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Decreased medical expenditures for care of HIV-seropositive patients. The impact of highly active antiretroviral therapy at a US Veterans Affairs Medical Center.

OBJECTIVE: To identify any changes in expenditures and in morbidity and mortality with the progression of treatment of the HIV-seropositive population from monotherapy with a nucleoside reverse transcriptase inhibitor (NRTI) [1993] through dual NRTI therapy (1995) to highly active antiretroviral therapy (HAART) [1997]. DESIGN AND SETTING: This study retrospectively compared 3 separate years of the total expenditures encountered in the management of HIV-seropositive individuals seen at a US Veterans Affairs Medical Center. INTERVENTIONS: Utilising a computerised hospital database, we identified those patients with HIV-related International Classification of Diseases, version 9 (ICD-9) codes and collected all healthcare-related expenditure data. The 3 eras selected for comparison were controlled for similar utilisation of prophylaxis against opportunistic infections, access to investigational antivirals, consistency between primary care providers and distribution of new anti-HIV therapies relative to that era. Cost data for inpatient and outpatient activities (visits and admissions) were derived from actual expenditures. Major categories were then compared, including total inpatient/outpatient expenditures and utilisation, laboratory and prescription costs, and morbidity and mortality rates. MAIN OUTCOME MEASURES AND RESULTS: The 3 periods had similar patient populations, with 86, 86 and 82% of patients in 1993, 1995 and 1997, respectively, having some degree of immunosuppression (defined as CD4+ lymphocyte counts < 500 cells/mm3). Morbidity and mortality were not changed by the addition of dual NRTI therapy. HAART therapy produced 60 and 70% declines in relative mortality when compared with the single and dual NRTI eras. Dual NRTI or HAART therapy decreased overall expenditures as compared with NRTI monotherapy. HIV-related outpatient resource utilisation other than pharmacy and laboratory costs fell by 25 and 59% in 1997 as compared with 1993 and 1995, respectively. The greatest fall in resource utilisation was for inpatient bed-days of care, where the average cost per patient fell by $US2782 between 1993 and 1997. Pharmacy and laboratory expenditures increased by $US1825 and $US231 per patient from 1993 to 1997, respectively. Overall, the impact of HAART was a decrease of $US1193 in the average total cost per patient from 1993 to 1997. CONCLUSIONS: The introduction of HAART provided a positive outcome on patient morbidity and mortality and on medical centre expenditures. The end result was a cost shift of expenditures from inpatient utilisation to outpatient pharmacy and laboratory costs. This information is important for patients and providers, who need to make clinical decisions on lifelong therapies, and for healthcare financial planners, who need to predict inpatient and outpatient healthcare utilisation during an era of limited healthcare dollars.

Anti-HIV Agents↗

Human placenta as a 'dual' biomarker for monitoring fetal and maternal environment with special reference to potentially toxic trace elements. Part 2: essential minor, trace and other (non-essential) elements in human placenta.

A survey of elemental composition of the human placenta was undertaken to evaluate reference values for minor and trace elements (essential and non-essential). The new data collection was narrowed down to results generated between the period of 1975-2000, since analytical methodology was becoming increasingly reliable with time for many elements. The search revealed the following results (microg/g, based on wet weight): Ca = 770; Cl = 1900; K = 1685; Mg = 100; Na = 360; P = 1700; and S = 350. However, Na, P and S need further confirmation. For a group of essential trace elements following average values were evaluated (microg/g, based on wet weight): Co = 0.007; Cr = 0.03; Cu = 0.9; Fe = 69; I = 0.005; Mn = 0.08; Mo = 0.02; Se = 0.2; and Zn = 10. However, the iodine value needs further confirmation. In addition, information values have been identified for a number of so-called non-essential elements such as Ag, Au, B, Ba, Br, Cs, F, La, Rb, Sb, Sc, Si, Sn, Sr, Ti, V and W. The survey results for toxic trace elements As, Cd, Hg, Ni and Pb are discussed in part 3 of this paper along with placenta as a biomonitor for toxic trace elements.

Adult↗

Effects of age and environmental factors on semen production and semen quality of Austrian Simmental bulls.

More than 90% of the breeding stock of Austrian dual purpose Simmental cows is artificially inseminated. Knowledge of factors affecting sperm production and semen quality is of importance with regard to reproductive efficiency and thus genetic improvement as well as for the productivity and profitability of AI centers. Hence, semen data from two Austrian AI centres collected in the years 2000 and 2001 were evaluated. In total, 3625 and 3654 ejaculates from 147 and 127 AI bulls, respectively, were analysed regarding ejaculate volume, sperm concentration, percentage of viable spermatozoa in the ejaculate, total spermatozoa per ejaculate and motility. Effects accounted for were the bull (random), age of bull, collection interval, number of collection on collection day, bull handler, semen collector, temperature on day of semen collection, in the course of epididymal maturation (average temperature of days 1-11 before collection) and during spermatogenesis (average temperature of days 12-65 before collection). Age of bull significantly affected all traits (P<0.01 to P<0.001) except motility score in center 2. Ejaculate volume and total number of spermatozoa increased with age of bull while sperm concentration was lower in higher age classes (center 1). The collection team was also found to significantly influence semen quality traits. With increasing collection interval ejaculate volume and total number of spermatozoa increased significantly (P<0.05 to P<0.001) while collection intervals between 4-9 days and 1-6 days were superior with regard to sperm concentration and percentage of viable spermatozoa, respectively (P<0.10 to P<0.001). First ejaculates were superior with respect to ejaculate volumes, sperm concentrations and total number of spermatozoa per ejaculate (P<0.001). Temperature, either on day of semen collection or during epididymal maturation or spermatogenesis, had important but inconsistent effects on semen production and sperm quality. Overall, however, ambient temperatures in the range of 5-15 degrees C were found to be optimal for semen production.

Age Factors↗

The communicating vein and its use in the radial forearm free flap.

Thrombosis is the most frequent cause of failure in microvascular free-tissue transfer. The large communicating vein of the cubital fossa connects the deep and superficial venous drainage of the radial forearm free flap (RFFF). This vein allows the surgeon to simultaneously drain both systems by means of the large veins of the cubital fossa. We prospectively collected data on the venous anatomy of the cubital fossa in 40 consecutive RFFFs over a 3-year period. We then retrospectively reviewed available data from the 14 cases preceding the cases in the prospective series. At least 78% of our patients had a communicating vein that facilitated dual venous drainage; 87% of our RFFFs were drained by both the superficial and deep venous systems, and 90% of our RFFFs had two or more venous anastomoses. We had no RFFF failures in our series of 54 flaps. We present our venous anatomy findings in this series of forearms as well as the venous anastomoses of our 54 patients. The surgi- cal-flap harvest, including the communicating vein and its use, may provide an advantage in the dependability and quality of venous outflow.

Forearm↗

Chronic manifestations of respiratory syncytial virus infection in premature infants.

BACKGROUND: Respiratory syncytial virus (RSV) infection in healthy infants born at term results in long term sequelae. Infants born prematurely are at increased risk of severe acute RSV infection; thus it would seem likely that such infants would be at increased risk of long term respiratory sequelae. METHODS: Methods of assessing the long term outcome of RSV infection are discussed and the results of retrospective and prospective studies investigating chronic respiratory morbidity after RSV infection in premature infants are reviewed. RESULTS: Documentation of all health care utilization, parental documentation of symptom status and lung function measurement provide a comprehensive and quantitative assessment of respiratory outcome. Studies that have included such outcome measures have demonstrated that RSV hospitalization in infants born between 32 and 35 weeks of gestational age and in those born more prematurely who developed chronic lung disease was associated with more hospital admissions, inpatient days, physician contacts and outpatient visits in the first 2 years after birth. Children born before 32 weeks of gestation who developed chronic lung disease also required more outpatient attendances and prescriptions and respiratory medications in years 2 through 4. Prospective data collection has demonstrated that chronic respiratory morbidity occurs in very premature infants, regardless of whether their RSV infection required hospitalization. CONCLUSION: Chronic respiratory morbidity is increased in premature infants after RSV infection. The duration of this increased morbidity and the impact of other viral infections, particularly dual infection with RSV, on long term sequelae merit investigation.

Chronic Disease↗

Effects of oral dehydroepiandrosterone on bone density in young women with anorexia nervosa: a randomized trial.

Young women with anorexia nervosa (AN) have subnormal levels of dehydroepiandrosterone (DHEA) and estrogen that may be mechanistically linked to the bone loss seen in this disease. The purpose of this study was to compare the effects of a 1-yr course of oral DHEA treatment vs. conventional hormonal replacement therapy (HRT) in young women with AN. Sixty-one young women were randomly assigned to receive oral DHEA (50 mg/d) or HRT (20 micro g ethinyl estradiol/0.1 mg levonorgestrel). Anthropometric, nutrition, and exercise data were acquired every 3 months, and bone mineral density (BMD) and body composition were measured by dual energy x-ray absorptiometry (DXA) every 6 months over 1 yr. Serum samples were obtained for measurements of hormones, proresorptive cytokines, and bone formation markers, and urine was collected for determinations of bone resorption markers at each visit. In initial analyses, total hip BMD increased significantly and similarly (+1.7%) in both groups. Hip BMD increases were positively correlated with increases in IGF-I (r = 0.44; P = 0.030) and the bone formation marker, bone-specific alkaline phosphatase increased significantly only in the DHEA treatment group (P = 0.003). However, both groups gained significant amounts of weight over the year of therapy, and after controlling for weight gain, no treatment effect was detectable. There was no significant change in lumbar BMD in either group. Both bone formation markers, bone-specific alkaline phosphatase and osteocalcin, increased transiently at 6-9 months in those subjects receiving DHEA compared with the estrogen-treated group (P < 0.05). Both DHEA and HRT significantly reduced levels of the bone resorption markers, urinary N-telopeptides (P < 0.05). There was a positive correlation between changes in IGF-I and changes in weight, body fat determined by DXA, and estradiol for both groups. In addition, patients receiving DHEA exhibited improvement on three validated psychological instruments (Eating Attitudes Test, Anorexia Nervosa Subtest, and Spielberger Anxiety Inventory). Both DHEA and HRT had similar effects on hip and spinal BMD. Over the year of treatment, maintenance of both hip and spinal BMD was seen, but there was no significant increase after accounting for weight gain. Compared with HRT, DHEA appeared to have anabolic effects, evidenced by the positive correlation between increases in hip DXA measurements and IGF-I and significant increases in bone formation markers. Both therapies significantly decreased bone resorption. Replicating results from studies of the elderly, DHEA resulted in improvements in specific psychological parameters in these young women.

Adipose Tissue↗

Evaluation of the HIV lipodystrophy case definition in a placebo-controlled, 144-week study in antiretroviral-naive adults.

OBJECTIVE: To compare three versions of the objective HIV-associated lipodystrophy (HIVLD) case definition (LDCD) and derived severity scale to spontaneous clinical LD assessment in adults initiating antiretroviral therapy. DESIGN AND MAIN OUTCOME MEASURES: The LDCD versions were the 'primary' LDCD [which includes dual-energy X-ray absorptiometry (DXA) and computerized tomography (CT)], a simpler 'central' LDCD that omits CT data, and a simpler but probably less accurate 'non-imaging' LDCD. Physician LD assessments were passively reported. Two of the 10 parameters in the primary LDCD were not collected and were imputed. Setting, participants and interventions: Retrospective analysis of a randomized, placebo-controlled, 144-week study of tenofovir DF or stavudine (d4T) in 600 antiretroviral-naive adults. RESULTS: Central LDCD and clinical assessment diagnosed LD in 27% and 19% of d4T recipients at week 144, respectively (P < 0.001), and 3% and 3% of tenofovir DF recipients, respectively (P = 0.248). The central LDCD performed at least as well as the primary LDCD; both were more sensitive than the non-imaging model. There was poor concordance between clinical and LDCD-based diagnosis (kappa 0.02-0.20); most clinical cases did not fulfill any LDCD. Using the central LDCD, most LD was grade 1; 6% of d4T recipients and no tenofovir DF recipient had grade 3-4 LD at week 144 (P = 0.007). Independent risk factors for LD using the central LDCD were d4T, increasing age, female sex and higher baseline triglycerides, whereas clinical assessment consistently identified only d4T. The LDCD score was more sensitive than DXA for assessing LD severity. CONCLUSIONS: In this prospective study of a first antiretroviral regimen, the LDCD was more sensitive for LD diagnosis and identified more lipodystrophy risk factors than spontaneous clinical assessment or DXA, and also objectively quantified LD severity. The central LDCD should make objective LD assessment cheaper and simpler. Spontaneous clinical LD assessment of is of limited value, even in placebo-controlled trials.

Absorptiometry, Photon↗

Hand cortical bone mass and its associations with radiographic joint damage and fractures in 50-70 year old female patients with rheumatoid arthritis: cross sectional Oslo-Truro-Amsterdam (OSTRA) collaborative study.

OBJECTIVE: To investigate the relationship between hand bone mineral density (BMD) and radiographic joint damage, and between hand BMD and fractures in 50-70 year old women with longstanding RA. METHODS: Demographic, clinical data, and imaging data on hand radiographs and Genants vertebral deformity score on spine radiographs were collected from 135 women with RA of > or =5 years, recruited from three European rheumatology clinics. Metacarpal hand BMD was measured by digital hand x ray radiogrammetry (DXR), and hip and lumbar spine BMD by dual x ray absorptiometry (DXA). Multiple regression analyses were used to examine associations between hand BMD and radiographic joint damage, and hand BMD and fractures. RESULTS: Hand BMD was strongly and independently associated with radiographic hand joint damage in a linear regression model adjusted for age, centre, BMI, disease duration, RF, 18 deformed joint count, ESR, and femoral neck BMD. In a multivariate logistic regression model adjusted for relevant variables, hand BMD and femoral neck BMD, but not spine BMD, were independently associated with vertebral deformities and with non-vertebral fractures. CONCLUSION: BMD measured by DXR on conventional hand radiographs in patients with RA may potentially be used as an indicator of joint damage and of vertebral and non-vertebral fracture risk.

Absorptiometry, Photon↗

Cigarette smoke composition. Part 2. Method for determining major components in smoke of cigarettes that heat instead of burn tobacco.

A method is described for determining major constituents in the smoke of a cigarette that heats, but does not burn, tobacco. Dual, simultaneous separations are performed in a single gas chromatographic oven to determine water, glycerol, nicotine, and propylene glycol in a rapid and cost-effective manner. A materials balance of new cigarette smoke total particulate matter was attempted from both Cambridge filter and electrostatic precipitation smoke collection data. Serious deficiencies were found when Cambridge filter smoke collection was applied for this purpose. Electrostatic precipitation smoke collection eliminated these problems. The data obtained by electrostatic precipitation smoke collection indicate that water, glycerol, nicotine, and propylene glycol make up about 94% of new cigarette smoke total particulate matter.

Filtration↗

Immunocytochemical analysis of D-serine distribution in the mammalian brain reveals novel anatomical compartmentalizations in glia and neurons.

D-Serine is a co-agonist at the NMDA receptor glycine-binding site. Early studies have emphasized a glial localization for D-serine. However the nature of the glial cells has not been fully resolved, because previous D-serine antibodies needed glutaraldehyde-fixation, precluding co-localization with fixation-sensitive antigens. We have raised a new D-serine antibody optimized for formaldehyde-fixation. Light and electron microscopic observations indicated that D-serine was concentrated into vesicle-like compartments in astrocytes and radial glial cells, rather than being distributed uniformly in the cytoplasm. In aged animals, patches of cortex and hippocampus were devoid of immunolabeling for D-serine, suggesting that impaired glial modulation of forebrain glutamatergic signaling might occur. Dual immunofluorescence labeling for glutamate and D-serine revealed D-serine in a subset of glutamatergic neurons, particularly in brainstem regions and in the olfactory bulbs. Microglia also contain D-serine. We suggest that some D-serine may be derived from the periphery. Collectively, our data suggest that the cellular compartmentation and distribution of D-serine may be more complex and extensive than previously thought and may have significant implications for our understanding of the role of D-serine in disease states including hypoxia and schizophrenia.

Aging↗

Powered liposuction: an evaluation of currently available instrumentation.

BACKGROUND: Over the past several years, powered liposuction instruments have become available to the dermatologic surgeon. These instruments all move the cannula forward and backward 2-12 mm with rapidity. This motion simulates the standard human movement of the cannula and facilitates movement through the tissue. Powered liposuction may help to prevent surgeon fatigue and has recently been shown to aid in the efficacy of fat removal. OBJECTIVE: To compare and contrast currently available powered liposuction instruments, to obtain objective engineering data on the instruments, and to compare the instruments when used on actual liposuction cases. METHODS: Five currently available powered liposuction systems were evaluated by the author. Each instrument was used with a 3 mm dual side port cannula on patients undergoing tumescent liposuction. An independent engineering firm, who collected objective measurements such as weight, stroke force, temperature, and vibration measurements on the instruments, evaluated the units. Noise measurements were obtained. RESULTS: Each of the five systems showed advantages and disadvantages. Important issues were the size and weight of the units, as well as whether they were driven electrically or pneumatically. Stroke force is variable (range 9.5-30 pounds). The noise of the units ranged between 60 and 87 dB. Vibration measurements varied from instrument to instrument. Units produced a variable amount of heat ranging from 77 degrees F to 102 degrees F. Most instruments are autoclavable, and one system is disposable. Build quality and reliability varied with the instrument. CONCLUSION: Instruments for powered liposuction have emerged in the last 2 years, with each instrument having distinct advantages and disadvantages. This article reviews five currently available powered liposuction instruments and presents objective measurements as well as the author's experience using the instruments.

Abdomen↗

A comparison of solid sampler methods for the determination of hexamethylene-based isocyanates in spray-painting operations.

A polyurethane foam sponge impregnated with 1-(2-methoxyphenyl) piperazine in dimethylsulfoxide was mounted in both cassette and inhalable organic monitor samplers and these were then compared with a dual-filter cassette. The samplers were used for the collection of hexamethylene diisocyanate (HDI) monomer and oligomers during actual spray-painting operations. The dual filter cassettes were positioned on a mannequin. The polyurethane foam cassette (PUF CAS) and polyurethane foam inhalable organic monitor (PUF IOM) samplers were positioned on a cart in the same maximum overspray area. Data from this pilot study suggest that there is no significant difference (P < 0.05, n = 6) in the amount of HDI monomer obtained with the PUF IOM sampler when compared with the amount obtained from the dual filter cassette. The data also suggest that the PUF IOM sampler yields a higher amount of HDI oligomer than either the dual filter cassette or the PUF CAS sampler, neither of which exhibited a significant difference (P < 0.05, n = 6) from each other.

Air Pollutants, Occupational↗

HIV prevalence and risk behaviors among men who have sex with men and inject drugs in San Francisco.

The dual risks of male-to-male sex and drug injection have put men who have sex with men and inject drugs (MSM-IDU) at the forefront of the HIV epidemic, with the highest rates of infection among any risk group in the United.States. This study analyzes data collected from 357 MSM-IDU in San Francisco between 1998 and 2002 to examine how risk behaviors differ by HIV serostatus and self-identified sexual orientation and to assess medical and social service utilization among HIV-positive MSM-IDU. Twenty-eight percent of the sample tested HIV antibody positive. There was little difference in risk behaviors between HIV-negative and HIV-positive MSM-IDU. Thirty percent of HIV-positive MSM-IDU reported distributive syringe sharing, compared to 40% of HIV negatives. Among MSM-IDU who reported anal intercourse in past 6 months, 70% of positives and 66% of HIV negatives reported unprotected anal intercourse. HIV status varied greatly by self-identified sexual orientation: 46% among gay, 24% among bisexual, and 14% among heterosexual MSM-IDU. Heterosexual MSM-IDU were more likely than other MSM-IDU to be homeless and to trade sex for money or drugs. Gay MSM-IDU were more likely to have anal intercourse. Bisexual MSM-IDU were as likely as heterosexual MSM-IDU to have sex with women and as likely as gay-identified MSM-IDU to have anal intercourse. Among MSM-IDU who were HIV positive, 15% were currently on antiretroviral therapy and 18% were currently in drug treatment, and 87% reported using a syringe exchange program in the past 6 months. These findings have implications for the development of HIV interventions that target the diverse MSM-IDU population.

Adolescent↗

Prevention of nosocomial catheter-associated urinary tract infections through computerized feedback to physicians and a nurse-directed protocol.

Catheter-associated urinary tract infections (CAUTIs) represent the most common nosocomial infection. The authors' baseline rate of CAUTI for general medical service was elevated at 36 per 1000 catheter-days. The medical literature has consistently linked inappropriate catheter use with the development of CAUTI. The baseline data also revealed a high rate of inappropriate use of indwelling urinary catheters. Using the dual modalities of technology through prompts in the computerized order/entry system and handheld bladder scanners, as well as in combination with staff education and nurse empowerment, the authors were successful in reducing the use and duration of urinary catheters as well as the incidence of CAUTI. In subsequent data collection cycles over the following 2 years, 81% reduction in device use and a 73% reduction in the clinical end point of nosocomial CAUTI (36/1000 catheter-days to 11/1000 catheter-days; P < .001) was demonstrated.

Aged↗

Influence of estrogen and osteopenia/osteoporosis on clinical periodontitis in postmenopausal women.

BACKGROUND: In Western societies, more than one-third of the female population above age 65 suffers from signs and symptoms of osteoporosis, a disorder characterized by low bone mass. Estrogen deficiency is the dominant pathogenic factor for osteoporosis in women. The impact of estrogen deficiency and osteopenia/osteoporosis on periodontitis is unclear, partially due to the lack of longitudinal studies evaluating clinical signs of gingival inflammation and periodontitis progression. The purpose of this investigation was to analyze prospectively the influence of serum estradiol levels and osteopenia/osteoporosis on common clinical measurements of periodontal disease over a 2-year period. METHODS: Fifty-nine moderate/advanced adult periodontitis patients and 16 non-periodontitis subjects, all within 5 years after menopause at baseline, completed the study. Serum estradiol levels (E2) were measured yearly by 125I radioimmunoassay, and osteopenia/osteoporosis was determined by dual energy x-ray absorptiometry of the lumbar spine. Posterior interproximal clinical measurements were obtained every 6 months for the periodontitis patients, including explorer-detectable supragingival plaque, bleeding on probing (BOP) and relative clinical attachment level (RCAL). Baseline probing depths, smoking history, and demographic data also were collected. RESULTS: Data indicated that baseline demographic measurements and bone mineral density (BMD) of the lumbar spine were not different between E2-deficient and E2-sufficient subjects. Smoking activity (packs smoked/day, years smoked) was higher in periodontitis patients (P=0.0001). E2-sufficient periodontitis subjects had a higher frequency of supragingival plaque without increasing gingival inflammation. E2 status did not influence the percentage of sites losing RCAL for either periodontitis or non-periodontitis groups, but when non-smoking osteopenic/osteoporotic periodontitis patients were evaluated, E2-deficient subjects had more BOP (43.8% versus 24.4%, P<0.04) and a trend toward a higher frequency of > or =2.0 mm RCAL loss (3.8% versus 1.2%, P<0.1) than E2-sufficient subjects. CONCLUSIONS: These data suggest that E2 supplementation (serum E2>40 pg/ml) is associated with reduced gingival inflammation and a reduced frequency of clinical attachment loss in osteopenic/osteoporotic women in early menopause.

Analysis of Variance↗

Concurrent alcoholism and social anxiety disorder: a first step toward developing effective treatments.

BACKGROUND: Social anxiety disorder (also called social phobia) is an anxiety disorder in which affected individuals fear the scrutiny of others. Clinical reports suggest that individuals with social anxiety disorder often use alcohol to alleviate anxiety symptoms, a practice that leads to alcohol abuse and/or dependence in approximately 20% of affected individuals. The present study investigated whether simultaneous treatment of social phobia and alcoholism, compared with treatment of alcoholism alone, improved alcohol use and social anxiety for clients with dual diagnoses of social anxiety disorder and alcohol dependence. METHODS: The design was a two-group, randomized clinical trial that used 12 weeks of individual cognitive behavioral therapy for alcoholism only (n = 44) or concurrent treatment for both alcohol and social anxiety problems (n = 49). Outcome data were collected at the end of 12 weeks of treatment and at 3 months after the end of treatment. RESULTS: Results with intent-to-treat analyses showed that both groups improved on alcohol-related outcomes and social anxiety after treatment. With baseline scores covaried, there was a significant effect of treatment group on several drinking measures. Counter to the hypothesis, the group treated for both alcohol and social anxiety problems had worse outcomes on three of the four alcohol use indices. No treatment group effects were observed on social anxiety indices. CONCLUSIONS: Implications for the staging of treatments for coexisting social phobia and alcoholism are discussed, as well as ways that modality of treatments might impact outcomes.

Adult↗

Pivot/Remote: a distributed database for remote data entry in multi-center clinical trials.

1. INTRODUCTION. Data collection is a critical component of multi-center clinical trials. Clinical trials conducted in intensive care units (ICU) are even more difficult because the acute nature of illnesses in ICU settings requires that masses of data be collected in a short time. More than a thousand data points are routinely collected for each study patient. The majority of clinical trials are still "paper-based," even if a remote data entry (RDE) system is utilized. The typical RDE system consists of a computer housed in the CC office and connected by modem to a centralized data coordinating center (DCC). Study data must first be recorded on a paper case report form (CRF), transcribed into the RDE system, and transmitted to the DCC. This approach requires additional monitoring since both the paper CRF and study database must be verified. The paper-based RDE system cannot take full advantage of automatic data checking routines. Much of the effort (and expense) of a clinical trial is ensuring that study data matches the original patient data. 2. METHODS. We have developed an RDE system, Pivot/Remote, that eliminates the need for paper-based CRFs. It creates an innovative, distributed database. The database resides partially at the study clinical centers (CC) and at the DCC. Pivot/Remote is descended from technology introduced with Pivot [1]. Study data is collected at the bedside with laptop computers. A graphical user interface (GUI) allows the display of electronic CRFs that closely mimic the normal paper-based forms. Data entry time is the same as for paper CRFs. Pull-down menus, displaying the possible responses, simplify the process of entering data. Edit checks are performed on most data items. For example, entered dates must conform to some temporal logic imposed by the study. Data must conform to some acceptable range of values. Calculations, such as computing the subject's age or the APACHE II score, are automatically made as the data is entered. Data that is collected serially (BP, HR, etc.) can be displayed graphically in a trend form along with other related variables. An audit trail is created that automatically tracks all changes to the original data, making it possible to reconstruct the CRF to any point in time. On-line help provides information on the study protocol as well as assistance with the use of the system. Electronic security makes it possible to lock certain parts of the CRF once it has been monitored. Completed CRFs are transmitted to the DCC via electronic mail where it is reviewed and merged into the study database. Questions about subject data are transmitted back to the CC via electronic mail. This approach to maintaining the study database is unique in that the study data files are distributed among the CC and DCC. Until a subject's CRF is monitored (verified against the original patient data residing in the hospital record), it logically resides at the CC where it was collected. Copies are transmitted to the DCC and are only read there. Any pre-monitoring changes must be made to the data at the CC. Once the subject's CRF is monitored, it logically moves to the DCC, and any subsequent changes are made at the DCC with copies of the CRF flowing back to the CC. 3. DISCUSSION. Pivot/Remote eliminates the need for paper forms by utilizing portable computers that can be used at the patient bedside. A GUI makes it possible to quickly enter data. Because the user gets instant feedback on possible error conditions, time is saved because the original data is close at hand. The ability to display trended data or variables in the context of other data allows detection of erroneous conditions beyond simple range checks. The logical construction of the database minimizes the problem of managing dual databases (at the CC and DCC) and keeps CC personnel in the loop until all changes are made.

Computer Communication Networks↗

A dual long-term effect of breastfeeding on atopy in relation to heredity in children at 4 years of age.

BACKGROUND: The long-term effect of early feeding on atopic sensitization is still unsolved. The aim of this study was to evaluate the long-term effect of breastfeeding on atopy in groups of 4-year-old children stratified by atopic heredity. METHODS: We collected four groups of 4-year-old children from a birth cohort: two groups with differing backgrounds of atopic heredity, all exclusively breast-fed for at least 3 months; and two groups with differing atopic heredity, but all fed with cow's milk-based formula during their first weeks. The data were collected with a questionnaire, skin prick testing, and measurement of serum total and allergen-specific IgE levels. RESULTS: Breastfeeding significantly decreased the risk of allergic rhino-conjunctivitis [odds ratio (OR) 0.41, 95% confidence interval (CI) 0.18-0.95] and sensitization to furred pets, as measured by skin prick results, in children with atopic heredity, whereas in children without atopic heredity, breastfeeding was related to an increased risk of symptomatic atopy (OR 2.57, 95% CI 1.16-5.70), and high serum IgE values. A significant interaction was found between heredity and breastfeeding. CONCLUSIONS: The long-term effect of breastfeeding was dual: in children with atopic heredity, breastfeeding protected against atopy, whereas in children without atopic heredity, it increased the risk of atopy.

Animals↗