Substance use and mental health factors associated with self-reported higher risk cannabis use among people with HIV screened in primary care.

Background: While cannabis use is prevalent among people with HIV (PWH), factors associated with higher-risk use require further study. We examined factors associated with indicators risk for cannabis use disorder (CUD) among PWH who used cannabis. Methods: Participants included adult (≥18 years old) PWH from 3 HIV primary care clinics in Kaiser Permanente Northern California who reported past three-month cannabis use through the computerized Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) screening. Primary outcome was TAPS cannabis score (range 1-3), categorized as any use (1) and higher risk for CUD (≥2). Measures included sociodemographics (age, sex, race, neighborhood deprivation index [NDI]), Charlson Comorbidity Index (CCI), HIV RNA, CD4 cell counts, higher risk tobacco use (TAPS tobacco score≥2), depression, and anxiety symptoms. Unadjusted and multivariable logistic regression examined factors associated with higher risk for CUD. Results: Of the complete sample (N=978; 94.1% Male; 58.3% White; Age Mode=51-60), 35.8% reported higher risk for CUD. Unadjusted models indicated younger age, Black race, higher CCI, depression, anxiety, and higher risk tobacco use were associated with higher risk, while only Black race (OR=1.84, 95% CI[1.29, 2.63]), anxiety (OR=1.91, 95% CI[1.22, 2.98]), and higher risk tobacco use (OR=2.27, 95% CI[1.47, 3.51]) remained significant in the multivariable model. Conclusions: Black race, anxiety and tobacco use, but not HIV clinical markers, were associated with higher risk for CUD among PWH. Clinical efforts to screen and provide interventions for preventing CUD alongside anxiety and tobacco use among PWH should be evaluated.

γδT Cells Are Essential for Orthodontic Tooth Movement.

Sustained mechanical forces applied to tissue are known to shape local immunity. In the oral mucosa, mechanical stress, either naturally induced by masticatory forces or externally via mechanical loading during orthodontic tooth movement (OTM), is translated, in part, by T cells to alveolar bone resorption. Nevertheless, despite being considered critical for OTM, depletion of CD4+ and CD8+ T cells is reported to have no impact on tooth movement, thus questioning the function of αßT cells in OTM-associated bone resorption. To further address the role of T cells in OTM, we first characterized the leukocytes residing in the periodontal ligament (PDL), the tissue of interest during OTM, and compared it to the neighboring gingiva. Unlike the gingiva, monocytes and neutrophils represent the major leukocytes of the PDL. These myeloid cells were also the main leukocytes in the PDL of germ-free mice, although at lower levels than SPF mice. T lymphocytes were more enriched in the gingiva than the PDL, yet in both tissues, the relative fraction of the γδT cells was higher than the αß T cells. We thus sought to examine the role of γδT cells in OTM. γδT cells residing in the PDL were mainly Vγ6+ and produced interleukin (IL)-17A but not interferon-γ. Using Tcrd-GDL mice allowing conditional ablation of γδT cells in vivo, we demonstrate that OTM was greatly diminished in the absence of γδT cells. Further analysis revealed that ablation of γδT cells decreased early IL-17A expression, monocyte and neutrophil recruitment, and the expression of the osteoclastogenic molecule receptor activator of nuclear factor-κß ligand. This, eventually, resulted in reduced numbers of osteoclasts in the pressure site during OTM. Collectively, our data suggest that γδT cells are essential in OTM for translating orthodontic mechanical forces to bone resorption, required for relocating the tooth in the alveolar bone.

Third trimester-equivalent ethanol exposure causes micro-hemorrhages in the rat brain.

Exposure to ethanol during fetal development produces long-lasting neurobehavioral deficits caused by functional alterations in neuronal circuits across multiple brain regions. Therapeutic interventions currently used to treat these deficits are only partially efficacious, which is a consequence of limited understanding of the mechanism of action of ethanol. Here, we describe a novel effect of ethanol in the developing brain. Specifically, we show that exposure of rats to ethanol in vapor chambers during the equivalent to the third trimester of human pregnancy causes brain micro-hemorrhages. This effect was observed both at low and high doses of ethanol vapor exposure, and was not specific to this exposure paradigm as it was also observed when ethanol was administered via intra-esophageal gavage. The vast majority of the micro-hemorrhages were located in the cerebral cortex but were also observed in the hypothalamus, midbrain, olfactory tubercle, and striatum. The auditory, cingulate, insular, motor, orbital, retrosplenial, somatosensory, and visual cortices were primarily affected. Immunohistochemical experiments showed that the micro-hemorrhages caused neuronal loss, as well as reactive astrogliosis and microglial activation. Analysis with the Catwalk test revealed subtle deficits in motor function during adolescence/young adulthood. In conclusion, our study provides additional evidence linking developmental ethanol exposure with alterations in the fetal cerebral vasculature. Given that this effect was observed at moderate levels of ethanol exposure, our findings lend additional support to the recommendation that women abstain from consuming alcoholic beverages during pregnancy.

Red grape berry-cultured cells reduce blood pressure in rats with metabolic-like syndrome.

PURPOSE: Cumulative evidence suggests that moderate red wine consumption protects the cardiovascular system. The effect of cultured cells derived from red grape berry (RGC) on blood pressure (BP) has not been investigated. We therefore studied the antihypertensive effects of oral consumption of RGC in experimental rat model of metabolic-like syndrome and assessed its effect on human umbilical vein endothelial cells (HUVECs). METHODS: Forty male Sprague-Dawley rats were fed for 5 weeks with either a high fructose diet (HFD) (n = 10) or HFD supplemented, during the last 2 weeks, with different doses (200, 400 and 800 mg/kg/day) of RGC suspended in their food (n = 30). BP, plasma triglycerides, insulin and adiponectin levels were measured at the beginning and after 3 and 5 weeks of diet. RGC effect on vasodilatation was evaluated by its ability to affect endothelin-1 (ET-1) production and endothelial nitric oxide synthase (eNOS) expression in HUVECs. RESULTS: BP, plasma triglycerides, insulin and adiponectin increased significantly in rats fed with a HFD. The increase in BP, plasma triglycerides and insulin was attenuated by RGC supplementation. Incubation of HUVECs with RGC demonstrated a concentration-dependent inhibition of ET-1 secretion and increase in the level of eNOS, signaling a positive effect of RGC on vasodilatation. CONCLUSION: In rats with metabolic-like syndrome, RGC decreased BP and improved metabolic parameters. These beneficial effects may be mediated by the cell constituents, highly rich with polyphenols and resveratrol, reside in their natural state.

Circumstances at HIV diagnosis and progression of disease in older HIV-infected Americans.

OBJECTIVES: This study identified age-related differences in diagnosis and progression of HIV by analyzing a nationally representative sample of HIV-infected adults under care in the United States. METHODS: We compared older (> or = 50 years) and younger participants stratified by race/ethnicity. Regression models controlled for demographic, therapeutic, and clinical factors. RESULTS: Older non-Whites more often had HIV diagnosed when they were ill. Older and younger patients were clinically similar. At baseline, however, older non-Whites had fewer symptoms and were less likely to have AIDS, whereas at follow-up they had a trend toward lower survival. CONCLUSIONS: Later HIV diagnosis in non-Whites merits public health attention; clinical progression in this group requires further study.

Expenditures for the care of HIV-infected patients in the era of highly active antiretroviral therapy.

BACKGROUND: The introduction of expensive but very effective antiviral medications has led to questions about the effects on the total use of resources for the care of patients with human immunodeficiency virus (HIV) infection. We examined expenditures for the care of HIV-infected patients since the introduction of highly active antiretroviral therapy. METHODS: We interviewed a random sample of 2864 patients who were representative of all American adults receiving care for HIV infection in early 1996, and followed them for up to 36 months. We estimated the average expenditure per patient per month on the basis of self-reported information about care received. RESULTS: The mean expenditure was $1,792 per patient per month at base line, but it declined to $1,359 for survivors in 1997, since the increases in pharmaceutical expenditures were smaller than the reductions in hospital costs. Use of highly active antiretroviral therapy was independently associated with a reduction in expenditures. After adjustments for the interview date, clinical status, and deaths, the estimated annual expenditure declined from $20,300 per patient in 1996 to $18,300 in 1998. Expenditures among subgroups of patients varied by a factor of as much as three. Pharmaceutical costs were lowest and hospital costs highest among underserved groups, including blacks, women, and patients without private insurance. CONCLUSIONS: The total cost of care for adults with HIV infection has declined since the introduction of highly active antiretroviral therapy. Expenditures have increased for medications but have declined for other services. However, there are large variations in expenditures across subgroups of patients.

The impact of state policy on the costs of HIV infection.

There is substantial variation in the generosity of public assistance programs that affect HIV+ patients, and these differences should affect the economic outcomes associated with HIV infection. This article uses data from a nationally representative sample of HIV+ patients to assess how differences across states in Medicaid and AIDS Drug Assistance Programs (ADAP) affect costs and labor market outcomes for HIV+ patients in care in that state. Making ADAP programs more generous in terms of drug coverage would reduce per patient total monthly costs, mainly through a reduction in hospitalization costs. In contrast, expanding ADAP eligibility by increasing the income threshold would increase the total cost of care. Expanding eligibility for Medicaid through the medically needy program would increase per patient total costs, but full-time employment would increase and so would monthly earnings. The authors conclude that more generous state policies toward HIV+ patients--especially those designed to provide access to efficacious treatment--could improve the economic outcomes associated with HIV.

Use of unpaid and paid home care services among people with HIV infection in the USA.

This paper examines utilization of paid and unpaid home health care using data from a nationally representative sample of HIV-positive persons receiving medical care in early 1996 (N = 2,864). Overall, 21.0% used any home care, 12.2% used paid care and 13.6% used unpaid care. Most (70.0%) users of home care received care from only one type of provider. Substantially more hours of unpaid than paid care were used. We also found evidence of a strong association between type of service used and type of care provider: 62.4% of persons who used nursing services only received paid care only; conversely, 55.5% of persons who used personal care services only received care only from unpaid caregivers. Use of home care overall was concentrated among persons with AIDS: 39.5% of persons with AIDS received any home health care, compared to 9.5% of those at earlier disease stages. In addition to having an AIDS diagnosis, logistic regression analyses indicated that other need variables significantly increased utilization; a higher number of HIV-related symptoms, lower physical functioning, less energy, a diagnosis of CMV and a recent hospitalization each independently increased the odds of overall home care utilization. Sociodemographic variables had generally weak relationships with overall home care utilization. Among users of home care, non-need variables had more influence on use of paid than unpaid care. Both paid and unpaid home health care is a key component of community-based systems of care for people with HIV infection. The results presented in this paper are the first nationally representative estimates of home care utilization by persons with HIV/AIDS and are discussed with reference to policy and future research.

Access of vulnerable groups to antiretroviral therapy among persons in care for HIV disease in the United States. HCSUS Consortium. HIV Cost and Services Utilization Study.

OBJECTIVE: To employ the behavioral model of health services use in examining the extent to which predisposing, enabling, and need factors explain the treatment of the HIV-positive population in the United States with highly active antiretroviral therapy (HAART). DATA SOURCE: A national probability sample of 2,776 adults under treatment for human immunodeficiency virus (HIV) infection. STUDY DESIGN: The article uses data from the baseline and six-month follow-up surveys. The key independent variables describe vulnerable population groups including women, drug users, ethnic minorities, and the less educated. The dependent variable is whether or not a respondent received HAART by December 1996. DATA COLLECTION: All interviews were conducted using computer-assisted personal interview instruments designed for this study. Ninety-two percent of the baseline interviews were conducted in person and the remainder over the telephone. PRINCIPAL FINDINGS: A multistage logit regression shows that the predisposing factors that have previously described vulnerable groups in the general population with limited access to medical care also define HIV-positive groups who are less likely to gain early access to HAART including women, injection drug users, African Americans, and the least educated (odds ratios, controlling for need, ranged from 0.35 to 0.59). CONCLUSIONS: Those HIV-positive persons with the greatest need (defined by a low CD4 count) are most likely to have early access to HAART, which suggests equitable access. However, some predisposing and enabling variables continue to be important as well, suggesting inequitable access, especially for African Americans and lower-income groups. Policymakers and clinicians need to be sensitized to the continued problems of African Americans and other vulnerable populations in gaining access to such potentially beneficial therapies. Higher income, anonymous test sites, and same-day appointments are important enabling resources.

National probability samples in studies of low-prevalence diseases. Part I: Perspectives and lessons from the HIV cost and services utilization study.

OBJECTIVE: To examine the trade-offs inherent in selecting a sample design for a national study of care for an uncommon disease, and the adaptations, opportunities and costs associated with the choice of national probability sampling in a study of HIV/AIDS. SETTING: A consortium of public and private funders, research organizations, community advocates, and local providers assembled to design and execute the study. DESIGN: Data collected by providers or collected for administrative purposes are limited by selectivity and concerns about validity. In studies based on convenience sampling, generalizability is uncertain. Multistage probability sampling through households may not produce sufficient cases of diseases that are not highly prevalent. In such cases, an attractive alternative design is multistage probability sampling through sites of care, in which all persons in the reference population have some chance of random selection through their medical providers, and in which included subjects are selected with known probability. DATA COLLECTION AND PRINCIPAL FINDINGS: Multistage national probability sampling through providers supplies uniquely valuable information, but will not represent populations not receiving medical care and may not provide sufficient cases in subpopulations of interest. Factors contributing to the substantial cost of such a design include the need to develop a sampling frame, the problems associated with recruitment of providers and subjects through medical providers, the need for buy-in from persons affected by the disease and their medical practitioners, as well as the need for a high participation rate. Broad representation from the national community of scholars with relevant expertise is desirable. Special problems are associated with organization of the research effort, with instrument development, and with data analysis and dissemination in such a consortium. CONCLUSIONS: Multistage probability sampling through providers can provide unbiased, nationally representative data on persons receiving regular medical care for uncommon diseases and can improve our ability to accurately study care and its outcomes for diseases such as HIV/AIDS. However, substantial costs and special circumstances are associated with the implementation of such efforts.

Job continuity among new mothers.

In the early 1990s, both state and federal governments enacted maternity-leave legislation. The key provision of that legislation is that after a leave of a limited duration, the recent mother is guaranteed the right to return to her preleave employer at the same or equivalent position. Using data from the National Longitudinal Survey of Youth, we correlate work status after childbirth with work status before pregnancy to estimate the prevalence, before the legislation, of returns to the preleave employer. Among women working full-time before the pregnancy, return to the prepregnancy employer was quite common. Sixty percent of women who worked full-time before the birth of a child continued to work for the same employer after the child was born. Furthermore, the labor market behavior of most of the remaining 40% suggests that maternity-leave legislation is unlikely to have a major effect on job continuity. Compared with all demographically similar women, however, new mothers have an excess probability of leaving their jobs.

Variation in inpatient resource use in the treatment of HIV: do the privately insured receive more care?

OBJECTIVE: To estimate the impact of insurance status on inpatient resource use after adjusting for health upon admission and site of care. DESIGN: Detailed patient information linked to billing records from the AIDS Cost and Service Utilization Survey (ACSUS), a longitudinal analysis of inpatient and outpatient care between March 1991 and August 1992. SETTING: Hospitalizations of human immunodeficiency virus (HIV) patients from 10 US cities with high incidence of AIDS. PATIENTS: One thousand, nine hundred and forty nine adolescents and adults at various stages of HIV. MAIN OUTCOME MEASURES: We estimate inpatient charges, payments and length of stay as a function of patient, and provider and reimbursement characteristics for more than 1,500 hospitalizations to HIV patients. We control for patient characteristics and underlying risk factors including disease stage, CD4 percentage, mode of transmission, discharge status, type of admission, and region. We use hospital-fixed effects to control for unmeasured differences across facilities. RESULTS: Unadjusted means indicate that uninsured patients or patients covered by public insurance have significantly lower charges and payments than privately insured patients with similar medical conditions. We find that those differences are substantially reduced after controlling for the hospital in which care is received. Further, we find little evidence that "underinsured" patients are discharged sooner on average. CONCLUSIONS: Inpatient resource use is affected by both the hospital in which care is received and the type of patient admitted. Failure to control for unmeasured differences across hospitals is likely to overstate the impact of insurance substantially.

The care of HIV-infected adults in the United States. HIV Cost and Services Utilization Study Consortium.

BACKGROUND AND METHODS: In order to elucidate the medical care of patients with human immunodeficiency virus (HIV) infection in the United States, we randomly sampled HIV-infected adults receiving medical care in the contiguous United States at a facility other than military, prison, or emergency department facility during the first two months of 1996. We interviewed 76 percent of 4042 patients selected from among the patients receiving care from 145 providers in 28 metropolitan areas and 51 providers in 25 rural areas. RESULTS: During the first two months of 1996, an estimated 231,400 HIV-infected adults (95 percent confidence interval, 162,800 to 300,000) received care. Fifty-nine percent had the acquired immunodeficiency syndrome according to the case definition of the Centers for Disease Control and Prevention, and 91 percent had CD4+ cell counts of less than 500 per cubic millimeter. Eleven percent were 50 years of age or older, 23 percent were women, 33 percent were black, and 49 percent were men who had had sex with men. Forty-six percent had incomes of less than $10,000 per year, 68 percent had public health insurance or no insurance, and 30 percent received care at teaching institutions. The estimated annual direct expenditures for the care of the patients seen during the first two months of 1996 were $5.1 billion; the expenditures for the estimated 335,000 HIV-infected adults seen at least as often as every six months were $6.7 billion, which is about $20,000 per patient per year. CONCLUSIONS: In this national survey we found that most HIV-infected adults who were receiving medical care had advanced disease. The patient population was disproportionately male, black, and poor. Many Americans with diagnosed or undiagnosed HIV infection are not receiving medical care at least as often as every six months. The total cost of medical care for HIV-infected Americans accounts for less than 1 percent of all direct personal health expenditures in the United States.

A computer alert system to prevent injury from adverse drug events: development and evaluation in a community teaching hospital.

CONTEXT: Adverse drug events (ADEs) are the most common type of iatrogenic injury occurring in hospitalized patients. Errors leading to ADEs are often due to restricted availability of information at the time of physician order writing. OBJECTIVES: To develop, implement, and evaluate a computer alert system designed to correct errors that might lead to ADEs and to detect ADEs before maximum injury occurs. DESIGN: Prospective case series. SETTING: A 650-bed community teaching hospital in Phoenix, Ariz. PATIENTS: Consecutive sample of 9306 nonobstetrical adult patients admitted during the last 6 months of 1997. INTERVENTIONS: Thirty-seven drug-specific ADEs were targeted. Our hospital information system was programmed to generate alerts in clinical situations with increased risk for ADE-related injury. A clinical system was developed to ensure physician notification of alerts. MAIN OUTCOME MEASURES: A true-positive alert was defined as one in which the physician wrote orders consistent with the alert recommendation after alert notification. RESULTS: During the 6-month study period, the alert system fired 1116 times and 596 were true-positive alerts (positive predictive value of 53%). The alerts identified opportunities to prevent patient injury secondary to ADEs at a rate of 64 per 1000 admissions. A total of 265 (44%) of the 596 true-positive alerts were unrecognized by the physician prior to alert notification. CONCLUSIONS: Clinicians can use hospital information systems to detect opportunities to prevent patient injury secondary to a broad range of ADEs.