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Biomedical subjects

D Cotton

Publications and source records attributed to D Cotton.

At least 19 recordsLinked to original sources

Safer sex decision-making among men with haemophilia and HIV and their female partners.

An exploratory qualitative study of adult heterosexual men with haemophilia and HIV and women who were their sexual partners was conducted as formative research to better understand cognitive factors involved in behavioural intentions and practices which comprise HIV risk-reduction for sexual transmission. The study sought to generate hypotheses, uncover themes, and develop a broad perspective on possible determinants of behaviours related to HIV transmission risk reduction. Qualitative analysis of these data served as a basis for developing a subsequent quantitative, hypothesis-testing survey and an intervention. Face-to-face interviews were conducted with 23 single men and 28 married men with haemophilia and HIV infection, and 28 married women partners selected through stratified, purposeful sampling. The interviews identified beliefs, attitudes, and values underlying decisions regarding target behaviours related to preventing sexual transmission of HIV, including (1) using condoms consistently during vaginal intercourse and (2) talking to partners about risk reduction. The interviews elicited information about perceived advantages and disadvantages of performing each of the targeted behaviours, and factors that facilitate or prevent performing them. Qualitative analysis of coded responses yielded important themes regarding how choices are made about sexual activity and safer sex. Most notably, communication between partners (1) plays a direct, key role in facilitating condom use and (2) forms the basis for maintaining emotional intimacy in these relationships. The link between condom use and communicating about safer sex was viewed as pivotal in achieving HIV prevention for individuals in serodiscordant couples. Recommendations for risk reduction intervention development are discussed.

Adult↗

High prevalence of the very rare Wilson disease gene mutation Leu708Pro in the Island of Gran Canaria (Canary Islands, Spain): a genetic and clinical study.

The molecular basis of Wilson disease (WD), an autosomal recessive disorder, is the presence of mutations in the ATP7B gene, a copper transporting ATPase. Hospital records indicated a higher prevalence of WD (1 in 2,600) in some counties in the northeastern region of the island of Gran Canaria (Canary Islands, Spain) that was around 10-fold higher than that described for European populations (1 in 30,000). The ATP7B gene was analyzed for mutations in 24 affected subjects, revealing a high prevalence of the rare Leu708Pro mutation present in 12 homozygous and 7 heterozygous individuals. In these patients, who constitute one of the largest described cohorts of WD homozygotes, we found a variable clinical presentation of the disease, although the biochemical picture was homogenous and characteristic, thereby confirming that the Leu708Pro change is indeed a mutation associated with WD. Haplotype analysis of subjects homozygous for the Leu708Pro mutation showed a conserved shared region smaller than 1 centimorgan (cM), and the region of linkage disequilibrium between the Leu708Pro mutation and neighboring microsatellite markers extended approximately 4.6 cM. When comparing the amount of linkage disequilibrium versus genetic distance from the disease mutation, it was estimated that a common ancestral Leu708Pro chromosome may have been introduced in Gran Canaria over 56 generations ago, dating it back to pre-Hispanic times. The prevalence, and the tight geographical distribution of the Leu708Pro chromosome suggests that the Canary Islands can be considered a genetic isolate for linkage disequilibrium studies.

Adenosine Triphosphatases↗

Evaluation and technical assistance for successful HIV program delivery.

Agencies that provide HIV prevention programs (including agencies using science-based interventions) need to conduct evaluation to facilitate the transfer of effective interventions, provide ongoing assistance to intervention providers, document services provided, demonstrate effectiveness, and improve programs. The Centers for Disease Control and Prevention (CDC) assists health departments, community-based organizations, and other CDC grantees with evaluation by providing direct, customized technical assistance and written guidance. Together, these activities assist grantees in conducting evaluations that provide the information that grantees need as their programs develop.

Centers for Disease Control and Prevention, U.S.↗

The association between primary source of ambulatory care and access to and outcomes of treatment among AIDS patients.

OBJECTIVES: To examine the relationship between having a primary source of ambulatory care (PSAC), access to AIDS treatment and prophylaxis for opportunistic infection, and hospital and mortality outcomes among heterosexual men and women with AIDS. METHODS: Using a linked AIDS Registry-Medicaid database, 366 adults were identified (1989-1991) with at least 1 year of continuous Medicaid enrollment before AIDS diagnosis, who survived 2 weeks after diagnosis, and with no antiretroviral use or Pneumocystis carinii pneumonia (PCP) prophylaxis during the pre-diagnosis year. Outcomes included times to zidovudine treatment, PCP prophylaxis, hospitalization and death following diagnosis. Multivariate proportional hazards models were used to estimate the effects of patients' PSAC status in the 12-month post-diagnosis period on outcomes, controlling for demographic and case-mix variables. RESULTS: Study criteria preferentially included females, non-whites and enrollees eligible on the basis of aid to families with dependent children. A total of 49% of the patients had no PSAC. Patients with a PSAC were more likely to have received zidovudine [relative risk (RR) = 1.75, 95% confidence interval (CI) = 1.2, 2.2] or PCP prophylaxis (RR = 2.22, 95% CI = 1.5, 3.3). Regression models simultaneously examining association of the propensity to use zidovudine and PCP prophylaxis agents with death indicated that zidovudine-treated and PCP-prophylaxed patients were 64% and 51% less likely to die, respectively (RRdeath,zidovudine = (.36, 95% CI = 0.2, 0.4; RRdeath, PCP prophylaxis = 0.49, 95% CI = 0.3, 0.8). CONCLUSIONS: Patients' underuse of zidovudine and PCP prophylaxis was systematically associated with not having a PSAC. Lack of PSAC, in turn, predicted shorter survival but not increased hospitalization. Female gender, injecting drug use, non-white race and earlier diagnosis year also predicted poorer outcomes.

AIDS-Related Opportunistic Infections↗

Perspective: human immunodeficiency virus type 1 (HIV-1) RNA end points in HIV clinical trials: issues in interim monitoring and early stopping.

Due to the desire to both shorten the length and reduce the size of clinical trials in human immunodeficiency virus (HIV) disease, the use of surrogate end points such as HIV-1 RNA is becoming increasingly standard. While these end points may be reasonable surrogates for the clinical effectiveness of drugs, a key point in their use as trial end points is the definition of a relevant duration of antiviral response. This definition is often complicated by the desire to perform interim reviews of ongoing laboratory end point trials. Unlike clinical end point trials, in which early clinical response is generally indicative of longer-term follow-up, it is yet to be determined whether short-term viral response adequately predicts the long-term durability of that response.

Acquired Immunodeficiency Syndrome↗

Transdermal testosterone administration in women with acquired immunodeficiency syndrome wasting: a pilot study.

Although human immunodeficiency virus (HIV) disease is increasing rapidly among women, no prior studies have investigated gender-based therapeutic strategies for the treatment of acquired immunodeficiency syndrome (AIDS) and its complications in this population. Markedly decreased serum androgen levels have been demonstrated in women with AIDS and may be a contributing factor to the wasting syndrome in this population. To assess the effects of androgen replacement therapy in women with AIDS wasting, we conducted a randomized, placebo-controlled, pilot study of transdermal testosterone administration. The primary aim of the study was to determine efficacy in terms of the change in serum testosterone levels, safety parameters and tolerability. A secondary aim of the study was to investigate testosterone effects on weight, body composition, quality of life, and functional indexes. Fifty-three ambulatory women with the AIDS wasting syndrome defined as weight less than 90% of ideal body weight or weight loss of more than 10% of the preillness maximum, free of new opportunistic infection within 6 weeks of study initiation, and with screening serum levels of free testosterone less than the mean of the normal reference range (< 3 pg/mL) were enrolled in the study. Subjects were age 37 +/- 1 yr old (mean +/- SEM), weighed 92 +/- 2% of ideal body weight, and had lost 17 +/- 1% of their maximum weight. CD4 count was 324 +/- 36 cells/mm3, and viral burden was 102,382 +/- 28,580 copies. Subjects were randomized into three treatment groups, in which two placebo patches (PP), one active/one placebo patch (AP group), or two active patches (AA group) were applied twice weekly to the abdomen for 12 weeks. The expected nominal delivery rates of testosterone were 150 and 300 microg/day, respectively, for the AP and AA groups. Forty-five subjects completed the study (PP group, n = 13; AP group, n = 14; AA group, n = 18). Two additional subjects from the PP group and two from the AP group were included in the intent to treat analysis. Serum free testosterone levels increased significantly from 1.2 +/- 0.2 to 5.9 +/- 0.8 pg/mL (AP) and from 1.9 +/- 0.4 to 12.4 +/- 1.6 pg/mL (AA) in response to testosterone administration (P < 0.0001 for comparison of AA vs. PP and AP vs. PP; normal range, 1.3-6.8 pg/mL). Testosterone administration was generally well tolerated locally and systemically, with no adverse trends in hirsutism scores, lipid profiles, or liver function tests. Weight increased significantly in the AP group (1.9 +/- 0.7 kg) vs. the PP group (0.6 +/- 0.8 kg; P = 0.043), but did not increase significantly in the AA group (0.9 +/- 0.4 kg; P = 0.263 vs. PP, by mixed effects model assessing the interaction of time and treatment on all available data, one-tailed test). Improved social functioning (P = 0.024, by one-tailed test) and a trend toward improved pain score (P = 0.059) were observed in the AP vs. the PP-treated patients (RAND 36-Item Health Survey questionnaire). Five of six previously amenorrheic patients in the AP group had spontaneous resumption of menses compared to only one of four amenorrheic patients in the AA group (P = 0.045 for comparison of actual number of periods during the study). This study is the first investigation of testosterone administration in women with AIDS wasting. We demonstrate a novel method to augment testosterone levels in such patients that is safe and well tolerated during short term administration. At the lower of the two doses administered in this study, testosterone therapy was associated with positive trends in weight gain and quality of life. Higher, more supraphysiological, dosing was not associated with positive trends in weight or overall well-being. These data suggest that testosterone administration may improve the status of women with AIDS wasting. Further studies are needed to assess the effects of testosterone on weight in HIV-infected women and to define the optimal therapeutic window for test

Administration, Cutaneous↗

Increased vertical transmission of human immunodeficiency virus from hepatitis C virus-coinfected mothers. Women and Infants Transmission Study.

To determine if hepatitis C virus (HCV) infection affects vertical transmission of human immunodeficiency virus (HIV), 487 HIV-infected pregnant women in the prospective, multicenter, Women and Infants Transmission Study had HCV antibody (anti-HCV by second-generation ELISA) and HCV RNA (by quantitative polymerase chain reaction) measured in peripartum maternal plasma; 161 (33%) were anti-HCV-positive. HIV vertical transmission occurred from 42 HCV-infected mothers (26.1%) versus 53 HCV-uninfected mothers (16.3%; odds radio [OR], 1.82; P = .01). In a logistic regression model that included maternal drug use, a potential confounder, HCV infection was marginally associated with perinatal HIV transmission (OR, 1.64; P = .05), whereas drug use was not. Women who transmitted HIV had higher levels of HCV RNA (median, 721,254 copies/mL) than those who did not (337,561 copies/mL; P = .01). Maternal HCV infection is associated with increased HIV vertical transmission. Further studies are needed to ascertain if HCV directly affects perinatal HIV transmission or is a marker for another factor, such as maternal drug use.

Adult↗

Evaluation of the module on domestic violence at the UCLA School of Medicine.

Physicians and other hospital staff have a unique opportunity to assist victims of abuse. It is imperative that they develop the skills necessary to identify and diagnose cases and provide the support and referral services needed to help victims end the cycle of violence. This paper describes a comprehensive evaluation of the instructional design, implementation, and learning outcomes of the Domestic Violence Module at the University of California, Los Angeles (UCLA) School of Medicine to determine the effectiveness of this curriculum in helping medical students develop such skills. Expert reviewers found it to be an innovative, well-planned curriculum, and students and faculty tutors expressed a great deal of interest in and satisfaction with the course as a whole. However, the different evaluation components identified the same areas for improvement: (1) students need more opportunity to practice skills and receive feedback during the module, (2) there is inconsistency across classes in what is learned, and (3) tutors need better preparation sessions. The student outcomes reflected these needs and therefore suggest that the study may be useful in determining the components of an effective curriculum. After the training, the students reported significant increases in their feelings of self-efficacy and in their intentions, especially in comparison with a group of control students. Therefore, the module seems to be successful in inspiring medical students to work with victims of abuse.

California↗

Patterns of opportunistic infections in patients with HIV infection.

The pattern of the development of opportunistic infections (OIs) in HIV-infected patients was evaluated, based on a cohort of 1,530 patients enrolled in two AIDS Clinical Trials Group anti-retroviral studies. We quantified the increase in risk of OIs associated with the occurrence of a previous OI. This assessment was based on the observed event rates of the more common AIDS-defining OIs: Pneumocystis carinii pneumonia (PCP), Mycobacterium avium complex (MAC), cytomegalovirus (CMV), and a systemic mycosis. Additionally, for each OI, we assessed the relative risks associated with a history of prior OIs, changes in CD4 levels, and baseline prognostic factors. We found that the occurrence of each of these OIs increased the risk of subsequent OIs, even after adjusting for the CD4 count. Specifically, the occurrence of PCP significantly increased the risk of MAC and CMV, and somewhat increased the risk of systemic mycoses. Diagnosis with MAC was associated with an increased risk of subsequent CMV, whereas the occurrence of CMV increased the risk of MAC. Finally, once patients were diagnosed with a systemic mycosis, they were at a somewhat increased risk of subsequently developing MAC or CMV. Although current practice for determining the timing and initiation of prophylactic therapies relies chiefly on CD4 count, the occurrence of specific AIDS-defining OIs in patients with HIV infection should also be taken into account in making decisions regarding prophylaxis strategies.

AIDS-Related Opportunistic Infections↗

Third-trimester arterial blood gas and acid base values in normal pregnancy at moderate altitude.

OBJECTIVE: To report arterial blood gas and acid base values of normal nulliparous patients at moderate altitude for commonly used maternal positions. METHODS: Ten normotensive nulliparous women between 36 and 38 weeks' gestation volunteered to undergo radial and pulmonary artery cannulation as part of a larger study. Following instrumentation, baseline assessments were made in the left lateral recumbent position after a 30-minute stabilization period. Sequential measurements were then obtained in the left lateral, right lateral, supine, knee-chest, sitting, and standing positions. Blood samples were analyzed in duplicate for oxygen content on a blood gas analyzer. Statistical analysis was performed by analysis of variance of repeated measures with significance defined at P < or = .05. RESULTS: There was no significant difference in arterial blood gas or acid base values between any positions in this antepartum population of term healthy women. The composite mean values were as follows: pH 7.46, arterial carbon dioxide pressure (PaCO2) 26.6 mmHg, arterial oxygen pressure 88.3 mmHg, bicarbonate 18.2 mEq/L, saturated arterial hemoglobin level 0.96. CONCLUSION: Arterial blood gas and acid base values are not altered by maternal position in the late third trimester of pregnancy. The PaO2 in these women studied at moderate altitude was lower than previously reported for healthy pregnant women studied at sea level. Appropriate interpretation of arterial blood specimens of pregnant women should take into account both the pregnancy and altitude at which the women reside.

Acid-Base Equilibrium↗