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Biomedical subjects

Joseph F Collins

Publications and source records attributed to Joseph F Collins.

15 recordsLinked to original sources
PubMed2006

Outcomes in patients having vitreous presentation during cataract surgery who lack capsular support for a nonsutured PC IOL.

PURPOSE: The study's purpose was to determine the effect that lack of capsular support for a nonsutured posterior chamber (PC) intraocular lens IOL has on 1-year postoperative vision in patients suffering vitreous presentation (VP) during extracapsular cataract surgery. DESIGN: The study was a prospective, long-term clinical trial. METHODS: The study was conducted at 19 Department of Veterans Affairs medical centers. Patients having VP during cataract surgery with sufficient capsular support for a nonsutured PC IOL were randomized to receive either a PC IOL (230 patients) or an anterior chamber (AC) IOL (208 patients). Patients having insufficient capsular support (ICS) for a nonsutured PC IOL (143 patients) were prospectively followed in the same fashion. Best-corrected visual acuity (BCVA) at 1 year was obtained by a masked, certified examiner. RESULTS: The ICS group had considerably fewer patients with BCVA of 20/40 or better at 1 year (P < .0001) than the randomized PC IOL group (66.7% vs 91.1%) with a trend (P = .04) for having fewer patients than the randomized AC IOL group (66.7% vs 79.0%). The ICS group had significantly poorer rating of vision at 1 year by study raters, and the patients themselves than either of the randomized VP groups. CONCLUSIONS: The lack of capsular support for the placement of a nonsutured PC IOL after VP during extracapsular cataract surgery or the severity of the complication of VP associated with lack of capsular support would appear to cause visual problems beyond that related to the type of intraocular lens implanted.

Aged↗
PubMed2006

What is the economic value of digoxin therapy in congestive heart failure patients? Results from the DIG trial.

BACKGROUND: The Digitalis Investigation Group (DIG) clinical train randomized 6800 congestive heart failure patients (ejection fraction > or =45%) to a daily regimen of either digoxin or placebo. At 37 months average follow-up, patients in both groups had similar mortality. We determined the incremental costs associated with the use of digoxin in this high-risk population. METHODS AND RESULTS: Hospitalizations and medical costs were compared by using a societal perspective. Hospitalizations were assigned Medicare DRG codes by using descriptive information from the clinical trial. Digoxin use was assigned a cost by using the 1998 average wholesale price as reported by Red Book. On average, there were fewer hospitalizations in digoxin-treated patients. These patients had lower heart failure yet higher non-heart failure hospitalization costs than placebo patients. Digoxin therapy was cost saving versus placebo in only 27% of 1000 bootstrap samples using Medicare costs (mean costs 12,648 dollars vs. 12,362 dollars) and in 44% of samples using commercial carrier costs (mean costs 17,400 dollars vs. 17,306 dollars). How ever, digoxin was cost saving in >50% of samples for several higher-risk patient subgroups. CONCLUSIONS: The use of digoxin therapy versus placebo was associated with reduced hospitalizations. Moreover, the resulting cost-savings could cover the costs of this inexpensive therapy in selected subgroups of higher-risk patients. In the remainder, there is a modest cost associated with this therapy.

Aged↗
PubMed2004

Benefits and harms of doxycycline treatment for Gulf War veterans' illnesses: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: It has been hypothesized that certain Mycoplasma species may cause Gulf War veterans' illnesses (GWVIs), chronic diseases characterized by pain, fatigue, and cognitive symptoms, and that affected patients may benefit from doxycycline treatment. OBJECTIVE: To determine whether a 12-month course of doxycycline improves functional status in Gulf War veterans with GWVIs. DESIGN: A randomized, double-blind, placebo-controlled clinical trial with 12 months of treatment and 6 additional months of follow-up. SETTING: 26 U.S. Department of Veterans Affairs and 2 U.S. Department of Defense medical centers. PARTICIPANTS: 491 deployed Gulf War veterans with GWVIs and detectable Mycoplasma DNA in the blood. INTERVENTION: Doxycycline, 200 mg, or matching placebo daily for 12 months. MEASUREMENTS: The primary outcome was the proportion of participants who improved more than 7 units on the Physical Component Summary score of the Veterans Short Form-36 General Health Survey 12 months after randomization. Secondary outcomes were measures of pain, fatigue, and cognitive function and change in positivity for Mycoplasma species at 6, 12, and 18 months after randomization. RESULTS: No statistically significant differences were found between the doxycycline and placebo groups for the primary outcome measure (43 of 238 participants [18.1%] vs. 42 of 243 participants [17.3%]; difference, 0.8 percentage point [95% CI, -6.5 to 8.0 percentage points]; P > 0.2) or for secondary outcome measures at 1 year. In addition, possible differences in outcomes at 3 and 6 months were not apparent at 9 or 18 months. Participants in the doxycycline group had a higher incidence of nausea and photosensitivity. LIMITATIONS: Adherence to treatment after 6 months was poor. CONCLUSION: Long-term treatment with doxycycline did not improve outcomes of GWVIs at 1 year.

Adult↗
PubMed2004

The effect of vitreous presentation during extracapsular cataract surgery on the postoperative visual acuity at one year.

PURPOSE: The purpose of this study was to determine the effects that vitreous presentation (VP) during extracapsular cataract surgery has on patients' 1-year postoperative vision. DESIGN: The study was a prospective, long-term, clinical trial. METHODS: The study took place at 19 Department of Veterans Affairs medical centers. Patients having VP during cataract surgery and receiving a posterior chamber (PC) intraocular lens (IOL) (230 patients) were prospectively compared with a 5% random sample of nonvitreous presentation (NVP) cataract surgery patients (521 patients). Best-corrected visual acuity (BCVA) at 1 year was obtained by a masked, certified examiner. RESULTS: There was no statistical difference (P = .089) between the VP patients receiving PC IOL and the NVP patients in percentage of patients having BCVA of 20/40 or better at 1 year (91.1% vs 94.9%). There were significantly more PC IOL VP patients than NVP patients with BCVA of 20/50 or worse at some time during the first postoperative year (21.6% vs 10.9%; P = .0003), significantly fewer with BCVA of 20/20 or better at 1 year (27.8% vs 38.8%; P = .013), and significantly more with cystoid macular edema (11.5% vs 3.6%; P = .0002), retinal detachment (4.3% vs 0.2%; P = .0002), and uveitis (3.4% vs 0.6%; P = .012). The NVP patients rated their vision as very good or excellent significantly more often than the VP patients (71% vs 58%; P = .025). CONCLUSIONS: Vitreous presentation during extracapsular cataract surgery leads to somewhat worse overall outcomes in patients, although the majority of patients with VP do reasonably well.

Aged↗
PubMed2004

The Warfarin and Antiplatelet Therapy in Heart Failure trial (WATCH): rationale, design, and baseline patient characteristics.

BACKGROUND: The role of anticoagulation in patients with chronic heart failure has long been an area of interest and controversy. Traditionally the goal of anticoagulation has been to prevent embolic events, but recent trials also demonstrated that oral anticoagulation also prevents vascular events in patients with prior myocardial infarction, who constitute the majority of heart failure patients. Although antiplatelet agents also reduce postinfarction vascular events, few data are available in heart failure patients, and some evidence suggests that aspirin may also have the potential to worsen heart failure morbidity and mortality, possibly by interfering with the effects of angiotensin-converting enzyme inhibitors. Methods and results The Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial was undertaken to determine the optimal antithrombotic agent for heart failure patients. WATCH was a prospective-randomized trial in which symptomatic heart failure patients in sinus rhythm with ejection fractions < or =35% taking angiotensin-converting enzyme inhibitors (unless not tolerated) and diuretics were randomized to open-label warfarin (target International Normalized Ratio 2.5-3.0) or double-blind antiplatelet therapy with aspirin 162 mg or clopidogrel 75 mg. Two primary comparisons were specified: anticoagulation with warfarin versus antiplatelet therapy with aspirin and antiplatelet therapy with clopidogrel versus antiplatelet therapy with aspirin. The primary outcome is the composite of death from all causes, nonfatal myocardial infarction, and nonfatal stroke analyzed as time to first event using the intent-to-treat approach. The secondary endpoint was the broader composite of death from all causes, nonfatal myocardial infarction, non-fatal stroke, and hospitalizations for worsening heart failure, unstable angina pectoris, and systemic or pulmonary artery embolic events. Additional prespecified analyses include heart failure events, coronary events, and resource utilization. CONCLUSIONS: Although the trial was designed to enter 4500 patients, it was terminated 18 months prematurely in June 2003 by the VA Cooperative Study Program because of poor enrollment with a resulting reduction of its power to achieve its original objective. This manuscript describes the study rationale, protocol design, and the baseline characteristics of the 1587 patients who were entered into the study. The WATCH trial will help define the optimal approach to antithrombotic therapy in the contemporary management of patients with chronic heart failure resulting from left ventricular systolic dysfunction.

Adult↗
PubMed2003

Determination of vital status at the end of the DIG trial.

The Digitalis Investigation Group (DIG) trial was a randomized, double-blind placebo-controlled trial whose primary objective was to determine whether digoxin had beneficial, harmful, or no effect on total mortality in patients with heart failure who were in sinus rhythm and whose ejection fraction was </=0.45. The study was designed as a large simple trial with a large number of centers (302) in the United States and Canada, many of which were inexperienced in research. To ensure that the results of the trial would be reported accurately without possible bias due to missing data, the study leadership decided that no outcome results would be reported until the vital status at the end of the study was known for at least 97% of the study participants. Planning for closeout of the study began a year prior to the common end date of December 31, 1995 and included plans for obtaining vital status on December 31, 1995. Participants were given postcards at their final study visit to be completed and mailed on or after January 1, 1996. Of 5602 postcards distributed, 5070 (90.5%) were completed and returned. A contract search agency was hired to locate the remaining participants. Of the total 7788 participants entered into the DIG trial, only 97 participants (1.2%) could not have their vital status as of December 31, 1995 determined. It is recommended that investigators having an outcome measure with a common end date include plans in their protocols for obtaining their measures and activate those plans as early as possible during the course of the study.

Digitalis Glycosides↗
PubMed2003

A comparison of anterior chamber and posterior chamber intraocular lenses after vitreous presentation during cataract surgery: the Department of Veterans Affairs Cooperative Cataract Study.

PURPOSE: To compare the efficacy and safety of anterior chamber (AC) intraocular lenses (IOLs) and posterior chamber (PC) IOLs implanted after vitreous presentation during extracapsular cataract extraction (ECCE). DESIGN: The study was a prospective, long-term, randomized clinical trial conducted at 19 Department of Veterans Affairs medical centers across the United States. METHODS: There were 438 eyes (438 patients) that met preliminary eligibility criteria, suffered vitreous presentation during ECCE (phacoemulsification or classical extracapsular technique), and had sufficient capsular support for a PC IOL without sutures after anterior vitrectomy randomized to either a PC IOL (230 patients) or an AC IOL (208 patients). Patients were examined at 3, 6, and 12 months post-surgery and yearly thereafter. Minimum follow-up was 1 year. The primary outcome measure of best-corrected visual acuity at 1 year was obtained by a masked certified examiner. RESULTS: More PC IOL patients (91%) achieved visual acuity of 20/40 or better at 1 year than AC IOL patients (79%), a highly significant difference (P =.003). There was no significant difference between the two groups for patient's rating of vision or adverse events. Over 84% of the PC IOL patients and over 77% of the AC IOL patients rated their vision as good or better at 1 year as opposed to only 7% giving such ratings before surgery. For at least one rating period during the first year, 13.2% of the combined study patients had cystoid macular edema, 8.5% had posterior capsule opacification, 5.7% had glaucoma, and 3.7% had retinal detachment. CONCLUSION: In the presence of sufficient capsular support, a PC IOL should be implanted after vitreous presentation during ECCE.

Aged↗
PubMed2003

Data and safety monitoring board issues raised in the VA Status Epilepticus Study.

The Department of Veteran Affairs Status Epilepticus Cooperative Study was a randomized, multicenter clinical trial testing four intravenous drug regimens (lorazepam, phenobarbital, phenytoin and diazepam followed by phenytoin) to treat generalized convulsive status epilepticus. During the course of the study, two problems emerged that the study's data and safety monitoring board (DSMB) was required to address: poor recruitment and an unexpected difference in 30-day mortality between treatment groups. By the first annual DSMB meeting, recruitment was only 25.6% of expected. The DSMB recommended placing the study on probation and replacing poorly performing sites. At their second annual meeting, the DSMB recommended approval of proposed changes to the study design contingent on the study leadership removing nonproductive sites. These changes were a 2-year increase in the recruitment period and a change in study design that decreased required sample size. Nonproductive centers were terminated and the approved changes allowed the study to be successfully completed. At the second annual DSMB meeting, an unexpected doubling of mortality rates between drug groups was observed. Although not statistically significant, the finding raised serious concerns for patient safety. The DSMB recommended instituting monthly reporting on mortality and suggested additional analyses for exploring why the differences could be occurring. These analyses indicated that, by chance, older and sicker patients were being randomized to the drugs with the higher mortality rates. By the end of the study, the observed differences in mortality between drug groups had evened out. The DSMB's thoughtful recommendations, support and monitoring ensured that the study was successfully completed without endangering the study patients.

Anticonvulsants↗
PubMed2003

Lessons learned from the DIG trial.

The Digitalis Investigation Group (DIG) trial was the first large simple trial conducted by the National Heart, Lung, and Blood Institute in conjunction with the Department of Veterans Affairs. A large simple trial is a major undertaking. Simplification at the sites requires careful planning and discipline. Lessons learned from the DIG trial were: (1) keep a large simple trial very simple and keep all study procedures very simple; (2) ancillary studies are important and can complement a large simple trial but require careful advanced planning; (3) anticipate special needs when shipping study drugs internationally; (4) regional coordinating centers can be very useful; (5) recruit as many capable sites as possible; (6) provide research-inexperienced sites/investigators with extra help to obtain federalwide assurance statements from the Office for Human Research Protections and institutional review board approvals; (7) adequately reimburse sites for the work completed; (8) maintain investigator enthusiasm; (9) monitor the slow performers and sites with numerous personnel changes; (10) choose an endpoint that is easy to ascertain; (11) keep the trial simple for participants; and (12) plan early for closeout and for activities between the end of the trial and publication of results.

Canada↗
PubMed2003

The role of the data coordinating center in the IRB review and approval process: the DIG trial experience.

Before any clinical trial can begin to recruit patients, participating clinical centers must obtain approval from their institutional review board (IRB). When studies are federally funded, such as by the U.S. Department of Health and Human Services (DHHS), centers must also have or obtain a federal compliance agreement from the Office of Human Research Protections (formerly the Office for Protection from Research Risks [OPRR]). The Digitalis Investigation Group trial was a large, international, double-blind, DHHS-funded randomized trial on the effect of digoxin on mortality in heart failure. Due to the anticipated number of centers (>200), the study's data coordinating center (DCC) was requested to assume additional responsibilities that included: (1) acting as a liaison between the OPRR and all study centers; (2) reviewing and correcting all assurance statements before submission to the OPRR; (3) reviewing and approving all centers' informed consent forms; and (4) helping the many research-inexperienced centers to establish IRBs or to locate an IRB in their region that would accept IRB responsibility for them. Although a heavy burden was placed on the DCC, the IRB and OPRR approval process was probably shortened by many weeks at those centers not already possessing a federal compliance agreement. This enabled the study to be completed on schedule and within budget.

Canada↗
PubMed2003

The use of regional coordinating centers in large clinical trials: the DIG trial.

The Digitalis Investigation Group (DIG) trial was a large simple clinical trial that involved 302 participating centers in the United States and Canada. In order to encourage participation by Canadian investigators, to provide additional help to what were expected to be largely research-inexperienced investigators in Canada, and to provide the study's data coordinating center with resources in Canada to deal with potentially different rules, regulations, and cultural differences, regional coordinating centers were established in four regions of Canada: the maritime provinces, Quebec, Ontario, and western Canada. Canadian centers recruited significantly better than their U.S. counterparts and had slightly better retention and follow-up. While it is not possible to declare that the regional coordinating centers were responsible for this improvement, it is believed that these regional centers did play a role. This role included being able to identify investigators who could be expected to do well, providing one-on-one training and instruction to investigators, and being able to solve problems and implement change in the relatively fewer centers in their regions. The regional coordinating center also reduced the intensity of the workload on the data coordinating center by serving as the primary point of contact for Canadian investigators. The use of regional coordinating centers in studies with a large number of participating centers is highly recommended.

Canada↗
PubMed2003

The role of the data coordinating center in the DIG trial.

The Digitalis Investigation Group (DIG) trial was a large simple trial (LST) begun in 1990 as a collaboration between the National Heart, Lung, and Blood Institute and the Department of Veterans Affairs (VA) Cooperative Studies Program (CSP). Its primary objective was to determine whether digitalis had beneficial, harmful, or no effect on total mortality in patients with congestive heart failure and an ejection fraction < or =0.45. The Perry Point VA CSP Coordinating Center served as the trial's data coordinating center (DCC). The DCC was involved in all phases of the study from planning and design, organization and start-up, and patient recruitment and follow-up through closeout, final analyses, and manuscript preparation. While DCC responsibilities for an LST are basically the same as for other multicenter randomized clinical trials, their size and the inclusion of many inexperienced research sites can add a complexity that the DCC must be prepared to handle from the beginning. This paper describes the role of the DCC in the DIG trial.

Canada↗
PubMed2003

Overview of the DIG trial.

Congestive heart failure is a major public health problem in the United States, Canada, and other Western countries. The Digitalis Investigation Group (DIG) trial was a randomized, double-blind placebo-controlled trial that evaluated the effects of digoxin on all-cause mortality and on hospitalization for heart failure in patients with heart failure and left ventricular ejection fraction < or =0.45 with normal sinus rhythm. It was designed as a large simple trial. There were 6800 patients entered into the main study over a 31.5-month recruitment period at 302 participating centers in the United States and Canada. All patients were followed for a minimum of 28 months. In order for this study to succeed, many groups had to work together successfully. In this supplement, we present practical aspects of organizing and conducting a large simple trial such as DIG.

Canada↗
PubMed2002

The antibiotic treatment trial of Gulf War Veterans' Illnesses: issues, design, screening, and baseline characteristics.

Many veterans who were deployed to the Persian Gulf during the 1990-1991 Gulf War developed multiple unexplained symptoms such as pain, fatigue, and neurocognitive problems. This constellation of symptoms has been termed Gulf War Veterans' Illnesses (GWVI). Although there is no proven explanation for the cause of GWVI, one fairly widespread explanation is systemic Mycoplasma fermentans infection. The Antibiotic Treatment Trial of GWVI is a randomized placebo-controlled trial to determine whether a 1-year course of doxycycline treatment in deployed Gulf War veterans with GWVI and testing as Mycoplasma species positive will improve their overall functional status as measured by the Physical Component Summary of the SF-36V questionnaire. The study of a multisymptom illness such as GWVI is complicated by the nonspecific nature of the illness, the unknown etiology, and the lack of a widely accepted outcome measure. The presumption of mycoplasma infection raises concerns regarding the methodology for determination of mycoplasma infection, the choice of treatment, and the duration of treatment. However, such a presumption allows the formulation of a clear testable hypothesis that can be tested with treatments with known rates of adverse events and known activity against Mycoplasma species. This paper describes the major issues faced by the investigators during planning, the study design, the patient screening results, and the baseline characteristics of the study patients. There were 2712 patients screened for study entry at 26 Department of Veterans Affairs and two Department of Defense medical centers. Of these, 491 met all study entry criteria and were randomized to either 1 year of doxycycline (200 mg/day) or 1 year of placebo. All patients were seen monthly during treatment and at 6 months after the end of treatment. Study patients had a mean age of 41 years and were mostly male (86%), white (64%), married (68%), and employed full-time (71%).

Adult↗