Outcomes of special histotypes of breast cancer after adjuvant endocrine therapy with letrozole or tamoxifen in the monotherapy cohort of the BIG 1-98 trial.

BACKGROUND: We investigated the outcomes of postmenopausal women with hormone receptor-positive, early breast cancer with special histotypes (mucinous, tubular, or cribriform) enrolled in the monotherapy cohort of the BIG 1-98 trial. PATIENTS AND METHODS: The intention-to-treat BIG 1-98 monotherapy cohort (5 years of therapy with tamoxifen or letrozole) included 4922 women, of whom 4091 had central pathology review. Histotype groups were defined as: mucinous (N = 100), tubular/cribriform (N = 83), ductal (N = 3257), and other (N = 651). Of 183 women with either mucinous or tubular/cribriform tumors, 96 were randomly assigned to letrozole and 87 to tamoxifen. Outcomes assessed were disease-free survival (DFS), overall survival (OS), breast cancer-free interval (BCFI), and distant recurrence-free interval (DRFI). Median follow-up in the analytic cohort was 8.1 years. RESULTS: Women with tubular/cribriform breast cancer had the best outcomes for all end points compared with the other three histotypes, and had less breast cancer recurrence (97.5% 5-year BCFI) than those with mucinous (93.5%), ductal (88.9%), or other (89.9%) histotypes. Patients with mucinous or tubular/cribriform carcinoma had better DRFI (5-year rates 97.8% and 98.8%, respectively) than those with ductal (90.9%) or other (92.1%) carcinomas. Within the subgroup of women with special histotypes, we observed a nonsignificant increase in the hazard of breast cancer recurrence with letrozole [hazard (letrozole versus tamoxifen): 3.31, 95% confidence interval 0.94-11.7; P = 0.06]. CONCLUSIONS: Women with mucinous or tubular/cribriform breast cancer have better outcomes than those with other histotypes, although the observation is based on a limited number of events. In postmenopausal women with these histotypes, the magnitude of the letrozole advantage compared with tamoxifen may not be as large in patients with mucinous or tubular/cribriform disease. CLINICALTRIALSGOV: NCT00004205.

Symptoms of endocrine treatment and outcome in the BIG 1-98 study.

There may be a relationship between the incidence of vasomotor and arthralgia/myalgia symptoms and treatment outcomes for postmenopausal breast cancer patients with endocrine-responsive disease who received adjuvant letrozole or tamoxifen. Data on patients randomized into the monotherapy arms of the BIG 1-98 clinical trial who did not have either vasomotor or arthralgia/myalgia/carpal tunnel (AMC) symptoms reported at baseline, started protocol treatment and were alive and disease-free at the 3-month landmark (n = 4,798) and at the 12-month landmark (n = 4,682) were used for this report. Cohorts of patients with vasomotor symptoms, AMC symptoms, neither, or both were defined at both 3 and 12 months from randomization. Landmark analyses were performed for disease-free survival (DFS) and for breast cancer free interval (BCFI), using regression analysis to estimate hazard ratios (HR) and 95 % confidence intervals (CI). Median follow-up was 7.0 years. Reporting of AMC symptoms was associated with better outcome for both the 3- and 12-month landmark analyses [e.g., 12-month landmark, HR (95 % CI) for DFS = 0.65 (0.49-0.87), and for BCFI = 0.70 (0.49-0.99)]. By contrast, reporting of vasomotor symptoms was less clearly associated with DFS [12-month DFS HR (95 % CI) = 0.82 (0.70-0.96)] and BCFI (12-month DFS HR (95 % CI) = 0.97 (0.80-1.18). Interaction tests indicated no effect of treatment group on associations between symptoms and outcomes. While reporting of AMC symptoms was clearly associated with better DFS and BCFI, the association between vasomotor symptoms and outcome was less clear, especially with respect to breast cancer-related events.

A randomized controlled trial of oral melatonin supplementation and breast cancer biomarkers.

We examined compliance with and the effects of melatonin supplementation on breast cancer biomarkers (estradiol, insulin-like growth factor I (IGF-1), insulin-like growth factor-binding protein 3 (IGFBP-3), and the IGF-1/IGFBP-3 ratio) in postmenopausal breast cancer survivors. In a double-blind, placebo-controlled study, postmenopausal women with a prior history of stages 0-III breast cancer who had completed active cancer treatment (including hormonal therapy) were randomly assigned to either 3 mg oral melatonin (n = 48) or placebo daily for 4 months. Plasma samples were collected at baseline and after the completion of the intervention. The primary endpoints were compliance and change in estradiol and IGF-1/IGFBP-3 levels. Ninety-five women were randomized (48 to melatonin and 47 to placebo). Eighty-six women (91%) completed the study and provided pre- and postintervention bloods. Melatonin was well tolerated without any grade 3/4 toxicity and compliance was high (89.5%). Overall, among postmenopausal women with a prior history of breast cancer, a 4-month course of 3 mg melatonin daily did not influence circulating estradiol, IGF-1, or IGFBP-3 levels. Compliance was comparable between the two groups. Short-term melatonin treatment did not influence the estradiol and IGF-1/IGBBP-3 levels. Effects of longer courses of melatonin among premenopausal women are unknown. Low baseline estradiol levels in our study population may have hindered the ability to detect any further estradiol-lowering effects of melatonin.

Bone mineral density in breast cancer patients treated with adjuvant letrozole, tamoxifen, or sequences of letrozole and tamoxifen in the BIG 1-98 study (SAKK 21/07).

BACKGROUND: The risk of osteoporosis and fracture influences the selection of adjuvant endocrine therapy. We analyzed bone mineral density (BMD) in Swiss patients of the Breast International Group (BIG) 1-98 trial [treatment arms: A, tamoxifen (T) for 5 years; B, letrozole (L) for 5 years; C, 2 years of T followed by 3 years of L; D, 2 years of L followed by 3 years of T]. PATIENTS AND METHODS: Dual-energy X-ray absorptiometry (DXA) results were retrospectively collected. Patients without DXA served as control group. Repeated measures models using covariance structures allowing for different times between DXA were used to estimate changes in BMD. Prospectively defined covariates were considered as fixed effects in the multivariable models. RESULTS: Two hundred and sixty-one of 546 patients had one or more DXA with 577 lumbar and 550 hip measurements. Weight, height, prior hormone replacement therapy, and hysterectomy were positively correlated with BMD; the correlation was negative for letrozole arms (B/C/D versus A), known osteoporosis, time on trial, age, chemotherapy, and smoking. Treatment did not influence the occurrence of osteoporosis (T score < -2.5 standard deviation). CONCLUSIONS: All aromatase inhibitor regimens reduced BMD. The sequential schedules were as detrimental for bone density as L monotherapy.

Benefits and adverse effects of endocrine therapy.

Endocrine-responsive tumors that are small and without nodal involvement (i.e. tumors classified as pT1 pN0) are a heterogeneous group of tumors that are associated with a low risk of relapse in the majority of the cases. Therefore, the costs and benefits of adjuvant endocrine therapy should be carefully considered within this subgroup of patients. Treatment decisions should take into consideration co-morbidities as well as the presence of other classical risk factors such as HER2 overexpression or extensive peritumoral vascular invasion. Tamoxifen or tamoxifen plus ovarian function suppression should be considered as proper endocrine therapies in premenopausal patients. Ovarian function suppression alone or ovarian ablation might also be considered adequate in selected patients (e.g. very low-risk patients, in the presence of co-morbidities or patient preference). An aromatase inhibitor should form part of standard endocrine therapy for most postmenopausal women with receptor-positive breast cancer, although patients at low risk or with co-morbid musculoskeletal or cardiovascular risk factors may be considered suitable for tamoxifen alone. Tailored endocrine treatments should be considered in patients with endocrine-responsive tumors classified as pT1 pN0. Issues focusing on safety, quality of life and subjective side effects should be routinely discussed.

Adverse prognostic value of peritumoral vascular invasion: is it abrogated by adequate endocrine adjuvant therapy? Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy for early breast cancer.

BACKGROUND: Peritumoral vascular invasion (PVI) may assist in assigning optimal adjuvant systemic therapy for women with early breast cancer. PATIENTS AND METHODS: Patients participated in two International Breast Cancer Study Group randomized trials testing chemoendocrine adjuvant therapies in premenopausal (trial VIII) or postmenopausal (trial IX) node-negative breast cancer. PVI was assessed by institutional pathologists and/or central review on hematoxylin-eosin-stained slides in 99% of patients (analysis cohort 2754 patients, median follow-up >9 years). RESULTS: PVI, present in 23% of the tumors, was associated with higher grade tumors and larger tumor size (trial IX only). Presence of PVI increased locoregional and distant recurrence and was significantly associated with poorer disease-free survival. The adverse prognostic impact of PVI in trial VIII was limited to premenopausal patients with endocrine-responsive tumors randomized to therapies not containing goserelin, and conversely the beneficial effect of goserelin was limited to patients whose tumors showed PVI. In trial IX, all patients received tamoxifen: the adverse prognostic impact of PVI was limited to patients with receptor-negative tumors regardless of chemotherapy. CONCLUSION: Adequate endocrine adjuvant therapy appears to abrogate the adverse impact of PVI in node-negative disease, while PVI may identify patients who will benefit particularly from adjuvant therapy.

Osteoporosis and risk of fracture in men with spinal cord injury.

STUDY DESIGN: Cross-sectional study to evaluate bone mineral density (BMD) and fracture history after spinal cord injury (SCI). OBJECTIVES: To determine frequency of osteoporosis and fractures after SCI, correlate extent of bone loss with frequency of fractures after SCI, and determine fracture risk in SCI patients. SETTING: The Hines Veterans Affairs Hospital in Hines, Illinois, USA. METHODS: Femoral neck BMD was measured in 41 individuals with a history of traumatic or ischemic SCI using dual-energy X-ray absorptiometry (DEXA Lunar Whole Body Densitometer Model). RESULTS: Twenty-five patients (61%) met the World Health Organization (WHO) criteria for osteoporosis, eight (19.5%) were osteopenic, and eight (19.5%) were normal. Fracture after SCI had occurred in 14 patients (34%). There were significant differences between the femoral neck BMD and SCI duration in patients with a fracture history compared to those without. For patients in the same age group, each 0.1 gm/cm(2) and each unit of standard deviation (SD) (t-value) decrement of BMD at the femoral neck increased the risk of fracture 2.2 and 2.8 times, respectively. Considered simultaneously with age, duration of SCI, and level of SCI, BMD was the only significant predictor of the number of fractures. CONCLUSION: Osteoporosis and an increased frequency of fractures occur after SCI. Measurement of femoral neck BMD can be used to quantify fracture risk in SCI patients.

Multisite randomized controlled trials in health services research: scientific challenges and operational issues.

Although well-designed randomized controlled trials (RCT) provide the strongest evidence regarding causation, only relatively recently have they been used by health services researchers to study the organization, delivery, quality, and outcomes of care. More recent yet is the extension of multisite RCTs to health services research. Such studies offer numerous methodological advantages over single-site trials: (1) enhanced external validity; (2) greater statistical power when studying conditions with a low incidence or prevalence, small event rate in the outcome (eg, mortality), and/or large variance in the outcome (eg, health care costs); and (3) rapid recruitment to provide health care organizations and policy makers with timely results. This paper begins by outlining the advantages of multisite RCTs over single-site trials. It then discusses both scientific challenges (ie, standardizing eligibility criteria, defining and standardizing the intervention, defining usual care, standardizing the data collection protocol, blinded outcome assessment, data management and analysis, measuring health care costs) and operational issues (ie, site selection, randomization procedures, patient accrual, maintaining enthusiasm, oversight) posed by multisite RCTs in health services research. Recommendations are offered to health services researchers interested in conducting such studies.

Predicting non-elective hospital readmissions: a multi-site study. Department of Veterans Affairs Cooperative Study Group on Primary Care and Readmissions.

OBJECTIVE: To determine clinical and patient-centered factors predicting non-elective hospital readmissions. DESIGN: Secondary analysis from a randomized clinical trial. CLINICAL SETTING: Nine VA medical centers. PARTICIPANTS: Patients discharged from the medical service with diabetes mellitus, congestive heart failure, and/or chronic obstructive pulmonary disease (COPD). MAIN OUTCOME MEASUREMENT: Non-elective readmission within 90 days. RESULTS: Of 1378 patients discharged, 23.3% were readmitted. After controlling for hospital and intervention status, risk of readmission was increased if the patient had more hospitalizations and emergency room visits in the prior 6 months, higher blood urea nitrogen, lower mental health function, a diagnosis of COPD, and increased satisfaction with access to emergency care assessed on the index hospitalization. CONCLUSIONS: Both clinical and patient-centered factors identifiable at discharge are related to non-elective readmission. These factors identify high-risk patients and provide guidance for future interventions. The relationship of patient satisfaction measures to readmission deserves further study.

The involvement of physicians in VA home care: results from a national survey.

OBJECTIVES: To examine the role of physicians in the Veteran Affairs (VA) home-based primary care (HBPC) program and to identify variables that predict whether physicians make home visits and volume of home visits made. DESIGN: Descriptive and regression analyses of responses from a mail survey. PARTICIPANTS: Forty-five physicians affiliated with VA HBPC programs. MAIN SURVEY TOPICS: Self-reported work load, attitudes toward home care, reasons for home visits, administrative policies regarding physicians' role in patient care management, and time commitment to home care. RESULTS: A majority of physicians believed strongly in the importance of home care and made home visits for reasons consistent with their training. Physician attitude toward home care and preoccupation with office or hospital practice were related to whether or not physicians made home visits. Degree of preoccupation with office practice and amount of salary support from VA HBPC were significant predictors of the number of visits made (R2 = 0.44). CONCLUSIONS: These findings indicate that most physicians will make home visits if they believe that home care is valuable and if their time commitment is supported financially. Managed care plans that own and operate home care programs and have the capacity to transfer primary care management to physicians who derive financial support from the programs should find this information particularly relevant.

Effectiveness of team-managed home-based primary care: a randomized multicenter trial.

CONTEXT: Although home-based health care has grown over the past decade, its effectiveness remains controversial. A prior trial of Veterans Affairs (VA) Team-Managed Home-Based Primary Care (TM/HBPC) found favorable outcomes, but the replicability of the model and generalizability of the findings are unknown. OBJECTIVES: To assess the impact of TM/HBPC on functional status, health-related quality of life (HR-QoL), satisfaction with care, and cost of care. DESIGN AND SETTING: Multisite randomized controlled trial conducted from October 1994 to September 1998 in 16 VA medical centers with HBPC programs. PARTICIPANTS: A total of 1966 patients with a mean age of 70 years who had 2 or more activities of daily living impairments or a terminal illness, congestive heart failure (CHF), or chronic obstructive pulmonary disease (COPD). Intervention Home-based primary care (n=981), including a primary care manager, 24-hour contact for patients, prior approval of hospital readmissions, and HBPC team participation in discharge planning, vs customary VA and private sector care (n=985). MAIN OUTCOME MEASURES: Patient functional status, patient and caregiver HR-QoL and satisfaction, caregiver burden, hospital readmissions, and costs over 12 months. RESULTS: Functional status as assessed by the Barthel Index did not differ for terminal (P=.40) or nonterminal (those with severe disability or who had CHF or COPD) (P=.17) patients by treatment group. Significant improvements were seen in terminal TM/HBPC patients in HR-QoL scales of emotional role function, social function, bodily pain, mental health, vitality, and general health. Team-Managed HBPC nonterminal patients had significant increases of 5 to 10 points in 5 of 6 satisfaction with care scales. The caregivers of terminal patients in the TM/HBPC group improved significantly in HR-QoL measures except for vitality and general health. Caregivers of nonterminal patients improved significantly in QoL measures and reported reduced caregiver burden (P=.008). Team-Managed HBPC patients with severe disability experienced a 22% relative decrease (0.7 readmissions/patient for TM/HBPC group vs 0.9 readmissions/patient for control group) in hospital readmissions (P=.03) at 6 months that was not sustained at 12 months. Total mean per person costs were 6.8% higher in the TM/HBPC group at 6 months ($19190 vs $17971) and 12.1% higher at 12 months ($31401 vs $28008). CONCLUSIONS: The TM/HBPC intervention improved most HR-QoL measures among terminally ill patients and satisfaction among non-terminally ill patients. It improved caregiver HR-QoL, satisfaction with care, and caregiver burden and reduced hospital readmissions at 6 months, but it did not substitute for other forms of care. The higher costs of TM/HBPC should be weighed against these benefits.

Relationship between caregiver burden and health-related quality of life.

This study tested the cross-sectional relationship between caregiver burden and health-related quality of life (HRQOL) among 1,594 caregivers of veterans identified to qualify for formal home care. A two-stage model found that familial relationship, coresidence, and low income predicted objective burden. Coresidence also predicted subjective burden, whereas being African American was protective. In the full model, spousal relationship, low income, and burden were associated with poor HRQOL scores. Total variance explained in HRQOL ranged from 14% to 29%, with objective burden contributing more than subjective burden. These findings suggest a direct effect of objective burden on caregiver HRQOL, indicating a need among caregivers for assistance in caring for disabled family members.

Sulfasalazine treatment for rheumatoid arthritis: a metaanalysis of 15 randomized trials.

OBJECTIVE: To assess the efficacy and safety of sulfasalazine (SSZ) compared to placebo and other disease modifying drugs. METHODS: A metaanalysis was performed on 15 randomized clinical trials of rheumatoid arthritis (RA) that included SSZ (2 g/day average dose, 36 weeks average followup) as a treatment. Eight trials included a placebo group (PL), 2 hydroxychloroquine (HCQ) (350 mg/day average dose), 3 D-penicillamine (D-Pen) (667 mg/day average dose), and 4 gold sodium thiomalate or aurothioglucose (GST) (25 mg, 1 g/wk). RESULTS: Compared to PL, SSZ was superior for improvement in erythrocyte sedimentation rate (ESR) (SSZ 37%, PL 14%; p < 0.0001), morning stiffness duration (SSZ 61%, PL 33%; p = 0.008), pain visual analog scale (SSZ 42%, PL 15%; p < 0.0001), articular index (SSZ 46%, PL 20%; p < 0.0001), number of swollen joints (SSZ 51%, PL 26%; p < 0.0001), number of painful joints (SSZ 59%, PL 33%; p = 0.004), and patient global assessment (SSZ 26%, PL 14%; p = 0.02). Withdrawals from study because of adverse drug reactions were increased (SSZ 24%, PL 7%; p < 0.0001), but lack of efficacy dropouts were decreased (SSZ 8%, PL 21%; p < 0.0001). Compared to HCQ, SSZ tended to have fewer lack of efficacy dropouts (SSZ 5%, HCQ 15%; p = 0.055) and improved ESR (SSZ 43%, HCQ 26%; p = 0.10) and morning stiffness duration (SSZ 59%, HCQ 40%; p = 0.09). Compared to GST, adverse drug reaction dropouts were significantly fewer (SSZ 12%, GST 29%; p < 0.0001), while withdrawals due to lack of efficacy were greater (SSZ 13%, GST 4%; p = 0.006). More patients tended to complete treatment taking SSZ (SSZ 69%, GST 61%; p = 0.09). CONCLUSION: Over all, the metaanalysis provides data that support the effectiveness of SSZ as a treatment for RA.

Measuring costs in multisite randomized controlled trials: lessons from the VA Cooperative Studies Program.

OBJECTIVES: The interest in the economic impact of new health care interventions has increased dramatically over recent years; however, the results can be highly variable depending upon the economic assumptions made and the approaches taken in collecting the data and in conducting the analyses. This paper describes experiences from the VA Cooperative Studies Program in measuring health care utilization and costs for studies that evaluate clinical interventions. METHODS: Experiences from two multisite randomized clinical trials (RCTs) are highlighted to illustrate strategies used to measure costs by directly measuring health care utilization and economic data within the context of the trials. CONCLUSIONS: Despite the substantial resources required to gather evidence about the cost of care for health care innovations, future VA multisite studies should include accepted health economic approaches to make important contributions to health planning and health policy within and outside the VA health care system.

Enhanced access to primary care for patients with congestive heart failure. Veterans Affairs Cooperative Study Group on Primary Care and Hospital Readmission.

OBJECTIVE: To determine whether enhanced access to primary care affects the diagnostic evaluation, pharmacologic management, or health outcomes of patients hospitalized with congestive heart failure (CHF). DESIGN: Multisite randomized, controlled trial. SETTING: Nine Veterans Affairs medical centers. PATIENTS: 443 patients who were hospitalized with a diagnosis of CHF. INTERVENTION: Enhanced access to primary care, including assignment of a primary care nurse and physician, increased telephone contact, additional outpatient visits, and patient education. MAIN OUTCOME MEASURES: Diagnostic evaluation, pharmacologic management, health-related quality of life, and hospital readmission rates. RESULTS: About 80% of patients who had enhanced access to care and patients receiving usual care underwent recommended evaluation of left ventricular ejection fraction. Among the subset of patients for whom an angiotensin-converting enzyme (ACE) inhibitor was recommended (i.e., ejection fraction < 40%), three quarters of the patients in both the enhanced access and usual care groups received the drug (75% vs. 73%; P > 0.2). Enhanced access to primary care did not improve quality of life and increased hospital readmissions, with an average of 1.5 +/- SD 2.0 readmissions per 6 months of follow-up for patients who had enhanced access compared with 1.1 +/- SD 1.8 for those who received usual care (P = 0.02). CONCLUSIONS: Compliance with recommended CHF testing and treatment guidelines was equally high in both study groups. Enhanced access to primary care did not improve patients' self-reported health status and was associated with more frequent hospitalizations.

Home medical equipment receipt in a home care appropriate population.

OBJECTIVES: This study examines home medical equipment (HME) receipt for 1,040 veterans considered appropriate for home health services. METHODS: HME receipt was monitored for 12 months using the Department of Veterans Affairs' Prosthetics database. RESULTS: Eighty-three percent received at least one item; averaging 7.4 items (SD = 6.8). The most common items included commodes/bath benches (9%), canes/walkers (7%), safety equipment (7%), liquid oxygen (6%), and wheelchairs (6%). Two functional status variables, home care use and race, correctly classified 69% of HME recipients. Logistic regressions were run for specific equipment; c-indices ranged from .64 to .75. Age, race, income, functional status, risk of hospital readmission, and home care use were significant predictors. DISCUSSION: HME accounted for $4.5 billion in sales (16% of total) for medical products in 1996. As the HME market continues to expand, the characteristics of HME recipients are necessary to project future HME needs in a growing, elderly population.

The Veterans Affairs Implantable Insulin Pump Study: effect on cardiovascular risk factors.

OBJECTIVE: To determine whether implantable insulin pump (IIP) and multiple-dose insulin (MDI) therapy have different effects on cardiovascular risk factors in insulin-requiring patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A randomized clinical trial was conducted at seven Veterans Affairs medical centers in 121 male patients with type 2 diabetes between the ages of 40 and 69 years receiving at least one injection of insulin per day and with HbA1c, levels of > or =8% at baseline. Weights, blood pressures, insulin use, and glucose monitoring data were obtained at each visit. Lipid levels were obtained at 0, 4, 8, and 12 months, and free and total insulin levels were obtained at 0, 6, and 12 months. All medications being taken were recorded at each visit. RESULTS: No difference in absolute blood pressure, neither systolic nor diastolic, was seen between patients receiving MDI or IIP therapy, but significantly more MDI patients required anti-hypertensive medications. When blood pressure was modeled against weight and time, IIP therapy was significantly better than MDI therapy for systolic blood pressure in patients with BMI <33 and for diastolic blood pressure in patients with BMI >34 kg/m2. Total cholesterol levels decreased in the overall sample, but IIP patients exhibited significantly higher levels than MDI patients. Triglyceride levels increased over time for both groups, with IIP patients having significantly higher levels than patients in the MDI group. BMI was a significant predictor of, and inversely proportional to, HDL cholesterol level. No difference in lipid-lowering drug therapy was seen between the two groups. Free insulin and insulin antibodies tended to decrease in the IIP group as compared with the MDI group. C-peptide levels decreased in both groups. CONCLUSIONS: IIP therapy in insulin-requiring patients with type 2 diabetes has advantages over MDI therapy in decreasing the requirement for antihypertensive therapy and for decreasing total and free insulin and insulin antibodies. Both therapies reduce total cholesterol and C-peptide levels.

Surgical experience with implantable insulin pumps. Department of Veterans Affairs Implantable Insulin Pump Study Group.

BACKGROUND: A recent Veterans Affairs cooperative trial demonstrated that intensive insulin therapy via an implantable pump with intraperitoneal insulin delivery reduced glycemic variability and improved quality of life compared with multiple daily insulin injections. Our aim was to determine perioperative morbidity and assess long-term function of the implantable insulin pump. METHODS: Fifty-one adult patients with type 2 diabetes had infusion pumps placed over a 2-year period at seven VA Medical Centers as part of a randomized prospective study. RESULTS: All pumps were placed successfully. There were two (4%) perioperative complications. There were no wound complications. Duration of pump use ranged from 12 to 25 months (mean 20). Catheter obstruction (57%) and pump malfunction (25%) were the most common reasons for pump explantation. Catheter occlusions increased after 12 months. Catheter occlusion was treated by percutaneous rinse procedure in 75% and revisional procedures in 31% of patients. CONCLUSIONS: Implantable insulin pumps can be placed with minimal surgical morbidity. Attention to surgical detail and infusion protocol permits satisfactory long-term function. Pump/catheter complications increase with time but are usually resolvable by either operative or percutaneous manipulations.

Implantable insulin pump vs multiple-dose insulin for non-insulin-dependent diabetes mellitus: a randomized clinical trial. Department of Veterans Affairs Implantable Insulin Pump Study Group.

OBJECTIVE: To determine whether implantable insulin pump (IIP) therapy and multiple daily insulin (MDI) injections could equally attain improved blood glucose control, and to compare the 2 treatments with respect to reducing daily blood glucose fluctuations, reducing serious hypoglycemic insulin reactions, and improving patients' quality of life. DESIGN: Randomized clinical trial. SETTING: Seven Veterans Affairs medical centers. PATIENTS: One hundred twenty-one male type II diabetic patients between the ages of 40 and 69 years, receiving at least 1 injection of insulin per day and having hemoglobin A1c (HbA1c) levels of 8% or above. INTERVENTION: Intensive therapy (IIP or MDI) for 1 year. MAIN OUTCOME MEASURES: Hemoglobin A1c and blood glucose levels. RESULTS: Blood glucose levels declined to 7.96+/-1.08 mmol/L (143.4+/-19.5 mg/dL) and 8.30+/-1.52 mmol/L (149.6+/-27.4 mg/dL) (mean +/- SD) for IIP and MDI, respectively (P=.57). Hemoglobin A1c levels improved in both groups (time effect P<.001), to means of 7.54%+/-0.83% (MDI) vs 7.34%+/-0.79% (IIP). IIP reduced blood glucose fluctuations compared with MDI (P<.001), and reduced the incidence of mild clinical hypoglycemia by 68% (P<.001); IIP also eliminated the weight gain associated with MDI therapy and yielded better overall quality-of-life (P=.03) and impact-of-disease subscale scores (P=.05). Adverse events included 25% of subjects with episodes of insulin underdelivery due to microprecipitates of insulin within the pump. CONCLUSIONS: Intensive insulin therapy with IIP and MDI is effective in controlling non-insulin-dependent diabetes mellitus. IIP has significant advantages in reducing glycemic variability, clinical hypoglycemia, and weight gain, while improving aspects of quality of life.