No abstract

Background Human papillomavirus (HPV)–related disease remains a significant source of morbidity and mortality, and this underscores the need to increase HPV vaccination to reduce the burden of the disease. The objective of this study was to examine the association between the number of HPV vaccine doses and the risk of histologically confirmed preinvasive cervical disease and high‐grade cytology. Methods This retrospective matched cohort study used administrative data from Optum's Clinformatics DataMart Database to identify females aged 9 to 26 years who received 1 or more quadrivalent HPV vaccine doses between January 2006 and June 2015. Cases and controls were matched on region, age, sexually transmitted disease history, and pregnancy. All had a Papanicolaou test ≥1 year after the date of the matched case's final dose. Cox proportional hazards models were used to examine the association between the number of HPV vaccine doses and the incidence of preinvasive cervical disease and high‐grade cytology. The Kaplan‐Meier method was used to estimate the cumulative incidence rate at the 5‐year follow‐up. Results The study included 133,082 females (66,541 vaccinated and 66,541 unvaccinated) stratified by the number of HPV vaccine doses and the vaccine initiation age. Among those aged 15 to 19 years, the hazard ratio (HR) for high‐grade cytology for the 3‐dose group was 0.84 (95% confidence interval [CI], 0.73‐0.97), whereas the HRs for histologically confirmed preinvasive cervical disease for 1, 2, and 3 doses were 0.64 (95% CI, 0.47‐0.88), 0.72 (95% CI, 0.54‐0.95), and 0.66 (95% CI, 0.55‐0.80), respectively. Conclusions The receipt of 1, 2, or 3 doses of an HPV vaccine by females aged 15 to 19 years was associated with a lower incidence of preinvasive cervical disease in comparison with unvaccinated females, and this supports the use of any HPV vaccination in reducing the burden of the disease.

cThe ClpXP protease is a critical bacterial intracellular protease that regulates protein turnover in many bacterial species. Here we identified a pharmacological inhibitor of the ClpXP protease, F2, and evaluated its action in Bacillus anthracis and Staphylococcus aureus. We found that F2 exhibited synergistic antimicrobial activity with cathelicidin antimicrobial peptides and antibiotics that target the cell well and/or cell membrane, such as penicillin and daptomycin, in B. anthracis and drug-resistant strains of S. aureus. ClpXP inhibition represents a novel therapeutic strategy to simultaneously sensitize pathogenic bacteria to host defenses and pharmaceutical antibiotics.

OBJECTIVE Determine if a standardized methadone and lorazepam weaning protocol that is based on dose and duration of exposure can reduce the length of opioid and benzodiazepine weaning and shorten hospital stay. METHODS Retrospective cohort study performed in a 24-bed medical/surgical PICU. A total of 177 patients on opioid and/or benzodiazepine infusions for >3 days were included; 75 patients pre protocol (June 2012– June 2013) were compared with 102 patients post implementation of a standardized weaning protocol of methadone and lorazepam (March 2014–March 2015). The recommended wean was based on duration of infusions of >3 days up to 5 days (no wean), 5 to 13 days (short wean), and ≥14 days (long wean). RESULTS Median number of days on methadone for patients on opioid infusions for 5 to 13 days was reduced from 8.5 to 5.7 days (p = 0.001; n = 45 [pre], n = 68 [post]) and for patients on opioid infusions for ≥14 days, from 29.7 to 11.5 days (p = 0.003; n = 9 [pre], n = 9 [post]) after protocol implementation. The median number of days on lorazepam for patients on benzodiazepine infusions for 5 to 13 days was reduced from 8.1 to 5.2 days (p = 0.020; n = 43 [pre], n = 55 [post]) and for patients on benzodiazepine infusions for ≥14 days, from 27.4 to 9.3 days (p = 0.011; n = 9 [pre], n = 8 [post]). There was no difference in methadone or lorazepam wean length for patients on 3 to 5 days of infusions. There was no difference in adverse events or hospital length of stay. CONCLUSIONS A methadone and lorazepam weaning protocol based on patient's exposure to opioids and benzodiazepines (dose and duration) reduces weaning length.

(Abstracted from Cancer 2020;126:1656–1667) Human papillomavirus (HPV) is the most common sexually transmitted disease in the United States, and persistent infection with 1 of the 12 high-risk genotypes has been causally linked with development of cervical cancer. Several vaccines targeting high-risk genotypes have been developed and implemented.