Alcohol and drug use severity are independently associated with antiretroviral adherence in the current treatment era.

Substance use in people with HIV (PWH) negatively impacts antiretroviral therapy (ART) adherence. However, less is known about this in the current treatment era and the impact of specific substances or severity of substance use. We examined the associations of alcohol, marijuana, and illicit drug use (methamphetamine/crystal, cocaine/crack, illicit opioids/heroin) and their severity of use with adherence using multivariable linear regression in adult PWH in care between 2016 and 2020 at 8 sites across the US. PWH completed assessments of alcohol use severity (AUDIT-C), drug use severity (modified ASSIST), and ART adherence (visual analogue scale). Among 9400 PWH, 16% reported current hazardous alcohol use, 31% current marijuana use, and 15% current use of ≥1 illicit drugs. In multivariable analysis, current methamphetamine/crystal use, particularly common among men who had sex with men, was associated with 10.1% lower mean ART adherence (p < 0.001) and 2.6% lower adherence per 5-point higher severity of use (ASSIST score) (p < 0.001). Current and more severe use of alcohol, marijuana, and other illicit drugs were also associated with lower adherence in a dose-dependent manner. In the current HIV treatment era, individualized substance use treatment, especially for methamphetamine/crystal, and ART adherence should be prioritized.

HCV viraemia associates with NK cell activation and dysfunction in antiretroviral therapy-treated HIV/HCV-co-infected subjects.

The impact of hepatitis C virus (HCV) RNA levels on immune status in chronically HCV mono-infected when compared to HIV/HCV co-infected on antiretroviral therapy (ART) remains poorly understood. A total of 78 African American subjects HCV viraemic/naïve to HCV treatment (33 HCV genotype 1 mono-infected, 45 ART-treated HIV/HCV genotype 1 co-infected) were studied. Clinical and liver enzyme measurements were performed. Whole blood was analysed for immune subset changes by flow cytometry. Peripheral blood mononuclear cells (PBMC) were used for same-day constitutive and in vitro Interferon (IFN)-α-induced signal transducer and activator of transcription (STAT) phosphorylation, K562 target cell lysis and K562 target cell recognition-mediated IFN-γ production. Statistical analysis was performed using R (2.5.1) or JMP Pro 11. While both groups did not differ in the level of liver enzymes, HIV/HCV had higher T-cell activation/exhaustion, and constitutive STAT-1 phosphorylation compared to HCV. In contrast, CD4+ FoxP3+ CD25+ frequency, IFN-αR expression on NK cells, as well as constitutive and IFN-α-induced direct cytotoxicity were lower in HIV/HCV. Linear regression models further supported these results. Finally, increase in HCV viral load and CD4+ T-cell count had an opposite effect between the two groups on NK cell activity and T-cell activation, respectively. HCV viral load in ART-treated HIV/HCV co-infection was associated with greater immune activation/exhaustion and NK dysfunction than HCV viral load alone in HCV mono-infection. The more pronounced immune modulation noted in ART-treated HIV-co-infected/untreated HCV viraemic subjects may impact HCV disease progression and/or response to immunotherapy.

Assessing risk of a short-term antiretroviral therapy discontinuation as a read-out of viral control in immune-based therapy.

Although analytical treatment interruption is used as a strategy to test immunotherapeutic agents in HIV-infection, it may pose a risk for study participants. The potential risks of short-term interruption of antiretroviral therapy (ART) during treatment with an autologous dendritic cell immune-based therapy (AGS-004-001) were assessed using data from a subgroup of subjects in the strategies for management of antiretroviral therapy (SMART) study with matched eligibility criteria. A retrospective subgroup analysis of the SMART study population using the eligibility criteria and treatment stopping rules of AGS-004-001 study was analyzed. Key inclusion criteria for AGS-004-001 study were applied to the data collected from participants of the SMART study. There were 440 of 2,720 on the drug conservation arm and 436 of 2,752 on the viral suppression arm that matched the AGS-004-001 inclusion criteria and were used in the SMART subgroup analysis. In the first 16 weeks following randomization into the SMART study there were no deaths in either subgroup. There were two AIDS-related events in the drug conservation subgroup and one in the viral suppression subgroup, making the overall risk of AIDS-related events 2 per 100 person years (0.005%) and 1 per 100 person years (0.002%) in the two subgroups, respectively. There were 6/440 subjects (1.4%) in the drug conservation subgroup and 4/436 subjects (0.92%) in the viral suppression subgroup who experienced Grade 2 adverse events. These results demonstrated that analytical treatment interruption within the context of highly selective, closely monitored studies assessing the antiviral activity of immune-based agents should be an acceptable strategy for at least 16 weeks.

Necrotizing fasciitis complicating intravenous drug abuse.

Two cases of necrotizing fasciitis in intravenous cocaine abusers are presented to alert the medical community to the possibility of these severe infections in such addicts. Antimicrobial therapy should include agents effective against Bacteroides species, streptococci, and Gram-negative aerobes; therapy directed only against staphylococci and Gram-negative aerobes is not sufficient.

Screening for diabetic retinopathy. The wide-angle retinal camera.

OBJECTIVE: To define the test characteristics of four methods of screening for diabetic retinopathy. RESEARCH DESIGN AND METHODS: Four screening methods (an exam by an ophthalmologist through dilated pupils using direct and indirect ophthalmoscopy, an exam by a physician's assistant through dilated pupils using direct ophthalmoscopy, a single 45 degrees retinal photograph without pharmacological dilation, and a set of three dilated 45 degrees retinal photographs) were compared with a reference standard of stereoscopic 30 degrees retinal photographs of seven standard fields read by a central reading center. Sensitivity, specificity, and positive and negative likelihood ratios were calculated after dichotomizing the retinopathy levels into none and mild nonproliferative versus moderate to severe nonproliferative and proliferative. Two sites were used. All patients with diabetes in a VA hospital outpatient clinic between June 1988 and May 1989 were asked to participate. Patients with diabetes identified from a laboratory list of elevated serum glucose values were recruited from a DOD medical center. RESULTS: The subjects (352) had complete exams excluding the exam by the physician's assistant that was added later. The sensitivities, specificities, and positive and negative likelihood ratios are as follows: ophthalmologist 0.33, 0.99, 72, 0.67; photographs without pharmacological dilation 0.61, 0.85, 4.1, 0.46; dilated photographs 0.81, 0.97, 24, 0.19; and physician's assistant 0.14, 0.99, 12, 0.87. CONCLUSIONS: Fundus photographs taken by the 45 degrees camera through pharmacologically dilated pupils and read by trained readers perform as well as ophthalmologists for detecting diabetic retinopathy. Physician extenders can effectively perform the photography with minimal training but would require more training to perform adequate eye exams. In this older population, many patients did not obtain adequate nonpharmacological dilation for use of the 45 degrees camera.

Dose-escalation, phase I/II study of azithromycin and pyrimethamine for the treatment of toxoplasmic encephalitis in AIDS.

OBJECTIVE: To assess the safety, tolerance and activity of increasing doses of azithromycin in combination with pyrimethamine for the treatment of toxoplasmic encephalitis (TE) in patients with AIDS. DESIGN: A phase I/II dose-escalation study of oral azithromycin in combination with pyrimethamine. SETTING: Eight clinical sites in the United States. PATIENTS: Forty-two adult HIV-infected patients with confirmed or presumed acute TE. METHODS: Patients were enrolled into three successive cohorts receiving azithromycin 900, 1200 and 1500 mg a day with pyrimethamine as induction therapy. The induction period was 6 weeks followed by 24 weeks of maintenance therapy. MAIN OUTCOME MEASURES: Patient response was evaluated clinically and radiologically. RESULTS: Of the 30 evaluable patients, 20 (67%) responded to therapy during the induction period. Ten experienced disease progression. Of the 15 patients who received maintenance therapy, seven (47%) relapsed. Six patients discontinued treatment during the induction period as a result of reversible toxicities. Treatment-terminating adverse events occurred most frequently among the patients receiving the 1500 mg dose. CONCLUSION: The combination of azithromycin (900-1200 mg a day) and pyrimethamine may be useful as an alternative therapy for TE among patients intolerant of sulfonamides and clindamycin, but maintenance therapy with this combination was associated with a high relapse rate. The combination was safe, but low-grade adverse events were common.

Reduced environmental exposure to aerosolized ribavirin using a simple containment system.

To minimize the exposure of health care workers to aerosolized ribavirin, we designed a double tent containment system with circulating mist and suction applied between the tents and we evaluated the ability of this system to contain and evacuate aerosolized ribavirin. While the drug was administered with this system at three institutions, three air sampling pumps at different locations in the room and one worn by the investigator (personal breathing zone) collected air samples onto filters for assay of ambient ribavirin. Ribavirin determinations were made by high performance liquid chromatography. A 5- to greater than 20-fold decrease in ambient ribavirin concentrations was observed with the containment system compared with those detected with a single oxyhood in use. The personal breathing zone concentration was 566.0 micrograms/m3 with the oxyhood alone and fell to a mean concentration of 43.81 +/- 33.40 micrograms/m3 with the containment system. Though the risk to exposed health care workers is unknown, this system offers a simple way to decrease significantly occupational exposure to ribavirin.

Gender differences in early suspicion of tuberculosis in hospitalized, high-risk patients during 4 epidemic years, 1987 to 1990.

OBJECTIVES: To assess the degree to which, from 1987 to 1990, physicians suspected tuberculosis (TB) in the first 2 hospital days in human immunodeficiency virus (HIV)-infected patients with pulmonary disease. DESIGN: Retrospective cohort study. SETTING: 96 hospitals in five US cities. PATIENTS: 2,174 adult patients with acquired immunodeficiency syndrome discharged with a diagnosis of Pneumocystis carinii pneumonia from 1987 to 1990. The diagnosis generally was not known on admission. RESULTS: Physicians suspected TB in the first 2 hospital days in 66% of these patients in 1987, a rate that increased steadily to 74% in 1990. However, the extent to which physicians considered TB among female patients decreased from 76% to 71% over the 4 years. Controlling for confounding variables by multiple logistic regression, the odds that TB would be suspected early increased 1.8-fold among men (odds ratio [OR], 1.8; 95% confidence interval [CI95], 1.4-2.4), but not in women (OR, 0.6; CI95, 0.2-1.9). Among the five cities, the odds of early suspicion of TB increased most in New York City (OR, 3.9; CI95, 2.0-7.9). CONCLUSIONS: Physicians considered TB in a timely manner in an increasing majority of male, but not female, high-risk patients during the first years of TB resurgence in the United States. Physicians must be aware of the changing epidemiology of HIV and TB, as well as their practice patterns, to prevent nosocomial transmission of this disease.

Antioxidants and antioxidant enzymes protect against pulmonary oxygen toxicity in the rabbit.

Two major lines of defense exist against oxidant lung injury: tissue antioxidants and antioxidant enzymes. We studied pretreatment with the antioxidants, vitamin E and butylated hydroxyanisole (BHA), and the antioxidant enzymes, superoxide dismutase (SOD) and catalase, in rabbits exposed to 100% O2 for 48 h. BHA (200 mg/kg ip) or vitamin E (50-100 mg/kg po) were given for 2 or 3 days, respectively, before O2 exposure. Combined therapy with polyethylene glycol- (PEG) conjugated SOD (12 mg/kg) and catalase (200,000 U/kg) was given intraperitoneally 1 h before and 24 h after beginning 100% O2. Hyperoxia significantly increased the pulmonary content of malondialdehyde, indicating enhanced lipid peroxidation. One hundred percent O2 also increased lung weight gain and alveolar-capillary permeability to aerosolized 99mTc-labeled diethylenetriaminepentaacetate (99mTc-DTPA, 500 mol wt) and fluorescein isothiocyanate-labeled dextran (7,000 mol wt). Pretreatment with vitamin E, BHA, or the combination of PEG-SOD and PEG-catalase prevented the increase in malondialdehyde, lung weight gain, and alveolar-capillary permeability caused by hyperoxia. These results indicate that augmenting either tissue antioxidants or antioxidant enzymes can prevent the pulmonary injury caused by 48 h of 100% O2 in rabbits.

Hyperbaric oxygen toxicity: role of thromboxane.

Exposing rabbits for 1 h to 100% O2 at 4 atm barometric pressure markedly increases the concentration of thromboxane B2 in alveolar lavage fluid [1,809 +/- 92 vs. 99 +/- 24 (SE) pg/ml, P less than 0.001], pulmonary arterial pressure (110 +/- 17 vs. 10 +/- 1 mmHg, P less than 0.001), lung weight gain (14.6 +/- 3.7 vs. 0.6 +/- 0.4 g/20 min, P less than 0.01), and transfer rates for aerosolized 99mTc-labeled diethylenetriamine pentaacetate (500 mol wt; 40 +/- 14 vs. 3 +/- 1 x 10(-3)/min, P less than 0.01) and fluorescein isothiocyanate-labeled dextran (7,000 mol wt; 10 +/- 3 vs. 1 +/- 1 x 10(-4)/min, P less than 0.01). Pretreatment with the antioxidant butylated hydroxyanisole (BHA) entirely prevents the pulmonary hypertension and lung injury. In addition, BHA blocks the increase in alveolar thromboxane B2 caused by hyperbaric O2 (10 and 45 pg/ml lavage fluid, n = 2). Combined therapy with polyethylene glycol- (PEG) conjugated superoxide dismutase (SOD) and PEG-catalase also completely eliminates the pulmonary hypertension, pulmonary edema, and increase in transfer rate for the aerosolized compounds. In contrast, combined treatment with unconjugated SOD and catalase does not reduce the pulmonary damage. Because of the striking increase in pulmonary arterial pressure to greater than 100 mmHg, we tested the hypothesis that thromboxane causes the hypertension and thus contributes to the lung injury. Indomethacin and UK 37,248-01 (4-[2-(1H-imidazol-1-yl)-ethoxy]benzoic acid hydrochloride, an inhibitor of thromboxane synthase, completely eliminate the pulmonary hypertension and edema.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical use of androgenic steroids at a major medical center: who prescribes androgens and how well do they do it?

To assess prescribing practices for androgens at Wilford Hall USAF Medical Center, the authors analyzed prescriptions for all patients receiving therapy during a 12-month period (n = 201) and reviewed the available outpatient records not maintained elsewhere (n = 105). The most commonly prescribed androgens were testosterone enanthate (144/201; 56.7%), and danazol (52/201; 25.9%). Review of the available outpatient medical records of 73 male patients using testosterone enanthate showed a mean age of 59.5 years, mean frequency of injection of 20 days, mean duration of therapy of 3.5 years, and mean dose of 226 mg. Therapy was initiated by a urologist (34/73; 46.6%), an endocrinologist (33/73; 45.2%), or an internist (6.73; 8.2%). Indications for therapy based on pretreatment laboratory and historical data included hypergonadotropic hypogonadism (24/73; 32.9%), hypogonadotropic hypogonadism (23/73; 31.5%), unspecified hypogonadism (7/73; 9.6%), and empiric treatment of elderly men with erectile dysfunction without evidence of hypogonadism (9/73; 26%). Pretreatment prostate examinations as well as measurement of serum testosterone (66/73; 90.4%) and serum gonadotropins (52/73; 71.2%) were often not performed. The authors conclude that records of patients treated with androgens show: 1) Doses are appropriate; 2) Empiric treatment of erectile dysfunction in elderly men is common despite the associated risks; 3) Laboratory and physical evaluation before treatment is often incomplete; 4) There was no evidence of androgenic substance abuse in patients studied.

Maximizing life's potentials in AIDS: a psychopharmacologic update.

Psychiatric factors play a major role in the AIDS pandemic. They have an impact on transmission, morbidity, coping, adherence, and quality of life and of death. Substance-related disorders are associated with HIV transmission through needle sharing, sexual transmission, exchange of sex for drugs, and perinatal transmission. Persons with AIDS have a high prevalence of substance-related disorders, mood disorders, dementia, mania, and delirium. Persons with AIDS require complex medications, including combination antiretroviral therapy and prophylaxis and treatment for opportunistic infections and cancers. Recognition and treatment of distressing symptoms can maximize life's potentials and enhance adherence with risk prevention and with care. We describe an integrated approach to the use of psychotropic medications in the care of persons with AIDS. With the new antiretroviral therapies available, psychotropic medications can be helpful in alleviating distressing symptoms, promoting less risk taking, and adhering to complex medical care. The intricacies and complexities of new medical and psychopharmacological issues are delineated in order to enable caregivers help persons with AIDS to maximize life's potentials.

Passive immunization for the treatment of HIV infection.

Neutralizing antibodies are a component of the immune response to acute human immunodeficiency virus infection. Levels of these antibodies diminish with the clinical progression of HIV disease. The results of several clinical studies of humoral passive immunization for advanced HIV disease suggest no clear antiviral or immune-enhancing effect. However, some studies reported delay in the occurrence of opportunistic infections and prolongation of life. Further studies are needed to more specifically define the role of humoral immune response in preventing and controlling HIV infection, and the potential for augmentation of these responses in prophylaxis and treatment.

Thalidomide: a remarkable comeback.

The thalidomide product is a racemic mixture of the L- and D-enantiomeric forms of a synthetic glutamic acid derivative that contains a phthalimide ring and a glutarimide ring. Initially marketed as a sedative, it was withdrawan from the world market after it was found to be associated with severe birth defects. Recently, the compound has generated renewed interest because of its immunomodulatory and anti-angiogenic properties. The nature of its immunologic effects is under active investigation. It is orally bioavailable and can be administered in once daily dosing. Its primary route of metabolism is spontaneous hydrolysis. In controlled clinical trials, thalidomide has proven effective in the treatment of erythema nodosum leprosum, oral and oesophageal aphthous ulceration associated with advanced HIV infection and oral ulceration associated with Behcet's syndrome. Promising results have been obtained in preliminary studies of other immunologic and neoplastic disorders, but controlled clinical studies are still lacking for these entities. Adverse effects include teratogenicity, peripheral neuropathy and sedation. In the US, thalidomide can be prescribed only through a restricted drug distribution program.

The radiology of necrotizing enterocolitis.

Imaging of necrotizing enterocolitis is frustrating, with no single imaging test that is both sensitive and specific for the diagnosis. Early, nonspecific findings on plain abdominal films before development of pneumatosis intestinalis is enough evidence in the proper clinical setting to institute medical treatment of necrotizing enterocolitis. Subsequent development of pneumatosis intestinalis will help confirm the clinical diagnosis, but treatment should not be withheld for its development. Delayed complications of necrotizing enterocolitis can be diagnosed by contrast enema examinations, and ultrasound is a helpful additional test in equivocal cases.

Human immunodeficiency virus and hepatitis B virus infections in a New York City alcoholic population.

Alcoholics have previously been reported to have an increased susceptibility to hepatitis B virus (HBV) infection. Since human immunodeficiency virus (HIV) is transmitted in a similar fashion, we studied 143 consecutive in- and outpatient alcoholics residing in New York City for HIV and HBV prevalence and associated risk factors. Of these alcoholics, 19 (13%) individuals were HIV positive, 57 (40%) were hepatitis B seropositive. Intravenous drug use and sexual contact with an IV drug user were the most important risk behaviors for HIV acquisition, with large numbers of partners and anal heterosexual intercourse being lesser factors. The only significant risk behavior determined for hepatitis B infection was IV drug use. These high-risk behaviors did not appear to be related to episodes of alcoholic intoxication. However, it is conceivable that alcoholism may, in other ways, affect susceptibility to HIV infection.

Changes in thyroid function and serum iodine levels after prepartum use of a povidone-iodine vaginal lubricant.

To determine if application of iodide to vaginal mucosa of pregnant women results in significant iodide absorption or changes in thyroid function, we studied 18 intrapartum women for whose examinations during labor povidone-iodine gel was used as a lubricant and 16 for whose examinations an iodine-free lubricant was used. Both serum inorganic iodine and total serum iodine increased significantly (p less than 0.001) after iodide exposure and fell (p = 0.003) to near baseline within two days. In both groups, serum thyroxine and triiodothyronine fell during labor and delivery; differences between groups were not significant. In the iodine-treated group, however, there was a significant increase in thyroid-stimulating hormone at two days postpartum (p less than 0.001). Iodide applied to vaginal mucosa of pregnant women is absorbed and affects the maternal pituitary-thyroid axis.

Switching requirements in a Head Start classroom.

Two experiments were conducted by the mothers of the children in a Head Start classroom. Both examined the effects of a switching task on the frequency with which children moved from one activity area of the classroom to another. The results indicated that the rate at which the children changed activities could be adjusted by varying the difficulty or magnitude of the switching task and that the task itself could be used to introduce academic subjects which would be poorly attended if initially presented in an activity area.

Stressful life events and accidents at school.

High school is a time of stress for most adolescents. School nurses need to be aware of the high levels of stress and the potential relationship stress has to accidental injury in order to plan better preventive care along with teachers, counselors, and coaches.

Effect of directional response variables on eye-hand reaction times and decision time.

To determine if direction of response affects reaction time, we measured the time for hand response to a visual stimulus, using a sensitive, microprocessor-based testing device to determine simple reaction time (RT), choice RT, and decision time. Mean simple RT was 207 +/- 3.7 msec. (mean +/- SEM); mean choice RT was 268 +/- 4.2 msec; and mean decision time was 61 msec. No differences were noted for leftward versus rightward movements, or midline versus lateral movements. Choice RT increased by 1.49 msec./yr. of age. Simple RT increased significantly with age for the nondominant hand, but not for the dominant hand. Right-handed subjects were more rapid with the dominant hand for choice RT. We conclude that dominance of hand tested and test initiation mechanism have major effects, but direction of movement in the lateral plane has little effect on reaction time.