The effects of diabetes clubs on peer-support, disclosure of diabetes status, and sources of information regarding diabetes management: results of a pilot-intervention in rural Vietnam.

OBJECTIVES: To measure the effects of diabetes clubs on peer support, disclosure of diabetes status, and the source of information regarding the management of diabetes among persons living with type-2 diabetes (T2D) in rural Vietnam. STUDY DESIGN: A pre- and post-pilot intervention study was carried out in Thai Binh Province, Vietnam (n = 222). RESULTS: Post-intervention, 57.7 % reported using experiences shared by other persons with T2D during the diabetes club sessions. Compared to pre-intervention, there was an increase in the proportion of persons with T2D who disclosed their diabetes status to friends and/or community members (an increase of 15.3 and 13.8 percentage points, respectively). The proportion of persons who reported gathering their own information regarding diabetes management without any support from others decreased from 15.7 % to 6.3 %. Those who reported a relative inside their home or a relative outside their household as their primary source of T2D-relevant information increased from 10.8 % to 18.6 % and from 2.7 % to 9.5 %, respectively. Persons who mentioned that they did not have a need for further support for their diabetes care increased from 18.5 % to 32.0 %. Specific support regarding diabetes-related knowledge received from family members, friends, and/or community members increased from 27.5 % to 62.2 % CONCLUSIONS: These findings suggest a promising potential for the implementation of diabetes clubs to enhance diabetes-relevant knowledge and the quality of self-management among persons living with T2D diabetes in rural areas of Vietnam.

Consulting the Digital Doctor: Google Versus ChatGPT as Sources of Information on Breast Implant-Associated Anaplastic Large Cell Lymphoma and Breast Implant Illness.

BACKGROUND: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare complication associated with the use of breast implants. Breast implant illness (BII) is another potentially concerning issue related to breast implants. This study aims to assess the quality of ChatGPT as a potential source of patient education by comparing the answers to frequently asked questions on BIA-ALCL and BII provided by ChatGPT and Google. METHODS: The Google and ChatGPT answers to the 10 most frequently asked questions on the search terms "breast implant associated anaplastic large cell lymphoma" and "breast implant illness" were recorded. Five blinded breast plastic surgeons were then asked to grade the quality of the answers according to the Global Quality Score (GQS). A Wilcoxon paired t-test was performed to evaluate the difference in GQS ratings for Google and ChatGPT answers. The sources provided by Google and ChatGPT were also categorized and assessed. RESULTS: In a comparison of answers provided by Google and ChatGPT on BIA-ALCL and BII, ChatGPT significantly outperformed Google. For BIA-ALCL, Google's average score was 2.72 ± 1.44, whereas ChatGPT scored an average of 4.18 ± 1.04 (p < 0.01). For BII, Google's average score was 2.66 ± 1.24, while ChatGPT scored an average of 4.28 ± 0.97 (p < 0.01). The superiority of ChatGPT's responses was attributed to their comprehensive nature and recognition of existing knowledge gaps. However, some of ChatGPT's answers had inaccessible sources. CONCLUSION: ChatGPT outperforms Google in providing high-quality answers to commonly asked questions on BIA-ALCL and BII, highlighting the potential of AI technologies in patient education. LEVEL OF EVIDENCE: Level III, comparative study LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Radiation doses and fractionation schedules in non-low-risk ductal carcinoma in situ in the breast (BIG 3-07/TROG 07.01): a randomised, factorial, multicentre, open-label, phase 3 study.

BACKGROUND: Whole breast irradiation (WBI) after conservative surgery for ductal carcinoma in situ (DCIS) reduces local recurrence. We investigated whether a tumour bed boost after WBI improved outcomes, and examined radiation dose fractionation sensitivity for non-low-risk DCIS. METHODS: The study was an international, randomised, unmasked, phase 3 trial involving 136 participating centres of six clinical trials organisations in 11 countries (Australia, New Zealand, Singapore, Canada, the Netherlands, Belgium, France, Switzerland, Italy, Ireland, and the UK). Eligible patients were women aged 18 years or older with unilateral, histologically proven, non-low-risk DCIS treated by breast-conserving surgery with at least 1 mm of clear radial resection margins. They were assigned to one of four groups (1:1:1:1) of no tumour bed boost versus boost after conventional versus hypofractionated WBI, or randomly assigned to one of two groups (1:1) of no boost versus boost after each centre prespecified conventional or hypofractionated WBI. The conventional WBI used was 50 Gy in 25 fractions, and hypofractionated WBI was 42·5 Gy in 16 fractions. A boost dose of 16 Gy in eight fractions, if allocated, was delivered after WBI. Patients and clinicians were not masked to treatment allocation. The primary endpoint was time to local recurrence. This trial is registered with ClinicalTrials.gov (NCT00470236). FINDINGS: Between June 25, 2007, and June 30, 2014, 1608 patients were randomly assigned to have no boost (805 patients) or boost (803 patients). Conventional WBI was given to 831 patients, and hypofractionated WBI was given to 777 patients. Median follow-up was 6·6 years. The 5-year free-from-local-recurrence rates were 92·7% (95% CI 90·6-94·4%) in the no-boost group and 97·1% (95·6-98·1%) in the boost group (hazard ratio 0·47; 0·31-0·72; p<0·001). The boost group had higher rates of grade 2 or higher breast pain (10% [8-12%] vs 14% [12-17%], p=0·003) and induration (6% [5-8%] vs 14% [11-16%], p<0·001). INTERPRETATION: In patients with resected non-low-risk DCIS, a tumour bed boost after WBI reduced local recurrence with an increase in grade 2 or greater toxicity. The results provide the first randomised trial data to support the use of boost radiation after postoperative WBI in these patients to improve local control. The international scale of the study supports the generalisability of the results. FUNDING: National Health and Medical Research Council of Australia, Susan G Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society, Canadian Cancer Trials Group.

Chronic Inhalation Exposure to Antimony Trioxide Exacerbates the MAPK Signaling in Alveolar Bronchiolar Carcinomas in B6C3F1/N Mice.

Antimony trioxide (AT) is used as a flame retardant in fabrics and plastics. Occupational exposure in miners and smelters is mainly through inhalation and dermal contact. Chronic inhalation exposure to AT particulates in B6C3F1/N mice and Wistar Han rats resulted in increased incidences and tumor multiplicities of alveolar/bronchiolar carcinomas (ABCs). In this study, we demonstrated Kras (43%) and Egfr (46%) hotspot mutations in mouse lung tumors (n = 80) and only Egfr (50%) mutations in rat lung tumors (n = 26). Interestingly, there were no differences in the incidences of these mutations in ABCs from rats and mice at exposure concentrations that did and did not exceed the pulmonary overload threshold. There was increased expression of p44/42 mitogen-activated protein kinase (MAPK) (Erk1/2) protein in ABCs harboring mutations in Kras and/or Egfr, confirming the activation of MAPK signaling. Transcriptomic analysis indicated significant alterations in MAPK signaling such as ephrin receptor signaling and signaling by Rho-family GTPases in AT-exposed ABCs. In addition, there was significant overlap between transcriptomic data from mouse ABCs due to AT exposure and human pulmonary adenocarcinoma data. Collectively, these data suggest chronic AT exposure exacerbates MAPK signaling in ABCs and, thus, may be translationally relevant to human lung cancers.

Externally validated prediction models for pre-eclampsia: systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the performance of existing externally validated prediction models for pre-eclampsia (specifically for any- early- late-onset and preterm pre-eclampsia). METHODS: A systematic search was conducted in five databases (MEDLINE, Embase, Emcare, CINAHL, and Maternity and Infant Care Database) to identify studies based on Population, Index model, Comparator, Outcome, Timing, and Setting (PICOTS) approach until May 20, 2023. We extracted data using the CHARMS checklist and appraised risk of bias using PROBAST tool. Discrimination and calibration performance were meta-analysed when appropriate. RESULTS: Twenty-three publications reported 52 externally validated prediction models on pre-eclampsia (twenty any-onset, seventeen early-onset, fourteen late-onset, and one preterm pre-eclampsia). No model had the same set of predictors. Fifteen, two, and three any-onset pre-eclampsia models were externally validated once, twice, and thrice, respectively, and the Fetal Medicine Foundation (FMF) preterm model was widely validated in sixteen different settings. The most common predictors were maternal characteristics (pre-pregnancy BMI, prior pre-eclampsia, family history of pre-eclampsia, chronic medical conditions, and ethnicity) and biomarkers (uterine artery pulsatility index and pregnancy-associated plasma protein-A). The model for preterm pre-eclampsia (triple test FMF) had the best performances with a pooled area under the receiver operating characteristics curve (AUROC) of 0.90 (95% prediction interval (PI) 0.76 - 0.96) and was well-calibrated. The other models generally had poor to fair discrimination performance (AUROC median 0.66, range 0.53 to 0.77) and were overfitted in calibration after external validation. Apart from the FMF model, only the two most validated models in any-onset pre-eclampsia using isolated maternal characteristics, produced reasonable pooled AUROCs of 0.71 (95% PI 0.66 - 0.76) and 0.73 (0.55 - 0.86). CONCLUSION: Existing externally validated prediction models for any-, early-, and late-onset pre-eclampsia have limited discrimination and calibration performance with inconsistent input variables. The triple test FMF model had excellent discrimination performance in predicting preterm pre-eclampsia in numerous settings, but the inclusion of specialised biomarkers may limit feasibility and implementation outside of high-resource settings. This article is protected by copyright. All rights reserved.

MR-based follow-up after brachytherapy and proton beam therapy in uveal melanoma.

PURPOSE: MRI is increasingly used in the diagnosis and therapy planning of uveal melanoma (UM). In this prospective cohort study, we assessed the radiological characteristics, in terms of anatomical and functional imaging, of UM after ruthenium-106 plaque brachytherapy or proton beam therapy (PBT) and compared them to conventional ultrasound. METHODS: Twenty-six UM patients were evaluated before and 3, 6 and 12 months after brachytherapy (n = 13) or PBT (n = 13). Tumour prominences were compared between ultrasound and MRI. On diffusion-weighted imaging, the apparent diffusion value (ADC), and on perfusion-weighted imaging (PWI), the time-intensity curves (TIC), relative peak intensity and outflow percentages were determined. Values were compared between treatments and with baseline. RESULTS: Pre-treatment prominences were comparable between MRI and ultrasound (mean absolute difference 0.51 mm, p = 0.46), but larger differences were observed post-treatment (e.g. 3 months: 0.9 mm (p = 0.02)). Pre-treatment PWI metrics were comparable between treatment groups. After treatment, brachytherapy patients showed favourable changes on PWI (e.g. 67% outflow reduction at 3 months, p < 0.01). After PBT, significant perfusion changes were observed at a later timepoint (e.g. 38% outflow reduction at 6 months, p = 0.01). No consistent ADC changes were observed after either treatment, e.g. a 0.11 × 10-3mm2/s increase 12 months after treatment (p = 0.15). CONCLUSION: MR-based follow-up is valuable for PBT-treated patients as favourable perfusion changes, including a reduction in outflow, can be detected before a reduction in size is apparent on ultrasound. For brachytherapy, a follow-up MRI is of less value as already 3 months post-treatment a significant size reduction can be measured on ultrasound.

Online physical exercise intervention in older adults during lockdown: Can we improve the recipe?

BACKGROUND: Recorded and live online physical exercise (PE) interventions are known to provide health benefits. However, the effects of prioritizing the number of live or recorded sessions remain unclear. AIMS: To explore which recorded-live sessions ratio leads to the best implementation and benefits in older adults. METHODS: Forty-six community-dwelling adults (> 60y.o.) were randomized into two groups completing a 12-week online PE intervention. Each group had a different ratio of live-recorded online sessions as follows: Live-Recorded-Live sessions (LRL; n = 22) vs. Recorded-Live-Recorded sessions (RLR; n = 24). RESULTS: Drop-out rates did not reach significance (LRL:14% vs. RLR: 29%, p = 0.20), and adherence was similar (> 85%) between groups. Both groups reported similar levels of satisfaction (> 70%), enjoyment (> 75%), and perceived exertion (> 60%). Both groups increased physical health and functional capacities, with greater improvements in muscle power (LRL: LRL: + 35 ± 16.1% vs. RLR: + 7 ± 13.9%; p = 0.010) and endurance (LRL: + 34.7 ± 15.4 vs. RLR: + 27.0 ± 26.5, p < 0.001) in the LRL group. DISCUSSION: Both online PE intervention modalities were adapted to the participants' capacities and led to a high level of enjoyment and retention. The greater physical improvements observed in the LRL group are likely due to the higher presence of the instructor compared to the RLR group. Indeed, participants received likely more feedback to appropriately adjust postures and movements, increasing the quality of the exercises. CONCLUSION: When creating online PE interventions containing both recorded and live sessions, priority should be given to maximizing the number of live sessions and not the number of recorded sessions.

Evaluation of Perioperative Versus Extended Courses of Antibiotic Prophylaxis After Immediate Implant-Based Breast Reconstruction.

BACKGROUND: Immediate implant-based breast reconstruction (IIBR) is the most commonly used method in breast reconstruction in the United States. However, postoperative surgical site infections (SSIs) can cause devastating reconstructive failure. This study evaluates the use of perioperative versus extended courses of antibiotic prophylaxis after IIBR for the prevention of SSI. METHODS: This is a single-institution retrospective study of patients who underwent IIBR between June 2018 and April 2020. Detailed demographic and clinical information was collected. Patients were divided into subgroups based on antibiotic prophylaxis regimen: group 1 consisted of patients who received 24 hours of perioperative antibiotics and group 2 consisted of patients who received ≥7 days of antibiotics. Statistical analyses were conducted using SPSSv26.0 with P ≤ 0.05 considered statistically significant. RESULTS: A total of 169 patients (285 breasts) who underwent IIBR were included. The mean age was 52.4 ± 10.2 years, and the mean body mass index (BMI) was 26.8 ± 5.7 kg/m2. Twenty-five percent of patients (25.6%) underwent nipple-sparing mastectomy, 69.1% skin-sparing mastectomy, and 5.3% total mastectomy. The implant was placed in the prepectoral, subpectoral, and dual planes in 16.7%, 19.2%, and 64.1% cases, respectively. Acellular dermal matrix was used in 78.7% of cases. A total of 42.0% of patients received 24-hour prophylaxis (group 1), and 58.0% of patients received extended prophylaxis (group 2). Twenty-five infections (14.8%) were identified, of which 9 (5.3%) resulted in reconstructive failure. In bivariate analyses, no significant difference was found between groups in rates of infection (P = 0.273), reconstructive failure (P = 0.653), and seroma (P = 0.125). There was a difference in hematoma rates between groups (P = 0.046). Interestingly, in patients who received only perioperative antibiotics, infection rates were significantly higher in those with BMI ≥ 25 (25.6% vs 7.1%, P = 0.050). There was no difference in overweight patients who received extended antibiotics (16.4% vs 7.0%, P = 0.160). CONCLUSIONS: Our data demonstrate no statistical difference in infection rates between perioperative and extended antibiotics. This suggests that the efficacies of current prophylaxis regimens are largely similar, with choice of regimen based on surgeon preference and patient-specific considerations. Infection rates in patients who received perioperative prophylaxis and were overweight were significantly higher, suggesting that BMI should be taken into consideration when choosing a prophylaxis regimen.

Microphthalmia-Associated Transcription Factor: A Differentiation Marker in Uveal Melanoma.

Microphthalmia-associated transcription factor (MITF) is an important regulator of melanogenesis and melanocyte development. In cutaneous melanoma, MITF loss has been linked to an increased expression of stem cell markers, a shift in epithelial-to-mesenchymal transition (EMT)-related factors, and increased inflammation. We explored the role of MITF in Uveal Melanoma (UM) using a cohort of 64 patients enucleated at the Leiden University Medical Center. We analysed the relation between MITF expression and clinical, histopathological and genetic features of UM, as well as survival. We performed differential gene expression and gene set enrichment analysis using mRNA microarray data, comparing MITF-low with MITF-high UM. MITF expression was lower in heavily pigmented UM than in lightly pigmented UM (p = 0.003), which we confirmed by immunohistochemistry. Furthermore, MITF was significantly lower in UM with monosomy 3/BAP1 loss than in those with disomy 3/no BAP1 loss (p < 0.001) and with 8q gain/amplification 8q (p = 0.02). Spearman correlation analysis showed that a low MITF expression was associated with an increase in inflammatory markers, hallmark pathways involved in inflammation, and epithelial-mesenchymal transition. Similar to the situation in cutaneous melanoma, we propose that MITF loss in UM is related to de-differentiation to a less favourable EMT profile and inflammation.

Modular desalination concept with low-pressure reverse osmosis and capacitive deionization: Performance study of a pilot plant in Vietnam in comparison to seawater reverse osmosis.

Membrane capacitive deionization (MCDI) has shown many advances, however, its performance in combination with other treatment technologies has not been widely reported. In this study, a pilot-scale low-pressure reverse osmosis (LPRO) (FilmTec™ XLE-2540) with MCDI (CapDI© C17, Voltea) was developed and tested as a promising modular desalination system. The systems were evaluated individually at different salinities and tested together as a modular system. The study focused in the comparison to conventional seawater reverse osmosis (SWRO) (FilmTec™ SW30-2540) at pilot-scale and in theory using the software Water Application Value Engine (WAVE, DuPont™), including a cost evaluation of the systems. Pilot tests were carried out in Can Gio, a riverine estuary region in South Vietnam, which is affected by progressive salinization (TDS ≈ 1-25 g/L). Drinking water quality (TDS < 600 mg/L) was achieved with a specific energy consumption (SEC) of 5.2 kWh/m³. Additionally, fouling mitigation was investigated for the ultrafiltration (UF) pre-treatment by periodic hydraulic and chemical enhanced backwashing. While the SWRO had a slightly lower SEC of 5.0 kWh/m³, WAVE calculations showed that lowering the SEC to 3.6 kWh/m³ is possible by improving the LPRO pump design and an optimization of the MCDI operation.

Transgender Mastectomy: Incidence of High-Risk Pathologic Findings and the Need for Postoperative Cancer Surveillance.

BACKGROUND: Chest masculinization surgeries are one of the most common gender-affirming procedures performed. There is a need for better understanding of the risk of breast cancer and postsurgical screening in female to male (FtM) individuals. This study aimed to evaluate the incidence of high-risk pathologic findings in FtM transgender patients undergoing gender-affirming chest reconstructive surgery. METHODS: Medical records were reviewed from all FtM patients undergoing gender-affirming chest reconstructive surgery from January 2010 to February 2021 by 3 plastic surgeons at the University of Pittsburgh Medical Center. Relative risk of malignant progression was used to stratify pathologic data. Subsequent management of atypical, in situ, and invasive pathology were recorded. RESULTS: A total of 318 patients were included in this study; the average age at surgery was 24.6 ± 8.1 years. Eighty-six patients (27%) had a family history of breast and/or ovarian cancer. Overall, 21 patients (6.6%) had some increased risk of breast cancer: 17 (5.3%) had proliferative lesions, mean age 38.2 ± 12.4 years; 2 had atypical ductal hyperplasia, ages 33.4 and 38.3 years; and 2 had invasive ductal carcinoma, ages 35.4 and 40.6 years. CONCLUSIONS: In this study, we found that 6.6% of FtM transgender patients undergoing top surgery had an elevated risk of breast cancer, with 1.2% of patients having a greater than 2 times risk of breast cancer. These results highlight the importance of appropriate preoperative screening as well as pathological analysis of surgical specimens to help guide clinical care. The authors advocate for a thorough breast cancer risk assessment before surgery for all patients, as well as using pathologic findings to guide postoperative cancer screening and follow-up.

Standard Fixed Enoxaparin Dosing for Venous Thromboembolism Prophylaxis Leads to Low Peak Anti-Factor Xa Levels in Both Head and Neck and Breast Free Flap Patients.

BACKGROUND: Venous thromboembolism (VTE) is a serious complication, particularly in cancer patients undergoing free flap reconstruction. Subcutaneous enoxaparin is the conventional prophylaxis for VTE prevention, and serum anti-factor Xa (afXa) levels are being increasingly used to monitor enoxaparin activity. In this study, free flap patients receiving standard enoxaparin prophylaxis were prospectively followed to investigate postoperative afXa levels and 90-day VTE and bleeding-related complications. METHODS: Patients undergoing free tissue transfer during an 8-month period were identified and prospectively followed. Patients received standard fixed enoxaparin dosing at 30 mg twice daily in head and neck (H&N) and 40 mg daily in breast reconstructions. Target peak prophylactic afXa range was 0.2 to 0.5 IU/mL. The primary outcome was the occurrence of 90-day postoperative VTE- and bleeding-related events. Independent predictors of afXa level and VTE incidence were analyzed for patients that met the inclusion criteria. RESULTS: Seventy-eight patients were prospectively followed. Four (5.1%) were diagnosed with VTE, and six (7.7%) experienced bleeding-related complications. The mean afXa levels in both VTE patients and bleeding patients were subprophylactic (0.13 ± 0.09 and 0.11 ± 0.07 IU/mL, respectively). Forty-six patients (21 breast, 25 H&N) had valid postoperative peak steady-state afXa levels. Among these, 15 (33%) patients achieved the target prophylactic range: 5 (33%) H&N and 10 (67%) breast patients. The mean afXa level for H&N patients was significantly lower than for breast patients (p = 0.0021). Patient total body weight was the sole negative predictor of afXa level (R 2 = 0.47, p < 0.0001). CONCLUSION: Standard fixed enoxaparin dosing for postoperative VTE prophylaxis does not achieve target afXa levels for the majority of our free flap patients. H&N patients appear to be a particularly high-risk group that may require a more personalized and aggressive approach. Total body weight is the sole negative predictor of afXa level, supporting a role for weight-based enoxaparin dosing.

[Sleep disorders in patients with a neurocognitive disorder]. / Les troubles du sommeil chez les patients atteints d'un trouble neurocognitif.

INTRODUCTION: Sleep disorders are prevalent in patients with a neurocognitive disorder, and diagnosis and treatment in these patients remain challenging in clinical practice. METHODS: This narrative review offers a systematic approach to diagnose and treat sleep disorders in neurocognitive disorders. RESULTS: Alzheimer's disease is often associated with circadian rhythm disorders, chronic insomnia, and sleep apnea-hypopnea syndrome. Alpha-synucleinopathies (e.g., Parkinson's disease and Lewy body dementia) are often associated with a rapid eye movement sleep behavior disorder, restless legs syndrome, chronic insomnia, and sleep apnea-hypopnea syndrome. A focused history allows to diagnose most sleep disorders. Clinicians should ensure to gather the following information in all patients with a neurocognitive disorder: (1) the presence of difficulties falling asleep or staying asleep, (2) the impact of sleep disturbances on daily functioning (fatigue, sleepiness and other daytime consequences), and (3) abnormal movements in sleep. Sleep diaries and questionnaires can assist clinicians in screening for specific sleep disorders. Polysomnography is recommended if a rapid eye movement sleep behavior disorder or a sleep apnea-hypopnea syndrome are suspected. Sleep complaints should prompt clinicians to ensure that comorbidities interfering with sleep are properly managed. The main treatment for moderate to severe obstructive sleep apnea-hypopnea syndrome remains continuous positive airway pressure, as its efficacy has been demonstrated in patients with neurocognitive disorders. Medications should also be reviewed, and time of administration should be optimized (diuretics and stimulating medications in the morning, sedating medications in the evening). Importantly, cholinesterase inhibitors (especially donepezil) may trigger insomnia. Switching to morning dosing or to an alternative drug may help. Cognitive-behavioral therapy for insomnia is indicated to treat chronic insomnia in neurocognitive disorders. False beliefs regarding sleep should be addressed with the patient and their caregiver. The sleep environment should be optimized (decrease light exposure at night, minimize noise, avoid taking vital signs, etc.). Sleep restriction can be considered as patients with a neurocognitive disorder often spend too much time in bed. The need for naps should be assessed case by case as naps may contribute to insomnia in some patients but allow others to complete their diurnal activities. Trazodone (50mg) may also be used under certain circumstances in chronic insomnia. Recent evidence does not support a role for exogenous melatonin in patients with a neucognitive disorder and insomnia. Patients in long-term care facilities are often deprived of an adequate diurnal exposure to light. Increasing daytime exposure to light may improve sleep and mood. Patients with circadian rhythm disorders can also benefit from light therapy (morning bright light therapy in case of phase delay and evening bright light therapy in case of phase advance). Rapid eye movement sleep behavior disorder can lead to violent behaviors, and the sleeping environment should be secured (e.g., mattress on the floor, remove surrounding objects). Medication exacerbating this disorder should be stopped if possible. High dose melatonin (6 to 18mg) or low dose clonazepam (0.125-0.25mg) at bedtime may be used to reduce symptoms. Melatonin is preferred in first-line as it is generally well tolerated with few side effects. Patients with restless legs syndrome should be investigated for iron deficiency. Medication decreasing dopaminergic activity should be reduced or stopped if possible. Behavioral strategies such as exercise and leg massages may be beneficial. Low-dose dopamine agonists (such as pramipexole 0.125mg two hours before bedtime) can be used to treat the condition, but a prolonged treatment may paradoxically worsen the symptoms. Alpha-2-delta calcium channel ligands can also be used while monitoring for the risk of falls. CONCLUSION: Multiple and sustained nonpharmacological approaches are recommended for the treatment of sleep disturbances in patients with neurocognitive disorder. Pharmacological indications remain limited, and further randomized clinical trials integrating a multimodal approach are warranted to evaluate the treatment of sleep disorders in specific neurocognitive disorders.

Cobalt-induced oxidative stress contributes to alveolar/bronchiolar carcinogenesis in B6C3F1/N mice.

Rodent alveolar/bronchiolar carcinomas (ABC) that arise either spontaneously or due to chemical exposure are similar to a subtype of lung adenocarcinomas in humans. B6C3F1/N mice and F344/NTac rats exposed to cobalt metal dust (CMD) by inhalation developed ABCs in a dose dependent manner. In CMD-exposed mice, the incidence of Kras mutations in ABCs was 67% with 80% of those being G to T transversions on codon 12 suggesting a role of oxidative stress in the pathogenesis. In vitro studies, such as DMPO (5,5-dimethyl-1-pyrroline N-oxide) immune-spin trapping assay, and dihydroethidium (DHE) fluorescence assay on A549 and BEAS-2B cells demonstrated increased oxidative stress due to cobalt exposure. In addition, significantly increased 8-oxo-dG adducts were demonstrated by immunohistochemistry in lungs from mice exposed to CMD for 90 days. Furthermore, transcriptomic analysis on ABCs arising spontaneously or due to chronic CMD-exposure demonstrated significant alterations in canonical pathways related to MAPK signaling (IL-8, ErbB, Integrin, and PAK pathway) and oxidative stress (PI3K/AKT and Melatonin pathway) in ABCs from CMD-exposed mice. Oxidative stress can stimulate PI3K/AKT and MAPK signaling pathways. Nox4 was significantly upregulated only in CMD-exposed ABCs and NOX4 activation of PI3K/AKT can lead to increased ROS levels in human cancer cells. The gene encoding Ereg was markedly up-regulated in CMD-exposed mice. Oncogenic KRAS mutations have been shown to induce EREG overexpression. Collectively, all these data suggest that oxidative stress plays a significant role in CMD-induced pulmonary carcinogenesis in rodents and these findings may also be relevant in the context of human lung cancers.

The PREvention Program for Alzheimer's RElated Delirium (PREPARED) cluster randomized trial: a study protocol.

BACKGROUND: Delirium is a significant cause of morbidity and mortality among older people admitted to both acute and long-term care facilities (LTCFs). Multicomponent interventions have been shown to reduce delirium incidence in the acute care setting (30-73%) by acting on modifiable risk factors. Little work, however, has focused on using this approach to reduce delirium incidence in LTCFs. METHODS: The objective is to assess the effectiveness of the multicomponent PREPARED Trial intervention in reducing the following primary outcomes: incidence, severity, duration, and frequency of delirium episodes in cognitively impaired residents. This 4-year, parallel-design, cluster randomized study will involve nursing staff and residents in 45-50 LTCFs in Montreal, Canada. Participating public and private LTCFs (clusters) that provide 24-h nursing care will be assigned to either the PREPARED Trial intervention or the control (usual care) arm of the study using a covariate constrained randomization procedure. Approximately 400-600 LTC residents aged 65 and older with dementia and/or cognitive impairment will be enrolled in the study and followed for 18 weeks. Residents must be at risk of delirium, delirium-free at baseline and have resided at the facility for at least 2 weeks. Residents who are unable to communicate verbally, have a history of specific psychiatric conditions, or are receiving end-of-life care will be excluded. The PREPARED Trial intervention consists of four main components: a decision tree, an instruction manual, a training package, and a toolkit. Primary study outcomes will be assessed weekly. Functional autonomy and cognitive levels will be assessed at the beginning and end of follow-up, while information pertaining to modifiable delirium risk factors, medical consultations, and facility transfers will be collected retrospectively for the duration of the follow-up period. Primary outcomes will be reported at the level of intervention assignment. All researchers analyzing the data will be blinded to group allocation. DISCUSSION: This large-scale intervention study will contribute significantly to the development of evidence-based clinical guidelines for delirium prevention in this frail elderly population, as it will be the first to evaluate the efficacy of a multicomponent delirium prevention program translated into LTC clinical practice on a large scale. TRIAL REGISTRATION: NCT03718156 , ClinicalTrials.gov .

Independent or Integrated Plastic Surgery Residency Pathways: Trends in Representation in Academic Plastic Surgery in the United States.

INTRODUCTION: The training pathway for plastic surgery has evolved in recent years with the adoption and rise in popularity of the integrated model. Studies have demonstrated that there may be differences between integrated graduates and independent graduates, specifically in career choices and type of practice. This study seeks to understand if there are differences in representation at academic and leadership positions between graduates of the 2 pathways. METHODS: A cross-sectional study was conducted in June of 2018 to assess integrated and independent pathway graduate's representation in academic plastic surgery in the United States. Factors examined were career qualifications, academic productivity, faculty positions, and influence of pathway on career advancement. RESULTS: A total of 924 academic plastic surgeons were analyzed, 203 (22.0%) of whom were integrated graduates and 721 (78.0%) of whom were independent graduates. Independent graduates had greater National Institutes of Health funding (integrated, $40,802; independent, $257,428; P = 0.0043), higher h-index (integrated, 7.0; independent, 10.0; P < 0.001), and higher publication number (integrated, 17; independent, 25; P = 0.0011). Integrated graduates were more likely to be assistant professors (integrated, 70%; independent, 40.7%; P < 0.001) and required a shorter postresidency time to reach all positions examined compared with independent graduates. CONCLUSIONS: Residency training pathway influences academic plastic surgeons in research output, qualifications, and academic positions. This is likely due to the relatively new nature of the integrated program compared with the independent, as well as the shorter length of training for integrated graduates. However, trends are moving toward integrated graduates showing increased interest and productivity in academic medicine.

The Impact of Fellowship Training in Academic Plastic Surgery.

BACKGROUND: The competitive nature of an academic plastic surgery career has contributed to an increase in sub-specialization. The aim of this study is to assess the benefits of subspecialty fellowship training to pursue a career in academic plastic surgery. METHODS: A cross-sectional study was conducted of all current academic plastic surgeons (APSs) participating in Accreditation Council for Graduate Medical Education-certified residency programs. Online faculty website listings were used to collect their demographics, training and practice characteristics, academic rank and leadership positions, and research productivity. RESULTS: A total of 927 APSs met the inclusion criteria, of which 70.2% had undergone fellowship training, with an overall significant increase in fellowship-trained surgeons within the last 10 years (odds ratio [OR], 1.66; P = 0.0005). Hand training was the most common fellowship (35.6%), followed by craniofacial (32.0%) and microsurgery (28.1%). Fellowship training was more prevalent among younger (48.7 vs 53.5 years, P < 0.0001), White (67.8%), and non-White (77.4%, P = 0.0058) APSs who had received either integrated (67.1%) or independent (81.8%, P < 0.0001) plastic surgery training and are currently working in a department (OR, 1.44; P = 0.028). Fellowship training was shown to influence academic rank (associate professor: OR, 1.68 [P = 0.0073]; full professor: OR, 0.58 [P = 0.0008]), leadership position (fellowship director OR, 10.09; P < 0.0001) and research productivity (publications: 26 vs 16.5; P = 0.0009). In addition, fellowship attainment did not correlate with the size of the employing academic program, population of the city of practice, or being a residency director or chair. CONCLUSION: The majority of APSs have undergone fellowship training, and there is very strong evidence supporting its impact in current entry and advancement in academic plastic surgery.

Characteristics and Academic Productivity Among Pediatric Plastic Surgeons in the United States.

BACKGROUND: The characteristics that predispose plastic surgeons to a career in pediatric plastic surgery remain unclear. Therefore, the aim of this study is to analyze the characteristics of current pediatric plastic surgeons and to determine their academic productivity. METHODS: Pediatric plastic surgeons were identified through an internet search of all academic children's hospitals affiliated with an Accreditation Council for Graduate Medical Education-accredited integrated or independent plastic surgery program. Demographics, training background, institutional and leadership positions, and academic productivity were determined. RESULTS: A total of 304 pediatric plastic surgeons were identified. The majority of pediatric plastic surgeons were white (n = 217, 71.8%) males (n = 235, 77.6%). Clinical fellowships were completed by 86.8% (n = 263) of the cohort, with craniofacial (n = 181, 59.7%) being the most common followed by hand (n = 54, 17.8%); 41.1% had clinical fellowship training at 10 institutions, with the top 3 most represented programs being University of Pennsylvania (n = 19, 6.2%), University of California-Los Angeles (n = 16, 5.3%), and Harvard University (n = 15, 4.9%); 25.7% (n = 78) held leadership positions within their institutions. A significant higher academic productivity was found among research fellowship-trained surgeons, chiefs of pediatric plastic surgery, fellowship directors, and members of departments of plastic surgery. Those who completed an independent residency had a significant higher H-index and number of citations. CONCLUSION: Pediatric plastic surgery is represented by surgeons of diverse training background. An elite cohort of programs has trained the most pediatric plastic surgeons. Lastly, high academic productivity was found to be correlated with certain demographic and leadership variables highlighting its impact on career advancement.

Description of a new species Coomansus batxatensis (Mononchida, Mononchidae) from Vietnam, with an updated key to species.

Coomansus batxatensis sp. nov., recorded from Vietnam, is described and illustrated and its phylogenetic relationship within the Mononchida is analysed. The molecular data (18S and 28S ribosomal DNA) are provided for the new species. The new species is characterized by small body size (body length, L = 0.7-0.9 mm); buccal cavity sub-rectangular in shape, flattened at base, 21-24 × 12-13 µm or 1.9 (1.7-2.0) times as long as wide; posterior position of dorsal tooth apex (59-63% from the base of buccal cavity); pars refringens vaginae with faint and small (2.5 × 1.7 µm) teardrop-shaped pieces, short pars distalis vaginae; and males with short spicules (50-51.5 µm) with rounded head and conical blade part. The new species is close to Coomansus parvus but differs from it by the smaller buccal cavity size, more posterior position of the dorsal tooth apex, longer tail and presence of males. An updated identification key to Coomansus species and a compendium of all the species known are presented.

Sources of Multidrug Resistance in Patients With Previous Isoniazid-Resistant Tuberculosis Identified Using Whole Genome Sequencing: A Longitudinal Cohort Study.

BACKGROUND: Meta-analysis of patients with isoniazid-resistant tuberculosis (TB) given standard first-line anti-TB treatment indicated an increased risk of multidrug-resistant TB (MDR-TB) emerging (8%), compared to drug-sensitive TB (0.3%). Here we use whole genome sequencing (WGS) to investigate whether treatment of patients with preexisting isoniazid-resistant disease with first-line anti-TB therapy risks selecting for rifampicin resistance, and hence MDR-TB. METHODS: Patients with isoniazid-resistant pulmonary TB were recruited and followed up for 24 months. Drug susceptibility testing was performed by microscopic observation drug susceptibility assay, mycobacterial growth indicator tube, and by WGS on isolates at first presentation and in the case of re-presentation. Where MDR-TB was diagnosed, WGS was used to determine the genomic relatedness between initial and subsequent isolates. De novo emergence of MDR-TB was assumed where the genomic distance was 5 or fewer single-nucleotide polymorphisms (SNPs), whereas reinfection with a different MDR-TB strain was assumed where the distance was 10 or more SNPs. RESULTS: Two hundred thirty-nine patients with isoniazid-resistant pulmonary TB were recruited. Fourteen (14/239 [5.9%]) patients were diagnosed with a second episode of TB that was multidrug resistant. Six (6/239 [2.5%]) were identified as having evolved MDR-TB de novo and 6 as having been reinfected with a different strain. In 2 cases, the genomic distance was between 5 and 10 SNPs and therefore indeterminate. CONCLUSIONS: In isoniazid-resistant TB, de novo emergence and reinfection of MDR-TB strains equally contributed to MDR development. Early diagnosis and optimal treatment of isoniazid-resistant TB are urgently needed to avert the de novo emergence of MDR-TB during treatment.