James Lewsey

Treatment of Type 2 Diabetes and Outcomes in Patients With Heart Failure: A Nested Case–Control Study From the U.K. General Practice Research Database

OBJECTIVE Diabetes and heart failure commonly coexist, and prior studies have suggested better outcomes with metformin than other antidiabetic agents. We designed this study to determine whether this association reflects a beneficial effect of metformin or a harmful effect of other agents. RESEARCH DESIGN AND METHODS We performed a case-control study nested within the U.K. General Practice Research Database cohort in which diagnoses were assigned by each patients primary care physician. Case subjects were patients 35 years or older, newly diagnosed with both heart failure and diabetes after January 1988, and who died prior to October 2007. Control subjects were matched to case subjects based on age, sex, clinic site, calendar year, and duration of follow-up. Analyses were adjusted for comorbidities, A1C, renal function, and BMI. RESULTS The duration of concurrent diabetes and heart failure was 2.8 years (SD 2.6) in our 1,633 case subjects and 1,633 control subjects (mean age 78 years, 53% male). Compared with patients who were not exposed to antidiabetic drugs, the current use of metformin monotherapy (adjusted odds ratio 0.65 [0.48–0.87]) or metformin with or without other agents (0.72 [0.59–0.90]) was associated with lower mortality; however, use of other antidiabetic drugs or insulin was not associated with all-cause mortality. Conversely, the use of ACE inhibitors/angiotensin receptor blockers (0.55 [0.45–0.68]) and β-blockers (0.76 [0.61–0.95]) were associated with reduced mortality. CONCLUSIONS Our results confirm the benefits of trial-proven anti-failure therapies in patients with diabetes and support the use of metformin-based strategies to lower glucose.

Long-term trends in first hospitalization for heart failure and subsequent survival between 1986 and 2003: a population study of 5.1 million people.

Background— We examined whether population-level hospitalization rates for heart failure (HF) and subsequent survival have continued to improve since the turn of the century. We also examined trends in the prescribing of evidence-based pharmacological treatment for HF. Methods and Results— All patients in Scotland hospitalized with a first episode of HF between 1986 and 2003 were followed up until death or the end of 2004. Prescriptions of evidence-based treatments issued from 1997 to 2003 by a sample of primary care practices were also examined. A total of 116 556 individuals (52.6% women) had a first hospital discharge for HF. Age-adjusted first hospitalization rates for HF (per 100 000; 95% CI in parentheses) rose from 124 (119 to 129) in 1986 to 162 (157 to 168) in 1994 and then fell to 105 (101 to 109) in 2003 in men; in women, they rose from 128 (123 to 132) in 1986 to 160 (155 to 165) in 1993, falling to 101 (97 to 105) in 2003. Case-fatality rates fell steadily over the period. Adjusted 30-day case-fatality rates fell after discharge (adjusted odds [2003 versus 1986] 0.59 [95% CI 0.45 to 0.63] in men and 0.77 [95% CI 0.67 to 0.88] in women). Adjusted 1- and 5-year survival improved similarly. Median survival increased from 1.33 to 2.34 years in men and from 1.32 to 1.79 years in women. Age-adjusted prescribing rates for angiotensin-converting enzyme inhibitors, β-blockers, and spironolactone increased from 1997 to 2003 (all P<0.0001 for trend). Conclusions— After rising between 1986 and 1994, rates of first hospitalization for HF declined. Case-fatality rates also fell. Prescribing rates for HF therapies increased from 1997 to 2003. These findings suggest that improvements in the prevention and treatment of HF may have had progressive, sustained effects on outcomes at the population level; however, prognosis remains poor in HF.

The role of pain and function in determining patient satisfaction after total knee replacement. Data from the National Joint Registry for England and Wales.

A postal questionnaire was sent to 10,000 patients more than one year after their total knee replacement (TKR). They were assessed using the Oxford knee score and were asked whether they were satisfied, unsure or unsatisfied with their TKR. The response rate was 87.4% (8231 of 9417 eligible questionnaires) and a total of 81.8% (6625 of 8095) of patients were satisfied. Multivariable regression modelling showed that patients with higher scores relating to the pain and function elements of the Oxford knee score had a lower level of satisfaction (p < 0.001), and that ongoing pain was a stronger predictor of this. Female gender and a primary diagnosis of osteoarthritis were found to be predictors of lower levels of patient satisfaction. Differences in the rate of satisfaction were also observed in relation to age, the American Society of Anesthesiologists grade and the type of prosthesis. This study has provided data on the Oxford knee score and the expected levels of satisfaction at one year after TKR. The results should act as a benchmark of practice in the United Kingdom and provide a baseline for peer comparison between institutions.

Effects of the Oral Direct Renin Inhibitor Aliskiren in Patients With Symptomatic Heart Failure

Background—Loss of negative feedback inhibition of renin release during chronic treatment with an angiotensin-converting enzyme (ACE) inhibitor leads to a compensatory rise in renin secretion and downstream components of the renin-angiotensin-aldosterone (RAAS) cascade. This may overcome ACE inhibition but should be blocked by a direct renin inhibitor. We studied the effects of adding the direct renin inhibitor aliskiren to an ACE inhibitor in patients with heart failure. Methods and Results—Patients with New York Heart Association class II to IV heart failure, current or past history of hypertension, and plasma brain natriuretic peptide (BNP) concentration >100 pg/mL who had been treated with an ACE inhibitor (or angiotensin receptor blocker) and β-blocker were randomized to 3 months of treatment with placebo (n=146) or aliskiren 150 mg/d (n=156). The primary efficacy outcome was the between-treatment difference in N-terminal pro-BNP (NT-proBNP). Patients’ mean age was 68 years, mean ejection fraction was 31%, and mean±SD systolic blood pressure was 129±17.4 mm Hg. Sixty-two percent of the patients were in New York Heart Association functional class II, and 33% were taking an aldosterone antagonist. Plasma NT-proBNP rose by 762±6123 pg/mL with placebo and fell by 244±2025 pg/mL with aliskiren (P=0.0106). BNP and urinary (but not plasma) aldosterone were also reduced by aliskiren. Clinically important differences in blood pressure and biochemistry were not seen between aliskiren and placebo. Conclusions—Addition of aliskiren to an ACE inhibitor (or angiotensin receptor blocker) and β-blocker had favorable neurohumoral effects in heart failure and appeared to be well tolerated.

Key messages from the National Prospective Tonsillectomy Audit.

Objectives: Investigation of the occurrence of postoperative hemorrhage after tonsillectomy and risk factors for these complications.

Pretransplant MELD score and post liver transplantation survival in the UK and Ireland

It has been shown that the model for end‐stage liver disease (MELD) score is an accurate predictor of survival in patients with liver disease without transplantation. Four recent studies carried out in the United States have demonstrated that the MELD score obtained immediately prior to transplantation is also associated with post‐transplant patient survival. Our aim was to evaluate how accurately the MELD score predicts 90‐day post‐transplant survival in adult patients with chronic liver disease in the UK and Ireland. The UK and Ireland Liver Transplant Audit has data on all liver transplants since 1994. We studied survival of 3838 adult patients after first elective liver transplantation according to United Network for Organ Sharing categories of their MELD scores (≤ 10, 11–18, 19–24, 25–35, ≥36). The overall survival at 90‐days was 90.2%. The 90‐day survival varied according to the United Network for Organ Sharing MELD categories (92.6%, 91.9%, 89.7%, 89.7%, and 70.8%, respectively; P < 0.01). Therefore, only those patients with a MELD score of 36 or higher (3% of the patients) had a survival that was markedly lower than the rest. As a consequence, the ability of the MELD score to discriminate between patients who were dead or alive was poor (c‐statistic 0.58). Re‐estimating the coefficients in the MELD regression model, even allowing for nonlinear relationships, did not improve its discriminatory ability. In conclusion, in the UK and Ireland the MELD score is significantly associated with post‐transplant survival, but its predictive ability is poor. These results are in agreement with results found in the United States. Therefore, the most appropriate system to support patient selection for transplantation will be one that combines a pretransplant survival model (e.g., MELD score) with a properly developed post‐transplant survival model. (Liver Transpl 2004;10:903–907.)

Video assisted thoracic surgery for treatment of pneumothorax and lung resections: systematic review of randomised clinical trials

Abstract Objectives To determine if video assisted thoracic surgery is associated with better clinical outcomes than thoracotomy for three common procedures: surgery for pneumothorax, minor resections, and lobectomy. Design Systematic review of randomised clinical trials. Data sources Medline, Embase, Cochrane database of systematic reviews, Cochrane controlled trials register. Reference lists of relevant articles and reviews. Methods Criteria for inclusion were random allocation of patients and no concurrent use of another experimental medication or device. At least two authors performed and confirmed data abstraction and analyses. Information on quality of trials, demographics, frequency of the events, and numbers randomised were collected. Results 12 trials randomised 670 patients. Video assisted thoracic surgery was associated with shorter length of stay (reduction ranged from 1.0 to 4.2 days) and less pain or use of pain medication than thoracotomy in the five out of seven trials in which the technique was used for pneumothorax or minor lung resection. In the treatment of pneumothorax, video assisted thoracic surgery was associated with substantially fewer recurrences than pleural drainage in two trials (from 20 to 53 events prevented per 100 treated patients). No substantial advantages were observed for video assisted thoracic surgery in lobectomies. Conclusions Video assisted thoracic surgery is associated with better outcomes and seems to have a complication profile comparable with that of thoracotomy for the treatment of pneumothorax and minor resections. As for lobectomy, further studies are needed to determine how it compares with thoracotomy.

The impact of serum sodium concentration on mortality after liver transplantation: A cohort multicenter study

Modification of the current allocation system for donor livers in the United States to incorporate recipient serum sodium concentration ([Na]) has recently been proposed. However, the impact of this parameter on posttransplantation mortality has not been previously examined in a large risk‐adjusted analysis. We assessed the effect of recipient [Na] on the survival of all adults with chronic liver disease who received a first single organ liver transplant in the UK and Ireland during the period March 1, 1994 to March 31, 2005 (n = 5,152) at 3 years, during the first 90 days, and beyond the first 90 days, adjusting for a wide range of recipient, donor, and graft characteristics. Compared to those with normal [Na] (135–145 meq/L; n = 3,066), severely hyponatremic recipients ([Na] <130 meq/L, n = 541), had a higher risk‐adjusted mortality at 3 years (hazard ratio [HR] 1.28; 95% confidence interval [CI], 1.04–1.59; P < 0.02). The excess mortality was, however, confined to the first 90 days (HR 1.55; 95% CI, 1.18–2.04; P < 0.002) with no significant difference thereafter. This was also true for hypernatremic recipients ([Na] >145 meq/L, n = 81), who had an even greater risk‐adjusted mortality compared to normonatremic recipients (overall: HR 1.85; 95% CI, 1.25–2.73; P < 0.002; ≤90 days: HR 2.29; 95% CI, 1.42–3.70; P < 0.001; >90 days: HR 1.12; 95% CI, 0.55–2.29; P = 0.8), whereas mildly hyponatremic recipients ([Na] 130–134 meq/L, n = 1,127) had similar risk‐adjusted mortality to those with normal [Na] at the same time points. In conclusion, recipient [Na] is an independent predictor of death following liver transplantation. Attempts to correct the [Na] toward the normal reference range are an important aspect of pretransplantation management. Liver Transpl 13:1115–1124, 2007.

Sex differences in incidence, mortality, and survival in individuals with stroke in Scotland, 1986 to 2005.

Background and Purpose— The aim of this study was to examine the effect of sex across different age groups and over time for stroke incidence, 30-day case-fatality, and mortality. Methods— All first hospitalizations for stroke in Scotland (1986 to 2005) were identified using linked morbidity and mortality data. Age-specific rate ratios (RRs) for comparing women with men for both incidence and mortality were modeled with adjustment for study year and socioeconomic deprivation. Logistic regression was used to model 30-day case-fatality. Results— Women had a lower incidence of first hospitalization than men and size of effect varied with age (55 to 64 years, RR=0.65, 95% CI 0.63 to 0.66; ≥85 years, RR=0.94, 95% CI 0.91 to 0.96). Women aged 55 to 84 years had lower mortality than men and again size of effect varied with age (65 to 74 years, RR=0.79, 95% CI 0.76 to 0.81); 75 to 84 years, RR=0.94, 95% CI 0.92 to 0.95). Conversely, women aged ≥85 years had 15% higher stroke mortality than men (RR=1.15, 95% CI 1.12 to 1.18). Adjusted risk of death within 30 days was significantly higher in women than men, and this difference increased over the 20-year period in all age groups (adjusted OR in 55 to 64 year olds 1.23, 95% CI 1.14 to 1.33 in 1986 and 1.51, 95% CI 1.39 to 1.63 in 2005). Conclusions— We observed lower rates of incidence and mortality in younger women than men. However, higher numbers of older women in the population mean that the absolute burden of stroke is greater in women. Short-term case-fatality is greater in women of all ages and, worryingly, these differences have increased from 1986 to 2005.

Characterization of subgroups of heart failure patients with preserved ejection fraction with possible implications for prognosis and treatment response

Patients with heart failure and preserved ejection fraction (HFpEF) have a poor prognosis, and no therapies have been proven to improve outcomes. It has been proposed that heart failure, including HFpEF, represents overlapping syndromes that may have different prognoses. We present an exploratory study of patients enrolled in the Irbesartan in Heart Failure with Preserved Ejection Fraction Study (I‐PRESERVE) using latent class analysis (LCA) with validation using the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM)‐Preserved study to identify HFpEF subgroups.