Genotypic resistance profiles associated with virological failure to darunavir-containing regimens: a cross-sectional analysis.

INTRODUCTION: This study aimed at defining protease (PR) resistance mutations associated with darunavir (DRV) failure and PR resistance evolution at DRV failure in a large database of treatment-experienced human immunodeficiency virus (HIV) patients. RESULTS: Overall, 1,104 patients were included: 118 (10.7%) failed at a median observation time of 16 months. The mean number of PR mutations at baseline was 2.7, but it was higher in patients who subsequently failed DRV. In addition, the number of PR mutations increased at failure. The increase in the mean number of mutations was completely related to mutations considered to be associated with DRV resistance following the indications of the main DRV clinical trials. DISCUSSION: The higher statistical difference at baseline between failing versus non-failing patients was observed for the V32I and I84V mutations. At DRV failure, the major increase was still observed for V32I; I54L, V11I, T74P and I50V also increased. Despite the increment in the mean number of mutations per patient between baseline and failure, in 21 patients (17.8%) at baseline and 36 (30.5%) at failure, no PR mutation was detected. CONCLUSION: The HIV-DB interpretation algorithm identified few patients with full DRV resistance at baseline and few patients developed full resistance at DRV failure, indicating that complete resistance to DRV is uncommon.

NCQA requirements: friend or foe?

In this time of intensified cost-containment pressures and low funding for behavioral healthcare services, organizations are particularly sensitive to externally imposed requirements that add expense and administrative burden. As a tradeoff, the contribution of such requirements to the overall quality of behavioral health services is vitally important. The requirements of the National Committee for Quality Assurance (NCQA) have stimulated many intensely felt reactions among a wide range of managed behavioral healthcare stakeholders, undoubtedly because of the substantial impact those requirements are creating. The reactions portrayed in this dialogue section, from representatives of the payor, purchaser, provider and consumer communities and from NCQA itself, indicate the ambivalence stakeholders have toward the quality-assurance movement.

Human immunodeficiency virus-1 B and non-B subtypes with the same drug resistance pattern respond similarly to antiretroviral therapy.

We analysed the 12-week virological response to protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) therapy in 1108 patients carrying B or non-B human immunodeficiency virus (HIV)-1 subtypes with matched resistance mutation patterns. Response rates were not significantly different for non-B and B subtypes stratified for treatment status (51.5% vs. 41.5% in naïve patients; 46.7% vs. 38.7% in experienced patients) or regimens (46.9% vs. 39.7% with PI; 56.7% vs. 40% with NNRTI). No difference in response was detected in patients harbouring B and non-B subtypes with any resistance profile. Further studies are advisable to fully test this approach on larger datasets.

Prevalence of HIV-1 integrase mutations related to resistance to dolutegravir in raltegravir naïve and pretreated patients.

The prevalence of HIV-1 integrase mutations related to resistance to the next-generation integrase inhibitor (INI), dolutegravir (DTG), was assessed in 440 INI-naïve subjects and in 120 patients failing a raltegravir (RTG)-containing regimen. Of the mutations selected by DTG in vitro, S153FY was not detected in any isolate while L101I and T124A were highly prevalent in both groups and significantly associated with non-B subtype. RTG-selected double and triple mutants, mostly the G140S/Q148H variant, were detected in only 32 (26.7%) RTG-treated patients. As L101I and T124A do not appear to exert any major effect in vivo and double and triple mutants resistant to DTG are infrequently selected by RTG, DTG can be effectively used in INI-naïve patients and may retain activity in many patients failing RTG.

Sulphate-reducing bacteria in bovine faeces.

Sulphate-reducing bacteria (SRB) were found in all of 200 bovine faeces examined. The number of SRB in bovine faeces ranged from 5 x 10(2) to 6 x 10(8) bacteria g-1. Of 50 isolates identified, all were assigned to the genus Desulfovibrio.

Painless referrals.

Referrals, far and away the most burdensome administrative problem created by managed care, can be automated using secure, private intranets. Hundreds of primary care physicians and their offices in the Northwest have begun using this approach to reduce the approval time to get patients to specialists and to cut administrative costs. Combined with intranet delivery of laboratory and imaging test results, the service allows primary care physicians to fulfill their responsibility as overseers of the health care delivery process.

Pretreatment nausea in cancer chemotherapy: a conditioned response?

Many patients receiving cancer chemotherapy become nauseated as they anticipate their treatments. We studied this phenomenon in eighteen cancer chemotherapy patients. The eight patients who reported pretreatment nausea had more extensive disease than the other patients and had received twice as much chemotherapy. In most cases pretreatment nausea developed only a after a number of months of treatment. Nausea was usually precipitated by the odor of the clinic and similar odors elsewhere also caused nausea. Patients continued to experience nausea during follow-up visits after treatment was completed. This syndrome of pretreatment nausea can be understood as a classically conditioned response. Clinical recommendations can be made on this basis.

Tinnitus and ECT.

We report the case of a 69-year-old man with major depressive disorder and occupational tinnitus; both problems were refractory to several different treatment modalities, but were successfully treated with electroconvulsive therapy (ECT). The tinnitus was present for 15-20 years, but had worsened during the 3 years before treatment, causing him significant distress. Extensive organic workup did not identify a treatable etiology for his symptoms. To date, he has been hospitalized four times due to depressive symptoms associated with tinnitus. He has received ECT each time, and has responded well on each occasion.