Early assessment of the efficacy of a human papillomavirus type 16 L1 virus-like particle vaccine

A post hoc analysis was performed using combined data from two Phase I tolerability/immunogenicity studies of monovalent human papillomavirus type 11 (HPV11) or HPV16 L1 virus-like particle (VLP) vaccines. The goal was to determine if the HPV16 L1 VLP vaccine protected against HPV16 infection. Vaccine or placebo was given at 0, 2 and 6 months. HPV16 infection was defined by positive polymerase chain reaction (PCR) results following vaccination. The incidence of HPV infection was observed to be 0 cases per 100 person-years at risk in the vaccine group, and 5 cases per 100 person-years at risk in the control group. These results support the institution of larger efficacy trials for HPV L1 VLP vaccines.     

Intralenticular metal foreign body: case report

Intralenticular foreign bodies comprise about 5% to 10% of all intraocular foreign bodies and can result in serious complications. The management depends on some factors like size, location, material type and the risk of infection. We present a patient with an intralenticular metal foreign body in the left eye that, following initial treatment with topical steroid and antibiotic, underwent lens aspiration with removal of the intralenticular foreign body and insertion of a posterior chamber intraocular lens with good visual outcome.     

Invasive candidiasis treated in the intensive care unit: observations from a randomized clinical trial

OBJECTIVES: The objectives of this study were to contrast risk factors, microbiology, and outcomes in patients with invasive candidiasis treated in an intensive care unit (ICU) with those in patients with invasive candidiasis treated outside an ICU and to describe therapeutic results with caspofungin in ICU patients. MATERIALS AND METHODS: We retrospectively identified patients with documented invasive candidiasis who received their first dose of the study drug in the ICU as part of a double-blind randomized trial. Participants were not stratified at entry by their ICU status. Patients received caspofungin (50 mg/d after a 70-mg loading dose) or conventional amphotericin B (0.6-1.0 mg/kg per day) for 10 to 14 days. A favorable response required resolution of signs and symptoms as well as eradication of Candida pathogens. RESULTS: Of the 224 patients, 97 (43%) received their first dose of the study drug in the ICU. Most patients had well-recognized risk factors for invasive candidiasis, including broad-spectrum antibiotics, central venous catheters, and hyperalimentation. Recent surgery was more common whereas malignancy, neutropenia, and immunosuppression were less common among ICU patients than among non-ICU patients. Candidemia was demonstrated in 81% of ICU patients and in 84% of non-ICU patients. Favorable response rates in the ICU patients vs the non-ICU patients were 68% (95% confidence interval [CI] = 53%, 82%) vs 77% (95% CI = 67%, 87%) for caspofungin and 56% (95% CI = 43%, 69%) vs 67% (95% CI = 55%, 79%) for amphotericin B. After accounting for differences in APACHE (Acute Physiology and Chronic Health Evaluation) II score, neutropenia status, and geographic region, we found that patients initiating the study therapy in an ICU were still more likely to die than patients initiating study therapy outside an ICU. For ICU patients, all-cause mortality rates were 45% (95% CI = 30%, 60%) for caspofungin recipients and 40% (95% CI = 28%, 53%) for amphotericin B recipients, whereas candidiasis-attributable mortality rates were 5% (95% CI = 0%, 12%) for caspofungin recipients and 11% (95% CI = 3%, 19%) for amphotericin B recipients. Overall, drug-related adverse events were reported less often among the ICU patients than among the non-ICU patients. CONCLUSIONS: In ICU patients treated with antifungal therapy, invasive candidiasis is associated with substantial mortality, but most deaths cannot be directly attributed to this infection.     

Surgical treatment of severe pancreatic fistula after pancreaticoduodenectomy by wirsungostomy and repeat pancreatico-jejunal anastomosis

Background

After pancreaticoduodenectomy, severe pancreatic fistula may require salvage relaparotomy in patients with largely disrupted pancreaticojejunal anastomosis. Completion pancreatectomy remains the gold standard but yields high mortality and severe long-term repercussions. The authors report the results of a pancreas-preserving strategy used in this life-threatening condition.

Methods

Two hundred fifty-four pancreaticoduodenectomies with pancreaticojejunal anastomosis were performed between 2005 and 2011; 21 patients underwent salvage relaparotomy for grade C pancreatic fistula. Largely dehiscent pancreaticojejunal anastomoses were dismantled in 16 patients. Four patients underwent completion pancreatectomy, whereas in 12 patients detailed here, the remaining pancreas was preserved and drained by wirsungostomy with exteriorization or closure of the jejunal stump. Repeat pancreaticojejunal anastomosis was later planned to preserve pancreatic function.

Results

One patient died of recurrent hemorrhage on day 1 after wirsungostomy (8.3%). All but 1 survivor developed postoperative complications, and 3 needed reoperation before hospital discharge. The median hospital stay was 62 days (range, 29 to 156 days). After a median delay of 130 days (range, 91 to 240 days) from salvage relaparotomy, repeat pancreaticojejunostomy was attempted in 10 patients and was successful in 9 (1 completion pancreatectomy was performed). One patient died postoperatively (10%). Long-term endocrine function was unaltered in 66% of patients who benefited from this conservative strategy.

Conclusions

This pancreas-preserving strategy yielded a whole mortality rate of 17% for largely disrupted pancreaticojejunal anastomosis requiring salvage relaparotomy. It compares favorably with systematic completion pancreatectomy and achieved preservation of remnant pancreatic function in 75% of patients.     

Comparison of twice-daily and three-times-daily dosing of dorzolamide in ocular hypertension and primary open-angle glaucoma patients treated with latanoprost

Introduction

Clinically, dorzolamide (Trusopt®; Merck &; Co Inc, West Point, PA, USA) is often used twice daily (b.i.d.) or three times daily (t.i.d.) as adjunctive therapy with prostaglandins. Our purpose was to determine the effect of dorzolamide on intraocular pressure (IOP) when added to latanoprost (Xalatan®; Pfizer Inc, New York, NY, USA) baseline treatment, and to evaluate potential efficacy differences between b.i.d. and t.i.d. dosing of dorzolamide.

Methods

This was a prospective, randomised, two-period crossover trial in ocular hypertensive or primary open-angle glaucoma patients (29 eyes in 15 patients) with an IOP of > 20 mmHg on latanoprost baseline treatment. Patients were randomly assigned to b.i.d. (08.00 and 20.00) or t.i.d. (08.00, 16.00 and 20.00) dosing of dorzolamide, treated in both eyes for 4 weeks, washed out for 3 weeks, then switched to the opposite dosing frequency for 4 weeks. Diurnal IOP measurements (every 2 hours from 08.00 to 20.00) were performed at baseline and at the end of treatment periods.

Results

The mean baseline IOP was 20.9±0.6 mmHg. After b.i.d. and t.i.d. dosing, the mean IOP was 17.7±0.6 mmHg (13.5% reduction) and 17.8±0.8 mmHg (16.5% reduction), respectively (both P<0.001 compared with baseline IOP). Diurnal IOP control was similar in the two groups, although mean IOP reduction was significantly lower at 18.00 on the t.i.d. regimen (4.7±3.3 mmHg) than with the b.i.d. regimen (2.3±2.7 mmHg, P=0.038). At other time points, no significant differences between the groups were observed.

Conclusion

Dorzolamide 2% added to latanoprost 0.005% baseline treatment caused a significant decrease in IOP. The b.i.d. versus t.i.d. dosing of dorzolamide did not significantly affect a change in IOP except at one afternoon time point.

     

Pelvic exenteration for T4 rectal cancer: a series of 15 ressectable cases

BACKGROUND: Pelvic exenteration is the best therapeutic choice for treatment of T4 rectal cancer. Although, this operation still presents considerable mortality and high morbidity. AIM: To report on a series of 15 patients with a T4 rectal cancer at a general hospital and describe the outcomes (morbidity, mortality and long-term survival) following pelvic exenteration. METHODS: Complete follow-up data were available on 15 patients who underwent pelvic exenteration for T4 rectal cancer between 1998 and 2006. These subjects comprised seven men and eight women with a mean age of 65 years. All of them presented serious incapacitating complaints. The surgical procedures included: infraelevator exenteration (n = 6), supraelevator exenteration (n = 4), posterior exenteration (n = 3) and, posterior exenteration plus partial cystectomy and ureterectomy (n = 2). RESULTS: The mean duration of surgery was 403 minutes (280-485). The mean blood loss was 1620 mL (300-4.800). The postoperative mortality was 6,66% (n = 1). The overall rate morbidity was 53,3% (n = 8). The pathological examination showed that all resections were R0. Lymph node involvement was present in four patients (26,66 %), and all of them died due to tumor recurrence. The overall 5-year survival rate was 35,7%. CONCLUSION: In spite of its aggressive nature and high morbidity, pelvic exenteration seems justified in rectal carcinoma when the disease extends to the urinary or genital tract. This procedure may offer long-term disease control.     

Cognitive behavioral therapy delivered via digital mobile application for the treatment of type 2 diabetes: Rationale,design, and baseline characteristics of a randomized,controlled trial

BackgroundThe prevalence of type 2 diabetes (T2D) continues to rise in the United States and worldwide. Cognitive behavioral therapy (CBT) has been shown to improve glycemic control in patients with T2D, but broad implementation has been limited by inherent access and resource constraints. Digital therapeutics have the potential to overcome these obstacles.HypothesisTo describe the rationale and design of a trial evaluating the efficacy and safety of a digital therapeutic providing CBT to improve glycemic control in adults with T2D.MethodsThis randomized, controlled, multicenter, Phase 3 trial evaluates the hypothesis that BT‐001, an investigational digital therapeutic intended to help patients with T2D improve their glycemic control, on top of standard of care therapy, will lower hemoglobin A1c (HbA1c) compared to a control app across a broad range of patients in a real‐world setting. The study is designed to provide evidence to support FDA review of this device as a digital therapeutic. The intervention is provided within the digital application (app) and includes no person‐to‐person coaching. The primary endpoint is the difference in HbA1c change from baseline to 90 days for BT‐001‐allocated subjects compared with those assigned to the control app. Safety assessment includes adverse events and adverse device effects. The study incorporates pragmatic features including entirely remote conduct with at‐home visits for physical measures and blood sample collection.ConclusionsThis randomized, controlled trial evaluates a cognitive behavioral intervention delivered via smartphone app which has the potential to provide a scalable treatment option for patients with T2D.