Reduced dopamine transporter binding predates impulse control disorders in Parkinson's disease

Impulse control disorders (ICD) are relatively common in Parkinson's disease (PD) and generally are regarded as adverse effects of dopamine replacement therapy, although certain demographic and clinical risk factors are also involved. Previous single‐photon emission computed tomography (SPECT) studies showed reduced ventral striatal dopamine transporter binding in Parkinson patients with ICD compared with patients without. Nevertheless, these studies were performed in patients with preexisting impulse control impairments, which impedes clear‐cut interpretation of these findings. We retrospectively procured follow‐up data from 31 medication‐naïve PD patients who underwent dopamine transporter SPECT imaging at baseline and were subsequently treated with dopamine replacement therapy. We used questionnaires and a telephone interview to assess medication status and ICD symptom development during the follow‐up period (31.5 ± 12.0 months). Eleven patients developed ICD symptoms during the follow‐up period, eight of which were taking dopamine agonists. The PD patients with ICD symptoms at follow‐up had higher baseline depressive scores and lower baseline dopamine transporter availability in the right ventral striatum, anterior‐dorsal striatum, and posterior putamen compared with PD patients without ICD symptoms. No baseline between‐group differences in age and disease stage or duration were found. The ICD symptom severity correlated negatively with baseline dopamine transporter availability in the right ventral and anterior‐dorsal striatum. The results of this preliminary study show that reduced striatal dopamine transporter availability predates the development of ICD symptoms after dopamine replacement therapy and may constitute a neurobiological risk factor related to a lower premorbid dopamine transporter availability or a more pronounced dopamine denervation in PD patients susceptible to ICD. © 2014 International Parkinson and Movement Disorder Society     

Developing a Competency‐based Curriculum in Basic and Clinical Pharmacology – A Delphi Study among Physicians

A new curriculum is planned for the medical school at Lund University, Sweden. Pharmacology, in a broad sense, has been identified as a subject that needs to be strengthened based on needs in the healthcare system. The aim was to identify the competencies in basic and clinical pharmacology that a newly qualified physician needs. Using a modified three‐round Delphi technique, 31 physicians were invited to list necessary competencies (round 1). After content analysis, these panel members classified the list by importance on two occasions (rounds 2 and 3) using a 4‐point scale (4 = necessary, 3 = desirable, 2 = useful, 1 = not necessary). Competencies with the highest ranks based on necessity were retained. Thirty physicians accepted the invitation and 25 (83%) of them completed all three rounds. Round 1 resulted in 258 suggestions, which were subsequently reduced to 95 competencies. Of these 95 competencies, 40 were considered necessary by at least 75% of the panel members. The degree of consensus increased between round 2 and round 3. Using a modified Delphi technique, we identified 40 competencies that could be transferred to learning outcomes for a new curriculum in basic and clinical pharmacology at medical school.     

Assessment of mouth-to-mask ventilation in resuscitation of asphyxic newborn babies. A pilot study

The aim of the study was to compare the effectiveness of mouth-to-mask ventilation (MM) in neonatal asphyxia with bag-and-mask ventilation (BM). A new mouth-to-mask infant resuscitation system was constructed. The study was performed in two university clinics with different resources. The KEM Hospital in Bombay was well equipped and neonatologists took part in all resuscitations; Muhimbili Medical Centre in Dar es Salaam was understaffed and had no physicians available at resuscitation. Therefore, different protocols had to be used. In Bombay, the study period was limited to 5 minutes. If needed, mask ventilation was then replaced by intubation. In Dar es Salaam, MM ventilation was continued for up to 10 minutes, the inspiratory pressure was adjusted to 30 cmH₂O and the ventilation was slow (8–10 breaths/min). In Bombay, 30 babies were allocated to the BM and 24 to the MM groups. In Dar es Salaam 56 were in the BM and 64 in the MM groups. The results for term babies in Bombay and both term and pre-term babies in Dar es Salaam showed no significant differences between the two groups of treatment, as determined by Apgar score 4 at 5 and 10 minutes, number of babies with their first gasp, heart rate >130 beats/min or pulse oximeter values above 75%, all at 5 minutes. An Apgar score 4 at 5 minutes was achieved in more than 75% of all infants, irrespective of treatment. The rates of early neonatal mortality and neonatal convulsions did not differ between the two methods of resuscitation. In Dar es Salaam, the low respiratory frequency used in both groups was associated with a slow increase in heart rate above 130 beats per min. This result indicates that further studies will be needed before such slow respiratory frequencies are used. We conclude that, if adequate training is provided and the respiratory frequency is kept within the normal range, MM ventilation is an alternative to assisted ventilation when no bag and mask is available. However, further studies are necessary, since this method has proved to be tiring and uncomfortable for the resuscitating health personnel.     

BRCA1 and BRCA2 pathogenic variants and prostate cancer risk: systematic review and meta-analysis

Background BRCA1 and BRCA2 pathogenic variants (PVs) are associated with prostate cancer (PCa) risk, but a wide range of relative risks (RRs) has been reported.Methods We systematically searched PubMed, Embase, MEDLINE and Cochrane Library in June 2021 for studies that estimated PCa RRs for male BRCA1/2 carriers, with no time or language restrictions. The literature search identified 27 studies (BRCA1: n = 20, BRCA2: n = 21).Results The heterogeneity between the published estimates was high (BRCA1: I² = 30%, BRCA2: I² = 83%); this could partly be explained by selection for age, family history or aggressive disease, and study-level differences in ethnicity composition, use of historical controls, and location of PVs within BRCA2. The pooled RRs were 2.08 (95% CI 1.38–3.12) for Ashkenazi Jewish BRCA2 carriers, 4.35 (95% CI 3.50–5.41) for non-Ashkenazi European ancestry BRCA2 carriers, and 1.18 (95% CI 0.95–1.47) for BRCA1 carriers. At ages <65 years, the RRs were 7.14 (95% CI 5.33–9.56) for non-Ashkenazi European ancestry BRCA2 and 1.78 (95% CI 1.09–2.91) for BRCA1 carriers.Conclusions These PCa risk estimates will assist in guiding clinical management. The study-level subgroup analyses indicate that risks may be modified by age and ethnicity, and for BRCA2 carriers by PV location within the gene, which may guide future risk-estimation studies.Subject terms: Cancer epidemiology, Cancer epigenetics, Prostate cancer, Risk factors     

Perioperative outcomes of laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy in super-obese and super-super-obese patients: a national database analysis

BackgroundEvidence remains contradictory for perioperative outcomes of super-obese (SO) and super-super-obese (SSO) patients undergoing bariatric surgery.ObjectiveTo identify national 30-day morbidity and mortality of laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) in SO and SSO patients.SettingThe Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database.MethodsAll LSG and LRYGB patients from 2015 through 2017 in the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database were grouped based on body mass index (BMI) as follows: morbidly obese (MO; BMI 35.0–49.9 kg/m²), SO (BMI 50.0–59.9 kg/m²), and SSO (BMI ≥60.0 kg/m²). Complications and mortality within 30 days were compared between BMI groups using Pearson X² or Fischer’s exact tests. Multivariate logistic regression was used to adjust for demographic characteristics and co-morbidities, and adjusted odds ratio (AOR) was reported for each outcome.ResultsOf 356,621 patients, 71.6% had LSG and 28.4% LRYGB. A total of 272,195 patients were in the MO group, 65,565 in the SO group, and 18,861 in the SSO group. Higher BMI was associated with increased overall morbidity and mortality. The overall complication rate was significantly higher for SO (AOR = 1.20, 95% confidence interval [CI] 1.13–1.28 for LSG; AOR = 1.08, 95% CI 1.01–1.15 for LRYGB) and SSO (AOR = 1.44, 95% CI 1.31–1.58 for LSG; AOR = 1.31, 95% CI 1.19–1.45 for LRYGB) compared with the MO group. Mortality was also significantly higher for SO (AOR = 1.65, 95% CI 1.10–2.48 for LSG; AOR = 1.85, 95% CI 1.23–2.80 for LRYGB) and SSO (AOR = 3.30, 95% CI 1.98–5.48 for LSG; AOR = 3.32, 95% CI 1.93–5.73 for LRYGB) compared with the MO group.ConclusionsSO and SSO patients are at increased risk of 30-day morbidity and mortality compared with MO patients. Despite this elevated perioperative risk, the overall risk of these procedures remains low and acceptable especially as bariatric surgery is the durable treatment option for obesity.     

Robot-assisted Radical Cystectomy: Description of an Evolved Approach to Radical Cystectomy

Background

Although open radical cystectomy (ORC) remains the gold standard of care for muscle-invasive bladder cancer, robot-assisted radical cystectomy (RARC) continues to gain wider acceptance. In this article, we focus on the steps of RARC, describing our approach, which has been developed over the past 10 yr. Totally intracorporeal RARC aims to offer the benefits of a complete minimally invasive approach while replicating the oncologic outcomes of open surgery.

Objective

We report our outcomes of a totally intracorporeal RARC procedure, describing step by step our technique and highlighting the variations on this standard template of nerve-sparing and female organ–preserving approaches in men and women.

Design, setting, and participants

Between December 2003 and October 2012, a total of 113 patients (94 male and 19 female) underwent totally intracorporeal RARC.

Surgical procedure

We performed RARC, extended pelvic lymph node dissection, and a totally intracorporeal urinary diversion (UD) in all patients. In the accompanying video, we focus on the standard template for RARC, also describing nerve-sparing and female organ–preserving approaches.

Outcome measurements and statistical analysis

Complications and oncologic outcomes are reported, including overall survival (OS) and cancer-specific survival (CSS) using Kaplan-Meier analysis.

Results and limitations

RARC with intracorporeal UD was performed in 113 patients. Mean age was 64 yr (range: 37–84). Forty-three patients underwent intracorporeal ileal conduit, and 70 had intracorporeal neobladder. On surgical pathology, 48% of patients had ≤pT1 disease, 27% had pT2 disease, 13% had pT3 disease, and 12% had pT4 disease. The mean number of lymph nodes removed was 21 (range: 0–57). Twenty percent of patients had lymph node–positive disease. Positive surgical margins occurred in six cases (5.3%). Median follow-up was 25 mo (range: 3–107). We recorded a total of 70 early complications (0–30 d) in 54 patients (47.8%), with 37 patients (32.7%) having Clavien grade ≥3. Thirty-six late complications (>30 d) were recorded in 30 patients (26.5%), with 20 patients (17.7%) having Clavien grade ≥3. One patient (0.9%) died within 90 days of operation from pulmonary embolism. Using Kaplan-Meier analysis, CSS was 81% at 3 yr and 67% at 5 yr.

Conclusions

Our structured approach to RARC has enabled us to develop this complex service while maintaining patient outcomes and complication rates comparable with ORC series. Our results demonstrate acceptable oncologic outcomes and encouraging long-term CSS rates.