Lopinavir protein binding in HIV‐1‐infected pregnant women

Background

Pregnancy may alter protein binding (PB) of highly bound protease inhibitors due to changes in plasma concentrations of albumin and α‐1 acid glycoprotein (AAG). Small changes in PB can greatly impact the fraction of drug unbound (FU) exerting pharmacological effect. We report lopinavir (LPV) PB during third trimester (antepartum, AP) compared to ≥1.7 weeks postpartum (PP) to determine if FU changes compensate for reduced total concentrations reported previously.

Methods

P1026s enrolled women receiving LPV/ritonavir, soft gel capsules 400/100 mg or 533/133 mg twice daily. LPV FU, albumin and AAG were determined AP and PP.

Results

AP/PP samples were available from 29/25 women respectively with all but one woman receiving the same dose AP/PP. LPV FU was increased 18% AP vs. PP (mean 0.96±0.16% AP vs. 0.82±0.21% PP, P=0.001). Mean protein concentrations were reduced AP (AAG=477 mg/L; albumin=3.28 mg/dL) vs. PP (AAG=1007 mg/L; albumin=3.85 mg/dL) (P<0.0001 for each comparison). AAG concentration correlated with LPV binding. Total LPV concentration did not correlate with LPV FU AP or PP. However, higher LPV concentration PP was associated with reduced PB and higher FU after adjustment for AAG.

Conclusions

LPV FU was higher and AAG lower AP vs. PP. The 18% increase in LPV FU AP is smaller than the reduction in total LPV concentration reported previously and is not of sufficient magnitude to eliminate the need for an increased dose during pregnancy.

     

Obituary for Razia Zaman and Shahanara Zaman Saroya

Pharmaceutical Research -     

Endocrine Profile of 45 Patients with Sertoli Cell Only Syndrome

Endokrines Profil bei 45 Männern mit Sertoli-Zell-Syndrom
Bei 45 Männern mit Sertoli-Zell-Syndrom wurden die Hormonbasiswerte für FSH, LH, Prolaktin und Testosteron mit denen von Klinefelter-Paitenten, Männern mit Oligozoospermie und gesunden, fertilen Männern verglichen. Dabei ergab sich, daß die FSH- und LH-Werte bei Sertoli-Zell-Syndrom signifikant höher lagen als bei Gesunden. Die Erhöhung der Gonadotropine bei Patienten mit Sertoli-Zell-Syndrom was allerdings nicht so hoch und Testosteron nicht so herabgesetzt wie man es bei Klinefelter-Paitenten gefunden hatte. Aus dem Resultat, daß die LH-Werte erhöhte waren, während Testosteron sich im normalen Rahmen bewegte wird die Schlußfolgerung gezogen, daß hier eine kompensierte Dysfunktion der Leydigzellen bei den Patienten mit Sertoli-Zell-Syndrom vorliegt. Für Oligozoo-spermie-Patienten ließ sich keine Differenz der Hormonwerte gegenüber Gesunden feststellen.     

Prognostic value of micrometastases in sentinel lymph nodes of patients with breast carcinoma: a cohort study

Background: The prognostic meaning and thus indication for adjuvanttherapy of lymphogenic micrometastases in breast cancer patientsis still under debate. Patients and methods: From 1999 to 2007, 703 patients with _cT_1–2N₀breast cancer underwent surgery including sentinel lymph nodebiopsy. Examination of sentinel lymph nodes consisted of hematoxylinand eosin and immunohistochemistry staining following serialsectioning of the sentinel node. Patients were divided intofour groups: _pN₀ (n = 423), _pN_1micro (n = 81), _pN_1a (n = 130)and _pN_1b (n = 69). Median follow-up was 40 months. Results: At the end of follow-up, 53 patients had died and 64had recurrent disease. Compared with _pN₀ and following adjustmentfor possible confounders, including adjuvant systemic treatment,overall survival was not significantly different for _pN_1microwhile significantly worse for _pN_1a and _pN_1b {hazard ratio (HR)[95% confidence interval (CI)]: 0.59 [0.14–2.58], 4.31[1.85–10.01], 10.66 [4.04–28.14], respectively}.Likewise, disease-free survival was not significantly differentfor _pN_1micro and worse for _pN_1a and _pN_1b (HR [95% CI]: 1.43[0.67–3.02], 2.79 [1.37–5.66], 7.13 [3.27–15.54],respectively). Distant metastases were more commonly observedin the _pN_1micro than in the _pN₀ group, but still not as commonas in the _pN_1a or _pN_1b group (HR [95% CI]: 4.85 [1.79–13.18],10.34 [3.82–28.00], 23.25 [7.88–68.56], respectively). Conclusion: Although the risk of distant metastases was higherin patients in the _pN_1micro than in the _pN₀ group, no statisticallysignificant differences were observed in overall or disease-freesurvival between _pN₀ and _pN_1micro. Micrometastatic lymph nodeinvolvement in itself should not be an indication for adjuvantchemotherapy in breast cancer patients. Key words: breast cancer, micrometastases, prognosis, sentinel lymph node Received for publication March 11, 2008. Revision received June 25, 2008. Accepted for publication July 1, 2008.     

Usability of quality measures for online health information: Can commonly used technical quality criteria be reliably assessed?

PURPOSE: Many criteria have been developed to rate the quality of online health information. To effectively evaluate quality, consumers must use quality criteria that can be reliably assessed. However, few instruments have been validated for inter-rater agreement. Therefore, we assessed the degree to which two raters could reliably assess 22 popularly cited quality criteria on a sample of 42 complementary and alternative medicine Web sites. METHODS: We determined the degree of inter-rater agreement by calculating the percentage agreement, Cohen's kappa, and prevalence- and bias-adjusted kappa (PABAK). RESULTS: Our un-calibrated analysis showed poor inter-rater agreement on eight of the 22 quality criteria. Therefore, we created operational definitions for each of the criteria, decreased the number of assessment choices and defined where to look for the information. As a result 18 of the 22 quality criteria were reliably assessed (inter-rater agreement > or = 0.6). CONCLUSIONS: We conclude that even with precise definitions, some commonly used quality criteria cannot be reliably assessed. However, inter-rater agreement can be improved with precise operational definitions.