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Erectile dysfunction (ED) remains a significant problem in up to 63% of men after robot-assisted radical prostatectomy (RARP). After the discovery of the neurovascular bundle (NVB), additional anatomic description and variation in nerve-sparing (NS) techniques have been described to improve post-RARP ED. However, it remains questionable whether ED rates have improved over time, and this is concerning as competing treatments are introduced that have better ED outcomes. In this review, we describe RARP NS technical modifications that improve erectile function recovery. We focused on reports that included detailed anatomical descriptions as well as video illustrations to disseminate technique. We found that the alternative RARP NS surgical techniques provide better outcomes compared with standard NS RARP. The use of validated quality of life questionnaires is necessary for the appropriate comparison of outcomes. However, the retrospective character and inherent weaknesses of the included studies do not allow one to conclude which is the best NS approach. Overall, there is significant variation in RARP NS techniques and outcomes, and the ideal technical maneuvers to optimize outcomes remains subject to debate. However, there is a consensus on the importance of anatomically dissecting the NVB, minimizing traction and thermal injury as well as preserving the periprostatic fascia. Well-designed randomized controlled trials with videos describing details of different surgical techniques for generalizability are needed to consistently and objectively evaluate sexual function outcomes after RARP to optimize postoperative potency.

Purpose: Salvage radical prostatectomy is rare due to the risk of postoperative complications. We compare salvage Retzius-sparing robotic assisted radical prostatectomy (SRS-RARP) with salvage standard robotic assisted radical prostatectomy (SS-RARP). Materials and Methods: A total of 72 patients across 9 centers were identified (40 SRS-RARP vs 32 SS-RARP). Demographics, perioperative data, and pathological and functional outcomes were compared using Student's t-test and ANOVA. Cox proportional hazard models and Kaplan-Meier curves were constructed to assess risk of incontinence and time to continence. Linear regression models were constructed to investigate postoperative pad use and console time. Results: Median followup was 23 vs 36 months for SRS-RARP vs SS-RARP. Console time and estimated blood loss favored SRS-RARP. There were no differences in complication rates or oncologic outcomes. SRS-RARP had improved continence (78.4% vs 43.8%, p 0-1 pad (HR 0.28, 95% CI 0.10-0.79, p=0.016), although not when defined as >0 pad (HR 0.56, 95% CI 0.31-1.01, p=0.053). On adjusted analysis SRS-RARP was associated with decreased pads per day. Lymph node dissection and primary treatment with stereotactic body radiation therapy were associated with longer console time. Conclusions: SRS-RARP is a feasible salvage option with significantly improved urinary function outcomes. This may warrant increased utilization of SRS-RARP to manage men who fail nonsurgical primary treatment for prostate cancer.

Anhedonia is usually defined as partial or total loss of the capacity for pleasure. People with anhedonia in the context of major depressive disorder may have an unexpected capacity for event-related mood brightening, observable when mood is assessed dynamically (with smartphone-based ecological momentary assessment [EMA]) rather than only statically via questionnaire. We used EMA to monitor mood and pleasant events for 4 weeks in 54 people being treated with opioid agonist medication for opioid-use disorder (OUD), which is also associated with anhedonia, said to manifest especially as loss of pleasure from nondrug reward. We compared OUD patients' EMA reports with those of 47 demographically similar controls. Background positive mood was lower in OUD patients than in controls, as we hypothesized (Cohen ds = .85 to 1.32, 95% CIs [.66, 1.55]), although, contrary to our hypothesis, background negative mood was also lower (ds = .82 to .85, 95% CIs [.73, .94]). As hypothesized, instances of nondrug pleasure were as frequent in OUD patients as in controls-and were not rated much less pleasurable (d = .18, 95% CI [-.03, .35]). Event-related mood brightening occurred in both abstinent and nonabstinent OUD patients (ds = .18 to .37, CIs [-.01, .57]) and controls (ds = .04 to .60, CIs [-.17, .79]), brightening before each event began earlier for controls than OUD patients, but faded similarly postevent across groups. Our findings add to the evidence that anhedonia does not rule out reactive mood brightening, which, for people with OUD being treated on opioid agonist medication, can be elicited by nondrug activities. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) has been shown to improve continence. However, questions remain regarding feasibility and generalizability of technique and outcomes.To compare the outcomes of 140 consecutive standard robot-assisted radical prostatectomy (S-RARP) versus RS-RARP.A total of 70 S-RARPs were performed followed by 70 RS-RARPs. Demographic, pathologic, and functional outcomes were compared preoperatively and through 12 mo. Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) was used to compare functional outcomes. Logistic and linear regression analyses were utilized to analyze variables associated with EPIC-CP urinary incontinence and overall quality of life (QOL) scores, and oncologic outcomes. Cox regression analysis was used to analyze incontinence at 12 mo.RS-RARP versus S-RARP.Patient and tumor characteristics (age, body mass index, prostate-specific antigen, Charlson Comorbidity Index, Gleason group, clinical stage, and Prostate Imaging Reporting and Data System score), perioperative outcomes (console time, estimated blood loss, postoperative complications, and length of stay), oncologic outcomes (positive surgical margin [PSM], and biochemical recurrence), overall and 12-mo continence rates (zero pads and zero to one safety pad), time to continence, potency (erection sufficient for sexual activity), EPIC-CP urinary incontinence, sexual function, and overall QOL scores.Median follow-up for S-RARP versus RS-RARP was 46.3 versus 12.3 mo. RS-RARP versus S-RARP had improved overall continence rates at total follow-up (95.7% vs 85.7%, p = 0.042) and 12-mo follow-up (97.6% vs 81.4%, p = 0.002), and faster return to continence (zero to one safety pad, 44 vs 131 d, p 0.001). RS-RARP EPIC-CP urinary incontinence and overall QOL scores remained significantly better at 12 mo. There were no differences in overall PSM rates, although RS-RARP had lower rates of nonfocal PSMs. There were no differences in sexual function. In multivariate analysis, RS-RARP was significantly associated with improved 12-mo EPIC-CP urinary incontinence and improved QOL scores, but was not associated with PSM or biochemical recurrence. Limitations include retrospective study design and unequal follow-up; however, significantly better RS-RARP continence at 12 mo is striking despite fewer patients attaining 12-mo follow-up.RS-RARP significantly improves early and long-term continence without compromising oncologic outcomes and leads to overall improved QOL.Retzius-sparing robot-assisted radical prostatectomy is an emerging technique for robotic radical prostatectomy that improves urinary function and quality of life without compromising cancer control.

Introduction Variation in CYP2A6, the primary enzyme responsible for nicotine metabolism, is associated with nicotine dependence, cigarette consumption, and abstinence outcomes in smokers. The impact of CYP2A6 activity on nicotine reinforcement and tobacco cue-reactivity, mechanisms that may contribute to these previous associations, has not been fully evaluated. Aims and Methods CYP2A6 activity was indexed using 3 genetic approaches in 104 daily smokers completing forced-choice and cue-induced craving tasks assessing nicotine reinforcement and tobacco cue-reactivity, respectively. First, smokers were stratified by the presence or absence of reduced/loss-of-function CYP2A6 gene variants (normal vs. reduced metabolizers). As nicotine metabolite ratio (NMR) is a reliable biomarker of CYP2A6 activity, our second and third approaches used additional genetic variants identified in genome-wide association studies of NMR to create a weighted genetic risk score (wGRS) to stratify smokers (fast vs. slow metabolizers) and calculate a wGRS-derived NMR. Results Controlling for race and sex, normal metabolizers (vs. reduced) selected a greater proportion of puffs from nicotine-containing cigarettes (vs. denicotinized) on the forced-choice task (p = .031). In confirmatory analyses, wGRS-based stratification (fast vs. slow metabolizers) produced similar findings. Additionally, wGRS-derived NMR, which correlated with actual NMR assessed in a subset of participants (n = 55), was positively associated with the proportion of puffs from nicotine-containing cigarettes controlling for race and sex (p = .015). None of the CYP2A6 indices were associated with tobacco cue-reactivity in minimally deprived smokers. Conclusions Findings suggest increased nicotine reinforcement is exhibited by smokers with high CYP2A6 activity, which may contribute to heavier smoking and poorer cessation outcomes previously reported in faster metabolizers. Implications CYP2A6 activity is a key determinant of smoking behavior and outcomes. Therefore, these findings support the targeting of CYP2A6 activity, either therapeutically or as a clinically relevant biomarker in a precision medicine approach, for tobacco use disorder treatment.

Objective Evidence suggests that blunted reward responsiveness may account for poor clinical outcomes in both opioid use disorder (OUD) and chronic pain. Understanding how individuals with OUD and comorbid chronic pain (OUD+CP) respond to rewards is, therefore, of clinical interest because it may reveal a potential point of behavioral intervention. Methods Patients with OUD (n = 28) and OUD+CP (n = 19) on opioid agonist treatment were compared on: 1) the Probabilistic Reward Task (an objective behavioral measure of reward response bias) and 2) ecological momentary assessment of affective responses to pleasurable events. Results Both the OUD and the OUD+CP groups evidenced an increase in reward response bias in the Probabilistic Reward Task. The rate of change in response bias across blocks was statistically significant in the OUD group (B = 0.06, standard error [SE] = 0.02, t = 3.92, P Conclusions Overall, findings across objective and subjective measures were mixed, necessitating follow-up with a larger sample. The results suggest that although there is a reward response bias in patients with OUD+CP treated with opioid agonist treatment relative to patients with OUD without CP, it is modest and does not appear to translate into patients’ responses to rewarding events as they unfold in daily life.

Intravenous dexmedetomidine 30 µg reduces shivering after cesarean delivery but can result in sedation and dry mouth. We hypothesized that prophylactic administration of 10 µg of IV dexmedetomidine would reduce the patient-reported severity of shivering after cesarean delivery, without an increased incidence of side effects.After institutional review board approval and informed written consent, women undergoing scheduled cesarean delivery with spinal or combined spinal-epidural anesthesia were randomized to receive either intravenous normal saline or dexmedetomidine 10 µg immediately after delivery. The primary outcome was a patient-rated subjective shivering score using a 10-cm visual analog scale at 30 and 60 min after arrival in the Post-Anesthesia Care Unit. Secondary outcomes included subjective scores for pain, nausea, itching, dry mouth, and sedation, as well as 24-h medication administration and investigator-rated observations of shivering, vomiting, pruritus, and sedation. Repeated measures ANOVA with Tukey-Kramer multiple-comparison test was applied for primary outcomes.One hundred patients were enrolled, and 85 completed the study and were included in analysis. The mean ± SD shivering score in the dexmedetomidine group was significantly lower by repeated measures analysis than among controls across the first 60 min (P=0.0002), and individually at both 30 and 60 min (placebo 1.8 ± 2.6 vs. dexmedetomidine 0.6 ± 1.4 at 30 min; 1.2 ± 2.1 vs. 0.3 ± 0.6 at 60 min; both P0.01). Patient-rated and observer-rated side effects did not significantly differ between groups.Prophylactic administration of intravenous dexmedetomidine 10 µg after delivery reduces shivering without notable side effects.

Radical prostatectomy has undergone many adaptations since its inception, including the Retzius-sparing robotic-assisted radical prostatectomy approach. In this article, we review the origins of radical prostatectomy, the theoretic basis for Retzius-sparing robotic-assisted radical prostatectomy, and outline the key steps of the procedure. To date, there have been 9 studies comparing the outcomes of Retzius-sparing robotic-assisted radical prostatectomy with standard robotic-assisted radical prostatectomy, which have demonstrated improved continence outcomes for Retzius sparing robotic assisted radical prostatectomy within the first year and equivalent oncologic efficacy out to 18 months. Further research is needed to evaluate sexual function outcomes as well as long-term oncologic outcomes.

AIM To assess the role of momentary pain on opioid craving and illicit opioid use among individuals receiving opioid agonist treatment. DESIGN Observational study using ecological momentary assessment. SETTING The National Institute of Drug Abuse Intramural Research Program in the United States. PARTICIPANTS Fifty-six adults who qualified for opioid agonist treatment. MEASUREMENTS Participants completed randomly prompted assessments of pain severity, stress, negative mood, opioid craving and illicit opioid use for a mean of 66 days [standard deviation (SD) = 27]. Urine samples were collected two to three times/week throughout. FINDINGS Almost 70% of participants reported moderate average pain severity in the past 24 hours at intake and 35% of participants reported chronic pain. There were no significant differences in percent of opioid-positive urine samples (P = 0.73) and average level of opioid craving during the study period (P = 0.91) among opioid agonist treatment only patients versus opioid agonist treatment patients with chronic pain. However, momentary pain severity significantly predicted concurrent opioid craving [B = 0.02, 95% confidence interval (CI) = 0.01, 0.04], over and above stress and negative mood. Momentary opioid craving, in turn, significantly predicted illicit opioid use that was assessed in the next moment [odds ratio (OR) = 1.72, 95% CI = 1.12, 2.64), while controlling for autocorrelation and the effects of pain, negative mood and stress. Momentary opioid craving significantly mediated the prospective association between momentary pain and illicit opioid use (95% CI = 0.003, 0.032). Exploratory analysis revealed that momentary pain severity also significantly moderated the momentary association between stress and opioid craving (B = 0.02, 95% CI = 0.00, 0.04), such that when momentary pain severity increased, the association between the two intensified. CONCLUSIONS Among people receiving opioid agonist treatment, momentary pain appears to be indirectly associated with illicit opioid use via momentary opioid craving.

Background Retzius-sparing robotic-assisted radical prostatectomy (RS-RARP) has improved urinary function compared with standard robotic-assisted radical prostatectomy (S-RARP). As RS-RARP spares the dorsal vascular complex, pelvic fascia, and anterior abdominal fascia, it may also lower the incidence of “neglected” postprostatectomy sequelae such as penile shortening, Peyronie’s disease, and inguinal hernias. Objective To determine whether there are patient-perceived differences in penile shortening, Peyronie’s disease, and inguinal hernia rates among men undergoing RS-RARP versus S-RARP. Design, setting, and participants Researchers uninvolved in clinical care and blinded to surgical approach surveyed 60 RS-RARP versus 57 S-RARP men with validated patient-reported items to assess penile shortening, Peyronie’s disease, and inguinal hernia sequelae following surgery. Intervention RS-RARP versus S-RARP. Outcome measurements and statistical analysis Univariate differences between the two cohorts were analyzed using Student t test. Logistic regression was used to analyze variables associated with postoperative penile shortening. Cox proportional hazards models were used to assess the risk of developing Peyronie’s disease and inguinal hernia postoperatively. Results and limitations RS-RARP was associated with less patient-reported penile shortening (41.7% vs 64.9%, p = 0.012), Peyronie’s disease (0% vs 8.7%, p = 0.020), and inguinal hernia (0.0% vs 13.0%, p = 0.004). In adjusted analyses, RS-RARP (odds ratio [OR] 0.24, 95% confidence interval [CI] 0.09–0.63, p = 0.004) was associated with lower odds of penile shortening, while a higher body mass index was associated with increased odds of penile shortening (OR 1.13, 95% CI 1.01–1.26, p = 0.037). RS-RARP was not associated with a decreased risk of Peyronie’s disease on Cox proportion hazard model; however, these models are limited due to a limited number of events in our cohort. Limitations include retrospective design, patient-reported outcomes, and small cohorts. Conclusions RS-RARP is associated with less patient-reported penile shortening and may decrease the risk of Peyronie’s disease and postoperative inguinal hernia development. These new findings add to research, showing improved urinary continence and quality of life following RS-RARP; however, a prospective study is needed to validate these findings. Patient summary Retzius-sparing robotic-assisted radical prostatectomy (RS-RARP) is an evolving surgical technique for prostate cancer treatment, which has shown improved postoperative urinary control compared with the standard technique, likely due to preservation of natural pelvic anatomy. Our findings suggest that the preservation of normal pelvic anatomy during RS-RARP may also reduce the risk of postprostatectomy penile shortening, Peyronie’s disease, and inguinal hernia., Take Home Message Retzius-sparing robotic-assisted radical prostatectomy (RS-RARP) is an evolving surgical technique for prostate cancer treatment that has shown improved postoperative urinary control compared with the standard technique, likely due to the preservation of natural pelvic anatomy. Our findings suggest that the preservation of normal pelvic anatomy during RS-RARP may also reduce the risk of postprostatectomy penile shortening, Peyronie’s disease, and inguinal hernia.

RATIONALE: Many people being treated for opioid use disorder continue to use drugs during treatment. This use occurs in patterns that rarely conform to well-defined cycles of abstinence and relapse. Systematic identification and evaluation of these patterns could enhance analysis of clinical trials and provide insight into drug use. OBJECTIVES: To evaluate such an approach, we analyzed patterns of opioid and cocaine use from three randomized clinical trials of contingency management in methadone-treated participants. METHODS: Sequences of drug-test results were analyzed with unsupervised machine-learning techniques, including hierarchical clustering of categorical results (i.e., whether any samples were positive during each week) and K-means longitudinal clustering of quantitative results (i.e., the proportion positive each week). The sensitivity of cluster membership as an experimental outcome was assessed based on the effects of contingency management. External validation of clusters was based on drug craving and other symptoms of substance use disorder. RESULTS: In each clinical trial, we identified four clusters of use patterns, which can be described as opioid use, cocaine use, dual use (opioid and cocaine), and partial/complete abstinence. Different clustering techniques produced substantially similar classifications of individual participants, with strong above-chance agreement. Contingency management increased membership in clusters with lower levels of drug use and fewer symptoms of substance use disorder. CONCLUSIONS: Cluster analysis provides person-level output that is more interpretable and actionable than traditional outcome measures, providing a concrete answer to the question of what clinicians can tell patients about the success rates of new treatments.

OBJECTIVE: Retzius-sparing robot-assisted radical prostatectomy (RSP) is a novel approach for radical prostatectomy that was described by our group for the first time in 2010 and is spreading all around the world. The aim of the present study was to assess the effect of surgical experience (SE) on perioperative, functional and oncological outcomes during the first 50 RSP cases performed by a naive surgeon for this novel approach. MATERIALS AND METHODS: We retrospectively evaluated the initial cases operated by 14 surgeons in 12 different international centers. Pre-, peri- and post- operative features of the first 50 patients operated by each surgeon in all the participating centers were collected. The effect of the SE on perioperative, functional and oncological outcomes was firstly evaluated after stratification of surgical experience in initial (≤25) and expert cases (>25) and after using locally weighted scatter-plot smoother (LOWESS) function to graphically explore the relationship between SE and the outcomes of interest. RESULTS: We evaluated 626 patients. Median follow-up was 13 months in the first group and 9 months in the second (p=0.002). Preoperative features were overlapping between the two groups. Lower console time (140 min vs 120 minutes, p=0.001) and a trend for lower complications rates (13 vs 5.5%, p=0.038) were observed in the second group. The relationship between SE and console time, immediate urinary continence recovery and Clavien Dindo complications ≥2 was linear without reaching a plateau after 50 cases. Conversely, a non-linear relationship was observed between SE and PSMs. CONCLUSIONS: We reported the first multi-center experience of Retzius-sparing RARP during the learning curve. We found that console time, immediate urinary continence recovery and postoperative complications are optimal from the beginning and further quickly improve during the learning process, while PSMs rates did not clearly enhance over the first 50 cases.

Purpose: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is standard of care for muscle-invasive bladder cancer (MIBC). However, NAC is used in less than 20% of patients with MIBC. Our goal is to investigate factors that contribute to underutilization NAC to facilitate more routine incorporation into clinical practice. Materials and Methods: We identified 5,915 patients diagnosed with cT2-T3N0M0 MIBC who underwent RC between 2004 and 2014 from the National Cancer Database. Univariate and multivariable models were created to identify variables associated with NAC utilization. Results: Only 18.8% of patients received NAC during the study period. On univariate analyses, NAC utilization was more likely at academic hospitals, US South and Midwest (p

Introduction Scabies is a widespread, contagious parasitic disease causing intense itching. Its detection is a significant problem while there are no internationally agreed standards. Aim To compare diagnostic methods: microscopy of skin scrapings, dermoscopy, and real-time polymerase chain reaction (PCR) of skin scrapings and wet skin swabs. Material and methods We included patients with clinical signs of scabies. After dermoscopic evaluation, scrapings were collected from skin lesions and assessed by light microscopy and real-time PCR. Wet skin swabs were also analysed by real-time PCR. Surveys on the presence and severity of pruritus and skin lesions were collected. Seventy-five skin scrapings and 41 wet swabs were examined by real-time PCR. Fifty-three patients completed the survey. All patients underwent dermoscopy and microscopy examinations. 6.67% were positive by microscopy, 10.7% by dermoscopy, 28.0% by real-time PCR from scrapings, and 36.6% when both scrapings and swabs were examined by real-time PCR. All microscopy-positive results were also positive by PCR. Results There was a correlation between real-time PCR from positive scrapings and pruritus (p = 0.023) and body surface area of lesions (p = 0.002), a correlation between copies from wet skin swabs and BSA of lesions (p = 0.002) in the whole group, and a correlation between copies of S. scabiei from scrapings and age (p = 0.038). Conclusions Real-time PCR testing of scrapings and dermoscopy are more effective than microscopy. Combined real-time PCR testing of scrapings and skin swabs seemed the most effective. Clinical signs alone should not be used as unambiguous criteria.

Just-in-time adaptive interventions (JITAIs), typically smartphone apps, learn to deliver therapeutic content when users need it. The challenge is to “push” content at algorithmically chosen moments without making users trigger it with effortful input. We trained a randomForest algorithm to predict heroin craving, cocaine craving, or stress (reported via smartphone app 3x/day) 90 min into the future, using 16 weeks of field data from 189 outpatients being treated for opioid-use disorder. We used only one form of continuous input (along with person-level demographic data), collected passively: an indicator of environmental exposures along the past 5 h of movement, as assessed by GPS. Our models achieved excellent overall accuracy—as high as 0.93 by the end of 16 weeks of tailoring—but this was driven mostly by correct predictions of absence. For predictions of presence, “believability” (positive predictive value, PPV) usually peaked in the high 0.70s toward the end of the 16 weeks. When the prediction target was more rare, PPV was lower. Our findings complement those of other investigators who use machine learning with more broadly based “digital phenotyping” inputs to predict or detect mental and behavioral events. When target events are comparatively subtle, like stress or drug craving, accurate detection or prediction probably needs effortful input from users, not passive monitoring alone. We discuss ways in which accuracy is difficult to achieve or even assess, and warn that high overall accuracy (including high specificity) can mask the abundance of false alarms that low PPV reveals.

Objective To evaluate the outcomes of men diagnosed with prostate cancer (CaP) following implanted treatments for advanced heart failure. Given the increasingly favorable 10-year life expectancy, MedStar Washington Hospital Center screens heart transplant (HT) candidates for CaP and other malignancies prior to intervention. Methods Men aged 18-90 with available pretransplant Prostate Specific Antigen (PSA) who underwent left ventricular assist device (LVAD) and/or HT at MedStar Washington Hospital Center from 2007 to 2018 were identified. Serum PSA, CaP diagnosis, and treatment were captured and analyzed. Survival was analyzed using Kaplan-Meier curves. Results Data were available for 34 patients. Median age was 53 [IQR = 51-58]. Median follow-up was 77 months (95% CI = 40-87 months). Six men had postimplant elevated PSA (5.3; SD = 8.5) and 4 were diagnosed with CaP. Median age of CaP diagnosis was 59 [IQR = 58.5-62). As of 2018, 31 of the 34 patients were living, and none died from CaP. Five-year survival was 96% in those without CaP and 100% in those with CaP (Figure 2). Conclusion Our cohort represents the largest known cohort with heart failure treated by LVAD and/or HT and CaP. Our median age of 59 at CaP diagnosis is considerably younger than the national median of 66. 1 Of the 4 individuals diagnosed with CaP, 3 had high-grade disease. Given the favorable long-term survival of these patients post-LVAD and/or HT, age-appropriate treatment for CaP should be continued postimplantation.

Number of deliveries is utilised to estimate obstetric anaesthesiologist workload; however, this may not reflect true workload. The goal of this analysis was to assess if including type of procedure, time required and length of each shift would better predict clinical workloads.We queried the electronic medical records at a high volume, academic centre for 12 consecutive months of maternal deliveries. Data extracted included delivery type, analgesic/anaesthetic procedure and whether delivery occurred during weekday, weeknight or weekend shifts. To generate an hourly comparison of shifts of varying duration, procedures were divided by the number of hours per shift. To calculate obstetric anaesthesiology time-based workload, delivery type was multiplied by estimated time associated with the analgesic/anaesthetic procedure.A total of 4,598 deliveries occurred in the 12-month study period. The caesarean delivery rate was 32%, and labour epidural rate was 85%. 1,564 anaesthetic procedures occurred during weekdays and 2,557 occurred during the weeknights and weekends. After accounting for the duration of each procedure and hours per shift, mean 6 standard deviation time-based workload ratio was 0.68 6 0.12 on weekdays versus 0.36 6 0.07 on weeknights and weekends.Relative workload based on deliveries alone suggests 41% less workload during the weekday, whereas accounting for duration of each procedure and hours per shift resulted in an 89% greater workload on weekday shifts. The study highlights the importance of considering analgesic/anaesthetic procedures and estimates of time taken to perform them, not just number of deliveries when considering obstetric anaesthesiology workload.

INTRODUCTION AND OBJECTIVE:The digital rectal exam (DRE), as a component of prostate cancer screening, may have predictive value complementary to or independent of serum prostate-specific antigen (...

Sleep problems are commonly reported during opioid agonist treatment (OAT) for opioid use disorders. Inpatient studies have found both sleep disturbances and improved sleep during OAT. Illicit opioids can also disrupt sleep, but it is unclear how they affect sleep in outpatients receiving OAT. Therefore, we used electronic diary entries and actigraphy to measure sleep duration and timing in opioid-dependent participants (n = 37) treated with methadone (n = 15) or buprenorphine (n = 22). For 16 weeks, participants were assigned to attend our clinic under different operating hours in a crossover design: Early hours (07:00–09:00) vs. Late hours (12:00–13:00) for 4 weeks each in randomized order, followed for all participants by our Standard clinic hours (07:00–11:30) for 8 weeks. Throughout, participants made daily electronic diary self-reports of their sleep upon waking; they also wore a wrist actigraph for 6 nights in each of the three clinic-hour conditions. Drug use was assessed by thrice-weekly urinalysis. In linear mixed models controlling for other sleep-relevant factors, sleep duration and timing differed by drug use and by clinic hours. Compared to when non-using, participants slept less, went to bed later, and woke later when using illicit opioids and/or both illicit opioids and cocaine. Participants slept less and woke earlier when assigned to the Early hours. These findings highlight the role OAT clinic schedules can play in structuring the sleep/wake cycles of OAT patients and clarify some of the circumstances under which OAT patients experience sleep disruption in daily life.

Recent clinical trials have investigated the benefit of combining tyrosine kinase inhibitors (TKIs) and cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma. Our goal is to determine whether the perioperative use of TKIs increases the postoperative morbidity following CN in renal cell carcinoma patients. We identified 627 patients with Stage IV renal cell carcinoma who underwent CN from 2007–2010 utilizing the SEER-Medicare database. Eighty-two patients treated with TKIs were matched (3:1) to 246 controls. We calculated 30- and 90-day incidence rates of postoperative complications and mortality. On unadjusted analysis, TKI use prior to CN was associated with higher overall complication rate within 30 days (HR = 2.73, 95% CI: 1.09–6.8) after surgery. On multivariate analysis, perioperative TKI use was independently associated with higher risk for postoperative complications within 30 days (HR = 2.93, 95% CI: 1.17–7.36), as well as 90 days (HR = 1.84, 95% CI: 1.02–3.32) after nephrectomy. A higher Charlson comorbidity index also emerged to represent an independent risk factor for postoperative complications within 30 days (HR = 2.41, 95% CI: 1.44–4.02) and 90 days (HR = 2.23, 95% CI: 1.51–3.29) after nephrectomy. TKI treatment was not associated with an increased postoperative mortality at 30 and 90 days after surgery. Thus, TKI treatment was associated with an increased complication rate but not overall mortality following CN. Our results suggest that renal surgeons should be aware of possibly increased complications following CN in renal cell carcinoma patients, when TKI treatment is administered.

Background Treatment with opioid agonists is effective for opioid use disorder, but early discontinuation of treatment is a major obstacle to success. Intensive longitudinal methods — which take many repeated measurements over time, usually in the field— have provided unique insight into the effects of stress, mood and craving on drug use while people are being treated; these methods might also be useful for studying the processes that lead people to drop out of treatment. Methods Ecological momentary assessment (EMA) was conducted for up to 17 weeks by obtaining multiple electronic diary entries per day from 238 participants being treated with methadone or buprenorphine-naloxone. Survival analysis was used to study two outcomes: dropping out of treatment and noncompliance with EMA self-report requirements. Self-reports of stress, craving, and mood were used as time-varying predictors. Demographic and psychosocial variables measured with the Addiction Severity Index at the start of treatment were used as time-invariant predictors. Results Dropping out of treatment was more likely in participants with more reported hassles (a measure of stress), higher levels of cocaine craving, lower levels of positive mood, a recent history of emotional abuse, a recent history of being bothered frequently by psychological problems, and with buprenorphine rather than methadone as their medication. In contrast, study noncompliance was not significantly associated with any of the variables analyzed. Conclusions Assessment of stress, craving and mood during treatment might identify people who are at greater risk of dropping out, and therapeutic interventions targeting these processes might increase retention.

The majority of women undergoing cesarean delivery in the United States receive neuraxial morphine, the most effective form of postoperative analgesia for this surgery. Current American Society of Anesthesiologists (ASA) and American Society of Regional Anesthesia and Pain Medicine (ASRA) recommend respiratory monitoring standards following neuraxial morphine administration in the general surgical population that may be too frequent and intensive when applied to the healthy obstetric population receiving a single dose of neuraxial morphine at the time of surgery. There is limited evidence to support or guide the optimal modality, frequency, and duration of respiratory monitoring in the postoperative cesarean delivery patient receiving a single dose of neuraxial morphine. Consistent with the mission of the Society for Obstetric Anesthesia and Perinatology (SOAP) to improve outcomes in pregnancy for women and neonates, the purpose of this consensus statement is to encourage the use of this highly effective analgesic technique while promoting safe practice and patient-centered care. The document aims to reduce unnecessary interruptions from respiratory monitoring in healthy mothers while focusing vigilance on monitoring in those women at highest risk for respiratory depression following neuraxial morphine administration. This consensus statement promotes the use of low-dose neuraxial morphine and multimodal analgesia after cesarean delivery, gives perspective on the safety of this analgesic technique in healthy women, and promotes patient risk stratification and perioperative risk assessment to determine and adjust the intensity, frequency, and duration of respiratory monitoring.

Lymphoceles are common following prostatectomy with lymph node dissection, but the vast majority are asymptomatic. We present a unique case of a large complex lymphocele tracking into the anterior space of Retzius following Retzius sparing prostatectomy and bilateral pelvic lymphadenectomy. The patient initially presented with shortness of breath and subsequent diagnosis of a submassive pulmonary embolism. Further evaluation revealed compression of the iliac vessels by the fluid collection. Following multiple failed attempts of drainage percutaneously, the patient required return to the operating room for peritoneal marsupialization, drainage of fluid collection, and evacuation of large amounts of clot within the collection.

Introduction The cannabinoid CB1 receptor (CB1R) has been shown in preclinical studies to be involved in nicotine reinforcement and relapse‐like behavior. The common single nucleotide polymorphism (SNP) rs2023239 may code for an alternative CB1R protein, alter CB1R expression, and be involved in nicotine dependence. To date, no study has explored the relationship between this SNP in CB1R and specific phenotypes of nicotine dependence. Methods The current study investigated the influence of CB1R rs2023239 in nicotine reinforcement and craving in regular cigarette smokers. Current smokers (n = 104, cigarettes per day ≥ 10) were genetically grouped (C allele group vs. No C allele group) and underwent laboratory measures of nicotine reinforcement and smoking cue‐elicited craving. Nicotine reinforcement was assessed using a forced choice paradigm, while a cue‐reactivity procedure measured cue‐elicited craving. Results These results show that smokers with the C allele variant (CC + CT genotypes) experienced a lower nicotine reinforcement effect compared to those without the C allele (TT genotype). These results were similar in both our subjective and behavioral reinforcement measures, though the subjective effects did not withstand controlling for race. There was no difference between genotype groups with respect to cue‐elicited craving, suggesting a lack of influence in cue reactivity. Conclusion Taken together, these results suggest that the variation in the CB1R (i.e., rs2023239 SNP) may play a larger role in nicotine reinforcement compared to cue reactivity. This work provides impetus to further understand the physiological mechanisms that explain how CB1Rs influence nicotine dependence phenotypes., This study investigates the effect of a CB1R single nucleotide polymorphism (rs2023239) on smoking phenotypes. The results show that smokers with the C allele variant (CC + CT genotypes) experienced a lower nicotine reinforcement effect compared to those without the C allele (TT genotype). This polymorphism does not seem to affect smoking cue reactivity.

Actinic keratosis (AK) is a common skin lesion often defined as premalignant with more evidence indicating it as early stage of cutaneous squamous cell carcinoma (cSCC). The AK may remain stable, transform towards incisive cSCC or in some cases revert spontaneously. Several different underlying conditions can increase risk of cSCC, however, advanced age represents major risk of AK and its progression towards cSCC indicating increased risk during chronological aging. Importantly, AK and cSCC are characterized by similar genetic profile, which lead researchers to search for novel biomarkers allowing early detection. As skin sampling is often invasive and causes scaring, in the current study, we investigated a novel approach to establish potential blood circulating genetic markers in patients diagnosed with AK and cSCC. Based on clinical diagnosis and dermoscopy, we recruited 13 patients with AK (divided into two groups: the first included patients with no more than three lesions, the second group included patients with at least ten lesions) and two additional individuals diagnosed with cSCC. Deep sequencing analysis of serum circulating miRNAs detected a total of 68 expressed miRNAs. Further analysis indicated 2 regulated miRNAs for AK cohort and 12 miRNAs for cSCC patients, while there were 26 miRNAs differentially regulated between cSCC and AK patients. There was also one commonly regulated miRNA between AK and cSCC patients and ten miRNAs that were regulated in cSCC when compared with both control and AK patients. We did not observe any differences between the AK groups. In conclusion, our analysis detected in circulation some miRNA that were previously recognized as important in AK, cSCC, and other type of skin cancer supporting this approach as potential non-invasive diagnosis of AK and cSCC.

INTRODUCTION AND OBJECTIVE:Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) is reported to improve urinary functional outcomes faster over standard RARP. However, there are reports of...

Currently, there is a concern at the national level of the overuse of both prescription and nonprescription opioid use. The purpose of this study was to identify whether the use of the intravenous (IV) formulation of acetaminophen (Ofirmev; Mallinckrodt Pharmaceuticals, Staines-upon-Thames, United Kingdom) is an effective tool in the reduction of postoperative pain, with a secondary goal of reduction of postoperative narcotic use.A total of 72 patients with previously diagnosed either partial bony or complete bony impacted third molars were selected with care to avoid long-acting local anesthetics or dissociative anesthetic agents. The patients' postoperative pain scores at 4 and 24 hours were collected via a verbal rating scale by the primary investigator. The exclusion criteria included administration of bupivacaine or ketamine, hepatic or renal impairment, pregnancy, or allergy to any of the normally administered sedation medications.At all postoperative increments (immediately, 4 hours, and 24 hours), there was no significant difference at P .05 between scores for either the IV acetaminophen or placebo group. Although there was a recorded difference in reduction of pain at both 4 and 24 hours postoperatively, these were not statistically significant variables.The use of IV acetaminophen showed no statistically significant decrease in patient pain at either 4 or 24 hours postoperatively. Although there are not representative data suggesting the routine use of IV acetaminophen, on the basis of the abundance of literature on the treatment of pain for other procedures, this medication should not be discarded as ineffective.

BACKGROUND: In a recent clinical trial (NCT00295308), we demonstrated that clonidine decreased the association between opioid craving and moderate levels of stress and affect in patients receiving buprenorphine-based opioid agonist therapy. OBJECTIVES: To examine the relationship between illicit opioid use and craving and affect during the evaluation of clonidine as an adjunct medication in buprenorphine treatment for opioid use disorder. Secondarily, to examine whether those relationships are driven by within- or between-participant factors. METHODS: This was a secondary data analysis from our original trial. Participants (N = 108, female: n = 23, male n =85) receiving buprenorphine were randomized to receive adjunct clonidine or placebo. Participants used portable electronic devices to rate stress, mood, and craving via ecological momentary assessment (EMA) four times randomly each day. To associate the EMA data with illicit opioid use, each EMA report was linked to participants’ next urine drug screen (thrice weekly). We used generalized linear mixed models to examine the interaction between treatment group and illicit opioid use, as well as to decompose the analysis into within- and between-participant effects. RESULTS: Craving for opioids and cocaine was increased when participants were using illicit opioids; this effect was greater in the clonidine group. For affect, mood was poorer during periods preceding opioid-positive urines than opioid-negative urines for clonidine-treated participants, whereas there was no difference for placebo participants. CONCLUSION. This secondary analysis provides evidence that illicit opioid use was linked to stronger negative affect and craving in participants maintained on clonidine in opioid agonist therapy.

Primary adenomas are common in the gastrointestinal tract but exceedingly rare on the periurethral surface and vagina. The pathogenesis remains unknown but vaginal adenomas are hypothesized to arise from vaginal adenosis or embryonic cloacal remnants and possess malignant potential. We present a case of a large primary vaginal tubulovillous adenoma in an eighty-one-year-old, likely diethylstilbestrol naïve patient. To the best of our knowledge the patient's 7.4 x 4.5 × 1.4 cm primary vaginal tubulovillous adenoma is the largest ever reported in literature., Highlights - Primary vaginal adenomas in diethylstilbestrol naïve patients are exceedingly rare - Vaginal adenomas have malignant potential and must be fully resected - There is no consensus on management of primary vaginal adenomas

In addiction, risk factors for craving and use include stress and drug-related cues. Stress and cues have additive or more-than-additive effects on drug seeking in laboratory animals, but, surprisingly, seem to compete with one another (ie, exert less-than-additive effects) in human laboratory studies of craving. We sought heretofore elusive evidence that human drug users could show additive (or more-than-additive) effects of stress and cues on craving, using ecological momentary assessment (EMA). Outpatients (N=182) maintained on daily buprenorphine or methadone provided self-reports of stress, craving, mood, and behavior on electronic diaries for up to 16 weeks. In three randomly prompted entries (RPs) per day, participants reported the severity of stress and craving and whether they had seen or been offered opioids, cocaine, cannabis, methamphetamine, alcohol, or tobacco. In random-effects models controlling for between-person differences, we tested effects of momentary drug-cue exposure and stress (and their interaction) on momentary ratings of cocaine and heroin craving. For cocaine craving, the Stress × Cue interaction term had a positive mean effect across participants (M=0.019; CL95 0.001-0.036), denoting a more-than-additive effect. For heroin, the mean was not significantly greater than 0, but the confidence interval was predominantly positive (M=0.019; CL95 -0.007-0.044), suggesting at least an additive effect. Heterogeneity was substantial; qualitatively, the Stress × Cue effect appeared additive for most participants, more than additive for a sizeable minority, and competitive in very few. In the field, unlike in human laboratory studies to date, craving for cocaine and heroin is greater with the combination of drug cues and stress than with either alone. For a substantial minority of users, the combined effect may be more than additive.

OBJECTIVE In a clinical trial examining daily clonidine as an adjunct to buprenorphine treatment for opioid dependence, we found that clonidine increased opioid abstinence and decoupled stress from craving. From a personalized-medicine perspective, the next step is to identify people for whom clonidine would be beneficial. To that end, using data from the same clinical trial, we examined the associations of daily-life activities with treatment success. METHODS Outpatients (N = 118) received clonidine (0.3 mg/d) or placebo during 18 weeks of buprenorphine treatment. Participants carried a smartphone that randomly prompted them 4 times per day to report their moods and activities. Using generalized linear mixed models, we assessed the likelihoods of different types of daily activity as a function of clonidine versus placebo, days of longest continuous opioid abstinence, and their interaction. RESULTS Participants in the buprenorphine-only (buprenorphine plus placebo) control group who engaged in more responsibilities (work and child/elder care) had longer streaks of abstinence, whereas those who engaged in more unstructured-time activities had shorter streaks of abstinence. Conversely, for participants in the buprenorphine-plus-clonidine group, longer streaks of abstinence were associated with higher frequencies of activities associated with "unstructured" time. CONCLUSIONS The study replicates findings that engaging in responsibilities is related to positive treatment outcomes in standard opioid agonist therapy. The pattern of results also suggests that clonidine helped participants engage in unstructured-time activities with less risk of craving or use than they might otherwise have had.

Knowing how stress manifests in the lives of people with substance-use disorders could help inform mobile “just in time” treatment. The purpose of this paper is to examine discrete episodes of stress, as distinct from the fluctuations in background stress assessed in most EMA studies. For up to 16 weeks, outpatients on opioid-agonist treatment carried smartphones on which they initiated an entry whenever they experienced a stressful event (SE) and when randomly prompted (RP) three times daily. Participants reported the severity of stress and craving and the context of the report (location, activities, companions). Decomposition of covariance was used to separate within-person from between-person effects; r effect sizes below are within-person. Participants (158 of 182; 87%) made 1787 stress-event entries. Craving for opioids increased with stress severity (r effect = 0.50). Stress events tended to occur in social company (with acquaintances, 0.63, friends, 0.17, or on the phone, 0.41) rather than with family (spouse, −0.14; child, −0.18), and in places with more overall activity (bars, 0.32; outside, 0.28; walking, 0.28) and more likelihood of unexpected experiences (with strangers, 0.17). Being on the internet was slightly protective (−0.22). Our prior finding that being at the workplace protects against background stress in our participants was partly supported in these stressful-event data. The contexts of specific stressful events differ from those we have seen in prior studies of ongoing background stress. However, both are associated with drug craving.

Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) maintains oxygenation and blunts the partial pressure of carbon dioxide (PaCO2) rise in nonpregnant subjects during apnea. Physiologic changes of pregnancy may attenuate the utility of THRIVE. We present a nulliparous patient at 31 weeks' gestation undergoing tracheal dilation requiring general anesthesia without intubation utilizing THRIVE. Our data confirms prior reports in nonpregnant patients showing markedly extended time to desaturation. However, PaCO2 rise more closely mirrors classic apneic oxygenation in nonobstetric patients. The PaCO2 elevation and subsequent acidosis may limit the utility of THRIVE for prolonged apnea in pregnant surgical patients.

Preclinical studies show that the dopamine D3 receptor (D3R) is involved in the reinstatement of drug seeking and motivation for drugs of abuse. A D3R gene variant, Ser9Gly (rs6280) has been linked to nicotine dependence, yet the mechanisms underlying its involvement in nicotine dependence is unclear. This study investigated the relationship between the Ser9Gly variant and measures of both nicotine reinforcement and cue-elicited craving. Phenotypes of smoking behaviors were assessed in genetically grouped (Glycine vs. No Glycine carriers) current smokers (n = 104, ≥ 10 cigarettes per day). Laboratory measures included a forced choice session (to measure reinforcement of nicotine containing vs. denicotinized cigarettes), and a cue-reactivity session (to measure smoking cues vs. neutral cues elicited craving). The forced choice procedure revealed that subjective ratings were significantly higher in response to nicotinized compared to denicotinized cigarettes; however the Ser9Gly variant did not influence this effect. By comparison, smoking cues elicited greater craving over time compared to neutral cues, and Glycine carriers of the Ser9Gly D3R variant seem to experience a significant blunted cue-elicited craving effect. Results support D3R involvement in nicotine cue reactivity. However, more research is needed to reveal how this gene variant modulates various aspects of nicotine dependence.

OBJECTIVE: Prolonged preoperative fasting may lead to dehydration, hypoglycaemia, ketoacidosis and delayed recovery. We hypothesised that a patient educational initiative would decrease our preoperative fasting periods for elective caesarean delivery. METHODS: This was an observational quality improvement impact study. Elective caesarean patients who delivered during our study period were included in the study, 40 patients in the pre-intervention and 40 patients in the post-intervention groups. Only English-speaking patients were included. We developed a patient educational pamphlet outlining preoperative fasting and analgesic expectations for caesarean delivery that was given to every patient at her preoperative anaesthesia consultation. The pamphlet included the American Society of Anesthesiologists’ preoperative fasting and enhanced recovery carbohydrate drink recommendations. The primary outcome measure was intended fasting duration for liquids (defined as time from last reported liquid consumption to scheduled caesarean delivery) before and after the patient educational initiative. Secondary outcomes included solid fasting time, types of liquids and solids consumed. RESULTS: The intended median (interquartile range) fasting time for liquids decreased from 10 (8.9–12) h to 3.5 (2.5–10) h (p

BACKGROUND Morphea, also known as localized scleroderma, is a rare autoimmune connective tissue disease characterized by skin fibrosis. UVA1 phototherapy is an important asset in the reduction of clinical manifestations in morphea. There are studies claiming that UV light modulates the expression of some human endogenous retroviral sequences. The aim of this study was to determine if the expression of HERV-K10 gag element is lowered by UVA1 phototherapy in morphea, a disease in which such irradiation has a soothing effect. MATERIAL AND METHODS The expression levels of the HERV-K10 gag were assessed by real-time PCR (polymerase chain reaction) in peripheral blood mononuclear cells (PBMC) and skin-punch biopsies of healthy volunteers and 9 morphea patients before and after phototherapy. Additionally, correlations between the HERV-K10 gag expression and age, disease duration, the Localized Scleroderma Skin Severity Index (LoSSI), and antinuclear antibody (ANA) titers were assessed. RESULTS In PBMC, HERV-K10 gag mRNA was significantly elevated after UVA1 phototherapy compared to healthy controls. Most of the patients responded with an increased expression level of this sequence. However, we found no statistical evidence at this point that phototherapy indeed has an effect on the HERV-K10 gag expression (there were no statistical differences in PBMC of morphea patients before and after phototherapy). Similarly, there was no statistically relevant effect of the UVA1 on the expression of HERV-K10 gag in skin. CONCLUSIONS At this point, the effect of UVA1 phototherapy on the expression of HERV-K10 gag cannot be statistically confirmed.

Introduction: Morphea (localized scleroderma) is a relatively rare disease characterized by excessive skin fibrosis. Human endogenous retroviruses (HERV) are largely distributed within the human genome with hundreds of thousands of elements. The HERV have been widely studied in autoimmune disorders, yet hardly ever assessed in diseases with a good prognosis such as morphea. Aim: In this study we focus on the possible relations between the expression of chosen HERV and factors influencing the pathomechanism of the disease, such as age, sex, titres of anti-nuclear antibodies, as well as duration, activity, and severity of the disease (LoSSI index). Material and methods: Real-time polymerase chain reaction (PCR) targeting six HERV sequences of interest were performed on samples derived from peripheral blood mononuclear cells (PBMC) and skin biopsies. Results: In PBMC we found a statistically significant negative correlation between HERV-W env expression and LoSSI index (p = 0.01). Additionally, HERV-W env was downregulated in patients with the active form of morphea. In all other cases we found no correlation whatsoever nor statistically significant differences below the p = 0.05 threshold. Conclusions : Morphea seems to be an autoimmune disease where the impact of HERV is not so apparent. It seems that probing many patients for the expression of just a few sequences is not as effective as previously expected. For initial studies of HERV in other diseases we recommend high throughput techniques such as HERV-dedicated DNA microarrays or massive parallel sequencing.

OBJECTIVE This study sought to examine the predictors of health risk perception in smokers with or without schizophrenia. METHODS The health risk subscale from the Smoking Consequences Questionnaire was dichotomized and used to measure health risk perception in smokers with (n = 67) and without schizophrenia (n = 100). A backward stepwise logistic regression was conducted using variables associated at the bivariate level to determine multivariate predictors. RESULTS Overall, 62.5% of smokers without schizophrenia and 40.3% of smokers with schizophrenia completely recognize the health risks of smoking (p ≤ .01). Multivariate predictors for smokers without schizophrenia included: sex (Exp (B) = .3; p < .05), Smoking Consequences Questionnaire state enhancement (Exp (B) = .69; p < .01), and craving relief (Exp (B) = 1.8; p < .01). Among smokers with schizophrenia, predictors were education (Exp (B) = .7; p < .05), nicotine dependence (Exp (B) = .5; p < .01), motivation to quit (Exp (B) = 1.8; p < .01), and Smoking Consequences Questionnaire craving relief (Exp (B) = 1.8; p < .01). CONCLUSIONS There was overlap and differences between predictors in smokers with and without schizophrenia. Commonly used techniques for education on the health consequences of cigarettes may work in smokers with schizophrenia, but intervention efforts specifically tailored to smokers with schizophrenia might be more efficacious.

Purpose. Vitamin D, besides its role in calcium-phosphorus metabolism, turned out to play a significant immunomodulating function. Until now four single nucleotide polymorphisms of vitamin D receptor gene (VDR), rs2228570 (FokI), rs1544410 (BsmI), rs7975232 (ApaI), and rs731236 (TaqI), have been studied in autoimmune thyroid disorders, with conflicting results. Another functional polymorphism of the VDR gene, rs11568820 (Cdx2), has been shown to influence the immune system, although it has not been studied for its association with autoimmune thyroiditis to date. Therefore, the study aimed to evaluate the association of these five VDR gene polymorphisms with susceptibility to autoimmune thyroiditis among Caucasian Polish population. A relationship between the studied polymorphisms and selected clinical features of the disease was additionally assessed. Methods. 223 patients with autoimmune thyroiditis and 130 control subjects were enrolled in the study. VDR polymorphisms were studied by PCR-RFLP or TaqMan real-time PCR. Results. Allele and genotype distributions of any of the studied polymorphisms did not differ significantly between patients and controls. Similarly, frequencies of haplotypes derived from rs1544410-rs7975232-rs731236 (BsmI-ApaI-TaqI) polymorphisms were not significantly different in the two studied groups. However, a weak association between rs1544410 (BsmI) or rs7975232 (ApaI) VDR polymorphisms and thyroid volume was found (p = 0.03 and p = 0.04, resp.). Conclusions. Our results suggest that VDR gene is not a major susceptibility factor for autoimmune thyroiditis development, at least in Caucasian Polish population.

Patients presenting with prostate cancers undergo clinical staging evaluations to determine the extent of disease to guide therapeutic recommendations. Management options may include watchful waiting, surgery, or radiation therapy. Thus, initial risk stratification of prostate cancer patients is important for achieving optimal therapeutic results or cancer cure and preservation of quality of life. Predictive biomarkers for risks of complications or late effects of treatment are needed to inform clinical decisions for treatment selection. Here, we analyzed pre-treatment plasma metabolites in a cohort of prostate cancer patients (N = 99) treated with Stereotactic Body Radiation Therapy (SBRT) at Medstar-Georgetown University Hospital in a longitudinal, quality-of-life study to determine if individuals experiencing radiation toxicities can be identified by a molecular profile in plasma prior to treatment. We used a multiple reaction mass spectrometry-based molecular phenotyping of clinically annotated plasma samples in a retrospective outcome analysis to identify candidate biomarker panels correlating with adverse clinical outcomes following radiation therapy. We describe the discovery of candidate biomarkers, based on small molecule metabolite panels, showing high correlations (AUCs ≥ 95%) with radiation toxicities, suitable for validation studies in an expanded cohort of patients.

Autoimmune blistering dermatoses (ABDs) are characterized by autoantibodies to keratinocyte surface antigens and molecules within the dermal&ndash, epidermal junction causing disruption of skin integrity. The affinity of Fc receptors (FcRs) causing an autoimmune response in ABDs may vary based on single-nucleotide polymorphisms (SNPs) in FcRs determining the course of disease. This study aimed to explore the effects of CD16A and CD32A SNPs on the autoimmune response in several ABDs. In total, 61 ABDs patients were investigated. ELISA tests, direct immunofluorescence (DIF), TaqMan SNP Genotyping Assays, and statistical analyses were performed. The CA genotype (composed of allele C and A) of rs396991 in CD16A had a higher affinity for tissue-bound IgG1 in pemphigus and for C3 in subepithelial ABDs, showing statistical significance. The greatest relative risk (odds ratio) was reported for AA (rs396991 of CD16A) and CC (rs1801274 of CD32A) homozygotes. There were no statistically significant differences between certain genotypes and specific circulating autoantibodies (anti-DSG1, anti-DSG3 IgG in pemphigus, anti-BP180, anti-BP230 IgG) in subepithelial ABDs. Our findings indicated that rs396991 in CD16A may be of greater importance in ABDs development. Moreover, FcR polymorphisms appeared to have a greater impact on tissue-bound antibodies detected using DIF than circulating serum antibodies in ABDs.

Background Sleep disturbance is common in patients with opioid use disorder (OUD) receiving medication for addiction treatment. Differences between patients on the two primary agonist medications—methadone and buprenorphine—are not well understood. Methods In patients receiving either methadone or buprenorphine treatment for OUD, we examined sleep continuity and architecture using ambulatory monitoring to gather both an objective measure (daily sleep EEG; M = 5.76 days, SD = 1.46) and a subjective measure (daily sleep diary; M = 54.10 days, SD = 25.10) of sleep. Results Patients treated with buprenorphine versus methadone did not differ on any measure of sleep continuity or architecture. Women had longer EEG-derived total sleep time than men (d = -0.68, 95 % CI -1.32 to -0.09), along with lower %N2 (d = 0.94, 95 % CI 0.34–1.64) and greater %N3 (d = -0.94, 95 % CI -1.61 to -0.32). Self-reported sleep differed from EEG-derived estimates: wake after sleep onset was greater by EEG than by diary (d = 2.58, 95 % CI 1.74–3.63), and total sleep time and sleep efficiency were lower by EEG than by diary (d for sleep time = 2.93, 95 % CI 2.06–4.14; d for efficiency = 1.69, 95 % CI 0.98–2.49). Conclusions Patients treated with buprenorphine or methadone did not substantively differ in ambulatory measures of sleep. With both medications, there was a discrepancy between objective and subjective sleep measures. Further confirmatory evidence would inform the development of sleep-related recommendations for OUD patients undergoing agonist treatment.

Background and aims Stress can be validly assessed “live” or by a summary evaluation of the very recent past. Using smartphone-based ecological momentary assessment (EMA) combined with end-of-day (EOD) entries, we assessed the association between daily hassles, stressful events and use of opioids and cocaine, in opioid- and cocaine-using men and women. Methods For up to 16 weeks, 161 outpatients in opioid-agonist treatment who reported cigarette smoking carried smartphones on which they reported stressful events (SEs) and drug use (DU) and completed an EOD questionnaire to report hassles encountered throughout the day, current perceived stress, cigarettes/day, and current mood. We compared EOD responses on days with and without SE and DU reports and on days when thrice-weekly urine drug screens indicated opioid or cocaine use or abstinence. Results Participants (N = 161) made 11,544 EOD entries; EMA SEs were reported on 861 (7.5%) days, and DUs on 1685 (14.6%) days. The most frequently reported hassles in EOD entries were “not enough money” (31.4% of daily reports) and maintaining abstinence (18.7%). Total EOD hassles showed small but statistically significant associations [odds ratios (95% CIs)] with EMA SEs [1.09 (1.06–1.13)], DUs [1.08 (1.06–1.10)], and urine-positive opioid [1.06 (1.04–1.09)] and cocaine [1.03 (1.00–1.06)] results. Men and women had similar rates (mean/day (SD)) of hassles: men 2.25 (3.55); women 2.55 (3.76) (F1,159 = 0.53, p = 0.47). Conclusions Daily hassles, reported at the end of the day, are associated with both same-day stressful events and drug use. Monitoring hassles and devising specific coping strategies might be useful therapeutic targets.