Paul Roderick

Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis.

BACKGROUND Substantial controversy surrounds the use of estimated glomerular filtration rate (eGFR) and albuminuria to define chronic kidney disease and assign its stages. We undertook a meta-analysis to assess the independent and combined associations of eGFR and albuminuria with mortality. METHODS In this collaborative meta-analysis of general population cohorts, we pooled standardised data for all-cause and cardiovascular mortality from studies containing at least 1000 participants and baseline information about eGFR and urine albumin concentrations. Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause and cardiovascular mortality associated with eGFR and albuminuria, adjusted for potential confounders. FINDINGS The analysis included 105,872 participants (730,577 person-years) from 14 studies with urine albumin-to-creatinine ratio (ACR) measurements and 1,128,310 participants (4,732,110 person-years) from seven studies with urine protein dipstick measurements. In studies with ACR measurements, risk of mortality was unrelated to eGFR between 75 mL/min/1.73 m(2) and 105 mL/min/1.73 m(2) and increased at lower eGFRs. Compared with eGFR 95 mL/min/1.73 m(2), adjusted HRs for all-cause mortality were 1.18 (95% CI 1.05-1.32) for eGFR 60 mL/min/1.73 m(2), 1.57 (1.39-1.78) for 45 mL/min/1.73 m(2), and 3.14 (2.39-4.13) for 15 mL/min/1.73 m(2). ACR was associated with risk of mortality linearly on the log-log scale without threshold effects. Compared with ACR 0.6 mg/mmol, adjusted HRs for all-cause mortality were 1.20 (1.15-1.26) for ACR 1.1 mg/mmol, 1.63 (1.50-1.77) for 3.4 mg/mmol, and 2.22 (1.97-2.51) for 33.9 mg/mmol. eGFR and ACR were multiplicatively associated with risk of mortality without evidence of interaction. Similar findings were recorded for cardiovascular mortality and in studies with dipstick measurements. INTERPRETATION eGFR less than 60 mL/min/1.73 m(2) and ACR 1.1 mg/mmol (10 mg/g) or more are independent predictors of mortality risk in the general population. This study provides quantitative data for use of both kidney measures for risk assessment and definition and staging of chronic kidney disease. FUNDING Kidney Disease: Improving Global Outcomes (KDIGO), US National Kidney Foundation, and Dutch Kidney Foundation.Background A comprehensive evaluation of the independent and combined associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality is required for assessment of the impact of kidney function on risk in the general population, with implications for improving the definition and staging of chronic kidney disease (CKD).

Study of infectious intestinal disease in England: rates in the community, presenting to general practice, and reported to national surveillance

Abstract Objective: To establish the incidence and aetiology of infectious intestinal disease in the community and presenting to general practitioners. Comparison with incidence and aetiology of cases reaching national laboratory based surveillance. Design: Population based community cohort incidence study, general practice based incidence studies, and case linkage to national laboratory surveillance. Setting: 70 general practices throughout England. Participants: 459 975 patients served by the practices. Community surveillance of 9776 randomly selected patients. Main outcome measures: Incidence of infectious intestinal disease in community and reported to general practice. Results: 781 cases were identified in the community cohort, giving an incidence of 19.4/100 person years (95% confidence interval 18.1 to 20.8). 8770 cases presented to general practice (3.3/100 person years (2.94 to 3.75)). One case was reported to national surveillance for every 1.4 laboratory identifications, 6.2 stools sent for laboratory investigation, 23 cases presenting to general practice, and 136 community cases. The ratio of cases in the community to cases reaching national surveillance was lower for bacterial pathogens (salmonella 3.2:1, campylobacter 7.6:1) than for viruses (rotavirus 35:1, small round structured viruses 1562:1). There were many cases for which no organism was identified. Conclusions: Infectious intestinal disease occurs in 1 in 5 people each year, of whom 1 in 6 presents to a general practitioner. The proportion of cases not recorded by national laboratory surveillance is large and varies widely by microorganism.Ways of supplementing the national laboratory surveillance system for infectious intestinal diseases should be considered.

Noninvasive markers of fibrosis in nonalcoholic fatty liver disease: Validating the European Liver Fibrosis Panel and exploring simple markers

The detection of fibrosis within nonalcoholic fatty liver disease (NAFLD) is important for ascertaining prognosis and the stratification of patients for emerging therapeutic intervention. We validated the Original European Liver Fibrosis panel (OELF) and a simplified algorithm not containing age, the Enhanced Liver fibrosis panel (ELF), in an independent cohort of patients with NAFLD. Furthermore, we explored whether the addition of simple markers to the existing panel test could improve diagnostic performance. One hundred ninety‐six consecutively recruited patients from 2 centers were included in the validation study. The diagnostic accuracy of the discriminant scores of the ELF panel, simple markers, and a combined panel were compared using receiver operator curves, predictive values, and a clinical utility model. The ELF panel had an area under the curve (AUC) of 0.90 for distinguishing severe fibrosis, 0.82 for moderate fibrosis, and 0.76 for no fibrosis. Simplification of the algorithm by removing age did not alter diagnostic performance. Addition of simple markers to the panel improved diagnostic performance with AUCs of 0.98, 0.93, and 0.84 for the detection of severe fibrosis, moderate fibrosis, and no fibrosis, respectively. The clinical utility model showed that 82% and 88% of liver biopsies could be potentially avoided for the diagnosis of severe fibrosis using ELF and the combined panel, respectively. The ELF panel has good diagnostic accuracy in an independent validation cohort of patients with NAFLD. The addition of established simple markers augments the diagnostic performance across different stages of fibrosis, which will potentially allow superior stratification of patients with NAFLD for emerging therapeutic strategies. (HEPATOLOGY 2007.)

Cigarette smoking by socioeconomic group, sex, and age: effects of price, income, and health publicity.

Abstract Objective: To assess effects of price, income, and health publicity on cigarette smoking by age, sex, and socioeconomic group. Design: Econometric multiple regression analysis of data on cigarette smoking from the British general household survey. Subjects: Random sample of adult population in Britain interviewed for biennial general household surveys 1972-90. Main outcome measures - Changes in cigarette consumption and prevalence of smoking. Results: Price elasticities of demand for cigarettes (percentage change in cigarette consumption for a 1% change in price) were significant at -0.5 (95% confidence interval -0.8 to -0.1) for men and -0.6 (-0.9 to -0.3) for women, were highest in socioeconomic group V (-1.0 for men and -0.9 for women), and lowest (not significantly different from zero) in socioeconomic groups I and II. The gradient in price elasticities by socioeconomic group was significant for men (F=5.6, P=0.02) and for women (F=6.1, P=0.02). Price was a significant factor in cigarette consumption by age for women in every age group and for men aged 25-34. Cigarette consumption by young men aged 16-34 increased with income. There was a significant decrease in smoking over time by women in socioeconomic groups I and II and by men in all age and social groups except socioeconomic group V attributable to health publicity. Price significantly affected smoking prevalence in socioeconomic group V (-0.6 for men and -0.5 for women) and for all women (-0.2). Conclusions: Men and women in lower socioeconomic groups are more responsive than are those in higher socioeconomic groups to changes in the price of cigarettes and less to health publicity. Women of all ages, including teenagers, appear to have been less responsive to health publicity than have men but more responsive to price. Response to health publicity decreased linearly with age. Real price increases in cigarettes could narrow differences between socioeconomic groups in smoking and the related inequalities in health, but specific measures would be necessary to ameliorate effects on the most deprived families that may include members who continue to smoke. The use of a policy to steadily increase cigarette tax is likely to help achieve the governments targets for smoking and smoking related diseases.

Frequency and impact of nonadherence to immunosuppressants after renal transplantation: A systematic review

Nonadherence to immunosuppressants is recognized to occur after renal transplantation, but the size of its impact on transplant survival is not known. A systematic literature search identified 325 studies (in 324 articles) published from 1980 to 2001 reporting the frequency and impact of nonadherence in adult renal transplant recipients. Thirty-six studies meeting the inclusion criteria for further review were grouped into cross-sectional and cohort studies and case series. Meta-analysis was used to estimate the size of the impact of nonadherence on graft failure. Only two studies measured adherence using electronic monitoring, which is currently thought to be the most accurate measure. Cross-sectional studies (n=15) tended to rely on self-report questionnaires, but these were poorly described; a median (interquartile range) of 22% (18%–26%) of recipients were nonadherent. Cohort studies (n=10) indicated that nonadherence contributes substantially to graft loss; a median (interquartile range) of 36% (14%–65%) of graft losses were associated with prior nonadherence. Meta-analysis of these studies showed that the odds of graft failure increased sevenfold (95% confidence interval, 4%–12%) in nonadherent subjects compared with adherent subjects. Standardized methods of assessing adherence in clinical populations need to be developed, and future studies should attempt to identify the level of adherence that increases the risk of graft failure. However, this review shows nonadherence to be common and to have a large impact on transplant survival. Therefore, significant improvements in graft survival could be expected from effective interventions to improve adherence.

Clinical outcomes, quality of life, and costs in the North Thames Dialysis Study of elderly people on dialysis: a prospective cohort study

BACKGROUND Evidence-based health policy is urgently needed to meet the increasing demand for health services among elderly people, particularly for expensive technologies such as renal-replacement therapy. Age has been used to ration dialysis, although not always explicitly, despite the lack of rigorous empirical evidence about how elderly people fare on dialysis. We undertook a comprehensive assessment of outcomes in patients 70 years or over. METHODS We did a 12-month prospective cohort study of outcomes in 221 patients with end-stage renal failure aged 70 years or over recruited from four hospital-based renal units. We assessed 1-year survival in 125 incident patients (70-86 years) and disease burden (hospital admissions, quality of life, costs) in 174 prevalent patients (70-93 years). FINDINGS 1-year survival rates were: 71% overall; 80%, 69%, and 54% in patients 70-74 years, 75-79 years, and 80 years and older, respectively (p=0.008); and 88%, 71%, and 64% in patients with no, one, or two or more comorbid conditions, respectively (p=0.056). Cox regression analyses showed that mortality was significantly associated with age 80 years and older (relative risk 2.79 [95% CI 1.28-6.93]) and peripheral vascular disease (2.83 [1.29-6.17]), but not with diabetes, ischaemic heart disease, cerebrovascular disease, chronic obstructive airways disease, sex, or treatment method. In terms of disease burden, hospital admissions represent a low proportion of costs and was not required by a third of patients, mental quality of life in elderly dialysis patients was similar to that of elderly people in the general population, and the average annual cost per patient of 20802 (US

A systematic review of the staging performance of endoscopic ultrasound in gastro-oesophageal carcinoma

31200) (68% dialysis treatment, 1% transport, 19% inpatient hospital admissions, 12% medications) was within the range of other life-extending interventions. INTERPRETATION Our results suggest that age alone should not be used as a barrier to referral and treatment and emphasise the need to consider the benefits of dialysis in elderly people. Indicators of the ability to benefit from treatment, rather than chronological age, should be used to develop policies that ensure equal access to care for all.

A population-based study of the incidence and outcomes of diagnosed chronic kidney disease

BACKGROUND Endoscopic ultrasound (EUS) may be used for preoperative staging of gastro-oesophageal carcinoma but performance values given in the literature differ. AIMS To identify and synthesise findings from all articles on the performance of EUS in tumour, node, metastasis (TNM) staging of gastro-oesophageal carcinoma. SOURCE Published and unpublished English language literature, 1981–1996. METHODS Data on the staging performance of EUS were retrieved and evaluated. Summary receiver operator characteristic methodology was used for synthesis, and a summary estimate of performance, Q*, obtained. Multiple regression analysis was used to assess study validity and investigate reasons for differences in performance. RESULTS Twenty seven primary articles were assessed in detail. Thirteen supplied results for staging oesophageal cancer, 13 for gastric cancer, and four for cancers at the gastro-oesophageal junction. For gastric T staging, Q*=0.93 (95% confidence interval (CI) 0.91–0.95) and for oesophageal T staging, Q*=0.89 (95% CI 0.88–0.92). For gastro-oesophageal T staging, including cancers at the gastro-oesophageal junction, Q*=0.91 (95% CI 0.89–0.93). Inclusion of cases with non-traversable stenosis was found to slightly reduce staging performance. For N staging, Q*=0.79 (95% CI 0.75–0.83). In articles that compared EUS directly with incremental computed tomography, EUS performed better. None of the variables assessed in the regression analysis was significant using a Bonferroni correction. Three variables (anatomical location, traversability, and blinding) showed strong relationships for future research and validation. CONCLUSIONS EUS is highly effective for discrimination of stages T1 and T2 from stages T3 and T4 for primary gastro-oesophageal carcinomas. The failure rate of EUS from non-traversability of a stenotic cancer may be a limitation in some patient groups.

Prednisolone or Pentoxifylline for Alcoholic Hepatitis

BACKGROUND This study aims to determine the incidence rate and prognosis of detected chronic kidney disease (CKD) in a defined population. METHODS This is a retrospective cohort study of all new cases of CKD from Southampton and South-West Hampshire Health Authority (population base, 405,000) determined by a persistently increased serum creatinine (SCr) level (>or=1.7 mg/dL [>or=150 micromol/L] for 6 months) identified from chemical pathology records. Follow-up was for a mean of 5.5 years for survival, cause of death, and acceptance to renal replacement therapy (RRT). RESULTS The annual incidence rate of detected CKD was 1,701 per million population (pmp; 95% confidence interval [CI], 1,613 to 1,793) and 1,071 pmp (95% CI, 1,001 to 1,147) in those younger than 80 years. There was a steep age gradient; median age was 77 years. The man-woman rate ratio was 1.6 (95% CI, 1.4 to 1.8), with a male excess in all age groups older than 40 years. Incidence increased in areas with greater socioeconomic deprivation. Median survival was 35 months. Age, SCr level, and deprivation index were all significantly associated with survival. Standardized mortality ratios were 36-fold in those aged 16 to 49 years, 12-fold in those aged 50 to 64 years, and more than 2-fold in those older than 65 years. Cardiovascular disease (CVD) was the most common cause of death (46%). Only 4% of patients were accepted to RRT. CONCLUSION The incidence of diagnosed CKD is common, especially in the elderly, and is greater in more deprived areas. Prognosis is poor, with CVD prominent. More research is needed to assess the effectiveness and costs of increasing referral to nephrologists of patients with CKD.

Estimating kidney function in adults using formulae

BACKGROUND Alcoholic hepatitis is a clinical syndrome characterized by jaundice and liver impairment that occurs in patients with a history of heavy and prolonged alcohol use. The short-term mortality among patients with severe disease exceeds 30%. Prednisolone and pentoxifylline are both recommended for the treatment of severe alcoholic hepatitis, but uncertainty about their benefit persists. METHODS We conducted a multicenter, double-blind, randomized trial with a 2-by-2 factorial design to evaluate the effect of treatment with prednisolone or pentoxifylline. The primary end point was mortality at 28 days. Secondary end points included death or liver transplantation at 90 days and at 1 year. Patients with a clinical diagnosis of alcoholic hepatitis and severe disease were randomly assigned to one of four groups: a group that received a pentoxifylline-matched placebo and a prednisolone-matched placebo, a group that received prednisolone and a pentoxifylline-matched placebo, a group that received pentoxifylline and a prednisolone-matched placebo, or a group that received both prednisolone and pentoxifylline. RESULTS A total of 1103 patients underwent randomization, and data from 1053 were available for the primary end-point analysis. Mortality at 28 days was 17% (45 of 269 patients) in the placebo-placebo group, 14% (38 of 266 patients) in the prednisolone-placebo group, 19% (50 of 258 patients) in the pentoxifylline-placebo group, and 13% (35 of 260 patients) in the prednisolone-pentoxifylline group. The odds ratio for 28-day mortality with pentoxifylline was 1.07 (95% confidence interval [CI], 0.77 to 1.49; P=0.69), and that with prednisolone was 0.72 (95% CI, 0.52 to 1.01; P=0.06). At 90 days and at 1 year, there were no significant between-group differences. Serious infections occurred in 13% of the patients treated with prednisolone versus 7% of those who did not receive prednisolone (P=0.002). CONCLUSIONS Pentoxifylline did not improve survival in patients with alcoholic hepatitis. Prednisolone was associated with a reduction in 28-day mortality that did not reach significance and with no improvement in outcomes at 90 days or 1 year. (Funded by the National Institute for Health Research Health Technology Assessment program; STOPAH EudraCT number, 2009-013897-42 , and Current Controlled Trials number, ISRCTN88782125 ).