Comparison of Preemptive Therapy and Antiviral Prophylaxis for Prevention of Cytomegalovirus in Seropositive Liver Transplant Recipients.

BACKGROUND: Few studies have directly compared preemptive therapy (PET) and antiviral prophylaxis (AP) for prevention of cytomegalovirus (CMV) disease in CMV seropositive (R+) orthotopic liver transplant (OLT) recipients. METHODS: We prospectively assessed CMV disease and clinical outcomes among 160 consecutive R+ OLT recipients who received PET (weekly plasma CMV PCR for 3 months, oral valganciclovir 900 mg twice daily for CMV viremia >250 IU/mL, until 2 consecutive negative weekly PCR results) and compared them with a historical cohort of 156 R+ recipients who received AP (valganciclovir, 900 mg daily for 3 months). RESULTS: Patient characteristics were similar between PET and AP cohorts (P > 0.05 all comparisons). In the PET group, 24% (39/160) developed CMV viremia greater than 250 IU/mL at a median of 42 (range, 7-93) days post-OLT. CMV monitoring adherence in the PET cohort was 85% (1488/1760 required tests) and 86% (30/36) initiated PET within 3 days of the CMV result. By 12 months post-OLT, the incidence of CMV disease, acute allograft rejection, major infection, or death in the PET and AP cohorts was not significantly different: 2% versus 2%, 19% versus 16%, 10.5% versus 10.8%, and 5% versus 8%, respectively (P > 0.05 all comparisons). The estimated proportion of drug-exposed patients and average antiviral drug exposure were significantly lower with PET versus AP: 24% versus 100%, P < 0.001, and 15.8 versus 81 g per patient, P < 0.001, respectively. CONCLUSIONS: PET is feasible in a nonresearch setting and is associated with similar CMV disease rates and other clinically relevant outcomes to AP in CMV seropositive liver transplant recipients.

The paradox of prematurity: the behavioral vulnerability of late preterm infants and the cognitive susceptibility of very preterm infants at 36 months post-term.

We explored associations among preterm status (very preterm infant (VPI: <30 weeks), moderate preterm (MPI: 30-33(6/7) weeks), late preterm (LPI: 34-36(6/7) weeks), parenting, and 3-year cognitive and behavioral outcomes. We hypothesized that LPIs would demonstrate better health and neurobehavioral outcomes compared with more premature infants, and that preterm status would moderate the association between parenting quality and 3-year outcomes. Sample included 123 preterm infants (gestation <37 weeks) and their mothers from a larger study of high-risk infants with measures of neonatal and socioeconomic risks at hospital discharge; maternal vocabulary at 9-months, child IQ and behavior at 36 months, and maternal depressive symptoms and parenting at all timepoints. Group differences were explored using MANOVAs while predictors of child outcomes were explored using hierarchical regression analyses. MANOVAs indicated that LPIs had more optimal neonatal health during the hospital stay, yet more externalizing (p=.043), aggressive (p=.006) and oppositional behaviors (p=.008) at 3 years compared with VPIs. There were no IQ differences between VPIs, MPIs and LPIs. However, preterm infants who experienced less negative parenting had higher IQs at 36 months (ß=-3.245, p=.017), with the greatest effects seen in VPIs (ß=0.406, p=.01) compared with LPIs (ß=0.148, p=.381). LPIs manifested similar IQ, but more externalizing, oppositional and aggressive behavior symptoms compared to VPIs. VPIs appeared to be differentially susceptible to parenting effects, with VPIs demonstrating the highest cognitive scores in the context of more positive parenting.

The cost, quality of life impact, and cost-utility of bariatric surgery in a managed care population.

Our purpose was to assess the cost, quality of life impact, and the cost-utility of bariatric surgery in a managed care population. We studied 221 patients who underwent bariatric surgery between 2001 and 2005. We analyzed medical claims data for all patients and survey data for 122 survey respondents (55% response rate). Patients were generally middle-aged, female, and white. Sixty-four percent underwent open and 33% underwent laparoscopic Roux-en-Y procedures. One year after surgery, mean body mass index fell from 51 to 31 kg/m(2) in women and from 59 to 35 kg/m(2) in men with substantial improvements in comorbidities. Postsurgical mortality and morbidity were low. Total per member per month costs increased in the 6 months before bariatric surgery, were lower in the 12 months after bariatric surgery, but increased somewhat over the next 12 months. When presurgical quality of life was assessed prospectively, average health utility scores improved by 0.14 one year after surgery. In analyses that took a lifetime time horizon, projected future costs based on age and obesity and discounted costs and health utilities at 3% per year, the cost-utility ratio for bariatric surgery versus no surgery was approximately $1,400 per quality-adjusted life-year gained. In sensitivity analyses, bariatric surgery was more cost-effective in women, non-whites, more obese patients, and when performed laparoscopically. Although not cost-saving, bariatric surgery represents a very good value for money. Its long-term cost effectiveness appears to depend on the natural history and cost of late postsurgical complications and the natural history and cost of untreated morbid obesity.

Unusual site of metastasis of bronchogenic carcinoma.

Metastasis of bronchogenic carcinoma to the chest wall and axillary lymphnodes is a rare occurrence. This study reports the case of a patient presenting with chest wall swelling as initial symptom which on evaluation was found to be a lymphnode metastasis. The patient also had axillary lymphnode metastasis on the same side as the chest swelling with a contralateral pleural effusion. Here, we discuss the pathways and possible mechanisms of contra lateral axillary and chest wall lymphnode involvement without ispilateral nodal involvement in bronchogenic carcinoma.

Novel indolo[2,1-b]quinazoline analogues as cytostatic agents: synthesis, biological evaluation and structure-activity relationship.

In our endeavor to design and synthesize novel anticancer agents, a new series of indoloquinazoline compounds were prepared and tested initially for anticancer activity in vitro against a panel of human cancer cell lines. Most of these compounds exhibited cytotoxic activity in in vitro screens. Compounds were selected and further evaluated using a modified Hollow Fiber Assay for their preliminary in vivo activity against 12 cell lines implanted in the subcutaneous and intraperitoneal compartments in mice. The results indicate that these compounds may constitute a new class of anticancer agents.

9-Deoxopodophyllotoxin derivatives as anti-cancer agents.

Several 9-deoxo-9-substituted podophyllotoxin derivatives were synthesised starting from naturally occuring podophyllotoxin and their anti-cancer activity was evaluated against in vitro human cancer cell line assay. It was observed that these compounds do possess good anti-cancer activity particularly against ovarian, renal and lung cancer cell lines.

Novel D-ring analogues of podophyllotoxin as potent anti-cancer agents.

Several D-ring modified analogues of podophyllotoxin were prepared viz semi-synthesis starting from naturally occurring podophyllotoxin and determined their in vitro anti-cancer activity. Most of the analogues have shown good activity towards human cancer cell lines.