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Biomedical subjects

J D Hamilton

Publications and source records attributed to J D Hamilton.

At least 19 recordsLinked to original sources

Improved medical and surgical management of cervical spine disease in patients with rheumatoid arthritis over 10 years.

OBJECTIVES: (1) To compare clinical outcome and symptomatology of rheumatoid cervical myelopathy between patients managed conservatively and surgically. (2) To determine if surgical outcome has improved since the series published from this unit in 1987. (3) To examine the role of magnetic resonance imaging (MRI) in the diagnosis of cervical myelopathy. METHODS: Patients undergoing MRI of the cervical spine between 1991 and 1996 were identified. Case records were reviewed retrospectively. RESULTS: 111 patients with RA underwent 124 MRI scans. The median age at onset of cervical spine symptoms was 58 years (range 16-87) with median disease duration of 16 years (range 1-59). 18 (16%) required surgery immediately after MRI. 93 (84%) were managed conservatively, 9 of whom (10%) later required surgery. 2/7 deaths in the conservative group were directly related to cervical myelopathy. Patients requiring surgery were more likely to report paraesthesia, weakness, unsteadiness and to exhibit extensor plantar reflexes, gait disturbance, and reduced power. MRI findings did not correlate with clinical features. When compared with the 1974-82 cohort, fewer patients had severe myelopathy (Ranawat grade IIIB) before surgery (34% versus 7%). Early postoperative mortality improved from 9% to 0% and surgical complication rate fell from 50% to 22%. 89% of patients in the 1991-96 cohort reported subjective improvement in overall function. CONCLUSION: In this series surgical outcome has improved. The major factor in this more favourable outcome is probably that patients presenting with rheumatoid cervical myelopathy are now referred for surgery at an earlier stage of disease. Clinical findings correlate poorly with MRI findings, therefore clinical history should remain the key to determining the need for MRI.

Adult↗

An analysis of the causes of adverse events from the Quality in Australian Health Care Study.

OBJECTIVE: To examine the causes of adverse events (AEs) resulting from healthcare to assist in developing strategies to minimise preventable patient injury. DESIGN: Descriptions of the 2353 AEs previously reported by the Quality in Australian Health Care Study (QAHCS) were reviewed. A qualitative approach was used to develop categories for human error and for prevention strategies to minimise these errors. These categories were then used to classify the AEs identified in the QAHCS, and the results were analysed with previously reported preventability and outcome data. RESULTS: 34.6% of the causes of AEs were categorised as "a complication of, or the failure in, the technical performance of an indicated procedure or operation", 15.8% as "the failure to synthesise, decide and/or act on available information", 11.8% as "the failure to request or arrange an investigation, procedure or consultation", and 10.9% as "a lack of care and attention or failure to attend the patient". AEs in which the cause was cognitive failure were associated with higher preventability scores than those involving technical performance. The main prevention strategies identified were "new, better, or better implemented policies or protocols" (23.7% of strategies), "more or better formal quality monitoring or assurance processes" (21.2%), "better education and training" (19.2%), and "more consultation with other specialists or peers" (10.2%). CONCLUSION: The causes of AEs or errors leading to AEs can be characterised, and human error is a prominent cause. Our study emphasises the need for designing safer systems for care which protect the patient from the inevitability of human error. These systems should provide new policies and protocols and technological support to aid the cognitive activities of clinicians.

Australia↗

Outcome at 6 months for 50 adolescents with major depression treated in a health maintenance organization.

OBJECTIVE: To examine the short-term outcome of adolescents with major depressive disorder treated in a health maintenance organization (HMO) setting. METHOD: Fifty consecutive adolescents meeting DSM-IV criteria for major depressive disorder at intake to an HMO clinic completed a Beck Depression Inventory (BDI), Columbia Impairment Scale, and Youth Self-Report (YSR), and a parent completed a Child Behavior Checklist at intake and 2, 4, and 6 months later. RESULTS: Thirty-three percent, 40.6%, and 33% of reporting subjects showed improved mood (defined as BDI score < 9), with 78%, 64%, and 72% reporting (defined as completing a BDI) at 2, 4, and 6 months, respectively. Initial level of impairment correlated with BDI score at 2 months (p = .02) and 4 months (p = .01). Attention problems at intake as measured by the YSR correlated with BDI score at 2 months (p = .002) and 6 months (p = .003). CONCLUSIONS: A minority of adolescents treated with limited, nonspecific psychotherapy and selective serotonin reuptake inhibitors have a BDI score of less than 9 at 2, 4, or 6 months. Self-report of attention problems at intake correlates with ongoing depressive symptomatology.

Adolescent↗

Persistence of combat-related posttraumatic stress symptoms for 75 years.

Investigations of the duration of combat-related posttraumatic stress symptoms have focused mainly on survivors of World War II and the Vietnam War, with little attention to surviving veterans of World War I. The authors describe a case in which posttraumatic stress symptoms persisted for 75 years in a World War I combat veteran and increased in frequency toward the end of his life accompanied by advancing dementia and hospitalization. The case illustrates that posttraumatic stress symptoms may be lifelong and exacerbated by various consequences of aging, even if they are not disabling.

Aged↗

Race and stress in the incidence of herpes zoster in older adults.

OBJECTIVES: To examine the effect of black race and acute (negative life events) and chronic (lack of social support) psychological stress on the risk of herpes zoster in late life. DESIGN: A population-based, prospective cohort study. SETTING: Central North Carolina. PARTICIPANTS: Duke Established Populations for Epidemiological Studies of the Elderly, a stratified probability sample of community-dwelling persons more than 65 years of age. MEASUREMENTS: Interviewers administered a comprehensive health survey to the participants in 1986-1987 (P1, n = 4162), 1989-1990 (P2, n = 3336), and 1992-1994 (P3, n = 2568). Incident cases of zoster between P1 and P2 and P2 and P3 served as the dependent variable. Hypothesis-testing variables included race, negative life events, and five measures of social support. Control variables included age, sex, education, cancer, chronic diseases, basic ADLs, instrumental ADLs, depression, self-rated health, hospitalization, and cigarette smoking. Statistical analyses employed chi-square tests and proportional hazards model. RESULTS: At baseline, the sample had a mean age of 73.6 years and was 55% black, 45% white, and 65% female. There were 65 cases of zoster between P1 and P2 and 102 cases of zoster between P2 and P3. From P1 to P2, 1.4% of blacks and 3.4% of whites developed zoster (P < .001). From P2 to P3, 2.9% of blacks and 7.5% of whites developed zoster (P < .001). After controlling for the above variables, blacks were significantly less likely to develop zoster (adjusted risk ratio = 0.35; 95% confidence interval (CI), 0.24-0.51; P < .001). Negative life events increased the risk of zoster, but the result was borderline for statistical significance (adjusted RR = 1.38, 95% CI 0.96-1.97; P = .078). No measures of social support were significantly associated with zoster. CONCLUSION: Black race decreased the risk of zoster in late life significantly. Measures of stress were not significantly related to zoster, but study limitations preclude definitive conclusions. Future research should focus on these factors in larger samples and different populations.

Black or African American↗

Changes in plasma HIV RNA levels and CD4+ lymphocyte counts predict both response to antiretroviral therapy and therapeutic failure. VA Cooperative Study Group on AIDS.

BACKGROUND: Markers are needed for assessing response to antiretroviral therapy over time. The CD4+ lymphocyte count is one such surrogate, but it is relatively weak. OBJECTIVE: To assess the association of changes in plasma human immunodeficiency virus (HIV) RNA level and CD4+ lymphocyte count with progression to the acquired immunodeficiency syndrome (AIDS). DESIGN: Analysis of data from a subset of patients in a multicenter, randomized, clinical trial. SETTING: Six Veterans Affairs medical centers and one U.S. Army medical center. PATIENTS: 270 symptomatic HIV-infected patients from the Veterans Affairs Cooperative Study on AIDS. INTERVENTION: Patients were randomly assigned to receive zidovudine or placebo initially; a cross-over protocol was established for patients receiving placebo who had disease progression. MEASUREMENTS: Reverse transcriptase polymerase chain reaction on cryopreserved plasma samples, previously obtained CD4+ lymphocyte counts, and clinical events. RESULTS: For each decrease of 0.5 log10 copies/mL in plasma HIV RNA level, averaged over the 6 months after randomization, the relative risk (RR) for progression to AIDS was 0.67 (P < 0.001). In a subset of 70 treated patients with long-term follow-up, a return to baseline plasma HIV RNA levels within 6 months of randomization was associated with progression to AIDS (RR, 4.28; P = 0.004). Plasma HIV RNA levels or CD4+ lymphocyte counts over time were more strongly associated with progression to AIDS than were baseline levels or counts. CONCLUSIONS: An adequate virologic response after initiation of antiretroviral therapy seems to require a decrease in plasma HIV RNA level of at least 0.5 log10 copies/mL that is sustained for at least 6 months. The independent relation between plasma HIV RNA level and CD4+ lymphocyte count over time and clinical outcome suggests that the measurement of plasma HIV RNA level, in addition to the CD4+ lymphocyte count, has a role in guiding the management of antiretroviral therapy.

Acquired Immunodeficiency Syndrome↗

Outcome of psychiatric hospitalization for very low-functioning demented patients.

The authors determined the outcome of geropsychiatric hospitalization for 73 very low-functioning demented patients (GAF score < 21). General psychiatric symptoms, depression, and agitation decreased significantly, and mean GAF scores increased significantly, with no significant change in cognitive function. Psychiatric hospitalization can meaningfully improve function and quality of life even in this very impaired population. Despite these improvements many patients are discharged to more restrictive settings.

Activities of Daily Living↗

Hepatitis C.

OBJECTIVES: To review the virology, epidemiology, pathogenesis, natural history, clinical manifestations, and current treatment of hepatitis C virus (HCV) infection. DATA SOURCES: The MEDLINE database (1966 to 1996) was searched for English-language articles and abstracts on HCV and non-A, non-B hepatitis. Papers cited in relevant primary articles were also reviewed. STUDY SELECTION: More than 500 original and review articles were evaluated, and the most relevant were selected. DATA EXTRACTION: Data were extracted and reviewed by all authors. DATA SYNTHESIS: In most patients, HCV infection results in chronic hepatitis. The disease is insidious and subclinical but may progress over decades into end-stage liver disease and hepatocellular carcinoma, which makes HCV cirrhosis a leading indication for orthotopic liver transplantation. Current diagnostic methods are highly sensitive and specific, and quantitative assessment of viral load may help to predict and monitor response to treatment. The only available therapeutic option is interferon, and this agent is effective in only a small subset of patients. CONCLUSIONS: Infection with HCV is a significant public health problem that has important clinical and financial consequences. The tailoring of specific therapy according to viral load or genotype, better patient selection, and use of combination drug regimens may improve the chance of viral clearance and sustained biochemical and histologic response. Further understanding of the basic virology of HCV and the exact mechanisms of viral persistence and tissue injury is needed to help define future therapeutic and preventive strategies.

Carcinoma, Hepatocellular↗

Changes in plasma HIV-1 RNA and CD4+ lymphocyte counts and the risk of progression to AIDS. Veterans Affairs Cooperative Study Group on AIDS.

BACKGROUND: Clinical trials of antiretroviral drugs can take years to complete because the outcomes measured are progression to the acquired immunodeficiency syndrome (AIDS) or death. Trials could be accelerated by the use of end points such as changes in CD4+ lymphocyte counts and plasma levels of human immunodeficiency virus type 1 (HIV-1) RNA and beta 2-microglobulin, but there is uncertainty about whether these surrogate measures are valid predictors of disease progression. METHODS: We analyzed data from the Veterans Affairs Cooperative Study on AIDS, which compared immediate with deferred zidovudine therapy. Patients' plasma levels of HIV-1 RNA and beta 2-microglobulin were measured in stored plasma. RESULTS: Among the 129 patients in the immediate-treatment group, 34 had disease that progressed to AIDS, as compared with 57 of the 141 patients in the deferred-treatment group (P = 0.03). Progression to AIDS correlated strongly with base-line CD4+ lymphocyte counts (P = 0.001) and plasma levels of HIV-1 RNA (P < 0.001), but not with base-line levels of beta 2-microglobulin (P = 0.14). A decrease of at least 75 percent in the plasma level of HIV-1 RNA over the first six months of zidovudine therapy accounted for 59 percent of the benefit of treatment, defined as the absence of progression to AIDS (95 percent confidence interval, 13 to 112 percent). Plasma beta 2-microglobulin levels and CD4+ lymphocyte counts explained less of the effect of treatment. A 75 percent decrease in the plasma HIV-1 RNA level plus a 10 percent increase in the CD4+ lymphocyte count could explain 79 percent of the treatment effect (95 percent confidence interval, 27 to 145 percent). CONCLUSIONS: Treatment-induced changes in the plasma HIV-1 RNA level and the CD4+ lymphocyte count, taken together, are valid predictors of the clinical progression of HIV-related disease and can be used to assess the efficacy of zidovudine and possibly other antiretroviral drugs as well.

Acquired Immunodeficiency Syndrome↗

Long-term follow-up of symptomatic HIV-infected patients originally randomized to early versus later zidovudine treatment; report of a Veterans Affairs Cooperative Study. VA Cooperative Study Group on AIDS Treatment.

Following a 4-year controlled trial comparing early and later zidovudine treatment, we conducted an additional 3-year follow-up. Of the original 338 patients, 275 participated. Clinical outcome measures were AIDS and death. In the early therapy group (n = 170), 67 patients progressed to AIDS compared with 85 in the later therapy group (n = 168); the relative risk (RR) comparing early with later therapy was 0.72% (95% confidence interval [CI] 0.52-0.99; p = 0.044). The early therapy group had 74 deaths compared with 73 in the later therapy (RR = 0.98; 95% CI, 0.71-1.36; p = 0.91). The early group had a peak CD4+ count increase at 1-2 months and a delay of 1 year before CD4+ counts fell below baseline. For patients who received zidovudine for more than the median duration (20.3 months) before their first AIDS diagnosis, the RR for death was 2.08 (95% CI, 1.36-3.19, p = 0.001). Additional factors independently associated with poor prognosis following AIDS were a CD4+ count of < 100 cells/mm3 and increased severity of the first AIDS diagnosis, whereas use of another antiretroviral agent was associated with improved survival. We conclude that early zidovudine therapy delays progression to AIDS but does not affect survival. Patients who progress to AIDS while on prolonged zidovudine monotherapy many benefit from a change to other antiretroviral therapy(ies).

Acquired Immunodeficiency Syndrome↗

Aquatic risk assessment of a polycarboxylate dispersant polymer used in laundry detergents.

Polycarboxylates enhance detergent soil removal properties and prevent encrustation of calcium salts on fabrics during washing. Laundry wastewater typically reaches wastewater treatment plants, which then discharge into aquatic environments. The yearly average concentration of a 4500 molecular weight (MW) sodium acrylate homopolymer reaching U.S. wastewater treatment plants will be approximately 0.7 mg/L. Publications showing the low to moderate acute aquatic toxicity of polycarboxylates are readily available. However, there are no published evaluations that estimate wastewater removal and characterize the probability of exceedance of acceptable chronic aquatic exposure. WW-TREAT can be used to estimate removal during wastewater treatment and PG-GRIDS can be applied to characterize risk for exceedance in wastewater treatment plant outfalls. After adjustments for the MW distribution of the homopolymer, WW-TREAT predicted that 6.5% will be removed in primary treatment plants and 60% will be removed in combined primary and activated sludge treatment plants. These estimates are consistent with wastewater fate tests, but underestimate homopolymer removal when homopolymer precipitation is included. Acceptable levels of chronic outfall (receiving water) exposure were based on aquatic toxicity testing in algae, fish, and Daphnia magna. PG-GRIDS predicted that no unreasonable risk for exceedance of acceptable chronic exposure will occur in the outfalls of U.S. wastewater plants. Future development of wastewater treatment models should consider polymer MW distribution and precipitation as factors that may alter removal of materials from wastewater.

Acrylates↗

Cytomegalovirus infection following liver transplantation: review of the literature.

Cytomegalovirus (CMV) remains a major cause of problems following solid organ transplantation, accounting for a significant increase in morbidity and affiliated costs. Infection with CMV following orthotopic liver transplantation (OLT) is commonly seen as a result of marked cell-mediated immunosuppression and is an independent risk factor for opportunistic and fungal infections. The role of CMV infection in acute cellular or chronic rejection remains unclear. Recent advances in diagnostic modalities, particularly the use of the antigenemia assay and the polymerase chain reaction, have provided ways to quantitate viral load during infection or disease, as well as providing a useful marker of response to therapy. Ganciclovir remains the best antiviral agent for the treatment of CMV disease, but the use of combination therapy with other antivirals or CMV immunoglobulin may improve outcome for patients with severe disease. The ideal prophylactic therapy for patients undergoing OLT remains to be identified, as tested regimens have shown variable efficacy when analyzed with regard to defined risk groups. The use of risk group-specific prophylaxis may prove to be most successful, however, in terms of efficacy and cost savings. Future advances in basic CMV virology and transplant immunology will be essential in defining rational approaches to control and prevention of CMV infection and disease following liver transplantation.

Animals↗

The Quality in Australian Health Care Study.

A review of the medical records of over 14,000 admissions to 28 hospitals in New South Wales and South Australia revealed that 16.6% of these admissions were associated with an "adverse event", which resulted in disability or a longer hospital stay for the patient and was caused by health care management; 51% of the adverse events were considered preventable. In 77.1% the disability had resolved within 12 months, but in 13.7% the disability was permanent and in 4.9% the patient died.

Adolescent↗

Influence of lead on mineralization during bone growth.

Lead will inhibit skeletal development and localize in areas of bone formation and resorption, but the mechanisms of lead toxicity in bone are largely unknown. This study used an ectopic bone (plaque) induction method to investigate the effect of lead on mineralization of cartilage in growing bone. Demineralized bone matrix was subcutaneously implanted in male Long-Evans rats to induce plaque formation. Of 64 rats which were provided deionized water, 32 were implanted with control matrix (control group). The remaining 32 rats were implanted with matrix containing a target concentration of 200 micrograms lead/g of plaque tissue as ectopic bone (lead-added group). Another group of 32 rats was continuously exposed to 1000 ppm lead in drinking water and subcutaneously implanted with control matrix (drinking water-lead group). Plaques were taken for analysis on Days 8 and 12 postimplantation. Alkaline phosphatase activity and cartilage mineralization were obliterated in lead-added plaques. However, calcium deposition was markedly enhanced in the lead-added plaques. Decreased alkaline phosphatase in Day 8 drinking water-lead plaques followed increased Day 12 drinking water lead plaque calcification. Enhanced cartilage calcification and reduced alkaline phosphatase activity in the drinking water-lead plaques was consistent with effects observed in the metaphyseal regions of bone in lead-exposed rats and pigs. The results of this study suggest that lead adversely influences bone development through disruption of mineralization during growth.

Alkaline Phosphatase↗