Simon M Collin

Prostate-cancer mortality in the USA and UK in 1975–2004: an ecological study

BACKGROUND There is no conclusive evidence that screening based on serum prostate-specific antigen (PSA) tests decreases prostate-cancer mortality. Since its introduction in the USA around 1990, uptake of PSA testing has been rapid in the USA, but much less common in the UK. Our aim was to study trends over time in prostate-cancer mortality and incidence in the USA and UK in 1975-2004, and compare these patterns with trends in screening and treatment. METHODS Joinpoint regression analysis of cancer-mortality statistics from Cancer Research UK (London, UK) and from the US National Cancer Institute Surveillance, Epidemiology and End Results (SEER) programme from 1975 to 2004 was used to estimate the annual percentage change in prostate-cancer mortality in both countries and the points in time when trends changed. The ratio of USA to UK age-adjusted prostate-cancer incidence was also assessed. FINDINGS Age-specific and age-adjusted prostate-cancer mortality peaked in the early 1990s at almost identical rates in both countries, but age-adjusted mortality in the USA subsequently declined after 1994 by -4.17% (95% CI -4.34 to -3.99) each year, four-times the rate of decline in the UK after 1992 (-1.14% [-1.44 to -0.84]). The mortality decline in the USA was greatest and most sustained in patients aged 75 years or older (-5.32% [-8.23 to -2.32]), whereas death rates had plateaued in this age group in the UK by 2000. The mean ratio of USA to UK age-adjusted prostate-cancer incidence rates in 1975-2003 was 2.5, with a pronounced peak around the time that PSA testing was introduced in the USA. Numbers needed to treat to prevent one death from prostate cancer were 33 000 in the 55-64-year age group. INTERPRETATION The striking decline in prostate-cancer mortality in the USA compared with the UK in 1994-2004 coincided with much higher uptake of PSA screening in the USA. Explanations for the different trends in mortality include the possibility of an early effect of initial screening rounds on men with more aggressive asymptomatic disease in the USA, different approaches to treatment in the two countries, and bias related to the misattribution of cause of death. Speculation over the role of screening will continue until evidence from randomised controlled trials is published.

Circulating Folate, Vitamin B12, Homocysteine, Vitamin B12 Transport Proteins, and Risk of Prostate Cancer: a Case-Control Study, Systematic Review, and Meta-analysis

Background: Disturbed folate metabolism is associated with an increased risk of some cancers. Our objective was to determine whether blood levels of folate, vitamin B12, and related metabolites were associated with prostate cancer risk. Methods: Matched case-control study nested within the U.K. population–based Prostate testing for cancer and Treatment (ProtecT) study of prostate-specific antigen–detected prostate cancer in men ages 50 to 69 years. Plasma concentrations of folate, B12 (cobalamin), holo-haptocorrin, holo-transcobalamin total transcobalamin, and total homocysteine (tHcy) were measured in 1,461 cases and 1,507 controls. ProtecT study estimates for associations of folate, B12, and tHcy with prostate cancer risk were included in a meta-analysis, based on a systematic review. Results: In the ProtecT study, increased B12 and holo-haptocorrin concentrations showed positive associations with prostate cancer risk [highest versus lowest quartile of B12 odds ratio (OR) = 1.17 (95% confidence interval, 0.95-1.43); Ptrend = 0.06; highest versus lowest quartile of holo-haptocorrin OR = 1.27 (1.04-1.56); Ptrend = 0.01]; folate, holo-transcobalamin, and tHcy were not associated with prostate cancer risk. In the meta-analysis, circulating B12 levels were associated with an increased prostate cancer risk [pooled OR = 1.10 (1.01-1.19) per 100 pmol/L increase in B12; P = 0.002]; the pooled OR for the association of folate with prostate cancer was positive [OR = 1.11 (0.96-1.28) per 10 nmol/L; P = 0.2) and conventionally statistically significant if ProtecT (the only case-control study) was excluded [OR = 1.18 (1.00-1.40) per 10 nmol/L; P = 0.02]. Conclusion: Vitamin B12 and (in cohort studies) folate were associated with increased prostate cancer risk. Impact: Given current controversies over mandatory fortification, further research is needed to determine whether these are causal associations. Cancer Epidemiol Biomarkers Prev; 19(6); 1632–42. ©2010 AACR.

Concordant HIV Infection and Visceral Leishmaniasis in Ethiopia: The Influence of Antiretroviral Treatment and Other Factors on Outcome

BACKGROUND Coinfection with human immunodeficiency virus (HIV) and Leishmania donovani visceral leishmaniasis (VL) in Africa is an emerging, poorly understood disease. METHODS We evaluated 356 consecutive patients coinfected with HIV and VL treated in Humera, northwest Ethiopia, from February 2003 to October 2006, for risk factors for VL relapse and death and the effect of antiretroviral therapy (ART). RESULTS During 2928 patient-months of follow-up, 256 VL episodes and 39 deaths occurred. Among 195 patients receiving ART, 31.3% had > or = 1 VL episode, and 14.4% died. Among 161 patients who did not receive ART, 26.1% had > or = 1 VL episodes, and 6.8% died. A total of 54 patients who received ART and 58 patients who did not receive ART had > or = 1 VL relapse. VL relapse among patients receiving ART was associated with a baseline CD4 cell count < 100 cells/microL (hazard ratio [HR], 2.50; 95% confidence interval [CI], 1.21-5.15) and > or = 2 previous VL episodes (HR, 3.74; 95% CI, 1.40-10.02). Failure to clear parasites after VL treatment was usually followed by symptomatic VL relapse. Patients who relapsed showed poor CD4 cell count recovery while receiving ART. ART was partially protective against VL relapse (HR, 0.46; 95% CI, 0.26-0.82). However, 28% of first VL relapses while receiving ART occurred despite a CD4 cell count > 200 cells/microL; in 5% of VL relapses, the CD4 cell count had been > 200 cells/microL for > 6 months. Factors associated with all-cause mortality among patients receiving ART were baseline CD4 cell count < 100 cells/microL (HR, 3.20; 95% CI, 1.30-7.87) and VL episodes during follow-up (HR for 1 episode, 4.97 [95% CI, 2.09-11.86]; HR for > 2 episodes, 3.22 [95% CI, 1.01-10.23]). CONCLUSIONS Concordant HIV infection and VL is a major, acquired immunodeficiency syndrome-defining illness with high relapse and mortality rates; ART reduces relapses; and secondary antileishmanial prophylaxis may benefit patients at risk of relapse.

Association of folate-pathway gene polymorphisms with the risk of prostate cancer: a population-based nested case-control study, systematic review, and meta-analysis.

Folate-pathway gene polymorphisms have been implicated in several cancers and investigated inconclusively in relation to prostate cancer. We conducted a systematic review, which identified nine case-control studies (eight included, one excluded). We also included data from four genome-wide association studies and from a case-control study nested within the UK population–based Prostate Testing for Cancer and Treatment study. We investigated by meta-analysis the effects of eight polymorphisms: MTHFR C677T (rs1801133; 12 studies; 10,745 cases; 40,158 controls), MTHFR A1298C (rs1801131; 5 studies; 3,176 cases; 4,829 controls), MTR A2756G (rs1805087; 8 studies; 7,810 cases; 37,543 controls), MTRR A66G (rs1801394; 4 studies; 3,032 cases; 4,515 controls), MTHFD1 G1958A (rs2236225; 6 studies; 7,493 cases; 36,941 controls), SLC19A1/RFC1 G80A (rs1051266; 4 studies; 6,222 cases; 35,821 controls), SHMT1 C1420T (rs1979277; 2 studies; 2,689 cases; 4,110 controls), and FOLH1 T1561C (rs202676; 5 studies; 6,314 cases; 35,190 controls). The majority (10 of 13) of eligible studies had 100% Caucasian subjects; only one study had <90% Caucasian subjects. We found weak evidence of dominant effects of two alleles: MTR 2756A>G [random effects pooled odds ratio, 1.06 (1.00-1.12); P = 0.06 (P = 0.59 for heterogeneity across studies)] and SHMT1 1420C>T [random effects pooled odds ratio, 1.11 (1.00-1.22); P = 0.05 (P = 0.38 for heterogeneity across studies)]. We found no effect of MTHFR 677C>T or any of the other alleles in dominant, recessive or additive models, or in comparing a/a versus A/A homozygous. Neither did we find any difference in effects on advanced or localized cancers. Our meta-analysis suggests that known common folate-pathway single nucleotide polymorphisms do not have significant effects on susceptibility to prostate cancer.(Cancer Epidemiol Biomarkers Prev 2009;18(9):2528–39)

Limited Effectiveness of High-Dose Liposomal Amphotericin B (AmBisome) for Treatment of Visceral Leishmaniasis in an Ethiopian Population With High HIV Prevalence

BACKGROUND Due to unacceptably high mortality with pentavalent antimonials, Médecins Sans Frontières in 2006 began using liposomal amphotericin B (AmBisome) for visceral leishmaniasis (VL) patients in Ethiopia who were severely ill or positive for human immunodeficiency virus (HIV). METHODS We used clinical data obtained from January 2007 to January 2009 to compare outcomes by HIV status and VL episode (primary vs relapse) and to identify risk factors for treatment failure among patients treated with AmBisome monotherapy at a total dose of 30 mg/kg in 6 doses on alternate days, a higher dose than recommended by the World Health Organization (20 mg/kg). RESULTS Among 94 HIV-negative severely ill VL patients, 93% had initial cure and 6% died. Among 195 HIV-positive patients (116 primary, 79 relapse VL), 60% had initial cure, 7% died, and 32% were parasitological failures. AmBisome was less effective in the 79 HIV-positive VL relapse patients (38% initial cure, 5% mortality, 56% parasitological failure) than in the 116 HIV-positive primary VL patients (74% initial cure, 8% mortality, 16% parasitological failure). Sodium stibogluconate (SSG) rescue treatment increased the overall cure rate among all HIV-positive VL patients from 60% to 83%, but 16% (9 of 59) of rescue treatment patients died, mainly due to SSG toxicity. CONCLUSIONS High-dose AmBisome for VL is safe and effective in severely ill HIV-negative patients, and safe but less effective in HIV-positive patients. Combining AmBisome with another drug may enhance its effectiveness in HIV-positive VL patients. SSG should be avoided for treatment of VL in HIV-positive patients.

A decade of inequality in maternity care: antenatal care, professional attendance at delivery, and caesarean section in Bangladesh (1991-2004).

BackgroundBangladesh is committed to the fifth Millennium Development Goal (MDG-5) target of reducing its maternal mortality ratio by three-quarters between 1990 and 2015. Since the early 1990s, Bangladesh has followed a strategy of improving access to facilities equipped and staffed to provide emergency obstetric care (EmOC).MethodsWe used data from four Demographic and Health Surveys conducted between 1993 and 2004 to examine trends in the proportions of live births preceded by antenatal consultation, attended by a health professional, and delivered by caesarean section, according to key socio-demographic characteristics.ResultsUtilization of antenatal care increased substantially, from 24% in 1991 to 60% in 2004. Despite a relatively greater increase in rural than urban areas, utilization remained much lower among the poorest rural women without formal education (18%) compared with the richest urban women with secondary or higher education (99%). Professional attendance at delivery increased by 50% (from 9% to 14%, more rapidly in rural than urban areas), and caesarean sections trebled (from 2% to 6%), but these indicators remained low even by developing country standards. Within these trends there were huge inequalities; 86% of live births among the richest urban women with secondary or higher education were attended by a health professional, and 35% were delivered by caesarean section, compared with 2% and 0.1% respectively of live births among the poorest rural women without formal education. The trend in professional attendance was entirely confounded by socioeconomic and demographic changes, but education of the woman and her husband remained important determinants of utilization of obstetric services.ConclusionDespite commendable progress in improving uptake of antenatal care, and in equipping health facilities to provide emergency obstetric care, the very low utilization of these facilities, especially by poor women, is a major impediment to meeting MDG-5 in Bangladesh.

Genetic Variants in the Vitamin D Receptor Are Associated with Advanced Prostate Cancer at Diagnosis: Findings from the Prostate Testing for Cancer and Treatment Study and a Systematic Review

Low levels of plasma vitamin D have been implicated as a possible risk factor for both prostate cancer incidence and advanced disease, and recent phase II trials suggest that vitamin D supplementation might delay progression of prostate cancer. Common polymorphisms in the vitamin D receptor (VDR) are associated with VDR activity and are therefore potentially useful proxies for assessing whether vitamin D is causally related to advanced prostate cancer. We genotyped five well-known VDR polymorphisms in 1,604 men with prostate cancer from the Prostate Testing for Cancer and Treatment study. Our aim was to examine the association between VDR polymorphisms and cancer stage (localized versus advanced) as well as cancer grade (Gleason score <7 versus ≥7). Moreover, we also carried out a systematic review and meta-analysis of 13 similar studies. As a result of our meta-analysis, we revealed three polymorphisms, BsmI, ApaI, and TaqI, associated with high Gleason score with an overall summary odds ratios (95% confidence intervals) of 1.12 (1.00-1.25; bb versus BB + Bb), 1.25 (1.02-1.53; aa versus AA + Aa), and 0.82 (0.69-0.98; Tt + tt versus TT), respectively. The haplotype analysis revealed that the BsmI (B)-ApaI (A)-TaqI (t) participants compared with BsmI (b)-ApaI (a)-TaqI (T) individuals were less likely to have high Gleason scores (odds ratio, 0.84; 95% confidence interval, 0.71-1.00; Punadjusted = 0.050; Padjusted = 0.014). Our finding provides some support for the hypothesis that low levels of vitamin D may increase the risk of prostate cancer progression. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2874–81)

Implementation of computerised physician order entry (CPOE) and picture archiving and communication systems (PACS) in the NHS: quantitative before and after study

Objective To assess the impact of components of the national programme for information technology (NPfIT) on measures of clinical and operational efficiency. Design Quasi-experimental controlled before and after study using routinely collected patient level data. Setting Four NHS acute hospital trusts in England. Data sources Inpatient admissions and outpatient appointments, 2000-5. Interventions A system for ordering pathology tests and browsing results (computerised physician order entry, CPOE) and a system for requesting radiological examinations and displaying images (picture archiving and communications system, PACS). Main outcome measures Requests per inpatient, outpatient, or day case patient for full blood count, urine culture and urea and electrolytes tests, and plain x ray film, computed tomography, and ultrasonography examinations. Results CPOE was associated with a reduction in the proportion of outpatient appointments at which full blood count (odds ratio 0.25, 95% confidence interval 0.16 to 0.40), urea and electrolytes (0.55, 0.39 to 0.77), and urine culture (0.30, 0.17 to 0.51) tests were ordered, and at which full blood count tests were repeated (0.73, 0.53 to 0.99). Conversely, the same system was associated with an almost fourfold increase in the use of urea and electrolytes tests among day case patients (3.63, 1.66 to 7.94). PACS was associated with a reduction in repeat plain x ray films at outpatient appointments (0.62, 0.44 to 0.88) and a reduction in inpatient computed tomography (0.83, 0.70 to 0.98). Conversely, it was associated with increases in computed tomography requested at outpatient appointments (1.89, 1.26 to 2.84) and computed tomography repeated within 48 hours during an inpatient stay (2.18, 1.52 to 3.14). Conclusions CPOE and PACS were associated with both increases and reductions in tests and examinations. The magnitude of the changes is potentially important with respect to the efficiency of provision of health care. Better information about the impact of modern IT is required to enable healthcare organisations to manage implementation optimally.

Depression in paediatric chronic fatigue syndrome

Objective To describe the prevalence of depression in children with chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) and investigate the relationship between depression in CFS/ME and clinical symptoms such as fatigue, disability, pain and school attendance. Design Cross-sectional survey data using the Hospital Anxiety and Depression Scale (HADS) collected at assessment. Setting Specialist paediatric CFS/ME service in the South West. Patients Children aged 12–18 years with CFS/ME. Main outcome measure Depression was defined as scoring >9 on the HADS depression scale. Results 542 subjects had complete data for the HADS and 29% (156/542) (95% CI 25% to 33%) had depression. In a univariable analysis, female sex, poorer school attendance, and higher levels of fatigue, disability, pain, and anxiety were associated with higher odds of depression. Age of child and duration of illness were not associated with depression. In a multivariable analysis, the factors most strongly associated with depression were disability, with higher scores on the physical function subscale of the 36 item Short Form (SF-36). Conclusions Depression is commonly comorbid with CFS/ME, much more common than in the general population, and is associated with markers of disease severity. It is important to screen for, identify and treat depression in this population.

Pet ownership is associated with increased risk of non-atopic asthma and reduced risk of atopy in childhood: findings from a UK birth cohort.

Studies have shown an inverse association of pet ownership with allergy but inconclusive findings for asthma.