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Biomedical subjects

J M Albert

Publications and source records attributed to J M Albert.

At least 19 recordsLinked to original sources
PubMed2006

Incidence and risk factors for hip or other bone fractures among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study.

The available data on bone fractures in hemodialysis (HD) patients are limited to results of a few studies of subgroups of patients in the United States. This study describes the prevalence of hip fractures and the incidence and risk factors associated with hip and other fractures in representative groups of HD facilities (n=320) and patients (n=12 782) from the 12 countries in the second phase of the Dialysis Outcomes and Practice Patterns Study (2002-2004). Among prevalent patients, 2.6% had a prior hip fracture. The incidence of fractures was 8.9 per 1000 patient years for new hip fractures and 25.6 per 1000 for any new fracture. Older age (relative risk (RR)(HIP)=1.91, RR(ANY)=1.33, P<0.0001), female sex (RR(HIP)=1.41, P=0.02; RR(ANY)=1.59, P<0.0001), prior kidney transplant (RR(HIP)=2.35, P=0.04; RR(ANY)=1.76, P=0.007), and low serum albumin (RR(HIP)=1.85, RR(ANY)=1.45, per 1 g/dl lower, P<0.0001) were predictive of new fractures. Elevated risk of new hip fracture was observed for selective serotonin reuptake inhibitors and combination narcotic medications (RR=1.63, RR=1.74, respectively, P<0.05). Several medications were associated with risk of any new fracture: narcotic pain medications (RR=1.67, P=0.02), benzodiazepines (RR=1.31, P=0.03), adrenal cortical steroids (RR=1.40, P<0.05), and combination narcotic medications (RR=1.72, P=0.001). Parathyroid hormone (PTH) levels >900 pg/ml were associated with an elevated risk of any new fracture (RR=1.72, P<0.05) versus PTH 150-300. The results suggest that greater selectivity in prescribing several classes of psychoactive drugs and more efficient treatment of secondary hyperparathyroidism may help reduce the burden of fractures in HD patients.

Adolescent↗
PubMed2001

Lack of health insurance and decline in overall health in late middle age.

BACKGROUND: The number of adults in their 50s and 60s in the United States who do not have health insurance is increasing. This group may be particularly vulnerable to the ill effects of being uninsured. METHODS: We conducted a prospective cohort study using files from the Health and Retirement Study, a national survey of adults who were 51 to 61 years old in 1992. We determined the risks of a major decline in overall health and of the development of new physical difficulties between 1992 and 1996 for participants who were continuously uninsured (uninsured in 1992 and in 1994), those who were intermittently uninsured (uninsured either in 1992 or in 1994), and those who were continuously insured. We used logistic regression to determine the independent effects of being uninsured on health outcomes after adjustment for base-line sociodemographic factors, preexisting medical conditions, and types of health-related behavior such as smoking and alcohol use. RESULTS: We analyzed data for 7577 participants. The 717 continuously uninsured participants and the 825 intermittently uninsured participants were more likely than the 6035 continuously insured participants to have a major decline in overall health between 1992 and 1996 (21.6 percent, 16.1 percent, and 8.3 percent of the three groups, respectively; P<0.001 for both comparisons). According to a multivariate analysis, the adjusted relative risk of a major decline in overall health was 1.63 (95 percent confidence interval, 1.26 to 2.08) for continuously uninsured participants and 1.41 (95 percent confidence interval, 1.11 to 1.78) for intermittently uninsured participants, as compared with continuously insured participants. A new difficulty in walking or climbing stairs was also more likely to develop in the continuously or intermittently uninsured participants than in the continuously insured participants (28.8 percent, 26.4 percent, and 17.1 percent of the three groups, respectively; P<0.001 for both comparisons). The adjusted relative risk of such a new physical difficulty was 1.23 (95 percent confidence interval, 1.02 to 1.47) for the continuously uninsured participants and 1.26 (95 percent confidence interval, 1.01 to 1.54) for the intermittently uninsured participants. CONCLUSIONS: The lack of health insurance is associated with an increased risk of a decline in overall health among adults 51 to 61 years old.

Activities of Daily Living↗
PubMed2001

Statistical advances in AIDS therapy trials.

This paper reviews recent statistical advances in HIV/AIDS therapy trials. Our emphasis is on three emerging areas that address key challenges in AIDS research: the determination of optimal treatment sequences, estimating efficacy of intended treatment, and inference for repeated measures with dependent censoring. A common theme of these topics is the use of observational data within clinical trials to answer questions not addressed by the conventional intent-to-treat analysis. We also give a brief overview of some recent contributions to other topics relevant to AIDS clinical trials, including modelling of treatment compliance data, modelling of repeated measures, and group sequential testing.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Impaired growth and elevated fas receptor expression in PIGA(+) stem cells in primary paroxysmal nocturnal hemoglobinuria.

The genetic defect underlying paroxysmal nocturnal hemoglobinuria (PNH) has been shown to reside in PIGA, a gene that encodes an element required for the first step in glycophosphatidylinositol anchor assembly. Why PIGA-mutated cells are able to expand in PNH marrow, however, is as yet unclear. To address this question, we compared the growth of affected CD59(-)CD34(+) and unaffected CD59(+)CD34(+) cells from patients with that of normal CD59(+)CD34(+) cells in liquid culture. One hundred FACS-sorted cells were added per well into microtiter plates, and after 11 days at 37 degrees C the progeny were counted and were analyzed for their differentiation pattern. We found that CD59(-)CD34(+) cells from PNH patients proliferated to levels approaching those of normal cells, but that CD59(+)CD34(+) cells from the patients gave rise to 20- to 140-fold fewer cells. Prior to sorting, the patients' CD59(-) and CD59(+)CD34(+) cells were equivalent with respect to early differentiation markers, and following culture, the CD45 differentiation patterns were identical to those of control CD34(+) cells. Further analyses of the unsorted CD59(+)CD34(+) population, however, showed elevated levels of Fas receptor. Addition of agonist anti-Fas mAb to cultures reduced the CD59(+)CD34(+) cell yield by up to 78% but had a minimal effect on the CD59(-)CD34(+) cells, whereas antagonist anti-Fas mAb enhanced the yield by up to 250%. These results suggest that expansion of PIGA-mutated cells in PNH marrow is due to a growth defect in nonmutated cells, and that greater susceptibility to apoptosis is one factor involved in the growth impairment.

Antigens, CD34↗
PubMed1999

A threshold causal model for clinical trials with departures from intended treatment.

Randomized clinical trials often are planned to study a specific intervention. However, the collection of data on treatment actually received often reveals variable levels of treatment exposure (or 'dose') across subjects, due to non-compliance or other reasons. This paper presents a new method, using such 'dose' data as well as control group responses, to assess a causal dose-response relationship. The specific model utilizes a threshold function and incorporates a random effect term to allow for heterogeneous treatment responses among subjects. Further modelling of the random effects allows for reduction of error variance and control for potential confounders. The threshold dose is estimated using a residual variance criterion based on a transformed model. Estimates of standard errors and confidence intervals are obtained using a bootstrap procedure. The method is applied to data from an AIDS clinical trial. A simulation study demonstrates the adequacy of the threshold estimates for particular sample sizes and error variances. The limitations of this essentially exploratory method, as well as some possible extensions, are discussed. Published in 1999 by John Wiley & Sons, Ltd. This article is a US Government Work and is in the public domain in the United States.

CD4 Lymphocyte Count↗
PubMed1999

Relationship between event rates and treatment effects in clinical site differences within multicenter trials: an example from primary Pneumocystis carinii prophylaxis.

The results of multicenter clinical trials may differ across participating clinical sites. We present a diagnostic approach for evaluating this diversity that emphasizes the relationship between the observed event rates and treatment effects. We use as an example a trial of sequential strategies of Pneumocystis prophylaxis in human immunodeficiency virus infection with 842 patients randomly allocated to start prophylaxis with trimethoprim/sulfamethoxazole, dapsone, or pentamidine. Prophylaxis failure rates varied significantly across the 30 clinical sites (0-30.3%, p = 0.002 by Fisher's exact test) with prominent variability in the pentamidine arm (0-63.6%). Starting with oral regimens was better than starting with pentamidine in sites with high rates of events, whereas the three strategies had more similar efficacy in other sites. Sites enrolling fewer patients had lower event rates and had more patients who withdrew prematurely or were lost to follow-up. In a hierarchical regression model adjusting for random measurement error in the observed event rates, starting with trimethoprim/sulfamethoxazole was predicted to be increasingly better than starting with aerosolized pentamidine as the risk of prophylaxis failure increased (p = 0.01), reducing the risk of failure by 47% when the failure rate of pentamidine was 30%, whereas the two regimens were predicted to be equivalent when the failure rate was 17%. Differences in event rates could reflect a combination of heterogeneity in diagnosis, administration of treatments, and disease risk in patients across sites. The evaluation of clinical site differences with a systematic approach focusing on event rates may give further insight in the interpretation of the results of multicenter trials beyond an average treatment effect.

AIDS-Related Opportunistic Infections↗
PubMed1999

A randomized trial of high- versus low-dose subcutaneous interleukin-2 outpatient therapy for early human immunodeficiency virus type 1 infection.

Forty-nine outpatients infected with human immunodeficiency virus with baseline CD4 cell counts >/=500/mm3, who were on stable antiretroviral therapy, were randomized to receive 5-day cycles of either low-dose (1.5 million IU [MIU] twice a day) or high-dose (7.5 MIU twice a day) subcutaneous (sc) interleukin (IL)-2 every 4 or every 8 weeks. High-dose recipients experienced mean slopes of +116.1 cells/month and +2.7 %/month in CD4 cells and percents, respectively, whereas low-dose recipients displayed mean slopes of +26.7 and +1.3% in the same parameters. At month 6, high-dose recipients achieved a 94.8% increase in mean CD4 cells over baseline compared with a 19.0% increase in low-dose recipients. While high-dose recipients encountered more constitutional side effects, these were generally not dose-limiting. High-dose scIL-2 therapy in outpatients with early HIV-1 infection was well tolerated and induced dramatic, sustained rises in CD4 cells.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Statistical issues for HIV surrogate endpoints: point/counterpoint. An NIAID workshop.

This paper summarizes the proceedings of an NIAID-sponsored workshop on statistical issues for HIV surrogate endpoints. The workshop brought together statisticians and clinicians in an attempt to shed light on some unresolved issues in the use of HIV laboratory markers (such as HIV RNA and CD4+ cell counts) in the design and analysis of clinical studies and in patient management. Utilizing a debate format, the workshop explored a series of specific questions dealing with the relationship between markers and clinical endpoints, and the choice of endpoints and methods of analysis in clinical studies. This paper provides the position statements from the two debaters on each issue. Consensus conclusions, based on the presentations and discussion, are outlined. While not providing final answers, we hope that these discussions have helped clarify a number of issues, and will stimulate further consideration of some of the highlighted problems. These issues will be critical in the proper assessment and use of future therapies for HIV disease.

Biomarkers↗
PubMed1996

Controlled trial of interleukin-2 infusions in patients infected with the human immunodeficiency virus.

BACKGROUND: Interleukin-2 is a cytokine that regulates the proliferation and differentiation of lymphocytes. In preliminary studies, intermittent infusions of interleukin-2 led to increases in CD4 counts in patients with human immunodeficiency virus (HIV) infection and more than 200 CD4 cells per cubic millimeter. We conducted a controlled study to evaluate the long-term effects of such therapy on both CD4 counts and the viral burden. METHODS: Sixty HIV-infected patients with base-line CD4 counts above 200 cells per cubic millimeter were randomly assigned to receive either interleukin-2 plus antiretroviral therapy (31 patients, 1 of whom was lost to follow-up) or antiretroviral therapy alone (29 patients). Interleukin-2 was administered every two months for six cycles of five days each, starting at a dosage of 18 million i.u. per day. Safety and immunologic and virologic measures were monitored monthly until four months after the last treatment cycle. RESULTS: In patients treated with interleukin-2, the mean (+/-SE) CD4 count increased from 428 +/- 25 cells per cubic millimeter at base line to 916 +/- 128 at month 12, whereas in the control group, the mean CD4 count decreased from 406 +/- 29 cells per cubic millimeter to 349 +/- 41 (P < 0.001). There were no significant differences between the groups in serial measurements of the plasma HIV RNA or p24 antigen concentration during the 12 months of treatment. Constitutional symptoms (fever, malaise, and fatigue) and asymptomatic hyperbilirubinemia were the chief dose-limiting toxic effects of interleukin-2 therapy. CONCLUSIONS: In patients with HIV infection and base-line CD4 counts above 200 cells per cubic millimeter, intermittent infusions of interleukin-2 produced substantial and sustained increases in CD4 counts with no associated increase in plasma HIV RNA levels.

AIDS-Related Opportunistic Infections↗
PubMed1995

Structure and induction pattern of a novel proteinase inhibitor class II gene of tobacco.

A cDNA and a corresponding genomic clone encoding a protein with partial identity to type II proteinase inhibitors from potato, tomato and Nicotiana alata, were isolated from tobacco libraries. The protein of 197 amino acids contains a putative signal peptide of 24 residues and three homologous domains, each with a different reactive site. The tobacco PI-II gene is not expressed in leaves of healthy plants, but is locally induced in leaves subjected to different types of stress (TMV infection, wounding, UV irradiation) and upon ethephon treatment. As opposed to the analogous PI-II genes of potato and tomato, the tobacco gene is not systemically induced by wounding or pathogenic infection. A far-upstream region in the PI-II promoter, containing various direct and indirect repeats, shares considerable sequence similarity to a similar region in the stress-inducible Cu/Zn-superoxide dismutase gene of N. plumbaginifolia.

Amino Acid Sequence↗
PubMed1995

Quantified EEG changes associated with a positive clinical response to clozapine in schizophrenia.

1. The authors conducted a retrospective exploratory computerized EEG study on the effect of clozapine in treatment-refractory schizophrenics, 10 high-responders (HRs) and 10 low-responders (LRs), in an attempt to correlate amplitude but especially coherence changes with a positive clinical response to clozapine. 2. EEGs with eyes closed were obtained before and during a clozapine treatment. Both groups had a similar drug profile with regards to non-clozapine medication. Probability maps were computed to illustrate changes of amplitude and coherence (for all combinations of paired electrodes) for 4 frequency bands (theta, alpha, beta 1 and 2). 3. The effect on AMPLITUDE was a generalized increase in lower bands and a decrease in anterior regions in higher bands of both HRs and LRs. Considerable changes of COHERENCE were observed on a wide set of paired electrodes in most frequency bands with some electrodes involved in HRs but uninvolved or differently involved in LRs suggesting differences in selected brain regions. 4. Changes of coherence but not amplitude were correlated with changes on the BPRS, thus to clinical improvement, and concerned mostly the right anterior-medial temporal (T4) and central (C4) electrodes paired with prefrontal electrodes, left central (C3), temporal (T3) and parietal (P3) electrodes in the theta band. 5. Clozapine has both generalized and regional effects as can be suspected considering its effect on many subtypes of brain receptors. A brain dysfunction centralized on the right anterior-medial temporal region may characterize treatment-refractory schizophrenics.

Adult↗
PubMed1994

Brain activation with a maze test: an EEG coherence analysis study in healthy subjects.

The maze test is a complex cognitive task involving visuoperceptual, planning and foresight abilities. EEGs were recorded from 20 healthy subjects according to the 10/20 system. Coherence is analogous to a correlation coefficient between the signals recorded by two electrodes and is computed between each electrode paired to all other electrodes. The maze test provoked changes of coherence mainly within the prefrontal regions, between parietal and central electrodes paired with frontal electrodes, especially the right frontopolar and the left prefrontal electrodes, and in the posterior temporal, parietal and occipital regions. EEG coherence analysis detects changes in regions known to be involved in visual processing and executive functions.

Adult↗
PubMed1994

On a model-based approach to estimating efficacy in clinical trials.

Treatment efficacy is of primary importance in phase III clinical trials. Determining the true size of the treatment effect is often complicated by patient non-compliance with the regimen. This paper examines a model-based approach in the spirit of Efron and Feldman utilizing drug and placebo compliance information. One of the assumptions of this analysis is 'comparability' of drug and placebo compliance. Robustness in estimation of subgroup and population treatment effects when this assumption is violated is investigated in a simulation study. We find that even moderate non-comparability (for example, normalized compliance correlations of 0.4) may produce severely biased estimates. The basis is modulated by the strength of the relationship between compliance and the response on placebo.

Bias↗
PubMed1990

Bronchopulmonary dysplasia and postnatal growth in extremely premature black infants.

Bronchopulmonary dysplasia (BPD) may adversely affect the postnatal growth of the extremely premature infant; however, most studies have not controlled for birth weight. We studied 90 Black premature infants (mean birth weight 989 +/- 148 g). Weight was recorded biweekly until discharge and at 4, 8, and 12 months of age corrected for prematurity. Infants with BPD (N = 23) were contrasted with infants without BPD (N = 67). Data were modeled using the Count model: Stage I birth to term and Stage II term to 12 months. Birth weight was considered part of growth beginning in utero and multivariate analyses were used to control for BPD, gestational age, duration of hospitalization and socioeconomic status. After adjustment for birth weight, BPD did not explain the growth pattern. A lower gestational age was associated with a slower establishment of steady growth (P less than 0.01), while an increased duration of hospitalization was associated with a lower growth rate (P less than 0.05). Growth in stage II was not explained by study variables. 'Catch-up' growth was seen in both infants with and without BPD. We conclude that differences in growth among infants with BPD are mainly attributable to birth weight. We speculate that poorer growth may be seen in a sub-group of infants with severe BPD.

Birth Weight↗
PubMed1988

Patient-controlled analgesia vs. conventional intramuscular analgesia following colon surgery.

Though patient-controlled analgesia (PCA) has been in use for over a decade, it has been popularized only recently. Conventional techniques of intermittent intramuscular (IM) administration of analgesia have fallen short of meeting the needs of patients following major abdominal surgery. This has prompted a search for methods to improve postoperative pain management. Though PCA has been accepted in many hospitals, few studies comparing conventional IM administration of morphine with PCA have been performed. A prospective randomized study comparing IM- and PCA-administered morphine in 62 patients undergoing colon surgery was performed. A comparison of the efficacy of analgesia and extent of sedation using these approaches shows that PCA allows for analgesia with less sedation and less drug requirement than that of IM administration. No differences were noted in postoperative duration of ileus, duration of hospitalization, and total hospital costs. This study confirms the safety and efficacy of PCA, and should be considered the current optimal method of controlling pain following major colonic surgery.

Adult↗
PubMed1983

Calcifying dermatomyositis following antitetanus vaccination.

In the course of dermatomyositis, calcinosis is a complication frequently seen in children but rarely seen in adults. Calcinosis often induces poor functional prognosis, reducing mobility of the joints and muscles. Dermatomyositis developed in a 59-year-old woman, following an antitetanus vaccination; the dermatomyositis later became calcifying. To our knowledge, similar cases have not been reported.

Calcinosis↗
PubMed1980

Comparison of SCH-12679 and thioridazine in aggressive mental retardates.

SCH-12679, a benzazepine derivative, was compared to thioridazine and to placebo on the aggressive behaviour of mentally retarded patients. After a three-week chlorpromazine (100 mg t.i.d.) standardizaton period, no significant differences between the three treatment groups were observed in their abnormal behaviour. During the comparative phase, patients treated with SCH-12679 became less hyperative and less agitated while those treated with thioridazine became more violent, more choleric and more provocative. The clinical investigator and the nursing staff found significant differences between the active drugs. As compared to the placebo, SCH-12679 improved the behaviour of the patients while thioridazine aggravated their condition. No important adverse reaction was found and the drugs did not interact with the sex of the patients and the presence of epilepsy. The results suggest that, in mental retardation, physical restraint of hyperactivity might induce aggressivity and that one should be cautious in using neuroleptics in nonpsychotic patients.

Aggression↗