Chemoprotective Antimalarial Activity of P218 against Plasmodium falciparum: A Randomized, Placebo-Controlled Volunteer Infection Study.

P218 is a highly selective dihydrofolate reductase inhibitor with potent in vitro activity against pyrimethamine-resistant Plasmodium falciparum. This single-center, randomized, double-blind, placebo-controlled phase Ib study evaluated P218 safety, pharmacokinetics, and chemoprotective efficacy in a P. falciparum sporozoite (PfSPZ) volunteer infection study (VIS). Consecutive dose safety and tolerability were evaluated (cohort 1), with participants receiving two oral doses of P218 1,000 mg 48 hours apart (n = 6), or placebo (n = 2). P218 chemoprotective efficacy was assessed (cohorts 2 and 3) with direct venous inoculation of 3,200 aseptic, cryopreserved PfSPZ (NF54 strain) followed 2 hours later with two P218 doses of 1,000 mg (cohort 2, n = 9) or 100 mg (cohort 3, n = 9) administered 48 hours apart, or placebo (n = 6). Parasitemia was assessed from day 7 using quantitative PCR targeting the var gene acidic terminal sequence (varATS qPCR). By day 28, all participants in cohort 2 (P218 1,000 mg) and 8/9 in cohort 3 (P218 100 mg) were sterilely protected post-PfSPZ VIS, confirming P218 P. falciparum chemoprotective activity. With placebo, all six participants became parasitemic (geometric mean time to positive parasitemia 10.6 days [90% CI: 9.9-11.4]). P218 pharmacokinetics were similar in participants with or without induced infection. Adverse events of any cause occurred in 45.8% (11/24) of participants who received P218 and 50.0% (4/8) following placebo; all were mild/moderate in severity, transient, and self-limiting. There were no clinically relevant changes in laboratory parameters, vital signs, or electrocardiograms. P218 displayed excellent chemoprotective efficacy against P. falciparum with favorable safety and tolerability.

Long-Term Outcome After Laparoscopic Repair of Primary, Unilateral Inguinal Hernia Using a Self-Adhering Mesh.

Following our previous study about a lightweight self-adhering mesh (Adhesix®, Cousin Biotech, Wervicq-Sud, France; distributed by Davol Inc., subsidiary of C.R. Bard, Inc.), we report the long-term results with the use of this mesh in patients treated for a primary, unilateral inguinal hernia without any other hernias. Prospectively collected data of 100 patients between February 2011 and February 2014 were analyzed. The mean follow-up time was 2.7 years (range 1-4), and mean length of hospital stay was 0.6 days (range 0.5-1). At the time of the last follow-up visit, two patients (2%) had a recurrent inguinal hernia. Compared to preoperative values, patients reported a significant reduction in their pain sensation (visual analogue scale, VAS) after one month (4.61 vs. 1.32; P<0.001). A difference in VAS scores remained significant at the last follow-up visit (1.31 vs. 0.28; P<0.001). Patients reported high quality of life scores. Only one patient (1%) developed a clinically significant seroma that required an evacuating puncture. Two patients (2%) had superficial wound infections. Neither mesh infections nor mortalities occurred. This study, with a long follow-up, confirms our previous results: use of the Adhesix® mesh is safe, feasible, and efficient in laparoscopic hernia repair.

A case of nosocomial Legionnaires' disease: The importance of early diagnosis, adequate prevention and eradication measures.

This case-report describes a patient with confirmed nosocomial Legionnaires' disease, a diagnosis which should be suspected when pneumonia does not respond to empiric therapy with beta-lactam antibiotics, or develops in the presence of certain risk factors. Culture is currently the golden standard for diagnosis, although the use of more modern techniques, such as a combination of urinary antigen testing and polymerase chain reaction, are on the rise. Specific detection and eradication methods are discussed.

Long-term Outcome on the use of the Ventralight™ ST Hernia Patch in Laparoscopic Ventral Hernia Repair.

BACKGROUND: Laparoscopic ventral hernia repair (LVHR) is a common procedure in abdominal surgery. Use of mesh has become the gold standard in the last decade because of significantly fewer recurrences. Subsequently, the attention shifted to reduce mesh related complications in the short- and long-term as well as to facilitate its handling and positioning. In continuation of our previous study, we conducted a final analysis about the use of the Ventralight™ ST hernia patch (Davol Inc, Subsidary of C. R. Bard, Inc. Warwick, RI). METHODS: Prospectively collected data of 61 consecutive patients (men/women: 44/17) from July 2011 to October 2013 were analysed in this final study. Patients were evaluated clinically at four time points in total. At the final clinical check- up, 97% of the total study population was reassessed. The primary outcome parameter was recurrence. Secondary outcome parameters were described in terms of mesh related complications, pain scores, and quality of life. RESULTS: Mean follow-up time was 23 months (range 16-44). Mean length of hospital stay was four days (range 2-17). There were no operative complications. Two patients (both>80 years old) died more than one year after the procedure because of a cardiovascular event. One morbidly obese patient (2%) treated for a recurrent incisional hernia showed a second recurrence at the last follow-up visit. A clinical significant seroma was observed in two patients (3%) one month postoperatively. At last follow-up, two patients (3%) reported persistent mild discomfort at one specific spot. There was a significant reduction in the visual analogue scale (VAS) scores at the last follow-up visit compared to preoperative scores (3.01 vs. 0.27; P<0.01). Quality of life measurements using the SF-36 questionnaire showed good results. CONCLUSION: This final analysis of long-term follow-up results on the use of the Ventralight™ ST hernia patch in laparoscopic ventral hernia repair confirms our preliminary findings of the previous two reports. Use of the Ventralight™ ST hernia patch is associated with good short- and long-term outcomes and can be considered as safe and feasible in LVHR.