Leo B. Hurley

Where's the high-grade cervical neoplasia? The importance of minimally abnormal Papanicolaou diagnoses.

Objective To characterize the relative contributions of the different abnormal Papanicolaou smear cytologic diagnoses in the Bethesda System to the subsequent histologic diagnosis of high-grade cervical neoplasia. Methods A total of 46,009 nonpregnant female members of the Kaiser Permanente Health Plan, Northern California Region, were studied prospectively. The main outcome measures included routine Papanicolaou smear diagnoses and subsequent histologic diagnosis of colposcopically directed cervical tissue specimens. Results Atypical squamous cells of undetermined significance (ASCUS) was the most common abnormal Papanicolaou diagnosis, representing 3.6% of the total number of smears. Of the total number of cases of histologically confirmed high-grade cervical neoplasia present in the population, the largest proportion (38.8%) was in women with smears showing ASCUS. Minimal abnormalities combined (ASCUS, atypical glandular cells of undetermined significance, and low-grade squamous intraepithelial lesion) were coincident with 68.6% of the cases of histologic high-grade cervical neoplasia diagnosed in this routine screening population. Conclusion Recognition of the importance of equivocal and mild Papanicolaou test abnormalities in the subsequent diagnosis of high-grade cervical neoplasia emphasizes the need for accurate and cost-effective triage of the large population of women with minimally abnormal Papanicolaou diagnoses.

Effects of depression and selective serotonin reuptake inhibitor use on adherence to highly active antiretroviral therapy and on clinical outcomes in HIV-infected patients.

Objectives:To determine the impact of depression on highly active antiretroviral therapy (HAART) adherence and clinical measures and investigate if selective serotonin reuptake inhibitors (SSRIs) improve these measures. Design:Retrospective cohort study. Methods:In 2 large health maintenance organizations, we measured the effects of depression (with and without SSRI use) on adherence and changes in viral and immunologic control among HIV-infected patients starting a new HAART regimen. HAART adherence, HIV RNA levels, and changes in CD4 T-cell counts through 12 months were measured. Results:A total of 3359 patients were evaluated; 42% had a depression diagnosis, and 15% used SSRIs during HAART. Depression without SSRI use was associated with significantly decreased odds of achieving ≥90% adherence to HAART (odds ratio [OR] = 0.81, 95% confidence interval [CI]: 0.70 to 0.98; P = 0.03). Depression was associated with significantly lower odds of an HIV RNA level <500 copies/mL (OR = 0.77, 95% CI: 0.62 to 0.95; P = 0.02). Depressed patients compliant with SSRI medication (>80% adherence to SSRI) had HAART adherence and viral control statistically similar to nondepressed HIV-infected patients taking HAART. Comparing depressed with nondepressed HIV-infected patients, CD4 T-cell responses were statistically similar; among depressed patients, those compliant with SSRI had statistically greater increases in CD4 cell responses. Conclusions:Depression significantly worsens HAART adherence and HIV viral control. Compliant SSRI use is associated with improved HIV adherence and laboratory parameters.

Review of medical encounters in the 5 years before a diagnosis of HIV-1 infection: Implications for Early detection

Early detection of HIV infection improves prognosis and reduces transmission, but 30%–40% of cases are diagnosed late. A comprehensive and systematic review of medical encounters before diagnosis has not been done. This study reviews 5 years of medical encounters before the diagnosis of HIV infection in members of a large managed care organization where access to care is reasonably good. Patient characteristics, HIV risk factors, and clinical events preceding diagnosis were examined and tested for association with late diagnosis (CD4 cell count of <200/&mgr;L at diagnosis). Of 440 HIV-infected patients, 62% had CD4 cell counts of <350/&mgr;L, 43% had CD4 cell counts of <200/&mgr;L, and 18% had CD4 cell counts of <50/&mgr;L at diagnosis. Twenty-six percent of all patients had risks documented >1 year before diagnosis. Only 22% of patients had one of eight clinical indicators suggested in the literature as reasons to test for HIV >1 year before diagnosis. In multiple logistic regression, older age, male sex, race, risk group, no prior HIV testing, physician-initiated testing, and having any of eight clinical indicators before diagnosis were each associated with late diagnosis (p ≤ .05). Late diagnosis remains a challenge despite good access to care. In our setting, effective risk assessment before symptoms arise offers greater potential for raising the mean CD4 cell count at diagnosis than does increased awareness of selected HIV-associated clinical prompts.

HOME BLOOD PRESSURE MONITORING : EFFECT ON USE OF MEDICAL SERVICES AND MEDICAL CARE COSTS

The objective of this study was to determine whether a hypertension management program in which patients monitor their own blood pressure (BF) at home can reduce costs without compromising BP control. The prospective, randomized, controlled 1-year clinical trial was conducted at four medical centers of the Kaiser Permanente Medical Care Program in the San Francisco Bay Area. Of 467 patients with uncomplicated hypertension who were referred by their physicians, 37 declined to participate in the study; 215 were randomly assigned to a Usual Care (UC) group and 215 to a Home BP group. Twenty-five UC patients and 15 Home BP patients did not return for year-end BP measurements. Patients in the UC group were referred back to their physicians. Patients in the Home BP group were trained to measure their own BP and return the readings by mail. Patients were given a standard procedure to follow in case of unusually high or low BP readings at home. The number and type of outpatient medical services used were obtained from patient medical records for the study year and the prior year. Costs of care for hypertension were calculated by assigning relative value units to each outpatient service. Trained technicians measured each patients BP at entry into the study and 1 year later. Home BP patients made 1.2 fewer hypertension-related office visits than UC patients during the study year (95% confidence interval (CI): 0.8,1.7). Mean adjusted cost for physician visits, telephone calls, and laboratory tests associated with hypertension care was

Atypical glandular cells of undetermined significance (AGUS): Cytopathologic features, histopathologic results, and human papillomavirus DNA detection☆

88.76 per patient per year in the Home BP group, 29% less than in the UC group (95% CI:

Impact of tenofovir on renal function in HIV-infected, antiretroviral-naive patients.

16.11,

HIV-1 Protease and Reverse-Transcriptase Mutations: Correlations with Antiretroviral Therapy in Subtype B Isolates and Implications for Drug-Resistance Surveillance

54.74). The annualized cost of implementing the home BP system was approximately

Iron stores are not associated with acute myocardial infarction.

28 per patient during the study year and would currently be approximately

Immunodeficiency and risk of myocardial infarction among HIV-positive individuals with access to care.

15. After 1 year, BP control in men in the Home BP group was better than in men in the UC group; BP control was equally good in women in both groups. Management of uncomplicated hypertension based on periodic home BP reports can achieve BP control with fewer physician visits, resulting in substantial cost savings.

Response to Newly Prescribed Lipid-Lowering Therapy in Patients With and Without HIV Infection

We intensively reviewed 137 smears initially classified as atypical glandular cells of undetermined significance (AGUS) to refine cytological criteria for evaluating these cases, evaluate histological outcomes, and assess the value of human papillomavirus (HPV) DNA testing in management. Consenting, nonpregnant study participants were identified from a cohort of 46,009 women receiving routine Pap smear screening in a managed care setting. Colposcopy was performed on all women, and at least one histological sample was obtained from each. Review diagnoses were assigned to smears and biopsy specimens by two separate panels of pathologists. DNA testing for cancer-associated HPV types was performed on rinses of cytological samplers after a smear and thin-layer slide had been made. On review, 47 (34%) smears were reclassified as negative, 44 (32%) as AGUS, 30 (22%) as atypical squamous cells of undetermined significance (ASCUS), and 16 (12%) as squamous intraepithelial lesions (SIL). The 19 smears interpreted as high-grade intraepithelial lesions on review included 13 high-grade SIL (HSIL), two HSIL with AGUS, favor neoplastic (endocervical adenocarcinoma in situ [AIS]), and four AGUS, favor neoplastic (AIS). Review histological diagnoses were negative in 105 (77%), squamous or glandular atypia in four (3%), low-grade SIL (LSIL) in nine (7%), HSIL in 12 (9%), AIS in five (4%, including two with concurrent HSIL), and endometrial carcinoma in one (1%). HPV testing identified 11 (92%) of 12 women with histologically confirmed HSIL and all five with AIS (100%). A high-grade intraepithelial lesion or carcinoma is detected in approximately 14% of women with community-based diagnoses of AGUS who are referred for immediate evaluation. Use of refined cytological criteria and HPV DNA testing may permit improved management of women with AGUS.