Douglas Y. Rowland

Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials

BACKGROUND Angiotensin-receptor blockers (ARBs) are a widely used drug class approved for treatment of hypertension, heart failure, diabetic nephropathy, and, recently, for cardiovascular risk reduction. Experimental studies implicate the renin-angiotensin system, particularly angiotensin II type-1 and type-2 receptors, in the regulation of cell proliferation, angiogenesis, and tumour progression. We assessed whether ARBs affect cancer occurrence with a meta-analysis of randomised controlled trials of these drugs. METHODS We searched Medline, Scopus (including Embase), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and the US Food and Drug Administration website for studies published before November, 2009, that included any of the seven currently available ARBs. Randomised controlled trials with an ARB given in at least one group, with a follow-up of at least 1 year, and that enrolled at least 100 patients were included. New-cancer data were available for 61,590 patients from five trials. Data on common types of solid organ cancers were available for 68,402 patients from five trials, and data on cancer deaths were available for 93,515 patients from eight trials. FINDINGS Telmisartan was the study drug in 30,014 (85.7%) patients who received ARBs as part of the trials with new cancer data. Patients randomly assigned to receive ARBs had a significantly increased risk of new cancer occurrence compared with patients in control groups (7.2%vs 6.0%, risk ratio [RR] 1.08, 95% CI 1.01-1.15; p=0.016). When analysis was limited to trials where cancer was a prespecified endpoint, the RR was 1.11 (95% CI 1.04-1.18, p=0.001). Among specific solid organ cancers examined, only new lung-cancer occurrence was significantly higher in patients randomly assigned to receive ARBs than in those assigned to receive control (0.9%vs 0.7%, RR 1.25, 1.05-1.49; p=0.01). No statistically significant difference in cancer deaths was observed (1.8%vs 1.6%, RR 1.07, 0.97-1.18; p=0.183). INTERPRETATION This meta-analysis of randomised controlled trials suggests that ARBs are associated with a modestly increased risk of new cancer diagnosis. Given the limited data, it is not possible to draw conclusions about the exact risk of cancer associated with each particular drug. These findings warrant further investigation.

Impact of QRS duration on clinical event reduction with cardiac resynchronization therapy: meta-analysis of randomized controlled trials.

BACKGROUND Cardiac resynchronization therapy (CRT) is effective in reducing clinical events in patients with heart failure and prolonged QRS interval. Studies using surrogate measures and subgroup analysis of large trials suggest that only patients with severely prolonged QRS benefit from CRT. Our objective was to determine whether the effect of CRT on adverse clinical events (eg, death, hospitalizations) is different in patients with moderately (ie, 120 to 149 milliseconds) [corrected] vs severely (ie, ≥150 milliseconds) prolonged QRS duration. METHODS Searches of MEDLINE, SCOPUS, and Cochrane databases were conducted for randomized controlled CRT trials. Trials reporting clinical events according to different QRS ranges were identified. Five randomized trials fulfilling the inclusion criteria (total patients, n = 5813) were included in the meta-analysis. RESULTS In patients with severely prolonged QRS, there was a reduction in composite clinical events with CRT (risk ratio, 0.60; 95% confidence interval [CI], 0.53-0.67) (P < .001). In contrast, there was no benefit of CRT in patients with moderately prolonged QRS (RR, 0.95; 95% CI, 0.82-1.10) (P = .49), resulting in a significantly different impact of CRT in the 2 QRS groups (P < .001). There was a significant relationship between baseline QRS duration and risk ratio (P < .001) with benefit of CRT appearing at a QRS of approximately 150 milliseconds and above. The differential response of the 2 QRS groups was evident for all New York Heart Association classes. CONCLUSIONS Cardiac resynchronization therapy was effective in reducing adverse clinical events in patients with heart failure and a baseline QRS interval of 150 milliseconds or greater, but CRT did not reduce events in patients with a QRS of less than 150 milliseconds. These findings have implications for the selection of patients for CRT.

Effect of QRS morphology on clinical event reduction with cardiac resynchronization therapy: meta-analysis of randomized controlled trials.

BACKGROUND Cardiac resynchronization therapy (CRT) is effective in reducing clinical events in systolic heart failure patients with a wide QRS. Previous retrospective studies suggest only patients with QRS prolongation due to a left bundle-branch block (LBBB) benefit from CRT. Our objective was to examine this by performing a meta-analysis of all randomized controlled trials of CRT. METHODS Systematic searches of MEDLINE and the Food and Drug Administration official website were conducted for randomized controlled CRT trials. Trials reporting adverse clinical events (eg, all-cause mortality, heart failure hospitalizations) according to QRS morphology were included in the meta-analysis. RESULTS Four randomized trials totaling 5,356 patients met the inclusion criteria. In patients with LBBB at baseline, there was a highly significant reduction in composite adverse clinical events with CRT (RR = 0.64 [95% CI (0.52-0.77)], P = .00001). However no such benefit was observed for patients with non-LBBB conduction abnormalities (RR = 0.97 [95% CI (0.82-1.15)], P = .75). When examined separately, there was no benefit in patients with right-bundle branch block (RR = 0.91 [95% CI (0.69-1.20)], P = .49) or non-specific intraventricular conduction delay (RR = 1.19 [95% CI (0.87-1.63)], P = .28). There was no heterogeneity among the clinical trials with regards to the lack of benefit in non-LBBB patients (I(2) = 0%). When directly compared, the difference in effect of CRT between LBBB versus non-LBBB patients was highly statistically significant (P = .0001 by heterogeneity analysis). CONCLUSIONS While CRT was very effective in reducing clinical events in patients with LBBB, it did not reduce such events in patients with wide QRS due to other conduction abnormalities.

Prognostic Factors in Vitrectomy for Epiretinal Membranes of the Macula

A retrospective multivariate analysis of 264 consecutive cases of vitrectomy for removal of epiretinal membranes of the macula was performed. Two main preoperative prognostic factors were identified that were associated with the visual outcome of surgery: (1) the preoperative visual acuity, and (2) the duration of blurred vision before surgery. Discriminant functions constructed using these two factors allowed correct classification of eyes into an outcome group with good visual acuity with a 69% accuracy, and an 80% accuracy in classifying eyes into a group showing significant improvement in the level of visual acuity. Eyes that began with vision better than 20/100 tended to have slightly better postoperative visions than eyes with poorer preoperative visual acuity. However, eyes with worse preoperative vision tended to improve the greatest amount after surgery. Eyes with a longer history of blurred vision had poorer visual acuity after surgery and also less improvement in vision. Other statistically significant prognostic factors were identified; however, they did not appreciably improve the accuracy of the discriminant function in predicting visual outcome.

Lifetime Histories of Trauma among Pathological Gamblers

This study extends the work completed with pathological gamblers and substance abusers, looking at associations between a history of trauma and comorbid substance dependence, impulsivity, measures of problem severity, and personality variables. We studied 111 patients admitted to the gambling treatment program at the Brecksville VA Medical Center and found that 64% of gamblers reported a history of emotional trauma; 40.5%, physical trauma; and 24.3%, sexual trauma. Most of this trauma occurred in childhood. A history of trauma was associated with a greater relative frequency of suicide attempts and drug and alcohol dependence, more severe scores in measures of psychiatric distress, and limited effects on personality functioning.

Early Follow-up of Reverse Total Shoulder Arthroplasty in Patients Sixty Years of Age or Younger

BACKGROUND Reverse shoulder arthroplasty (RSA) is an accepted treatment that provides reproducible results in the treatment of shoulder arthritis and rotator cuff deficiency. Concerns over the longevity of the prosthesis have resulted in this procedure being reserved for the elderly. There are limited data in the literature with regard to outcomes in younger patients. We report on the early outcomes of RSA in a group of patients who were sixty years or younger and who were followed for a minimum of two years. METHODS A retrospective multicenter review of sixty-six patients (sixty-seven RSAs) with a mean age of 52.2 years was performed. The indications included rotator cuff insufficiency (twenty-nine), massive rotator cuff disorder with osteoarthritis (eleven), failed primary shoulder arthroplasty (nine), rheumatoid arthritis (six), posttraumatic arthritis (four), and other diagnoses (eight). Forty-five shoulders (67%) had at least one prior surgical intervention, and thirty-one shoulders (46%) had multiple prior surgical procedures. RESULTS At a mean follow-up time of 36.5 months, mean active forward elevation of the arm as measured at the shoulder improved from 54.6° to 134.0° and average active external rotation improved from 10.0° to 19.6°. A total of 81% of patients were either very satisfied or satisfied. The mean American Shoulder and Elbow Surgeons (ASES) score and visual analog scale (VAS) score for pain improved from 40.0 to 72.4 and 7.5 to 3.0, respectively. The ability to achieve postoperative forward arm elevation of at least 100° was the only significant predictor of overall patient satisfaction (p < 0.05) that was identified in this group. There was a 15% complication rate postoperatively, and twenty-nine shoulders (43%) had evidence of scapular notching at the time of the latest follow-up. CONCLUSIONS RSA as a reconstructive procedure improved function at the time of short-term follow-up in our young patients with glenohumeral arthritis and rotator cuff deficiency. Objective outcomes in our patient cohort were similar to those in previously reported studies. However, overall satisfaction was much lower in this patient population (81%) compared with that in the older patient population as reported in the literature (90% to 96%).

Validation of a telephone cognitive assessment battery

OBJECTIVE: To present and evaluate an instrument, the Telephone Cognitive Assessment Battery (TCAB), designed to be administered over the telephone to assess the cognitive status of older individuals. The TCAB addresses mental status, reasoning and executive ability, primary and secondary memory, and language. It consists of six neuropsychological tests and takes approximately 15 to 20 minutes to complete.

On the Use of Surrogate Respondents for Controls in a Case-Control Study of Alzheimer's Disease

OBJECTIVE: To examine the presence and extent of bias introduced by using surrogate respondents for healthy controls in a case‐control study of Alzheimers disease (AD).

Statistical certification of eradication of poliomyelitis in the Americas.

The last confirmed case of paralytic poliomyelitis due to indigenous wild poliovirus in the Americas occurred in Peru in 1991. In 1994 the International Commission on Polio Eradication of the Pan American Health Organization (PAHO) deemed eradication of polio from the area to have occurred, based on its strategic efforts and the observed results. A mathematical model is presented here which relates the time elapsed since that last detected case of paralytic poliomyelitis caused by wild poliovirus to the probability that the transmission of indigenous wild poliovirus has been stopped. The appropriateness of applying the model to various geographical areas of the Americas is investigated using data about the occurrence of confirmed cases of polio since 1984, the time of the eradication initiative adopted by PAHO. The model suggests that if four year have elapsed since the last reported confirmed case of polio caused by wild poliovirus, and no other confirmed cases have been identified, the probability of undetected indigenous wild poliovirus transmission is less than 5%. An important assumption is that the eradication strategy implemented by PAHO has yielded steady improvements. A consequence of this approach is that the annual probabilities of persistence given by the model are conservative, in the sense of being higher than the true, but unknown a priori probabilities, and more so with each passing year. It is thus seen that the model results are compatible with the conclusion reached by PAHO in 1994. The model takes into account the intensity of surveillance of each country in the region, measured by the corresponding rates of acute flaccid paralysis (AFP). Because importations of wild poliovirus may occur from other regions of the world, surveillance efforts are being maintained in the Americas until global eradication has been achieved.

Use of Fibrinolytic Agents to Coat Wire Implants to Decrease Infection: An Animal Model

RATIONALE AND OBJECTIVES. Infection is a serious complication of metallic prosthesis implantation and may necessitate removal of the prosthesis. This study uses an animal model to evaluate the effects of coating stainless steel wire implants with fibrinolytic agents to prevent infection after bacterial contamination. METHODS. Three types of steel wire implants were used: plain stainless steel, heparin-coated steel, and urokinase-heparin- coated steel. Wire implants were incubated in a known concentration of Staphylococcus epidermidis and placed into the subcutaneous tissues of three groups of anesthetized hamsters. The implants and surrounding tissues were excised after 1 week and submitted for quantitative cultures. RESULTS. Using 100 organisms as the upper allowable limit to categorize abscesses as noninfected, the following rates of noninfectivity were observed: group 1 (control), 0% noninfected; group 2 (heparin-coated wire), 40% noninfected; and group 3 (urokinasc-heparin-coated wire), 50% noninfected. The noninfectivity rates of groups 2 and 3 were significantly higher than the rate of group 1 (P < 0.001). There was no significant difference between groups 2 and 3 (P=0.19). CONCLUSIONS.Both the heparin-coated and urokinase-heparin-coated wire exhibited significantly decreased infection rates compared with uncoated wire; the heparin coating may inhibit bacterial adherence. The urokinase coating of the heparin-coated to further decrease the infection rate, but not to a statistically significant degree.