High-Dose Celecoxib for Pain After Pediatric Tonsillectomy: A Randomized Controlled Trial.

OBJECTIVE: Pediatric tonsillectomy causes significant postoperative pain. Newer nonsteroidal anti-inflammatory drugs such as celecoxib control pain without increasing bleeding risk, but in prior studies provided only modest pain reduction at standard doses. We aimed to determine if high-dose celecoxib (double the usual pediatric dose) is effective for pain, without increasing bleeding or other risks. STUDY DESIGN: Randomized double-blind trial. SETTING: Pediatric tertiary center. METHODS: Children aged 3 to 11 years undergoing total tonsillectomy were randomized to receive celecoxib (6 mg/kg/dose) or placebo, twice daily, for up to 10 days. All cases were supplemented with acetaminophen and oxycodone as needed. All participants and personnel were blinded to treatment group. Subjects recorded coanalgesic consumption, pain, diet, and activity. RESULTS: The celecoxib group (n = 68) consumed 0.72 mg/kg of oxycodone, as compared with 1.12 mg/kg in the placebo group (n = 62), a 36% difference that was not significant. However, multivariate analysis by treatment group, separate from pain levels, confirmed that this reduction was due to celecoxib treatment (P = .03). In subjects with more prolonged pain (n = 88), celecoxib reduced consumption by 52% (P = .02). Celecoxib showed greater benefit for subjects in the prolonged pain group than for those in the lesser pain group (P = .006). Incidence of adverse events was similar between groups. Minor hemorrhage occurred in 4.6% (5 placebo, 3 celecoxib). CONCLUSION: High-dose celecoxib is effective in controlling pain after tonsillectomy, with no adverse effects in this relatively small sample. It reduces narcotic consumption, and its impact appears greater in children with higher degrees of pain. Celecoxib can be considered an effective alternative to ibuprofen after tonsillectomy. This trial was registered at ClinicalTrials.gov: NCT02934191.

A Phase 1 Dose-Escalation Study of PF-06671008, a Bispecific T-Cell-Engaging Therapy Targeting P-Cadherin in Patients With Advanced Solid Tumors.

P-cadherin is a cell-cell adhesion molecule that is overexpressed in several solid tumors. PF-06671008 is a T-cell-redirecting bispecific antibody that engages both P-cadherin on tumors and CD3ϵ on T cells and induces antitumor activity in preclinical models. We conducted a phase 1, open-label, first-in-human, dose-escalation study to characterize the safety and tolerability of PF-06671008, towards determining the recommended phase 2 dose. Adult patients with treatment-refractory solid tumors received PF-06671008 (1.5-400 ng/kg) as a weekly intravenous (IV) infusion on a 21-day/3-week cycle. Parallel cohorts evaluated dosing via subcutaneous injection (SC) or an IV-prime dose. Of the 27 patients enrolled in the study, 24 received PF-06671008 IV in escalating doses, two received SC, and one IV-prime. A dose-limiting toxicity of cytokine release syndrome (CRS) occurred in the 400-ng/kg IV group, prompting evaluation of SC and IV-prime schedules. In all, 25/27 patients who received PF-06671008 reported at least one treatment-related adverse event (TRAE); the most common were CRS (21/27), decreased lymphocyte count (9/27), and hypophosphatemia (8/27). Seven patients permanently discontinued treatment due to adverse events and no treatment-related deaths occurred. Cytokine peak concentrations and CRS grade appeared to positively correlate with Cmax. Although the study was terminated due to limited antitumor activity, it provides important insights into understanding and managing immune-related adverse events resulting from this class of molecules. Clinical Trial Registration: URL: https://clinicaltrials.gov/ct2/show/NCT02659631, ClinicalTrials.gov Identifier: NCT02659631.

Preoperative Music Listening in Pelvic Reconstructive Surgery: A Randomized Trial.

OBJECTIVES: We aimed to investigate the effect of music listening on preoperative anxiety compared with usual care in patients undergoing pelvic reconstructive surgery. METHODS: Patients scheduled for pelvic reconstructive surgery were enrolled on the day of surgery. Participants were randomized to either the usual care (control group) or to music listening on headphones (music group) before their surgery. Participants completed the Spielberg State-Trait Anxiety Inventory form Y1 to measure baseline state anxiety levels before surgery and again after 30 minutes of usual care or music listening. The primary outcome was the change in state anxiety score as measured by the State-Trait Anxiety Inventory form Y1. RESULTS: Sixty-nine women completed the study (35 assigned to the control group and 34 assigned to the music group). Analysis of the primary outcome included 66 participants (34 in the control group and 32 in the music group). Improvement in state anxiety was significantly better for patients assigned to music listening (-6.69; SD, 6.98) than for patients assigned to the control group (-1.32; SD, 8.03; P = 0.01). Six weeks postoperatively, patients in the music group (n = 29) reported higher overall satisfaction when compared with those in the control group (n = 31, P = 0.03). CONCLUSION: Patients undergoing pelvic reconstructive surgery present with moderate anxiety on the day of surgery. Allowing patients to listen to their preferred music is a simple intervention that may lower preoperative anxiety and improve satisfaction in this patient population.

Patient Preferences and Knowledge Regarding Hysterectomy: A Study from the Fellows' Pelvic Research Network (FPRN)®.

OBJECTIVE: The purpose of this study was to describe preference for and knowledge of hysterectomy routes in women presenting to urogynecology/gynecology clinics throughout the United States and to determine association with health literacy. Our primary aim was preference for hysterectomy route, and secondary aims were knowledge of basic pelvic structures and function, knowledge of various hysterectomy routes, and baseline health literacy level. METHODS: This multicenter, cross-sectional study was conducted through the Fellows' Pelvic Research Network. Patients' preference and knowledge for hysterectomy routes were assessed at initial presentation to the urogynecology/gynecology clinic with an anonymous, voluntary, self-administered questionnaire along with a validated health literacy test (Medical Term Recognition Test). RESULTS: Two hundred four women participated. Forty-five percent of patients were unsure which hysterectomy modality they would choose. Of patients who selected a preferred modality, 50% selected laparoscopic and 33% selected vaginal. Patients indicated that safety was considered highest priority when selecting route. The mean score for "knowledge about gynecology/hysterectomy" was 68%, with the high literacy group scoring higher compared with the low health literacy group (70% vs 60.1%, P = 0.01). More than 50% of patients incorrectly answered knowledge questions related to vaginal hysterectomy. Majority of the respondents had high health literacy (79.4%). CONCLUSIONS: Patients prefer laparoscopic hysterectomy approach, although have limited understanding of vaginal hysterectomy. Higher health literacy levels are associated with increased knowledge of gynecology and hysterectomy routes, but were not found to influence patient preference for hysterectomy route. Overall, patients have limited knowledge of vaginal hysterectomy.

Complications After Reperitonealization of Mesh at Time of Sacrocolpopexy: A Retrospective Cohort Study.

OBJECTIVES: To determine if there is a difference in rates of surgical complications among patients who have reperitonealization of mesh versus no reperitonealization at time of sacrocolpopexy. METHODS: This was a retrospective cohort study of all patients who underwent sacrocolpopexy at an academic medical center between 2008 and 2017. The medical record was reviewed for the operative method of sacrocolpopexy, concomitant surgeries, intraoperative or postoperative complications, and readmissions. Groups were compared on whether mesh was reperitonealized under pelvic peritoneum or not. RESULTS: A total of 209 patients underwent sacrocolpopexy, with mesh reperitonealization performed in 115 (55%). Demographics were similar in both groups, except race/ethnicity and stage of prolapse. The majority (190 [91%]) of surgeries included concomitant procedures. A total of 18 intraoperative or postoperative complications (8.6%) were recorded. Relative risk of complication with mesh reperitonealization is 0.81 (95% confidence interval, 0.1-1.70). Complications for subjects without mesh reperitonealization included 4 cystostomies, 1 urethrotomy, 3 postoperative ileuses, and 1 small bowel obstruction. Among subjects with mesh reperitonealization, complications included 5 cystotomies, 2 proctotomies, 1 ureteral obstruction, and 1 small bowel obstruction. Rates of hospital readmission among both groups were not significantly different, with 3.2% of subjects without mesh reperitonealization versus 3.5% of mesh reperitonealization patients (P = 0.91) (relative risk, 1.09; 95% confidence interval, 0.38-2.56). CONCLUSIONS: There is no significant difference in rates of complications or readmissions among patients with and without mesh reperitonealization at time of sacrocolpopexy. The only intraoperative complication solely attributed to mesh closure was a case with ureteral obstruction at time of reperitonealization.

Increasing Age Predicts Increasing Residual Urine Volume.

OBJECTIVES: To determine reference values for postvoid residual (PVR) volume for patients referred to a tertiary urogynecology center. METHODS: After Institutional Review Board approval, we performed a retrospective chart review of all new patients presenting to our referral center. We assessed associations between PVR and patient demographics, pelvic floor symptoms, and physical examination by Wilcoxon rank sum or Kruskal-Wallis tests as appropriate. A multivariable logistic regression model was used to calculate odds ratios for patient characteristics associated with PVR in the top age range-specific decile. RESULTS: Three hundred sixty-one patients were included in the analysis. The median PVR was 20 mL (interquartile range, 1st, 3rd quartiles, 10, 50). Older age was associated with higher PVR (P < 0.001). The median PVR in participants younger than 40 years was 10 mL, ages 40 to 49 years was 18 mL, 50 to 69 years was 20 mL, 70 to 79 years was 38 mL and in women older than 79 years was 50 mL. A multivariable analysis showed that prolapse stage (odds ratio [OR], 3.46 with prolapse stage 2-4 vs stage 0-1; P = 0.001), history of stroke (OR, 7.62; [95% CI 2.17-26.77, P = 0.002]), narcotic use (OR, 2.45; [95% CI 1.01-5.92; P = 0.047]), and urinary frequency (OR, 2.61; [95% CI, 1.14-5.98; P = 0.024]) were risk factors for increased PVR (as defined at >90%ile for age), independent of the age-related elevation. CONCLUSIONS: The majority of patients presenting for urogynecologic evaluation had a low PVR with a median of 20 mL. Postvoid residual was higher for older age groups but nearly all volumes were less than 100 mL. The utility of a PVR measurement is highest for patients with pelvic organ prolapse, urinary frequency, narcotic use, or history of stroke.

Broken Sacral Neuromodulation Lead Migration Into the Sigmoid Colon: A Case Report.

Sacral neuromodulation is an effective treatment of urinary incontinence, fecal incontinence, and idiopathic urinary retention. The procedure is considered low risk with overall low complication rates. This report describes a 40-year-old woman who underwent sacral neuromodulation explant and full-system implant for weaning efficacy of her device. During device removal, the tined lead broke and was left in situ. Four months later, she was diagnosed as having a wound infection at the site of the retained lead. Imaging revealed lead fragment migration into the sigmoid colon. A colocutaneous fistula was noted soon thereafter. The retained lead was removed during a colonoscopy and the fistula healed. A retained lead can result in migration through the peritoneum and into the colon. This can be managed with assistance from colorectal or gastroenterology consultants.

Does Patient Education Augment Pelvic Floor Physical Therapy Preparedness and Attendance? A Randomized Controlled Trial.

OBJECTIVES: The objective of this study was to evaluate patient attendance and preparedness for pelvic floor physical therapy (PFPT) after comparing standard counseling versus standard counseling plus an educational video. METHODS: A randomized controlled trial of 200 patients in a Female Pelvic Medicine and Reconstructive Surgery practice was performed in a tertiary care referral center. Participants were randomized to 1 of 2 educational modalities after being prescribed PFPT. Women either received standard handout counseling or enhanced video counseling. A sample size of 96 per group (N = 192) was needed to detect a 20% difference in PFPT attendance corresponding to a priori estimates of 50% compliance for the standard counseling group (handout) versus 70% compliance for the enhanced counseling group (handout plus video). Compliance data were assessed at least 3 months after the initial referral to determine attendance at PFPT. RESULTS: Sixty-five percent of patients attended at least 1 PFPT visit, whereas 46.5% completed therapy. There was no difference between the standard and enhanced counseling groups in PFPT attendance (P = 0.056) or in completion of half the recommended visits (P = 0.17). Similarly, level of preparedness after viewing the assigned counseling modality did not differ between standard and enhanced counseling groups. For each additional completed visit, the odds of successfully completing PFPT increased by approximately 38% (odds ratio, 1.38; 95% confidence interval, 1.19-1.59). CONCLUSIONS: The addition of enhanced patient counseling did not improve patient preparedness or odds of attending PFPT. Adherence behaviors surrounding PFPT attendance are multifactorial and require further qualitative research to elucidate barriers to PFPT attendance.

Bosutinib versus Placebo for Autosomal Dominant Polycystic Kidney Disease.

Overactivation of Src has been linked to the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). This phase 2, multisite study assessed the efficacy and safety of bosutinib, an oral dual Src/Bcr-Abl tyrosine kinase inhibitor, in patients with ADPKD. Patients with ADPKD, eGFR≥60 ml/min per 1.73 m2, and total kidney volume ≥750 ml were randomized 1:1:1 to bosutinib 200 mg/d, bosutinib 400 mg/d, or placebo for ≤24 months. The primary endpoint was annualized rate of kidney enlargement in patients treated for ≥2 weeks who had at least one postbaseline magnetic resonance imaging scan that was preceded by a 30-day washout (modified intent-to-treat population). Of 172 enrolled patients, 169 received at least one study dose. Per protocol amendment, doses for 24 patients who initially received bosutinib at 400 mg/d were later reduced to 200 mg/d. The annual rate of kidney enlargement was reduced by 66% for bosutinib 200 mg/d versus placebo (1.63% versus 4.74%, respectively; P=0.01) and by 82% for pooled bosutinib versus placebo (0.84% versus 4.74%, respectively; P<0.001). Over the treatment period, patients receiving placebo or bosutinib had similar annualized eGFR decline. Gastrointestinal and liver-related adverse events were the most frequent toxicities. In conclusion, compared with placebo, bosutinib at 200 mg/d reduced kidney growth in patients with ADPKD. The overall gastrointestinal and liver toxicity profile was consistent with the profile in prior studies of bosutinib; no new toxicities were identified. (ClinicalTrials.gov: NCT01233869).

A randomized, open-label, multicentre, phase 2/3 study to evaluate the safety and efficacy of lumiliximab in combination with fludarabine, cyclophosphamide and rituximab versus fludarabine, cyclophosphamide and rituximab alone in subjects with relapsed chronic lymphocytic leukaemia.

Lumiliximab is a chimeric monoclonal antibody that targets CD23 on the surface of chronic lymphocytic leukaemia (CLL) B-cells. Early phase clinical studies with lumiliximab alone and in combination with fludarabine, cyclophosphamide and rituximab (FCR) established its potential efficacy and tolerability. The 152CL201 trial [Lumiliximab with fludarabine, cyclophosphamide and rituximab (FCR) versus FCR alone in subjects with relapsed CLL; LUCID] was a phase 2/3, randomized (1:1), open-label, multicentre study of lumiliximab in combination with FCR versus FCR alone in patients with relapsed CLL. Six hundred and twenty-seven patients were randomized to either arm. Overall the combination of lumiliximab with FCR was not significantly better than FCR alone (overall response rate 71% vs. 72%, complete response rate 16% vs. 15%, median progression-free survival 24.6 vs. 23.9 months respectively, for FCR with and without lumiliximab). There was a slightly increased incidence of adverse events with lumiliximab but these increases did not appear to lead to differences in eventual outcomes. An interim analysis failed to show sufficient efficacy of the combination of lumiliximab with FCR. The study was therefore stopped early for lack of efficacy. Despite the eventual outcome, the LUCID trial is one of the largest studies that provides valuable insight into the efficacy and tolerability of FCR as a therapeutic option for patients with relapsed CLL.