Trends in Research Data Management and Academic Health Sciences Libraries.

Spurred by the National Institute of Health mandating a data management and sharing plan as a requirement of grant funding, research data management has exploded in importance for librarians supporting researchers and research institutions. This editorial examines the role and direction of libraries in this process from several viewpoints. Key markers of success include collaboration, establishing new relationships, leveraging existing relationships, accessing multiple avenues of communication, and building niche expertise and cachè as a valued and trustworthy partner.

Barriers to enrollment in a randomized controlled trial of hydrocortisone for cardiovascular insufficiency in term and late preterm newborn infants.

OBJECTIVE: To analyze reasons for low enrollment in a randomized controlled trial (RCT) of the effect of hydrocortisone for cardiovascular insufficiency on survival without neurodevelopmental impairment (NDI) in term/late preterm newborns. STUDY DESIGN: The original study was a multicenter RCT. Eligibility: ⩾34 weeks' gestation, <72 h old, mechanically ventilated, receiving inotrope. Primary outcome was NDI at 2 years; infants with diagnoses at high risk for NDI were excluded. This paper presents an analysis of reasons for low patient enrollment. RESULTS: Two hundred and fifty-seven of the 932 otherwise eligible infants received inotropes; however, 207 (81%) had exclusionary diagnoses. Only 12 infants were randomized over 10 months; therefore, the study was terminated. Contributing factors included few eligible infants after exclusions, open-label steroid therapy and a narrow enrollment window. CONCLUSION: Despite an observational study to estimate the population, very few infants were enrolled. Successful RCTs of emergent therapy may require fewer exclusions, a short-term primary outcome, waiver of consent and/or other alternatives.

Delayed sodium thiosulfate as an otoprotectant against carboplatin-induced hearing loss in patients with malignant brain tumors.

Carboplatin is effective in the treatment of malignant brain tumors. However, when administered in conjunction with osmotic opening of the blood-brain barrier (BBB), carboplatin is ototoxic. The purpose of this study was to determine whether delayed administration of sodium thiosulfate (STS), given after BBB closure, provided protection against carboplatin ototoxicity. Patients underwent monthly treatment with intra-arterial carboplatin (200 mg/m2/day x 2) in conjunction with osmotic opening of the BBB, for up to 1 year. Audiological assessment was conducted at baseline and within 24 h before each monthly treatment. STS was administered i.v. as one (20 g/m2) or two (20 g/m2 and 16 g/m2) 15-min doses, depending on baseline hearing status. The initial group received the first STS dose 2 h (or 2 and 6 h) after carboplatin (STS2) and a subsequent group received STS 4 h (or 4 and 8 h) after carboplatin (STS4). Audiological data were compared with a historical comparison group (HCG) treated with carboplatin without STS. Spearman correlation coefficients comparing STS 2 (n = 24), STS4 (n = 17), and HCG (n = 19) indicated significantly lower rates of ototoxicity with increased delay in STS (P = 0.0006). On the basis of the analysis of hearing levels, there were significant differences among the two STS groups and HCG at 8000 Hz (P = 0.0010) and at 4000 Hz (P = 0.0075). The log-rank test for time to ototoxicity indicated a significant difference between STS4 and HCG (P = 0.0018). Delayed STS was effective in protecting against carboplatin-induced hearing loss. STS delayed to 4 h after carboplatin significantly decreased time to development of ototoxicity and rate of ototoxicity when compared with HCG.

Effects of reduced sodium intake on hypertension control in older individuals: results from the Trial of Nonpharmacologic Interventions in the Elderly (TONE).

BACKGROUND: Few trials have evaluated the effects of reduced sodium intake in older individuals, and no trial has examined the effects in relevant subgroups such as African Americans. PATIENTS AND METHODS: The effects of sodium reduction on blood pressure (BP) and hypertension control were evaluated in 681 patients with hypertension, aged 60 to 80 years, randomly assigned to a reduced sodium intervention or control group. Participants (47% women, 23% African Americans) had systolic BP less than 145 mm Hg and diastolic BP less than 85 mm Hg while taking 1 antihypertensive medication. Three months after the start of intervention, medication was withdrawn. The primary end point was occurrence of an average systolic BP of 150 mm Hg or more, an average diastolic BP of 90 mm Hg or more, the resumption of medication, or a cardiovascular event during follow-up (mean, 27.8 months). RESULTS: Compared with control, mean urinary sodium excretion was 40 mmol/d less in the reduced sodium intervention group (P<.001); significant reductions in sodium excretion occurred in subgroups defined by sex, race, age, and obesity. Prior to medication withdrawal, mean reductions in systolic and diastolic BPs from the reduced sodium intervention, net of control, were 4.3 mm Hg (P<.001) and 2.0 mm Hg (P =.001). During follow-up, an end point occurred in 59% of reduced sodium and 73% of control group participants (relative hazard ratio = 0.68, P<.001). In African Americans, the corresponding relative hazard ratio was 0.56 (P =.005); results were similar in other subgroups. In dose-response analyses, end points were progressively less frequent with greater sodium reduction (P for trend =.002). CONCLUSION: A reduced sodium intake is a broadly effective, nonpharmacologic therapy that can lower BP and control hypertension in older individuals.

Cardiac luxation: an unusual complication of a log roll.

Cardiac luxation is a rare but potentially fatal consequence of blunt thoracic trauma. We present a case of a pericardial tear with cardiac luxation following blunt chest trauma. It is hypothesised that the cardiac luxation occurred while log rolling the patient during the initial assessment. This report stresses the need to be aware of the potential for such a complication.

Delay in presentation and evaluation for acute stroke: Stroke Time Registry for Outcomes Knowledge and Epidemiology (S.T.R.O.K.E.).

BACKGROUND AND PURPOSE: Early treatment is a critical determinant of successful intervention in acute stroke. The study was designed to find current patterns of stroke care by determining delays in time from onset of signs or symptoms to arrival at the emergency department and to initial evaluation by physicians and by identifying factors associated with these delays. METHODS: Data were prospectively collected by nurses and physicians from patients, patients' family members, and medical records from 10 hospitals of the Robert Wood Johnson Health System in New Jersey. RESULTS: A total of 553 patients who presented with signs or symptoms of acute stroke were studied. Thirty-two percent of patients arrived at the emergency department within 1.5 hours of stroke onset. Forty-six percent of patients arrived within 3 hours and 61% within 6 hours. Delays in arrival time were significantly associated with sex, race, transportation mode, and history of cardiovascular disease. Patients arriving by ambulance were more likely to present earlier (odds ratio [OR] 3.7 for arrival within 3 hours; OR 4.5 for arrival within 6 hours). Patients arriving by ambulance (OR 2.3 within 15 minutes; OR 1.7 within 30 minutes) and those requiring admission to intensive care units (OR 4.5 within 15 minutes and OR 5.2 within 30 minutes) were examined sooner by physicians. CONCLUSIONS: Despite national efforts to promote prompt stroke evaluation and treatment, significant delays still exist. The lack of improvement throughout the past decade underscores the need for implementation of effective public health programs designed to minimize the time to evaluation and treatment of stroke.

The effect of chlorthalidone on ventricular ectopic activity in patients with isolated systolic hypertension. The SHEP Study Group.

In an ancillary study of the Systolic Hypertension in the Elderly Program (SHEP), the effects of diuretics on ventricular ectopic activity were investigated in 186 patients with isolated systolic hypertension. Ventricular premature complexes (VPCs) were examined as the number of VPCs/24 hours, presence of > or = 1 VPC, presence of > or = 10 VPCs/24 hours, and presence of VPC pairs or ventricular tachycardia. Significant changes in VPCs were not observed either in the 92 patients randomized to chlorthalidone stepped-care (12.5 and 25 mg/day) or in the 94 placebo-treated patients (p > 0.1 for all VPC definitions and both groups). Serum potassium decreased from 4.4 +/- 0.5 to 4.1 +/- 0.5 mEq/liter (p = 0.002) in the chlorthalidone group and did not change (4.4 +/- 0.5 to 4.5 +/- 0.4 mEq/liter) in the placebo group. Potassium was prescribed routinely for confirmed hypokalemia < 3.5 mEq/liter. A relation between serum potassium and VPC or change in serum potassium and change in VPC was not observed in the chlorthalidone group. In summary, in patients with isolated systolic hypertension, chlorthalidone in doses that are effective in decreasing stroke and cardiovascular event rates (12.5 or 25 mg/day), did not increase VPCs.

Time trends in the occurrence and outcome of acute myocardial infarction and coronary heart disease death between 1986 and 1996 (a New Jersey statewide study).

Most reports of the decrease in age-adjusted coronary heart disease (CHD) are based on databases with upper age cut-offs that exclude approximately half of the events. We report changes in rates of acute myocardial infarction (AMI) and of out-of-hospital coronary death between 1986 and 1996 among New Jersey residents > or =15 years old. Data on patients discharged with the diagnosis of AMI from nonfederal acute care hospitals in the state (n = 270,091) and all records in the New Jersey death registration files with CHD (n = 172,175) listed as the cause of death from 1986 to 1996 (total study n = 442,266) were analyzed. The rate of hospitalized AMI cases in the state remained essentially unchanged during these 11 years, whereas in-hospital and 30-day case fatality among all age groups and both sexes declined. Age-adjusted CHD rates showed a decrease in fatal events, a smaller decrease in total events, and a slight increase in nonfatal events. The proportion of fatal CHD events occurring out-of-hospital decreased especially among men. The median age at occurrence of events increased by 1 year. Despite a decrease in CHD mortality, the rate of nonfatal events increased, especially among persons > or =75 years old. Thus, the decrease in age-adjusted CHD mortality is not all due to treatment and true prevention of CHD, but the disease simply occurs at an older age.

Impact of presentation of research results on likelihood of prescribing medications to patients with left ventricular dysfunction.

This study was conducted to evaluate willingness to prescribe medication based on identical data presented in different outcome terms to health professionals of varied discipline, geographic location, and level of training. Cross-sectional survey using a self-administered questionnaire was performed in 400 health professionals (physicians, pharmacists, physicians-in-training, and pharmacy students) in the United States and Europe. Data reflecting a clinical trial were presented in 6 outcome terms: 3 terms describing identical mortality (relative risk reduction, absolute risk reduction, and number of patients needed to be treated to prevent 1 death); and 3 distractors (increased life expectancy, decreased hospitalization rate, and decreased cost). Willingness to prescribe and rank order of medication preference assuming willingness to prescribe were measured. The results of the study showed that willingness to prescribe and first choice preference were significantly greater when study results were presented as relative risk reduction than when identical mortality data were presented as absolute risk reduction or number of patients needed to be treated to avoid 1 death (p <0.001). Increase in life expectancy was the most influential distractor. In conclusion, this study, performed in the era of "evidence-based medicine," demonstrates that the method of reporting research trial results has significant influence on health professionals' willingness to prescribe. The high numerical value of relative risk reduction and the concrete and tangible quality of increased life expectancy exert greater influence on health professionals than other standard outcome terms.

DPI 201-106 for severe congestive heart failure.

DPI 201-106 is a new oral inotropic agent that exerts its effects through a novel mechanism of action, namely, by enhancing sensitivity of myofilaments to calcium and prolonging inward sodium current. In a double-blind, randomized, placebo-controlled fashion, single oral doses (80 and 100 mg) of DPI 201-106 were administered to 15 patients with severe congestive heart failure. Dose-dependent increases in cardiac index (25%, p = 0.016), left ventricular stroke work index (24%, p = 0.018), left ventricular stroke volume index (32%,p = 0.005) and QTc interval (7%, p = 0.009) were observed. Significant effects on heart rate and systemic arterial pressure were not observed. Positive correlations of QTc interval with DPI plasma level (r = 0.64, p = 0.0001), stroke work index (r = 0.47, p = 0.0001) and ventricular ectopic activity on ambulatory electrocardiography (r = 0.49, p = 0.0001) were observed. Maximum changes occurred approximately 3 to 4 hours after ingestion and lasted more than 8 hours. Plasma drug levels were consistent with a 2-compartment model exhibiting first-order absorption and elimination kinetics. DPI 201-106 produced hemodynamic improvement in patients with severe congestive heart failure.

Trial of Nonpharmacologic Intervention in the Elderly (TONE). Design and rationale of a blood pressure control trial.

National and international policy-making organizations advocate nonpharmacologic therapies to reduce blood pressure (BP). However, data to support such recommendations in older persons are virtually nonexistent. The Trials of Nonpharmacologic Intervention in the Elderly (TONE) is a randomized, controlled trial that will test whether weight loss or a reduced sodium (Na) intake or both can maintain satisfactory BP control, without unacceptable side effects, after withdrawal of antihypertensive drug therapy. Medication-treated hypertensives (aged 60 to 80 years) with a systolic BP less than 145 mm Hg and a diastolic BP less than 85 mm Hg who are taking one antihypertensive medication are randomly assigned to one of four groups: (1) weight loss alone, (2) reduced Na intake alone, (3) combined weight loss and reduced Na intake, or (4) usual life-style (control group). Overweight participants are randomized to one of these four groups, while nonoverweight individuals are assigned to either the reduced Na intake or the usual life-style group. The interventions, tailored to the needs of older persons, use behavioral approaches to accomplish intervention-specific goals (weight loss > or = 10 lb, daily Na intake < or = 80 mEqa). Three months after the start of intervention, antihypertensive drug therapy is withdrawn. The primary trial end point is a BP of 150/90 mm Hg or higher, resumption of antihypertensive drug therapy, or the occurrence of a BP-related clinical complication during 2 to 3 years of follow-up. It is anticipated that TONE findings may identify an effective and acceptable nonpharmacologic approach to control hypertension in the increasingly large number of older persons treated with antihypertensive drug therapy.

Resolution of coronary ischemic syndrome due to dislodgement of intraluminal thrombus during diagnostic cardiac catheterization.

Dislodgement of an intraluminal coronary thrombus occurred in a patient with unstable angina during diagnostic cardiac catheterization. The thrombus propagated into the systemic circulation without clinical manifestation of embolism. The procedure rendered the patient asymptomatic. The case illustrates the role of intraluminal coronary thrombus in unstable angina.

Recruitment in the Trial of Nonpharmacologic Intervention in the Elderly (TONE).

OBJECTIVE: To compare the effectiveness of different approaches to participant enrollment in a behavior modification trial. DESIGN: Concurrent, prospective evaluation performed in context of recruitment for a randomized, controlled trial. SETTING: Four study centers located in Baltimore, Maryland, Memphis, Tennessee New Brunswick, New Jersey, and Winston-Salem, North Carolina. PARTICIPANTS: Men and women aged 60 to 80 years who were being treated with a prescription medication for control of hypertension. MAIN OUTCOME MEASURES: Visit counts and percent yields were assessed at each stage of the screening and randomization process. Logistic regression was used to contrast the randomization yields for different recruitment strategies and to explore the impact of sociodemographic characteristics and geographic location on recruitment yields. RESULTS: The overall randomization yields from a prescreen contact and a first screening visit to enrollment in the trial were 11% and 31%, respectively. Randomization yields varied significantly by participant age, education, and marital status. CONCLUSIONS: Our results demonstrate the feasibility of recruitment for trials of nonpharmacologic interventions in older people and suggest that mass mailing and mass media advertising campaigns provide an effective means of enrolling in such studies participants with a broad range of personal characteristics.

Association of increased pulse pressure with the development of heart failure in SHEP. Systolic Hypertension in the Elderly (SHEP) Cooperative Research Group.

The aim of this study was to assess the relationship between pulse pressure (PP) and the occurrence of heart failure (HF) in older persons with isolated systolic hypertension. Data from a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial were analyzed. A total of 4736 persons aged > or = 60 years with systolic blood pressure (SBP) between 160 and 219 mm Hg and diastolic blood pressure (DBP) < 90 mm Hg who participated in the Systolic Hypertension in the Elderly Program (SHEP) were studied. The main outcome measures were fatal and nonfatal HF. During 4.5 years average follow-up, fatal or nonfatal HF occurred in 160 of 4736 patients. The SBP, PP, and mean arterial pressure (MAP) were strong predictors of the development of HF (P < .0002). Cox proportional hazards regression using time-dependent covariates and controlling for MAP indicated that HF was inversely related to DBP (P = 0.002) and was directly related to pulse pressure (P = 0.002). Data were similar when patients who developed myocardial infarction during follow up were excluded. These data indicate that, in older persons with isolated systolic hypertension, high pulse pressure is associated with increased risk of heart failure independently of MAP and of the occurrence of acute myocardial infarction during follow-up.

Factors contributing to trends in prescription drug expenditures.

Between 1970 and 1995, national prescription drug expenditures and Medicaid drug expenditures increased proportionately less than did total health care expenditures and total Medicaid expenditures, respectively, although they increased to a greater extent than did expenditures in other sectors of the economy. General inflation, which cannot be controlled by health care policy, has been the major factor contributing to the growth in national prescription drug expenditures. Other contributors were population growth, increases in per capita prescription use, increases in per-prescription intensity (ie, real drug expenditures), and the fact that prescription drug prices exceeded general inflation. Medicaid drug expenditures have increased mainly because of growth in the number of drug recipients, increases in prescription drug prices, and economy-wide inflation.

Combined intraarterial carboplatin, intraarterial etoposide phosphate, and IV Cytoxan chemotherapy for progressive optic-hypothalamic gliomas in young children.

BACKGROUND AND PURPOSE: Optic pathway and/or hypothalamic astrocytomas in children are often quiescent, but in some cases, more aggressive tumors may cause progressive visual, endocrine, and neurologic deterioration. The initial treatment of these gliomas includes surgery and IV chemotherapy. Radiotherapy is not recommended in young children because of its severe adverse effects on cognitive and neuroendocrine function. This report suggests a new approach using combined intraarterial and IV carboplatin-based chemotherapy for patients for whom first line treatment has already failed. METHODS: Six children (mean age, 57 months) with the diagnosis of optic pathway hypothalamic gliomas, who had tumor progression after surgery and underwent IV chemotherapy, were treated monthly with intraarterially administered carboplatin, intraarterially administered etoposide phosphate, and IV administered Cytoxan. Four of the children had histologically verified pilocytic astrocytomas, and in two cases, diagnosis was made on the basis of clinical findings. Administration of the intraarterial chemotherapy required catheter placement in both internal carotid arteries at the level of C2-C3 and into one of the vertebral arteries at the level of C6-C7, with the patient under general anesthesia. RESULTS: Four of six patients had partial radiographic response, one had stable disease, and one had progressive disease after one cycle. Three patients showed clinical improvement. There were no serious complications associated with the angiographic procedures. Toxicities included bronchospasm that resolved after 3 to 4 minutes in one patient. One patient showed mild ototoxicity, and four patients needed platelet transfusion because of hematologic toxicity of drugs. CONCLUSION: These results suggest that this modality of chemotherapy (administered after failure of systemic [ie, IV] chemotherapy), of progressive optic-hypothalamic astrocytomas in young children may be an effective treatment prior to radiotherapy.

Cognitive outcomes and long-term follow-up results after enhanced chemotherapy delivery for primary central nervous system lymphoma.

OBJECTIVE: Patients with non-acquired immunodeficiency syndrome-related primary central nervous system lymphomas have the potential to achieve durable complete responses without radiotherapy, with treatment using enhanced chemotherapy delivery with blood-brain barrier disruption (BBBD). Reported 5-year survival rates with combined chemotherapy and radiotherapy were generally only 9 to 22% and were associated, in one study, with an overall 32% incidence of overt dementia and ataxia, which are dramatically increased among patients more than 60 years of age. METHODS: At the Oregon Health Sciences University, 111 consecutive patients with non-acquired immunodeficiency syndrome-related central nervous system lymphomas were prospectively treated with methotrexate-based, BBBD-enhanced chemotherapy and underwent formal neuropsychological evaluations. Of those, 74 patients had no systemic lymphoma and had received no prior irradiation; those 74 patients are described in this report. RESULTS: The estimated 5-year survival rate for this group was 42%, and the median survival time was 40.7 months. Overall, 48 patients (65%) exhibited complete responses and 36 patients continued to exhibit complete responses after 1 year of BBBD-enhanced chemotherapy. Of those 36 patients, none demonstrated evidence of cognitive loss in neuropsychological tests and/or clinical examinations. CONCLUSION: BBBD-enhanced chemotherapy delivery, without subsequent radiotherapy, resulted in favorable survival and cognitive outcomes for patients with primary central nervous system lymphomas who had not previously undergone irradiation. A cooperative multicenter study of intravenous chemotherapy without radiotherapy versus BBBD-enhanced chemotherapy would address the feasibility and necessity of performing a Phase III study for these rare central nervous system malignancies.

Peripheral vascular complications from percutaneous transluminal coronary angioplasty: a comparison with transfemoral cardiac catheterization.

The peripheral vascular complications associated with percutaneous transfemoral coronary angioplasty were compared with those that occurred during conventional transfemoral cardiac catheterization. Among 644 patients undergoing percutaneous transluminal coronary angioplasty (PTCA), 6 patients (0.9%) suffered peripheral vascular complications, whereas 35 of 2904 patients having cardiac catheterizations (1.2%) had a peripheral vascular complication. The types of complications associated with both procedures were similar and included groin hematomas, false aneurysms, arterial dissection, arterial perforation, and neurological deficits. The frequency of surgical repair of these complications also was similar in the two groups (50% required repair for a PTCA complication, 34% were repaired after a catheterization complication). The PTCA-associated complications included one myocardial infarction and one death, whereas neither of these occurred in association with a catheterization-induced vascular complication. The surgical management of five of the six PTCA complications was difficult, largely because of the size of the sheath-related puncture site and the presence of active bleeding from the associated systemic anticoagulation. PTCA carries the same risk of development of a peripheral vascular complication as found in transfemoral cardiac catheterization. Care must be taken to prevent sheath-related injury to the aorta-iliac-femoral system and hemorrhagic complications at the puncture site are of particular concern and require urgent surgical attention.

Quality of pharmacists' documentations in patients' medical records.

Training pharmacists to appropriately document patient-specific problems and recommendations in patients' medical records and subsequent monitoring of pharmacist-written documentation are described. The medical staff of a tertiary care teaching hospital recommended that pharmacists be allowed to write in the permanent portion of patients' medical records. A six-month pilot program was approved to train pharmacists in writing chart notes. Notes would be assessed according to the following criteria: necessity (i.e., a chart note was the appropriate means of communication), clarity, legibility, completeness, correct format, and lack of judgmental language. Initial training was by physicians from the pharmacy and therapeutics committee, with more extensive training by a committee composed of clinical and administrative pharmacists. After training ended, each pharmacist's first few notes were reviewed by a member of the pharmacy committee. The quality of pharmacist-written notes is reviewed quarterly. The first quarterly evaluation and another review 1 1/2 years later showed that all pharmacist notes met all of the established criteria. A multidisciplinary approach was effective in training pharmacists to document interventions appropriately in patients' permanent records. Ongoing monitoring ensures the continuing quality of such documentation.