (SF-36) were found between the treatment groups. Patients allocated to UCandAD were slightly more satisfied with their treatment at 13 weeks follow-up (but not at 52 weeks follow-up) than patients allocated to UCnoAD. Preliminary analyses suggested that subgroups such as patients with mild-major (instead of a minor) depression might benefit from antidepressant treatment. Patients who were assigned to their preferred treatment (in particular to UCnoAD) were more often compliant and had better clinical outcomes.
Conclusion
UCandAD was as effective as UCnoAD over the first 6 weeks, but not at 13, 26, and 52 weeks. However, superiority of either treatment could not be demonstrated either. The question whether antidepressants add any clinical effect to usual care remains unresolved. We recommend future studies to look for subgroups of patients who may benefit from antidepressants.
Trial registration
Dutch Trial Registry ISRCN03007807.
doi:10.1186/1741-7015-5-36
PMCID: PMC2234409  PMID: 18067659
5.  Validity of electron beam computed tomography for coronary artery disease: asystematic review and meta-analysis 
BMC Medicine  2007;5:35.
Background
Electron beam computed tomography (EBCT) is a method for measuring coronary calcification and has been promoted as a possible non-invasive screening/diagnostic tool for coronary artery disease (CAD). Our objective was to carry out a systematic review and meta-analysis of EBCT for the screening of asymptomatic patients and the diagnosis of symptomatic patients for CAD.
Methods
Studies were identified from the PUBMED, MEDLINE, EMBASE, Current Contents, INAHTA and Cochrane Collaboration databases. We identified studies published in English evaluating EBCT using: (1) a prospective design among asymptomatic patients where CAD was measured in terms of clinical outcomes (e.g. myocardial infarction, death, revascularization); and (2)a cross-sectional design among symptomatic patients where CAD was measured by coronary angiography. We compared the risk of CAD in EBCT score categories defined as low (0–10), moderate (11–400) and high (>400). A hierarchical meta-analysis was used to pool risk ratios comparing categories across studies.
Results
We identified 9 studies of asymptomatic patients and 10 studies of symptomatic patients. In both types of studies, we found variability in EBCT category distribution and risk of CAD within categories. For studies of asymptomatic patients we estimated the following risk ratios (95% credible intervals): moderate versus low 3.5 (2.4, 5.1) and high versus low 9.9 (5.3, 17.6). Similar results were obtained for studies of symptomatic patients. Ratios comparing the risk of no CAD among symptomatic patients were as follows: moderate versus low 0.5 (0.3, 0.8) and high versus low 0.12 (0.05, 0.2).
Conclusion
Increasing EBCT scores indicate higher risk for CAD in both asymptomatic and symptomatic patients. In general, asymptomatic patients with EBCT scores in the high category can perhaps be considered for preventive medical therapy and risk factor modification. Symptomatic patients with EBCT scores in the low category can perhaps, at least temporarily, avoid invasive coronary angiography. However, the non-uniform quality of studies and the lack of availability of individual-level data preclude the extension of our results to individual patients.
doi:10.1186/1741-7015-5-35
PMCID: PMC2228285  PMID: 18036252
6.  Predictability and epidemic pathways in global outbreaks of infectious diseases: the SARS case study 
BMC Medicine  2007;5:34.
Background
The global spread of the severe acute respiratory syndrome (SARS) epidemic has clearly shown the importance of considering the long-range transportation networks in the understanding of emerging diseases outbreaks. The introduction of extensive transportation data sets is therefore an important step in order to develop epidemic models endowed with realism.
Methods
We develop a general stochastic meta-population model that incorporates actual travel and census data among 3 100 urban areas in 220 countries. The model allows probabilistic predictions on the likelihood of country outbreaks and their magnitude. The level of predictability offered by the model can be quantitatively analyzed and related to the appearance of robust epidemic pathways that represent the most probable routes for the spread of the disease.
Results
In order to assess the predictive power of the model, the case study of the global spread of SARS is considered. The disease parameter values and initial conditions used in the model are evaluated from empirical data for Hong Kong. The outbreak likelihood for specific countries is evaluated along with the emerging epidemic pathways. Simulation results are in agreement with the empirical data of the SARS worldwide epidemic.
Conclusion
The presented computational approach shows that the integration of long-range mobility and demographic data provides epidemic models with a predictive power that can be consistently tested and theoretically motivated. This computational strategy can be therefore considered as a general tool in the analysis and forecast of the global spreading of emerging diseases and in the definition of containment policies aimed at reducing the effects of potentially catastrophic outbreaks.
doi:10.1186/1741-7015-5-34
PMCID: PMC2213648  PMID: 18031574
7.  Kisspeptin and GPR54 immunoreactivity in a cohort of 518 patients defines favourable prognosis and clear cell subtype in ovarian carcinoma 
BMC Medicine  2007;5:33.
Background
Kisspeptins and their G-protein coupled receptor, GPR54 are required for GnRH release and have been associated with anti-metastatic tumour cell behaviour in model systems. The latter might suggest that their overexpression would be associated with a better prognosis in cancer. However, kisspeptin/GPR54 interactions (autocrine, paracrine, and/or endocrine) could also impact tumour behaviour in a negative manner. Here, for the first time, we associate the immunoreactivity of the kisspeptin/GPR54 ligand-receptor pair with favourable prognosis in a large cohort of ovarian carcinomas.
Methods
Immunohistochemical analysis for kisspeptin and GPR54 was performed on a tissue microarray (TMA) consisting of 518 early stage ovarian carcinomas, all with linked clinical outcome data. The TMA was scored using a staining intensity scale of 0 (negative), +1 (mild-moderate), and +2 (strong). Strong staining cases were considered either kisspeptin or GPR54 positive and designated as 1, while all other cases were considered negative and designated 0. All statistical analysis was conducted using two-sided tests and a p value equal to or less than 0.05 was considered significant.
Results
Kisspeptin and GPR54 immunoreactive cases show a favourable prognosis in univariable disease specific survival (p = 0.0023, p = 0.0092), as well as in overall survival (p = 0.0006, p = 0.0002). Furthermore, kisspeptin is an independent marker for favourable prognosis as determined by multivariable disease specific (p = 0.0046) and overall survival analysis (p = 0.0170), while GPR54 is an independent marker for overall survival only (p = 0.0303). Both kisspeptin positive and GPR54 positive cases are strongly associated with the ovarian carcinoma clear cell subtype (p < 0.0001, p < 0.0001), and GPR54 is significantly associated with favourable prognosis in overall survival within the clear cell subtype (p = 0.0102).
Conclusion
Kisspeptin and GPR54 immunoreactivity are significantly associated with favourable prognosis in both disease specific and overall survival, as well as being significantly associated with the clear cell ovarian carcinoma subtype, thereby creating the first independent prognostic biomarkers specific for ovarian clear cell carcinomas.
doi:10.1186/1741-7015-5-33
PMCID: PMC2200658  PMID: 18005407
8.  A meta-analysis of N-acetylcysteine in contrast-induced nephrotoxicity: unsupervised clustering to resolve heterogeneity 
BMC Medicine  2007;5:32.
Background
Meta-analyses of N-acetylcysteine (NAC) for preventing contrast-induced nephrotoxicity (CIN) have led to disparate conclusions. Here we examine and attempt to resolve the heterogeneity evident among these trials.
Methods
Two reviewers independently extracted and graded the data. Limiting studies to randomized, controlled trials with adequate outcome data yielded 22 reports with 2746 patients.
Results
Significant heterogeneity was detected among these trials (I2 = 37%; p = 0.04). Meta-regression analysis failed to identify significant sources of heterogeneity. A modified L'Abbé plot that substituted groupwise changes in serum creatinine for nephrotoxicity rates, followed by model-based, unsupervised clustering resolved trials into two distinct, significantly different (p < 0.0001) and homogeneous populations (I2 = 0 and p > 0.5, for both). Cluster 1 studies (n = 18; 2445 patients) showed no benefit (relative risk (RR) = 0.87; 95% confidence interval (CI) 0.68–1.12, p = 0.28), while cluster 2 studies (n = 4; 301 patients) indicated that NAC was highly beneficial (RR = 0.15; 95% CI 0.07–0.33, p < 0.0001). Benefit in cluster 2 was unexpectedly associated with NAC-induced decreases in creatinine from baseline (p = 0.07). Cluster 2 studies were relatively early, small and of lower quality compared with cluster 1 studies (p = 0.01 for the three factors combined). Dialysis use across all studies (five control, eight treatment; p = 0.42) did not suggest that NAC is beneficial.
Conclusion
This meta-analysis does not support the efficacy of NAC to prevent CIN.
doi:10.1186/1741-7015-5-32
PMCID: PMC2200657  PMID: 18001477
9.  Contraception use and pregnancy among 15–24 year old South African women: a nationally representative cross-sectional survey 
BMC Medicine  2007;5:31.
Background
Adolescent reproductive health has not continued to receive the attention it deserves since the start of the HIV epidemic. In South Africa, high numbers of adolescent women report pregnancies that are unwanted and yet few have accessed available termination of pregnancy services. Enabling contraception use is vital for meeting the goals of HIV prevention.
Methods
A nationally representative survey of South African 15–24 year olds was undertaken. Participants completed a questionnaire on sexual behaviour and provided an oral fluid sample for HIV testing. Analysis of the data was restricted to women (n = 6217), particularly those who reported being sexual active in the last 12 months (n = 3618) and was conducted using svy methods in the program STATA 8.0 to take account of sampling methods. Univariate and multivariate analyses were conducted to explore factors associated with contraceptive use.
Results
Two thirds of all women reported having ever been sexually active and among these 87% were sexually active in the past 12 months. Among women who reported currently being sexually active, 52.2% reported using contraceptives. There was evidence of association between contraceptive use and being employed or a student (vs unemployed); fewer sex partners; type of last sex partner; having talked to last partner about condom use and having ever been pregnant.
Conclusion
Specific emphasis must be placed on encouraging young women to use contraceptive methods that offer protection against pregnancy and STIs/HIV. Our consistent finding of a relationship between discussing condom use with partners and condom use indicates the importance of involvement of male partners in women's contraceptive decisions.
doi:10.1186/1741-7015-5-31
PMCID: PMC2190760  PMID: 17963521
10.  International ranking systems for universities and institutions: a critical appraisal 
BMC Medicine  2007;5:30.
Background
Ranking of universities and institutions has attracted wide attention recently. Several systems have been proposed that attempt to rank academic institutions worldwide.
Methods
We review the two most publicly visible ranking systems, the Shanghai Jiao Tong University 'Academic Ranking of World Universities' and the Times Higher Education Supplement 'World University Rankings' and also briefly review other ranking systems that use different criteria. We assess the construct validity for educational and research excellence and the measurement validity of each of the proposed ranking criteria, and try to identify generic challenges in international ranking of universities and institutions.
Results
None of the reviewed criteria for international ranking seems to have very good construct validity for both educational and research excellence, and most don't have very good construct validity even for just one of these two aspects of excellence. Measurement error for many items is also considerable or is not possible to determine due to lack of publication of the relevant data and methodology details. The concordance between the 2006 rankings by Shanghai and Times is modest at best, with only 133 universities shared in their top 200 lists. The examination of the existing international ranking systems suggests that generic challenges include adjustment for institutional size, definition of institutions, implications of average measurements of excellence versus measurements of extremes, adjustments for scientific field, time frame of measurement and allocation of credit for excellence.
Conclusion
Naïve lists of international institutional rankings that do not address these fundamental challenges with transparent methods are misleading and should be abandoned. We make some suggestions on how focused and standardized evaluations of excellence could be improved and placed in proper context.
doi:10.1186/1741-7015-5-30
PMCID: PMC2174504  PMID: 17961208
11.  The influence of gender on the effects of aspirin in preventing myocardial infarction 
BMC Medicine  2007;5:29.
Background
There is considerable variation in the effect of aspirin therapy reducing the risk of myocardial infarction (MI). Gender could be a potential explanatory factor for the variability. We conducted a systematic review and meta-analysis to determine whether gender mix might play a role in explaining the large variation of aspirin efficacy across primary and secondary MI prevention trials.
Methods
Randomized placebo-controlled clinical trials that examined the efficacy of aspirin therapy on MI were identified by using the PUBMED database (1966 to October 2006). Weighted linear regression technique was used to determine the relationship between log-transformed relative risk (RR) of MI and the percentage of male participants in each trial. The reciprocal of the standard error of the RR in each trial (1/SE) was used as the weight.
Results
A total of 23 trials (n = 113 494 participants) were identified. Overall, compared with placebo, aspirin reduced the risk of non-fatal MI (RR = 0.72, 95% confidence interval (CI) 0.64–0.81, p < 0.001) but not of fatal MI (RR = 0.88, 95% CI 0.75–1.03, p = 0.120). A total of 27% of the variation in the non-fatal MI results could be accounted for by considering the gender mix of the trials (p = 0.017). Trials that recruited predominantly men demonstrated the largest risk reduction in non-fatal MI (RR = 0.62, 95% CI 0.54–0.71), while trials that contained predominately women failed to demonstrate a significant risk reduction in non-fatal MI (RR = 0.87, 95% CI 0.71–1.06).
Conclusion
Gender accounts for a substantial proportion of the variability in the efficacy of aspirin in reducing MI rates across these trials, and supports the notion that women might be less responsive to aspirin than men.
doi:10.1186/1741-7015-5-29
PMCID: PMC2131749  PMID: 17949479
12.  A new therapy for highly effective tumor eradication using HVJ-E combined with chemotherapy 
BMC Medicine  2007;5:28.
Background
Inactivated HVJ (hemagglutinating virus of Japan; Sendai virus) particles (HVJ envelope vector; HVJ-E can incorporate and deliver plasmid DNA, siRNA, antibody and peptide and anti-cancer drugs to cells both in vitro and in vivo. We attempted to eradicate tumors derived from mouse colon cancer cells, CT26, by combining bleomycin (BLM)-incorporated HVJ-E (HVJ-E/BLM) with cisplatin (CDDP) administration.
Methods
CT-26 tumor mass was intradermally established in Balb/c mice. HVJ-E/BLM was directly injected into the tumor mass with or without intraperitoneal administration of CDDP. The anti-tumor effect was evaluated by measuring tumor size and cytotoxic T cell activity against CT26. Re-challenge of tumor cells to treated mice was performed 10 days or 8 months after the initial tumor inoculation.
Results
We found that three intratumoral injections of HVJ-E/BLM along with a single intraperitoneal administration of CDDP eradicated CT26 tumors with more than 75% efficiency. When tumor cells were intradermally re-injected on day 10 after the initial tumor inoculation, tumors on both sides disappeared in most of the mice that received the combination therapy of HVJ-E/BLM and CDDP. Eight months after the initial tumor eradication, surviving mice were re-challenged with CT26 cells. The re-challenged tumors were rejected in all of the surviving mice treated with the combination therapy. Cytotoxic T lymphocytes specific for CT26 were generated in these surviving mice.
Conclusion
Combination therapy consisting of HVJ-E and chemotherapy completely eradicated the tumor, and generated anti-tumor immunity. The combination therapy could therefore be a promising new strategy for cancer therapy.
doi:10.1186/1741-7015-5-28
PMCID: PMC2039728  PMID: 17883878
13.  Parasitological impact of 2-year preventive chemotherapy on schistosomiasis and soil-transmitted helminthiasis in Uganda 
BMC Medicine  2007;5:27.
Background
Schistosomiasis and soil-transmitted helminthiasis (STH) are among the neglected tropical diseases in Africa. A national control program for these diseases was initiated in Uganda during March 2003. Annual treatment with praziquantel and albendazole was given to schoolchildren in endemic areas and to adults in selected communities where local prevalence of Schistosoma mansoni in schoolchildren was high.
Methods
The impact of the treatment program was monitored through cohorts of schoolchildren and adults. Their infection status with S. mansoni and STH was determined by parasitological examinations at baseline and at annual follow-ups. The prevalence and intensity of S. mansoni and STH before and after treatment were analyzed.
Results
Two rounds of treatment significantly reduced the prevalence of S. mansoni infection in schoolchildren across three regions in the country from 33.4–49.3% to 9.7–29.6%, and intensity of infection from 105.7–386.8 eggs per gram of faeces (epg) to 11.6–84.1 epg. The prevalence of hookworm infection was reduced from 41.2–57.9% to 5.5–16.1%, and intensity of infection from 186.9–416.8 epg to 3.7–36.9 epg. The proportion of children with heavy S. mansoni infection was significantly reduced from 15% (95% CI 13.4–16.8%) to 2.3% (95% CI 1.6–3.0%). In adults, significant reduction in the prevalence and intensity of S. mansoni and hookworm infections was also observed. More importantly, the prevalence and intensity of both S. mansoni and hookworm infections in the cohorts of newly-recruited 6-year-olds who had never previously received treatment decreased significantly over 2 years: 34.9% (95% CI 31.9–37.8%) to 22.6% (95% CI 19.9–25.2%) and 171.1 epg (95% CI 141.5–200.7) to 72.0 epg (95% CI 50.9–93.1) for S. mansoni; and 48.4% (95% CI 45.4–51.5) to 15.9% (95% CI 13.6–18.2) and 232.7 epg (95% CI 188.4–276.9) to 51.4 epg (95% CI 33.4–69.5) for hookworms, suggesting a general decline in environmental transmission levels.
Conclusion
Annual anthelminthic treatment delivered to schoolchildren and to adults at high risk in Uganda can significantly reduce the prevalence and intensity of infection for schistosomiasis and STH, and potentially also significantly reduce levels of environmental transmission of infection.
doi:10.1186/1741-7015-5-27
PMCID: PMC2014753  PMID: 17767713
14.  Which doctors and with what problems contact a specialist service for doctors? A cross sectional investigation 
BMC Medicine  2007;5:26.
Background
In the United Kingdom, specialist treatment and intervention services for doctors are underdeveloped. The MedNet programme, created in 1997 and funded by the London Deanery, aims to fill this gap by providing a self-referral, face-to-face, psychotherapeutic assessment service for doctors in London and South-East England. MedNet was designed to be a low-threshold service, targeting doctors without formal psychiatric problems. The aim of this study was to delineate the characteristics of doctors utilising the service, to describe their psychological morbidity, and to determine if early intervention is achieved.
Methods
A cross-sectional study including all consecutive self-referred doctors (n = 121, 50% male) presenting in 2002–2004 was conducted. Measures included standardised and bespoke questionnaires both self-report and clinician completed. The multi-dimensional evaluation included: demographics, CORE (CORE-OM, CORE-Workplace and CORE-A) an instrument designed to evaluate the psychological difficulties of patients referred to outpatient services, Brief Symptom Inventory to quantify caseness and formal psychiatric illness, and Maslach Burnout Inventory.
Results
The most prevalent presenting problems included depression, anxiety, interpersonal, self-esteem and work-related issues. However, only 9% of the cohort were identified as severely distressed psychiatrically using this measure. In approximately 50% of the sample, problems first presented in the preceding year. About 25% were on sick leave at the time of consultation, while 50% took little or no leave in the prior 12 months. A total of 42% were considered to be at some risk of suicide, with more than 25% considered to have a moderate to severe risk. There were no significant gender differences in type of morbidity, severity or days off sick.
Conclusion
Doctors displayed high levels of distress as reflected in the significant proportion of those who were at some risk of suicide; however, low rates of severe psychiatric illness were detected. These findings suggest that MedNet clients represent both ends of the spectrum of severity, enabling early clinical engagement for a significant proportion of cases that is of importance both in terms of personal health and protecting patient care, and providing a timely intervention for those who are at risk, a group for whom rapid intervention services are in need and an area that requires further investigation in the UK.
doi:10.1186/1741-7015-5-26
PMCID: PMC2025601  PMID: 17725835
15.  Gestational diabetes as a risk factor for pancreatic cancer: a prospective cohort study 
BMC Medicine  2007;5:25.
Background
Diabetes is known to be associated with cancer of the pancreas, though there is some debate as to whether it is a cause or a consequence of the disease. We investigated the incidence of pancreatic cancer in a cohort of 37926 Israeli women followed for 28–40 years for whom information on diabetes had been collected at the time they gave birth, in 1964–1976, in Jerusalem. There were 54 cases of pancreatic cancer ascertained from the Israel Cancer Registry during follow-up.
Methods
We used Cox proportional hazards models to adjust for age at baseline and explore effects of other risk factors, including ethnic groups, preeclampsia, birth order and birth weight of offspring.
Results
We observed no cases of pancreatic cancer in the women with insulin dependent diabetes; however, there were five cases in the women with gestational diabetes. The interval between the record of diabetes in pregnancy and the diagnosis of pancreatic cancer ranged from 14–35 years. Women with a history of gestational diabetes showed a relative risk of pancreatic cancer of 7.1 (95% confidence interval, 2.8–18.0).
Conclusion
We conclude that gestational diabetes is strongly related to the risk of cancer of the pancreas in women in this population, and that gestational diabetes can precede cancer diagnosis by many years.
doi:10.1186/1741-7015-5-25
PMCID: PMC2042496  PMID: 17705823
16.  Planning an integrated disease surveillance and response system: a matrix of skills and activities 
BMC Medicine  2007;5:24.
Background
The threat of a global influenza pandemic and the adoption of the World Health Organization (WHO) International Health Regulations (2005) highlight the value of well-coordinated, functional disease surveillance systems. The resulting demand for timely information challenges public health leaders to design, develop and implement efficient, flexible and comprehensive systems that integrate staff, resources, and information systems to conduct infectious disease surveillance and response. To understand what resources an integrated disease surveillance and response system would require, we analyzed surveillance requirements for 19 priority infectious diseases targeted for an integrated disease surveillance and response strategy in the WHO African region.
Methods
We conducted a systematic task analysis to identify and standardize surveillance objectives, surveillance case definitions, action thresholds, and recommendations for 19 priority infectious diseases. We grouped the findings according to surveillance and response functions and related them to community, health facility, district, national and international levels.
Results
The outcome of our analysis is a matrix of generic skills and activities essential for an integrated system. We documented how planners used the matrix to assist in finding gaps in current systems, prioritizing plans of action, clarifying indicators for monitoring progress, and developing instructional goals for applied epidemiology and in-service training programs.
Conclusion
The matrix for Integrated Disease Surveillance and Response (IDSR) in the African region made clear the linkage between public health surveillance functions and participation across all levels of national health systems. The matrix framework is adaptable to requirements for new programs and strategies. This framework makes explicit the essential tasks and activities that are required for strengthening or expanding existing surveillance systems that will be able to adapt to current and emerging public health threats.
doi:10.1186/1741-7015-5-24
PMCID: PMC1988797  PMID: 17697387
17.  Health inequalities, physician citizens and professional medical associations: an Australian case study 
BMC Medicine  2007;5:23.
Background
As socioeconomic health inequalities persist and widen, the health effects of adversity are a constant presence in the daily work of physicians. Gruen and colleagues suggest that, in responding to important population health issues such as this, defining those areas of professional obligation in contrast to professional aspiration should be on the basis of evidence and feasibility. Drawing this line between obligation and aspiration is a part of the work of professional medical colleges and associations, and in doing so they must respond to members as well as a range of other interest groups. Our aim was to explore the usefulness of Gruen's model of physician responsibility in defining how professional medical colleges and associations should lead the profession in responding to socioeconomic health inequalities.
Methods
We report a case study of how the Royal Australian College of General Practitioners is responding to the issue of health inequalities through its work. We undertook a consultation (80 interviews with stakeholders internal and external to the College and two focus groups with general practitioners) and program and policy review of core programs of College interest and responsibility: general practitioner training and setting of practice standards, as well as its work in public advocacy.
Results
Some strategies within each of these College program areas were seen as legitimate professional obligations in responding to socioeconomic health inequality. However, other strategies, while potentially professional obligations within Gruen's model, were nevertheless contested. The key difference between these lay in different moral orientations. Actions where agreement existed were based on an ethos of care and compassion. Actions that were contested were based on an ethos of justice and human rights.
Conclusion
Colleges and professional medical associations have a role in explicitly leading a debate about values, engaging both external stakeholder and practicing member constituencies. This is an important and necessary step in defining an agreed role for the profession in addressing health inequalities.
doi:10.1186/1741-7015-5-23
PMCID: PMC1995197  PMID: 17697318
18.  Methodological issues in detecting gene-gene interactions in breast cancer susceptibility: a population-based study in Ontario 
BMC Medicine  2007;5:22.
Background
There is growing evidence that gene-gene interactions are ubiquitous in determining the susceptibility to common human diseases. The investigation of such gene-gene interactions presents new statistical challenges for studies with relatively small sample sizes as the number of potential interactions in the genome can be large. Breast cancer provides a useful paradigm to study genetically complex diseases because commonly occurring single nucleotide polymorphisms (SNPs) may additively or synergistically disturb the system-wide communication of the cellular processes leading to cancer development.
Methods
In this study, we systematically studied SNP-SNP interactions among 19 SNPs from 18 key genes involved in major cancer pathways in a sample of 398 breast cancer cases and 372 controls from Ontario. We discuss the methodological issues associated with the detection of SNP-SNP interactions in this dataset by applying and comparing three commonly used methods: the logistic regression model, classification and regression trees (CART), and the multifactor dimensionality reduction (MDR) method.
Results
Our analyses show evidence for several simple (two-way) and complex (multi-way) SNP-SNP interactions associated with breast cancer. For example, all three methods identified XPD-[Lys751Gln]*IL10-[G(-1082)A] as the most significant two-way interaction. CART and MDR identified the same critical SNPs participating in complex interactions. Our results suggest that the use of multiple statistical approaches (or an integrated approach) rather than a single methodology could be the best strategy to elucidate complex gene interactions that have generally very different patterns.
Conclusion
The strategy used here has the potential to identify complex biological relationships among breast cancer genes and processes. This will lead to the discovery of novel biological information, which will improve breast cancer risk management.
doi:10.1186/1741-7015-5-22
PMCID: PMC1976420  PMID: 17683639
19.  The effects of dictatorship on health: the case of Turkmenistan 
BMC Medicine  2007;5:21.
Background
There is a health crisis in Turkmenistan similar to, but more severe than, in other Central Asian countries. This paper asks whether the health crisis in Turkmenistan is attributable to the consequences of the dictatorship under president Niyazov, who died in 2006.
Methods
The basis for this paper was a series of semi-structured in-depth interviews with key informants complemented by an iterative search of internet sites, initially published as a report in April 2005, and subsequently updated with feedback on the report as well as a comprehensive search of secondary information sources and databases.
Results
This paper describes in depth three areas in which the dictatorship in Turkmenistan had a negative impact on population health: the regime's policy of secrecy and denial, which sees the "solution" to health care problems in concealment rather than prevention; its complicity in the trafficking of drugs from Afghanistan; and the neglect of its health care system.
Conclusion
The paper concludes that dictatorship has contributed to the health crisis facing Turkmenistan. One of the first tests of the new regime will be whether it can address this crisis.
doi:10.1186/1741-7015-5-21
PMCID: PMC1948003  PMID: 17663794
20.  Simvastatin is associated with a reduced incidence of dementia and Parkinson's disease 
BMC Medicine  2007;5:20.
Background
Statins are a class of medications that reduce cholesterol by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Whether statins can benefit patients with dementia remains unclear because of conflicting results. We hypothesized that some of the confusion in the literature might arise from differences in efficacy of different statins. We used a large database to compare the action of several different statins to investigate whether some statins might be differentially associated with a reduction in the incidence of dementia and Parkinson's disease.
Methods
We analyzed data from the decision support system of the US Veterans Affairs database, which contains diagnostic, medication and demographic information on 4.5 million subjects. The association of lovastatin, simvastatin and atorvastatin with dementia was examined with Cox proportional hazard models for subjects taking statins compared with subjects taking cardiovascular medications other than statins, after adjusting for covariates associated with dementia or Parkinson's disease.
Results
We observed that simvastatin is associated with a significant reduction in the incidence of dementia in subjects ≥65 years, using any of three models. The first model incorporated adjustment for age, the second model included adjusted for three known risk factors for dementia, hypertension, cardiovascular disease or diabetes, and the third model incorporated adjustment for the Charlson index, which is an index that provides a broad assessment of chronic disease. Data were obtained for over 700000 subjects taking simvastatin and over 50000 subjects taking atorvastatin who were aged >64 years. Using model 3, the hazard ratio for incident dementia for simvastatin and atorvastatin are 0.46 (CI 0.44–0.48, p < 0.0001) and 0.91 (CI 0.80–1.02, p = 0.11), respectively. Lovastatin was not associated with a reduction in the incidence of dementia. Simvastatin also exhibited a reduced hazard ratio for newly acquired Parkinson's disease (HR 0.51, CI 0.4–0.55, p < 0.0001).
Conclusion
Simvastatin is associated with a strong reduction in the incidence of dementia and Parkinson's disease, whereas atorvastatin is associated with a modest reduction in incident dementia and Parkinson's disease, which shows only a trend towards significance.
doi:10.1186/1741-7015-5-20
PMCID: PMC1955446  PMID: 17640385
21.  Migraine aura or transient ischemic attacks? A five-year follow-up case-control study of women with transient central nervous system disorders in pregnancy 
BMC Medicine  2007;5:19.
Background
Migraine aura may be difficult to differentiate from transient ischemic attacks and other transient neurological disorders in pregnant women. The aims of the present study were to investigate and diagnose all pregnant women with transient neurological disorders of suspected central nervous system origin, and to compare this group with a control group of pregnant women with regard to vascular risk factors and prognosis.
Methods
During a 28 month period, 41 patients were detected with transient neurological symptoms during pregnancy. These were studied in detail with thorough clinical and laboratory investigations in order to make a certain diagnosis and to evaluate whether the episodes might be of a vascular nature. For comparison, the same investigations were performed in 41 pregnant controls. To assess the prognosis, both patients and controls were followed with questionnaires every year for five years.
Results
Migraine with aura was the most common cause of symptoms during pregnancy, occurring in 34 patients, while 2 were diagnosed with stroke, 2 with carpal tunnel syndrome, 1 with partial epilepsy, 1 with multiple sclerosis and 1 with presyncope. Patients had more headache before pregnancy than controls, but the average levels of vascular risk factors were similar. None of the patients or the controls reported cerebrovascular episodes during the five-year follow-up.
Conclusion
The diagnosis of migraine aura was difficult because for many patients it was their first ever attack and headache tended to be absent or of non-migraineous type. The aura features were more complex, with several aura symptoms and a higher prevalence of sensory and dysphasic aura than usual. Gradually developing aura symptoms, or different aura symptoms occurring in succession as described in the International Classification of Headache Disorders, seem to be useful for differentiating aura from other transient disorders. A meticulous history and clinical neurological examination are more useful than routine supplementary investigations for cerebrovascular disease. The five-year follow-up clearly indicates that migraine with aura in pregnancy usually has a good prognosis with regard to cerebrovascular events.
doi:10.1186/1741-7015-5-19
PMCID: PMC1939710  PMID: 17640340
22.  Corticortophin releasing factor 2 receptor agonist treatment significantly slows disease progression in mdx mice 
BMC Medicine  2007;5:18.
Background
Duchenne muscular dystrophy results from mutation of the dystrophin gene, causing skeletal and cardiac muscle loss of function. The mdx mouse model of Duchenne muscular dystrophy is widely utilized to evaluate the potential of therapeutic regimens to modulate the loss of skeletal muscle function associated with dystrophin mutation. Importantly, progressive loss of diaphragm function is the most consistent striated muscle effect observed in the mdx mouse model, which is the same as in patients suffering from Duchenne muscular dystrophy.
Methods
Using the mdx mouse model, we have evaluated the effect that corticotrophin releasing factor 2 receptor (CRF2R) agonist treatment has on diaphragm function, morphology and gene expression.
Results
We have observed that treatment with the potent CRF2R-selective agonist PG-873637 prevents the progressive loss of diaphragm specific force observed during aging of mdx mice. In addition, the combination of PG-873637 with glucocorticoids not only prevents the loss of diaphragm specific force over time, but also results in recovery of specific force. Pathological analysis of CRF2R agonist-treated diaphragm muscle demonstrates that treatment reduces fibrosis, immune cell infiltration, and muscle architectural disruption. Gene expression analysis of CRF2R-treated diaphragm muscle showed multiple gene expression changes including globally decreased immune cell-related gene expression, decreased extracellular matrix gene expression, increased metabolism-related gene expression, and, surprisingly, modulation of circadian rhythm gene expression.
Conclusion
Together, these data demonstrate that CRF2R activation can prevent the progressive degeneration of diaphragm muscle associated with dystrophin gene mutation.
doi:10.1186/1741-7015-5-18
PMCID: PMC1936998  PMID: 17626629
23.  Association between cancer prevalence and use of thiazolidinediones: results from the Vermont Diabetes Information System 
BMC Medicine  2007;5:17.
Background
Peroxisome proliferator-activated receptors (PPARs) have emerged as important drug targets for diabetes. Drugs that activate PPARγ, such as the thiazolidinediones (TZDs), are widely used for treatment of Type 2 diabetes mellitus. PPARγ signaling could also play an anti-neoplastic role in several in vitro models, although conflicting results are reported from in vivo models. The effects of TZDs on cancer risk in humans needs to be resolved as these drugs are prescribed for long periods of time in patients with diabetes.
Methods
A total of 1003 subjects in community practice settings were interviewed at home at the time of enrolment into the Vermont Diabetes Information System, a clinical decision support program. Patients self-reported their personal and clinical characteristics, including any history of malignancy. Laboratory data were obtained directly from the clinical laboratory and current medications were obtained by direct observation of medication containers. We performed a cross-sectional analysis of the interviewed subjects to assess a possible association between cancer diagnosis and the use of TZDs.
Results
In a multivariate logistic regression model, a diagnosis of cancer was significantly associated with TZD use, even after correcting for potential confounders including other oral anti-diabetic agents (sulfonylureas and biguanides), age, glycosylated hemoglobin A1C, body mass index, cigarette smoking, high comorbidity, and number of prescription medications (odds ratio = 1.59, P = 0.04). This association was particularly strong among patients using rosiglitazone (OR = 1.89, P = 0.02), and among women (OR = 2.07, P = 0.01).
Conclusion
These data suggest an association between TZD use and cancer in patients with diabetes. Further studies are required to determine if this association is causal.
doi:10.1186/1741-7015-5-17
PMCID: PMC1934377  PMID: 17584937
24.  How far will we need to go to reach HIV-infected people in rural South Africa? 
BMC Medicine  2007;5:16.
Background
The South African Government has outlined detailed plans for antiretroviral (ART) rollout in KwaZulu-Natal Province, but has not created a plan to address treatment accessibility in rural areas in KwaZulu-Natal. Here, we calculate the distance that People Living With HIV/AIDS (PLWHA) in rural areas in KwaZulu-Natal would have to travel to receive ART. Specifically, we address the health policy question 'How far will we need to go to reach PLWHA in rural KwaZulu-Natal?'.
Methods
We developed a model to quantify treatment accessibility in rural areas; the model incorporates heterogeneity in spatial location of HCFs and patient population. We defined treatment accessibility in terms of the number of PLWHA that have access to an HCF. We modeled the treatment-accessibility region (i.e. catchment area) around an HCF by using a two-dimensional function, and assumed that treatment accessibility decreases as distance from an HCF increases. Specifically, we used a distance-discounting measure of ART accessibility based upon a modified form of a two-dimensional gravity-type model. We calculated the effect on treatment accessibility of: (1) distance from an HCF, and (2) the number of HCFs.
Results
In rural areas in KwaZulu-Natal even substantially increasing the size of a small catchment area (e.g. from 1 km to 20 km) around an HCF would have a negligible impact (~2%) on increasing treatment accessibility. The percentage of PLWHA who can receive ART in rural areas in this province could be as low as ~16%. Even if individuals were willing (and able) to travel 50 km to receive ART, only ~50% of those in need would be able to access treatment. Surprisingly, we show that increasing the number of available HCFs for ART distribution ~ threefold does not lead to a threefold increase in treatment accessibility in rural KwaZulu-Natal.
Conclusion
Our results show that many PLWHA in rural KwaZulu-Natal are unlikely to have access to ART, and that the impact of an additional 37 HCFs on treatment accessibility in rural areas would be less substantial than might be expected. There is a great length to go before we will be able to reach many PLWHA in rural areas in South Africa, and specifically in KwaZulu-Natal.
doi:10.1186/1741-7015-5-16
PMCID: PMC1906822  PMID: 17577418
25.  Multidisciplinary team meetings and their impact on workflow in radiology and pathology departments 
BMC Medicine  2007;5:15.
Background
The development of multidisciplinary team meetings (MDTMs) for radiology and pathology is a burgeoning area that increasingly impacts on work processes in both of these departments. The aim of this study was to examine work processes and quantify the time demands on radiologists and pathologists associated with MDTM practices at a large teaching hospital. The observations reported in this paper reflect a general trend affecting hospitals and our conclusions will have relevance for others implementing clinical practice guidelines.
Methods
For one month, all work related to clinical meetings between pathology and radiology with clinical staff was documented and later analysed.
Results
The number of meetings to which pathology and radiology contribute at a large university teaching hospital, ranges from two to eight per day, excluding grand rounds, and amounts to approximately 50 meetings per month for each department. For one month, over 300 h were spent by pathologists and radiologists on 81 meetings, where almost 1000 patients were discussed. For each meeting hour, there were, on average, 2.4 pathology hours and 2 radiology hours spent in preparation. Two to three meetings per week are conducted over a teleconferencing link. Average meeting time is 1 h. Preparation time per meeting ranges from 0.3 to 6 h for pathology, and 0.5 to 4 for radiology. The review process in preparation for meetings improves internal quality standards. Materials produced externally (for example imaging) can amount to almost 50% of the material to be reviewed on a single patient. The number of meetings per month has increased by 50% over the past two years. Further increase is expected in both the numbers and duration of meetings when scheduling issues are resolved. A changing trend in the management of referred patients with the development of MDTMs and the introduction of teleconferencing was noted.
Conclusion
Difficulties are being experienced by pathology and radiology departments participating fully in several multidisciplinary teams. Time spent at meetings, and in preparation for MDTMs is significant. Issues of timing and the coordination of materials to be reviewed are sometimes irreconcilable. The exchange of patient materials with outside institutions is a cause for concern when full data are not made available in a timely fashion. The process of preparation for meetings is having a positive influence on quality, but more resources are needed in pathology and radiology to realise the full benefits of multidisciplinary team working.
doi:10.1186/1741-7015-5-15
PMCID: PMC1919390  PMID: 17567904

Results 1-25 (39)