Choice of Initial Combination Antiretroviral Therapy in Individuals With HIV Infection: Determinants and Outcomes

BACKGROUND Current guidelines give recommendations for preferred combination antiretroviral therapy (cART). We investigated factors influencing the choice of initial cART in clinical practice and its outcome. METHODS We analyzed treatment-naive adults with human immunodeficiency virus (HIV) infection participating in the Swiss HIV Cohort Study and starting cART from January 1, 2005, through December 31, 2009. The primary end point was the choice of the initial antiretroviral regimen. Secondary end points were virologic suppression, the increase in CD4 cell counts from baseline, and treatment modification within 12 months after starting treatment. RESULTS A total of 1957 patients were analyzed. Tenofovir-emtricitabine (TDF-FTC)-efavirenz was the most frequently prescribed cART (29.9%), followed by TDF-FTC-lopinavir/r (16.9%), TDF-FTC-atazanavir/r (12.9%), zidovudine-lamivudine (ZDV-3TC)-lopinavir/r (12.8%), and abacavir/lamivudine (ABC-3TC)-efavirenz (5.7%). Differences in prescription were noted among different Swiss HIV Cohort Study sites (P < .001). In multivariate analysis, compared with TDF-FTC-efavirenz, starting TDF-FTC-lopinavir/r was associated with prior AIDS (relative risk ratio, 2.78; 95% CI, 1.78-4.35), HIV-RNA greater than 100 000 copies/mL (1.53; 1.07-2.18), and CD4 greater than 350 cells/μL (1.67; 1.04-2.70); TDF-FTC-atazanavir/r with a depressive disorder (1.77; 1.04-3.01), HIV-RNA greater than 100 000 copies/mL (1.54; 1.05-2.25), and an opiate substitution program (2.76; 1.09-7.00); and ZDV-3TC-lopinavir/r with female sex (3.89; 2.39-6.31) and CD4 cell counts greater than 350 cells/μL (4.50; 2.58-7.86). At 12 months, 1715 patients (87.6%) achieved viral load less than 50 copies/mL and CD4 cell counts increased by a median (interquartile range) of 173 (89-269) cells/μL. Virologic suppression was more likely with TDF-FTC-efavirenz, and CD4 increase was higher with ZDV-3TC-lopinavir/r. No differences in outcome were observed among Swiss HIV Cohort Study sites. CONCLUSIONS Large differences in prescription but not in outcome were observed among study sites. A trend toward individualized cART was noted suggesting that initial cART is significantly influenced by physician's preference and patient characteristics. Our study highlights the need for evidence-based data for determining the best initial regimen for different HIV-infected persons.

Pancreatic endocrine function in cystic fibrosis

To characterize pancreatic endocrine secretion and to examine interrelationships among alterations in alpha, beta, and pancreatic polypeptide cell function in patients with cystic fibrosis (CF), we studied 19 patients with exocrine insufficiency (EXO), including 9 receiving insulin therapy (EXO-IT); 10 patients with no exocrine insufficiency (NEXO); and 10 normal control subjects. First-phase C-peptide response to intravenously administered glucose was significantly impaired in CF patients with exocrine insufficiency (EXO-IT = 0.02 +/- 0.01; EXO = 0.11 +/- 0.02; NEXO = 0.25 +/- 0.05; control subjects = 0.30 +/- 0.04 nmol/L). Lowering fasting glucose levels with exogenous insulin administration in EXO-IT did not improve beta cell responsivity to glucose. The C-peptide response to arginine was less impaired (EXO-IT = 0.12 +/- 0.02; EXO = 0.15 +/- 0.02; NEXO = 0.23 +/- 0.06; control subjects = 0.28 +/- 0.04 nmol/L). Alpha cell function, measured as peak glucagon secretion in response to hypoglycemia, was diminished in EXO but not NEXO (EXO-IT = 21 +/- 10; EXO = 62 +/- 19; NEXO = 123 +/- 29; control subjects = 109 +/- 12 ng/L). Despite diminished glucagon response, EXO patients recovered normally from hypoglycemia. Peak pancreatic polypeptide response to hypoglycemia distinguished CF patients with exocrine insufficiency from those without exocrine insufficiency (EXO-IT = 3 +/- 2; EXO = 3 +/- 1; NEXO = 226 +/- 68; control subjects = 273 +/- 100 pmol/L). Thus CF patients with exocrine disease have less alpha, beta, and pancreatic polypeptide cell function than CF patients without exocrine disease. These data suggest either that exocrine disease causes endocrine dysfunction in CF or that a common pathogenic process simultaneously and independently impairs exocrine and endocrine function.

Different dark conformations function in color-sensitive photosignaling by the sensory rhodopsin I-HtrI complex.

The haloarchaeal phototaxis receptor sensory rhodopsin I (SRI) in complex with its transducer HtrI delivers an attractant signal from excitation with an orange photon and a repellent signal from a second near-UV photon excitation. Using a proteoliposome system with purified SRI in complex with its transducer HtrI, we identified by site-directed fluorescence labeling a site (Ser(155)) on SRI that is conformationally active in signal relay to HtrI. Using site-directed spin labeling of Ser(155)Cys with a nitroxide side chain, we detected a change in conformation following one-photon excitation such that the spin probe exhibits a splitting of the outer hyperfine extrema (2A'(zz)) significantly smaller than that of the electron paramagnetic resonance spectrum in the dark state. The dark conformations of five mutant complexes that do not discriminate between orange and near-UV excitation show shifts to lower or higher 2A'(zz) values correlated with the alterations in their motility behavior to one- and two-photon stimuli. These data are interpreted in terms of a model in which the dark complex is populated by two conformers in the wild type, one that inhibits the CheA kinase (A) and the other that activates it (R), shifted in the dark by mutations and shifted in the wild-type SRI-HtrI complex in opposite directions by one-photon and two-photon reactions.

Temporal variations of dyspnea, fatigue, and lung function in chronic lung disease

Background. Research investigating symptom management in patients with chronic obstructive pulmonary disease (COPD) largely has been undertaken assuming the homeostatic construct, without regard to potential roles of circadian rhythms. Temporal relations among dyspnea, fatigue, peak expiratory flow rate (PEFR) and objective measures of activity/rest have not been reported in COPD. ^ Objectives. The specific aims of this study were to (1) explore the 24-hour patterns of dyspnea, fatigue, and PEFR in subjects with COPD; (2) examine the relations among dyspnea, fatigue, and PEFR in COPD; and (3) examine the relations among objective measures of activity/rest and dyspnea, fatigue, and PEFR in COPD. ^ Methods. The repeated-measures design involved 10 subjects with COPD who self-assessed dyspnea and fatigue by 100 mm visual analog scales, and PEFR by peak flow meter in their home 5 times a day for 8 days. Activity/rest was measured by wrist actigraphy. Single and population mean cosinor analyses and correlations were computed for dyspnea, fatigue, and PEFR; correlations were done among these variables and activity/rest. ^ Results. Circadian rhythms were documented by single cosinor analysis in 40% of the subjects for dyspnea, 60% for fatigue, and 60% for PEFR. The population cosinor analysis of PEFR yielded a significant rhythm (p < .05). The 8-day 24-hour means of dyspnea and fatigue was moderately correlated (r = .48, p < .01). Dyspnea and PEFR, and fatigue and PEFR, were weakly correlated in a negative way (r = −.11, p < .05 and r = −.15, p < .01 respectively). Weak to moderate correlations (r = .12–.34, p < .05) were demonstrated between PEFR and mean activity level measured up to 4 hours before PEFR measurement. ^ Conclusions. The findings suggest that (1) the dyspnea and fatigue experienced by COPD patients are moderately related, (2) there is a weak to modest positive relation between PEFR and activity levels, and (3) temporal variation in lung function may not affect the dyspnea and fatigue experienced by patients with COPD. Further research, examining the relations among dyspnea, fatigue, PEFR, and activity/rest is needed. Replication of this study is suggested with a larger sample size. ^

Revue des deux mondes.

Sér. 13, v. 1-5 omitted in numbering.

Abregé chronologique de l'histoire de France /

Mode of access: Internet.

Price-support program. : Hearings before the Committee on Agriculture and Forestry, United States Senate, Eighty-fourth Congress, first [-second] session, on proposed modifications of the general farm program.

Pt. 9 has subtitle: Hearing before the Committee on Agriculture and Forestry, United States Senate, Eighty-fourth Congress, second session, on the Veto message of the President on H.R. 12, the Agricultural act of 1946 (H. Doc. 380).

Booklet IL-700 /

Description based on: 1995 (R-12/95).

Entanglement of two atoms

We discuss the problem of creation of entangled states in a system of two two-level atoms which are separated by an arbitrary distance r(12) and interact with each other via the dipole-dipole interaction and both are driven by a laser field. The entangled antisymmetric state of the system is included throughout, even for small inter-atomic separations. Different mechanisms leading to effective transfer of population to the antisymmetric state are identified. The steady-state values of concurrence which is a measure of entanglement are calculated showing that perfect entanglement can be reached in case of two non-identical atoms.

Hedonisme en Eudemonisme bij Activiteiten in Verband met Depressieve Symptomen en Welbevinden bij Ouderen in Verpleeghuizen

Het onderzoek beoogt het vergroten van het inzicht in het verband tussen het ervaren van hedonisme en eudemonisme bij activiteiten enerzijds en depressie en welbevinden anderzijds bij ouderen op somatische afdelingen in verpleeghuizen, teneinde te kunnen bijdragen aan een verbetering van hun kwaliteit van leven. Het betrof een cross-sectioneel survey onderzoek met het ervaren hedonisme en eudemonisme als predictoren, de ernst van depressieve symptomen als primaire uitkomstmaat en welbevinden als secundaire uitkomstmaat. In totaal namen 59 bewoners deel aan dit onderzoek met een gemiddelde leeftijd van 87.9 jaar (SD = 5.9), waarvan 51 (86.4%) vrouwen. Bewoners met ernstige gedrags- of communicatiestoornissen werden uitgesloten. De mate van depressieve symptomen werd gemeten met de Geriatrische Depressie Schaal (GDS-8) (Gerritsen et al., 2007); de levenstevredenheid met de Satisfaction With Life Scale (SWSL) (Arrindell, Heesink, & Feij, 1999); het positief en negatief affect met de Positive and Negative Affect Schedule (PANAS) (Engelen, Peuter, Victoir, Diest, & Van den Bergh, 2006); de hedonische en eudemonische ervaringen bij activiteiten met een voor dit onderzoek ontwikkelde vragenlijst; en de afhankelijkheid bij de Activiteiten Dagelijks Leven (ADL) met de Barthel Index (Mahoney & Barthel, 1965). Er waren significante negatieve verbanden tussen depressieve symptomen en het ervaren van hedonisme, R² = .14, B = -.56, 95% Cl [-1.07, -.06] en van eudemonisme, R² = .12, B = -.53, 95% Cl [-1.05, .00]. De regressieanalyse van hedonisme én eudemonisme samen gaf echter geen significante effecten op depressieve symptomen. Opvallend was de sterke correlatie (r = .90) tussen hedonische en eudemonische ervaringen. Er zijn geen verbanden gevonden tussen het ervaren van hedonisme en eudemonisme aan de ene kant en het subjectief welbevinden aan de andere kant, te weten levenstevredenheid, positief en negatief affect. Echter bij instrumentele activiteiten van het dagelijks leven (o.a. boodschappen doen en bed opmaken) had eudemonisme een positief verband, R² = .20, B = 3.55, 95% Cl [.75, 6.34] en hedonisme een negatief verband, R² = .20, B = -2.71, 95% Cl [-.5.50, .08] met negatief affect.