Inhibition of gonadotropin-releasing hormone release as the basis of pituitary-gonadal dysfunction during treatment with 4-aminopyrazolo-(3,4-d)-pyrimidine

The inhibitor of hepatic lipoprotein release, 4-aminopyrazolo-(3,4-d)-pyrimidine (4-APP), has been shown to reduce testosterone production via impairment of pituitary gonadotropin secretion rather than through decreased cholesterol availability. It was previously shown that serum LH levels were reduced by more than 75% in male rats treated with 4-APP, but pituitary stores of LH and the gonadotropin response to exogenous GnRH were maintained. Also, there was a reduction in pituitary GnRH receptors which was consistent with hypothalamic GnRH deficiency. The present studies were undertaken to examine the mechanism by which 4-APP inhibits GnRH synthesis and/or release. Intact, adult male or 2-week ovariectomized female rats were treated daily with 25 mg/kg 4-APP for 3 days. Both sexes showed lowered basal serum levels of LH and absence of the elevations in serum LH normally elicited by the opiate antagonist, naloxone. In pituitary portal plasma collected from normal male rats, GnRH was significantly elevated by naloxone treatment, confirming that naloxone acted at the level of hypothalamic GnRH release. However, naloxone stimulation of GnRH secretion into portal blood was absent in rats treated with 4-APP. In vitro, the potassium-induced release of GnRH from perifused medial hypothalami was reduced by 60% in 4-APP-treated male rats while hypothalamic GnRH content remained unchanged. These data indicate that 4-APP has an inhibitory effect on the mechanism of GnRH release, and that analysis of its actions should clarify the processes involved in neurohormone secretion.     

Determining the Cost-Savings Threshold for HIV Adherence Intervention Studies for Persons with Serious Mental Illness and HIV

Persons with serious mental illnesses are at increased risk for contracting and transmitting HIV and often have poor adherence to medication regimens. Determining the economic feasibility of different HIV adherence interventions among individuals with HIV and serious mental illness is important for program planners who must make resource allocation decisions. The goal of this study was to provide a methodology to estimate potential cost savings from an HIV medication adherence intervention program for a new study population, using data from prior published studies. The novelty of this approach is the way CD4 count data was used as a biological marker to estimate costs averted by greater adherence to anti-retroviral treatment. Our approach is meant to be used in other adherence intervention studies requiring cost modeling.     

Cutaneous Acanthamoeba in a patient with AIDS: a case study with a review of new therapy; quiz 386

GOAL: To describe the presenting signs of an Acanthamoeba infection. OBJECTIVES: Upon completion of this activity, dermatologists and general practitioners should be able to: 1. Discuss the clinical presentation of Acanthamoeba infection. 2. Describe the conditions that make a patient susceptible to Acanthamoeba. 3. Outline treatment options for Acanthamoeba infection. CME: This article has been peer reviewed and approved by Michael Fisher, MD, Professor of Medicine, Albert Einstein College of Medicine. Review date: April 2001. This activity has been planned and implemented in accordance with the Essentials and Standards of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Albert Einstein College of Medicine and Quadrant HealthCom, Inc. The Albert Einstein College of Medicine is accredited by the ACCME to provide continuing medical education for physicians. Albert Einstein College of Medicine designates this educational activity for a maximum of 1.0 hour in category 1 credit toward the AMA Physician's Recognition Award. Each physician should claim only those hours of credit that he/she actually spent in the educational activity. This activity has been planned and produced in accordance with ACCME Essentials.     

Targeting the Use of Pooled HIV RNA Screening to Reduce Cost in Health Department STD Clinics: New York City, 2009–2011

Objective

Staff at public New York City sexually transmitted disease (STD) clinics screen patients for acute HIV infection (AHI) using pooled nucleic acid amplification tests. AHI screening is expensive but important for populations at high risk of acquiring HIV. We analyzed if targeting AHI screening in STD clinics could reduce program costs while maintaining AHI case detection.

Methods

From January 2009 through May 2010, we screened all patients with negative rapid HIV tests for AHI. Using risk information on cases detected during this universal screening period, we developed criteria for targeted AHI screening and compared case yields and testing costs during 12 months of universal screening (June 2009 through May 2010) vs. 12 months of targeted screening (June 2010 through May 2011).

Results

During the defined period of universal screening, we identified 40 AHI cases, and during targeted screening, we identified 35 AHI cases. Because of targeting efforts, the number needed to test to find one AHI case dropped from 1,631 to 254. With targeted screening, it cost an average of $4,535 per case detected and 39.3 cases were detected per 10,000 specimens; using universal screening, $29,088 was spent per case detected and 6.1 cases were detected per 10,000 specimens processed.

Conclusion

Targeted screening identified similar numbers of AHI cases as when screening all clinic patients seeking HIV testing, but at one-seventh the cost.During the acute phase of human immunodeficiency virus (HIV) infection (AHI), infected people are often unaware of their condition, as AHI symptoms—which include fever, sore throat, fatigue, myalgia, lymphadenopathy, rash, joint pain, night sweats, and diarrhea—are nonspecific.¹ During AHI, patients are highly viremic (and, thus, highly infectious), and antibodies to HIV have not yet developed.² This stage of infection, therefore, is not detected by traditional antibody tests. Detecting AHI requires nucleic acid amplification or antigen tests and enables infected people to adopt safer behaviors and be linked to earlier treatment and care, all of which may reduce HIV transmission.^3,4 A multisite study conducted in 14 clinics in New York City (NYC); Los Angeles, California; and four counties in Florida from 2006 to 2008 found that AHI screening, when added to point-of-care rapid testing, increased HIV detection by 8.2% across all sites; in three NYC clinics, 24% more HIV infections were detected using AHI screening than with HIV detection using rapid antibody tests alone (seven cases detected by nucleic acid amplification testing [NAAT]; 22 cases detected by rapid test).⁵ NAAT is an important tool for identifying AHI, and NAAT pooling methods (pNAATs) help to contain the costs of screening.⁶ By 2009, the NYC Department of Health and Mental Hygiene (NYC DOHMH) had implemented routine AHI screening via pNAAT for all patients with negative rapid HIV tests in all of its sexually transmitted disease (STD) clinics. At that time, the NYC DOHMH joined just a handful of state and local health departments in the United States that were routinely using pNAAT.⁷While AHI screening increased HIV detection in NYC STD clinics, it came at a considerable cost. Annualized other-than-personnel costs of this screening were more than $1 million, or approximately $30,000 per new diagnosis, which was as much as 16 times greater than the average cost of routine opt-out HIV screening in health-care facilities in the U.S.⁸ We present our evaluation of a strategy to reduce program costs while maintaining a high level of AHI case detection among clinic patients.