Standardised definitions and diagnostic criteria for extranodal extension detected on histopathological examination in head and neck cancer: Head and Neck Cancer International Group consensus recommendations.

Detection of extranodal extension on histopathology in surgically treated head and neck squamous cell carcinoma indicates poor prognosis. However, there is no consensus on the diagnostic criteria, interpretation, and reporting of histology detected extranodal extension, which has contributed to conflicting evidence in the literature, and likely clinical inconsistency. The Head and Neck Cancer International Group conducted a three-round modified Delphi process with a group of 19 international pathology experts representing 15 national clinical research groups to generate consensus recommendations for histology detected extranodal extension diagnostic criteria. The expert panel strongly agreed on terminology and diagnostic features for histology detected extranodal extension and soft tissue metastasis. Moreover, the panel reached consensus on reporting of histology detected extranodal extension and on nodal sampling. These consensus recommendations, endorsed by 19 organisations representing 34 countries, are a crucial development towards standardised diagnosis and reporting of histology detected extranodal extension, and more accurate data collection and analysis.

Vascular feature identification in actinic keratosis grades I-III using dynamic optical coherence tomography with automated, quantitative analysis.

Clinical grading of actinic keratosis (AK) is based on skin surface features, while subclinical alterations are not taken into consideration. Dynamic optical coherence tomography (D-OCT) enables quantification of the skin´s vasculature, potentially helpful to improve the link between clinical and subclinical features. We aimed to compare microvascular characteristics across AK grades using D-OCT with automated vascular analysis. This explorative study examined AK and photodamaged skin (PD) on the face or scalp. AKs were clinically graded according to the Olsen Classification scheme before D-OCT assessment. Using an open-source software tool, the OCT angiographic analyzer (OCTAVA), we quantified vascular network features, including total and mean vessel length, mean vessel diameter, vessel area density (VAD), branchpoint density (BD), and mean tortuosity from enface maximum intensity projection images. Additionally, we performed subregional analyses on selected scans to overcome challenges associated with imaging through hyperkeratosis (each lesion group; n = 18). Our study included 45 patients with a total of 205 AKs; 93 grade I lesions, 65 grade II, 47 grade III and 89 areas with PD skin. We found that all AK grades were more extensively vascularized relative to PD, as shown by greater total vessel length and VAD (p ≤ 0.009). Moreover, AKs displayed a disorganized vascular network, with higher BD in AK I-II (p < 0.001), and mean tortuosity in AK II-III (p ≤ 0.001) than in PD. Vascularization also increased with AK grade, showing significantly greater total vessel length in AK III than AK I (p = 0.029). Microvascular quantification of AK unveiled subclinical, quantitative differences among AK grades I-III and PD skin. D-OCT-based microvascular assessment may serve as a supplement to clinical AK grading, potentially raising perspectives to improve management strategies.

An Explorative Study on Calcium Electroporation for Low-risk Basal Cell Carcinoma.

In electrochemotherapy, permeabilization of the cell membrane by electric pulses increases the anti-tumour effect of chemotherapeutics. In calcium electroporation, chemotherapy is replaced by calcium chloride with obvious benefits. This study explores the effect and underlying mechanisms of calcium electroporation on basal cell carcinomas using either high- or low-frequency electroporation. Low-risk primary basal cell carcinomas were treated in local anaesthesia with intratumoral calcium chloride followed by electroporation with high (167 kHz) or low (5 kHz) frequencies. Non-complete responders were retreated after 3 months. The primary endpoint was tumour response 3 months after last calcium electroporation. Plasma membrane calcium ATPase was examined in various cell lines as plasma membrane calcium ATPase levels have been associated with calcium electroporation efficacy. Twenty-two out of 25 included patients complete the study and 7 of these (32%) achieved complete response at 3 months with no difference in efficacy between high- and low-frequency pulses. High-frequency calcium electroporation was significantly less painful (p=0.03). Plasma membrane calcium ATPase was increased 16-32-fold in basal cell carcinoma cell lines compared with 4 other cancer cell lines. Calcium electroporation for low-risk basal cell carcinomas does not fulfil the requirements of a new dermatological basal cell carcinoma treatment but may be useful as adjuvant treatment to surgery in more advanced basal cell carcinomas. The elevated PMCA levels in basal cell carcinomas may contribute to low efficacy.

Lower vs Higher Oxygenation Target and Days Alive Without Life Support in COVID-19: The HOT-COVID Randomized Clinical Trial.

Importance: Supplemental oxygen is ubiquitously used in patients with COVID-19 and severe hypoxemia, but a lower dose may be beneficial. Objective: To assess the effects of targeting a Pao2 of 60 mm Hg vs 90 mm Hg in patients with COVID-19 and severe hypoxemia in the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized clinical trial including 726 adults with COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 11 ICUs in Europe from August 2020 to March 2023. The trial was prematurely stopped prior to outcome assessment due to slow enrollment. End of 90-day follow-up was June 1, 2023. Interventions: Patients were randomized 1:1 to a Pao2 of 60 mm Hg (lower oxygenation group; n = 365) or 90 mm Hg (higher oxygenation group; n = 361) for up to 90 days in the ICU. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (mechanical ventilation, circulatory support, or kidney replacement therapy) at 90 days. Secondary outcomes included mortality, proportion of patients with serious adverse events, and number of days alive and out of hospital, all at 90 days. Results: Of 726 randomized patients, primary outcome data were available for 697 (351 in the lower oxygenation group and 346 in the higher oxygenation group). Median age was 66 years, and 495 patients (68%) were male. At 90 days, the median number of days alive without life support was 80.0 days (IQR, 9.0-89.0 days) in the lower oxygenation group and 72.0 days (IQR, 2.0-88.0 days) in the higher oxygenation group (P = .009 by van Elteren test; supplemental bootstrapped adjusted mean difference, 5.8 days [95% CI, 0.2-11.5 days]; P = .04). Mortality at 90 days was 30.2% in the lower oxygenation group and 34.7% in the higher oxygenation group (risk ratio, 0.86 [98.6% CI, 0.66-1.13]; P = .18). There were no statistically significant differences in proportion of patients with serious adverse events or in number of days alive and out of hospital. Conclusion and Relevance: In adult ICU patients with COVID-19 and severe hypoxemia, targeting a Pao2 of 60 mm Hg resulted in more days alive without life support in 90 days than targeting a Pao2 of 90 mm Hg. Trial Registration: ClinicalTrials.gov Identifier: NCT04425031.

Changes in Metabolic Parameters and Body Weight in Patients With Prediabetes Treated With Adjunctive Brexpiprazole for Major Depressive Disorder: Pooled Analysis of Short- and Long-Term Clinical Studies.

Objective: Certain atypical antipsychotics, while efficacious as adjunctive treatments in major depressive disorder (MDD), are associated with metabolic adverse effects and weight gain. This analysis determined the effect of adjunctive brexpiprazole on metabolic parameters and body weight in adults with MDD and prediabetes (ie, at risk of developing diabetes) based on pooled data from 3 short-term studies and 1 long-term study.Methods: The short-term studies were 6-week, randomized, double-blind, placebo-controlled studies of adjunctive oral brexpiprazole 1-3 mg/d in outpatients with MDD (DSM-IV-TR criteria) and inadequate response to antidepressant treatment, conducted between June 2011 and May 2016. The long-term study was a 26- to 52-week, open-label extension study conducted between October 2011 and May 2017. Prediabetes was defined based on fasting serum glucose and glycated hemoglobin (HbA1c) levels. Shifts in diabetes status and shifts/changes in fasting metabolic parameters and body weight were determined.Results: Most patients receiving adjunctive brexpiprazole maintained their baseline diabetes status in the short term (568/751; 75.6%) and long term (1,919/2,746; 69.9%). The incidence of categorical shifts in fasting metabolic parameters generally did not differ between treatment groups or between prediabetes and non-diabetes subgroups. Mean changes from baseline in metabolic parameters were small in the short term (all < 5 mg/dL) and long term (all < 6 mg/dL, except < 20 mg/dL for triglycerides). Moderate weight gain was observed in the short term (1.5 kg) and long term (3.4-4.1 kg).Conclusions: Adjunctive brexpiprazole had a limited impact on the metabolic profile of patients with MDD, regardless of diabetes status (prediabetes/non-diabetes).Trial Registration: Data used in this post hoc analysis came from studies with ClinicalTrials.gov identifiers NCT01360645, NCT01360632, NCT02196506, and NCT01360866.

Managing Cardiovascular and Cancer Risk Associated with JAK Inhibitors.

Janus kinase inhibitors (JAKi) have enormous appeal as immune-modulating therapies across many chronic inflammatory diseases, but recently this promise has been overshadowed by questions regarding associated cardiovascular and cancer risk emerging from the ORAL Surveillance phase 3b/4 post-marketing requirement randomized controlled trial. In that study of patients with rheumatoid arthritis with existing cardiovascular risk, tofacitinib, the first JAKi registered for chronic inflammatory disease, failed to meet non-inferiority thresholds when compared with tumor necrosis factor inhibitors for both incident major adverse cardiovascular events and incident cancer. While this result was unexpected by many, subsequently published observational data have also supported this finding. Notably, however, such a risk has largely not yet been demonstrated in patients outside the specific clinical situation examined in the trial, even in the face of many studies examining this. Nevertheless, this signal has practically re-aligned approaches to both tofacitinib and other JAKi to varying extents, in other patient populations and contexts: within rheumatoid arthritis, but also in psoriatic arthritis, axial spondyloarthritis, inflammatory bowel disease, atopic dermatitis, and beyond. Application to individual patients can be more challenging but remains important to harness the substantive potential of JAKi to the maximum extent safely possible. This review not only explores the evolution of the regulatory response to the signal, its informing data, biological plausibility, and its impact on guidelines, but also the many factors that clinicians must consider in navigating cardiovascular and cancer risk for their patients considering JAKi as immune-modulating therapy.

Effects of adjunctive brexpiprazole on patient life engagement in major depressive disorder: Post hoc analysis of Inventory of Depressive Symptomatology Self-Report data.

BACKGROUND: Patient-reported outcomes can capture domains that are meaningful to patients, such as life engagement in major depressive disorder (MDD), which reflects life fulfillment, well-being, and participation in valued and meaningful activities. This analysis investigated the effects of brexpiprazole adjunct to antidepressant treatment (ADT) on patient life engagement over the short and long term, using the 10-item Inventory of Depressive Symptomatology Self-Report (IDS-SR10) Life Engagement subscale. METHODS: Short-term data were pooled from three 6-week, randomized, double-blind studies of ADT + brexpiprazole 2-3 mg/day versus ADT + placebo in adult outpatients with MDD (DSM-IV-TR criteria) and inadequate response to ADTs. Long-term data were from a 26-52-week, open-label extension study of ADT + brexpiprazole 0.5-3 mg/day. RESULTS: Over 6 weeks, ADT + brexpiprazole (n = 579) showed greater improvement in IDS-SR10 Life Engagement subscale score than ADT + placebo (n = 583), with a least squares mean difference of -1.19 (95% confidence limits: -1.78, -0.59; p = 0.0001; Cohen's d effect size: 0.23). Greater improvement for ADT + brexpiprazole versus ADT + placebo (p < 0.05) was also observed on eight life engagement items, with effect sizes ranging from 0.12 to 0.24. In the long-term study, mean (standard deviation) IDS-SR10 Life Engagement subscale score changed by -2.4 (4.9) points to Week 26 (n = 2047), and -3.7 (5.3) points to Week 52 (n = 768), with mean improvements on all ten items. CONCLUSIONS: Beyond its efficacy on depressive symptoms, adjunctive brexpiprazole may improve patient life engagement, thereby helping patients with MDD to achieve personally meaningful functional outcomes.

Assessment of patient life engagement in major depressive disorder using items from the Inventory of Depressive Symptomatology Self-Report (IDS-SR).

BACKGROUND: Patient-reported outcomes can measure domains that are personally meaningful, such as life engagement, which reflects motivation, pleasure, and well-being. This study explored whether certain items from the Inventory of Depressive Symptomatology Self-Report (IDS-SR) can capture patient life engagement in major depressive disorder (MDD). METHODS: IDS-SR life engagement items were identified by a) a panel of expert psychiatrists (n = 4), b) patient interviews (n = 20), and c) a principal component analysis (PCA) to explore clustering of items. Psychometric analyses were performed on potential subscales, and a minimal clinically important difference (MCID) was estimated by anchor- and distribution-based methods. IDS-SR data were obtained from three randomized controlled trials of adjunctive brexpiprazole in MDD. RESULTS: Expert psychiatrists selected 10 items by consensus from the IDS-SR that might capture patient life engagement (Cronbach's alpha, 0.82; item-total correlations, 0.36-0.58). Patient interviews identified 13 items as moderately to very relevant to life engagement (Cronbach's alpha, 0.85; item-total correlations, 0.35-0.61). The PCA revealed a cluster that included all 10 items selected by psychiatrists and 11 items identified by patients. Expert psychiatrists intentionally distinguished life engagement and core depressive symptoms, although patient insights and the PCA indicated that these aspects of MDD are strongly linked. The 10-item IDS-SR life engagement subscale had an MCID of 3-5 points. CONCLUSIONS: Different approaches consistently identified a subset of 10 IDS-SR items that can measure life engagement in MDD, which may be suitable to group into an IDS-SR life engagement subscale.

Exploring life engagement from the perspective of patients with major depressive disorder: a study using patient interviews.

BACKGROUND: Patient-reported outcomes can measure health aspects that are meaningful to patients, such as 'life engagement' in major depressive disorder (MDD). Expert psychiatrists recently identified ten items from the Inventory of Depressive Symptomatology Self-Report (IDS-SR) that can be used to measure patient life engagement. This study aimed to explore the concept of patient life engagement and provide support for the IDS-SR10 Life Engagement subscale from the patient perspective. METHODS: Semi-structured video interviews were conducted with adults with MDD in the United States. Patients were asked if they ever felt engaged with life, and how this affected their feelings, activities, socializing, and thoughts. Then, patients discussed the ten expert-selected IDS-SR items, and rated the relevance of all 30 items to patient life engagement on a 4-point scale. RESULTS: Patients (N = 20) understood the 'engaged with life' concept and could provide examples from their own lives, such as increased energy/motivation (100%), being more social/spending time with others (85%), being more communicative (80%), and having better mood (75%). Nineteen patients (95%) indicated that all ten IDS-SR10 Life Engagement items were relevant to patient life engagement, and nine of the ten items had a mean score ≥ 3 (moderately relevant). Four additional items (all relating to mood) also scored ≥ 3. CONCLUSIONS: Patients found the concept of life engagement to be important and relatable, and confirmed the IDS-SR10 captures the defining non-mood-related aspects of patient life engagement. This research supports the relevance of patient life engagement as a potential clinical outcome beyond core mood symptoms, and the use of the IDS-SR10 Life Engagement subscale in patient-oriented research.

Patient-reported outcome measures for life engagement in mental health: a systematic review.

BACKGROUND: Life engagement in the context of mental health is a broad term that describes positive health aspects relating to cognition, vitality, motivation and reward, and the ability to feel pleasure-concepts that are meaningful to patients. The aim of this systematic literature review was to identify validated patient-reported outcomes (PROs) that can assess any aspect of life engagement in adults, in the field of general mental health. METHODS: This was a systematic literature review of articles in English from the MEDLINE database (date of search: September 9, 2020). The search strategy had three components: (1) terms to capture PROs; (2) terms to capture mental health; and (3) terms to capture aspects of life engagement. Articles were eligible if they included a PRO that: (1) is named; (2) can be used across mental health disorders; (3) is used to assess any aspect of life engagement; and (4) has undergone psychometric validation and/or qualitative content validation. A list of PROs was extracted. RESULTS: A total of 1585 records were screened and 233 articles were eligible for inclusion. Within these 233 articles, 49 distinct PROs were identified, two of which specifically captured their authors' interpretation of life engagement: the Engaged Living Scale (ELS) and the Life Engagement Test (LET). However, while the ELS and LET covered motivation and reward, life fulfillment, and value-based living, neither scale captured the cognitive or vitality aspects of life engagement. The remaining identified PROs generally captured single aspects of life engagement, most commonly motivation/reward/energy-apathy, pleasure-anhedonia, and mental/psychological well-being. CONCLUSION: Numerous PROs are available that may capture aspects of life engagement. However, a need remains for a new PRO that can be used in clinical trials to provide a more comprehensive description of the improvements in life engagement that patients with mental health disorders may experience with successful treatment.

Detecting SARS-CoV-2 Omicron B.1.1.529 Variant in Wastewater Samples by Using Nanopore Sequencing.

We report wastewater surveillance for SARS-CoV-2 variants of concern by using mutation-specific, real-time PCR and rapid nanopore sequencing. This surveillance might be useful for an early warning in a scenario in which a new variant is emerging, even in areas that have low virus incidences.

Effects of Brexpiprazole on Functioning in Patients With Schizophrenia: Post Hoc Analysis of Short- and Long-Term Studies.

Objective: To evaluate the short- and long-term effects of brexpiprazole on patient functioning in schizophrenia.Methods: Data were included from three 6-week, randomized, double-blind, placebo-controlled studies (hospitalized patients); a 52-week, randomized, double-blind, placebo-controlled maintenance treatment study (terminated early by the study sponsor based on the positive result of an interim analysis); and two 52-week, open-label extension studies-all in patients with schizophrenia (DSM-IV-TR criteria) and conducted from July 2011-February 2016. Patients allocated to oral brexpiprazole received 2-4 mg/d (short-term studies) or 1-4 mg/d (long-term studies). Functioning was measured using the Personal and Social Performance (PSP) and Global Assessment of Functioning (GAF) scales, with response defined as a PSP/GAF increase of ≥ 10 points and remission as PSP score ≥ 71 or GAF score ≥ 61.Results: Patients receiving brexpiprazole (n = 831) showed greater improvement than those receiving placebo (n = 490) from baseline to week 6 in PSP score (least squares mean difference, 3.20; 95% confidence interval, 1.82-4.58; P < .0001; Cohen d = 0.31) and in all 4 PSP domains. At week 52 of the maintenance study (which had a low completion rate primarily due to the early termination), GAF functional remission was achieved by 65.3% (62/95) of stabilized patients randomized to brexpiprazole and 47.1% (48/102) of stabilized patients randomized to placebo, with a number needed to treat of 6 (95% confidence interval, 4-22; P = .0076). At week 52 of the open-label studies (n = 177), PSP functional response and remission were achieved by 84.2% and 41.8% of patients receiving brexpiprazole, respectively.Conclusions: Although limited by the lack of an active comparator, analyses of this large dataset demonstrate that brexpiprazole treatment is associated with clinically relevant improvement in functioning among patients with schizophrenia, in the short term and long term.Trial Registration: Data used in this post hoc analysis were from studies with ClinicalTrials.gov identifiers: NCT01396421, NCT01393613, NCT01810380, NCT01668797, NCT01397786, and NCT01810783.

A one-time pneumatic jet-injection of 5-fluorouracil and triamcinolone acetonide for treatment of hypertrophic scars-A blinded randomized controlled trial.

BACKGROUND: Patients with hypertrophic scars (HTS) risk reduced quality of life due to itching, pain, poor cosmesis, and restriction of movement. Despite good clinical efficacy, patients are often reluctant to undergo repeated needle injections due to pain or needle phobia. OBJECTIVES: To evaluate the applicability of needle-free pneumatic jet injection (PJI) and assess changes in hypertrophic scars following a single PJI treatment with 5-fluorouracil (5-FU) and triamcinolone acetonide (TAC). METHODS: Twenty patients completed this blinded, randomized, controlled, split-scar trial. The intervention side of the HTS received a one-time treatment with PJIs containing a mixture of TAC + 5-FU injected at 5 mm intervals (mean 7 PJI per HTS); the control side received no treatment. Assessments were made at baseline and 4 weeks posttreatment. Outcome measures included change in (1) Vancouver Scar Scale (VSS) total score and subscores, (2) scar volume and surface area assessed by three-dimensional imaging, (3) skin microarchitecture measured by optical-coherence tomography (OCT), (4) photo-assessed scar cosmesis (0-100), (5) patient-reported pain and satisfaction (0-10), and (6) depiction of drug biodistribution after PJI. RESULTS: PJI with TAC + 5-FU significantly decreased both HTS height (-1 VSS; p = 0.01) and pliability (-1 VSS; p < 0.01) with a nonstatistically significant reduction of -1 in total VSS score (0 in control; p = 0.09). On 3D imaging, a 33% decrease in scar volume (p = 0.016) and a 37% decrease in surface area (p = 0.008) was observed. OCT indicated trends towards smoother scar surface (Ra 11.1-10.3; p = 0.61), normalized dermal microarchitecture (attenuation coefficient: 1.52-1.68; p = 0.44), and a reduction in blood flow between 9% and 17% (p = 0.50-0.79). Despite advances in VSS subscores and OCT, no improved photo-assessed cosmesis was found (-3.2 treatment vs. -1.4 control; p = 0.265). Patient-reported pain was low (2/10) and 90% of the patients that had previously received needle injections preferred PJI to needle injection. Depositions of TAC + FU were imaged reaching deep into the scar at levels corresponding to the reticular dermis. CONCLUSION: A single PJI injection containing 5-FU and TAC can significantly improve the height and pliability of HTS. PJI is favored by the patients and may serve as a complement to conventional needle injections, especially for patients with needle phobia.

Effects of Brexpiprazole Across Symptom Domains in Patients With Schizophrenia: Post Hoc Analysis of Short- and Long-Term Studies.

The successful treatment of schizophrenia entails improvement across a spectrum of symptoms. The aim of this post hoc analysis was to characterize the short- and long-term effects of brexpiprazole on Positive and Negative Syndrome Scale (PANSS) 'Marder factors.' Data were included from three 6-week, randomized, double-blind, placebo-controlled studies; a 52-week, randomized, double-blind, placebo-controlled maintenance treatment study; and two 52-week open-label extension (OLEx) studies-all in schizophrenia (DSM-IV-TR criteria). Patients receiving oral brexpiprazole were dosed at 2-4 mg/day (short-term studies) or 1-4 mg/day (long-term studies). At Week 6, least squares mean differences (LSMDs, with 95% confidence limits [CLs]) for brexpiprazole (n = 868) vs placebo (n = 517) were: Positive symptoms: -1.55 (-2.30, -0.80), P < .0001, Cohen's d effect size (ES) = 0.27; Negative symptoms: -1.12 (-1.63, -0.61), P < .0001, ES = 0.29; Disorganized thought: -1.26 (-1.78, -0.74), P < .0001, ES = 0.32; Uncontrolled hostility/excitement: -0.76 (-1.15, -0.37), P = .0002, ES = 0.26; Anxiety/ depression: -0.56 (-0.91, -0.22), P = .0014, ES = 0.22. At last visit of the maintenance study, LSMDs (95% CLs) for brexpiprazole (n = 96) vs placebo (n = 104) were: Positive symptoms: -3.44 (-4.99, -1.89), P < .0001, ES = 0.62; Negative symptoms: -1.23 (-2.52, 0.07), P = .063, ES = 0.27; Disorganized thought: -1.69 (-2.81, -0.56), P = .0035, ES = 0.42; Uncontrolled hostility/excitement: -1.26 (-2.12, -0.39), P = .0046, ES = 0.41; Anxiety/depression: -0.72 (-1.47, 0.03), P = .061, ES = 0.27. In the OLEx studies, improvements were maintained over 58 (6 + 52) weeks of brexpiprazole treatment. In conclusion, these data suggest that brexpiprazole treats the continuum of schizophrenia symptoms, in the short- and long-term. Trial Registration: Data used in this post hoc analysis came from ClinicalTrials.gov identifiers: NCT01396421, NCT01393613, NCT01810380, NCT01668797, NCT01397786, NCT01810783.

Effects of adjunctive brexpiprazole on calmness and life engagement in major depressive disorder: post hoc analysis of patient-reported outcomes from clinical trial exit interviews.

BACKGROUND: Though often overlooked, calming patients and increasing their life engagement are key factors in the treatment of major depressive disorder (MDD). This study aimed to test the hypothesis that adjunctive brexpiprazole increases calmness and life engagement among patients with MDD, based on clinical trial exit interviews. METHODS: This was a pooled analysis of exit interview data from three exploratory, open-label studies of adjunctive brexpiprazole 1-3 mg/day. The studies enrolled 105 outpatients with MDD (DSM-IV-TR criteria), a current depressive episode, and inadequate response to antidepressant treatment during the current episode. Patients were interviewed if they completed the end-of-treatment visit (Week 6 or Week 12, depending on the study). Exit interviews took the form of semi-structured telephone interviews in which patients were asked mostly qualitative questions about their symptoms prior to the start of the study, and about improvements they had noted during treatment. Interview transcripts were reviewed and codes were assigned to calmness and life engagement vocabulary, allowing aggregation of the frequency of improvement in various domains. RESULTS: 79.8% (83/104) of patients described improvements consistent with at least one calmness term, most commonly feeling less anxious (46.2%) or less irritable (44.2%). A four-domain concept of patient life engagement was developed in which 88.6% (93/105) of patients described improvements consistent with at least one domain, specifically, emotional (77.1%), physical (75.2%), social (41.9%), and/or cognitive (36.2%). Of the patients who described improvement in calmness, 96.4% (80/83) also described improvement in life engagement. CONCLUSIONS: Analysis of exit interview data suggests that patients were calmer and more engaged with life following treatment with adjunctive brexpiprazole. Thus, adjunctive brexpiprazole may provide a benefit on subjective patient outcomes in addition to the improvement in depressive symptoms shown by clinical rating scale data. TRIAL REGISTRATION: Data used in this post hoc analysis came from ClinicalTrials.gov identifiers: NCT02012218, NCT02013531, NCT02013609.

Characterization of the mitogenomes of long-tailed giant rat, Leopoldamys sabanus and a comparative analysis with other Leopoldamys species.

Two mitogenomes of long-tailed giant rat, Leopoldamys sabanus (Thomas, 1887), which belongs to the family Muridae were sequenced and assembled in this study. Both mitogenomes have a length of 15,973 bp and encode 13 protein-coding genes (PCGs), 22 transfer RNA genes, two ribosomal RNA genes and one control region. The circular molecule of L. sabanus has a typical vertebrate gene arrangement. Phylogenetic and BLASTn analysis using 10 Leopoldamys species mitogenomes revealed sequence variation occurred within species from different time zones. Along with the taxonomic issues, this suggests a landscape change might influence genetic connectivity.

The first mitochondrial genome data of an old world fruit bat, Cynopterus sphinx from Malaysia.

We assembled the complete mitogenome of Cynopterus sphinx (Vahl, 1797) of the family Pteropodidae originating from Malaysia. The total mitogenome size was 16,710bp which consists of 37 genes (13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes and one control region). A phylogenetic and BLASTn result showed the mitogenome sequence in this study varies by nearly 7% (93.48% similarity) from the same species in Cambodia. The next closest match of BLASTn was at 92% similarity to the C. brachyotis. This suggests the species-complex in Cynopterus sp. has given rise to the genetic variability.

The impact of shared decision making on time consumption and clinical decisions. A prospective cohort study.

OBJECTIVE: Concerns of increased time consumption and of the impact on clinical decisions may restrain doctors from shared decision making (SDM). This paper evaluates consultation length and decisions made when using an in-consult patient decision aid (PtDA). METHODS: This prospective cohort study compared an unexposed cohort with a cohort exposed to SDM and a PtDA in two preference-sensitive decision situations: invasive lung cancer diagnostics and adjuvant treatment for early breast cancer. Outcome measures were consultation length and decisions made. RESULTS: The study included 261 consultations, 115 were in the SDM-exposed cohort. Consultations were inconsiderably longer in the SDM cohort; 2 min, 11 s (p = 0.2217) for lung cancer diagnostics and 3 min, 57 s (p = 0.1128) for adjuvant breast cancer treatment. In lung cancer diagnostics, consultation length became more uniform and decisions tended to become conservative after introduction of SDM. For adjuvant breast cancer, slightly more patients in the SDM cohort chose to decline treatment. CONCLUSION: Shared decision making did not take significantly longer time and led to slightly more conservative decisions. PRACTICE IMPLICATIONS: SDM may be implemented without considerable impact on consultation length. The impact on clinical decisions depends mainly on the clinical situation.

Correction to: The impact on functioning of second-generation antipsychotic medication side effects for patients with schizophrenia: a worldwide, cross-sectional, web-based survey.

[This corrects the article DOI: 10.1186/s12991-020-00292-5.].

The impact on functioning of second-generation antipsychotic medication side effects for patients with schizophrenia: a worldwide, cross-sectional, web-based survey.

BACKGROUND: It is well established that the different antipsychotics used for schizophrenia symptoms differ substantially in their side effects. However, relatively little is known about the impact of these side effects on functioning from the patient's perspective. We aimed to understand how key side effects of second-generation antipsychotics impact the functioning and quality of life (QoL) of patients with schizophrenia. METHODS: This is a cross-sectional, web-based survey of patient-reported side effect burden of antipsychotic drugs in adults with schizophrenia. The survey was deployed in the United States, Canada, Australia, Spain, Italy, Norway, and Denmark. It included sociodemographic and clinical questions, the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF), and the Glasgow Antipsychotic Side-Effect Scale (GASS). Eight pre-defined key side effects classified as activating ("Shaky hands or arms," "Restlessness," and "Difficulty sleeping"), sedating ("Sleepy during the day", "Feeling drugged or like a zombie," and "Feeling dizzy/Fainted") or other side effects ("Problems enjoying sex" and "Gaining weight"), and additional questions related to impacts on function and quality of life were asked. RESULTS: In total, 435 participants (mean age: 38 years, 53.8% female) were included. The total Q-LES-Q-SF score indicated overall medium satisfaction with their quality of life (score of 44.3; possible range 14-70). The most prevalent side effects were "Sleepy during the day" (83.2%), "Difficulty sleeping" (74.7%), "Dry mouth" (63.9%), "Problems enjoying sex" (53.4%) and "Gaining weight" (52.4%). Women reported the side effects of "Sleepy during the day", "Problems enjoying sex" and "Gaining weight" more frequently than men. Key side effects impacted physical, social, occupational and psychological aspects of functioning. Patients with key side effects often felt frustrated by their experiences. Total Q-LES-Q-SF score showed a significant inverse correlation with the score of pre-defined groups of side effects indicating worse QoL in association with more severe key side effects in these patients. CONCLUSION: Stable patients with schizophrenia taking second-generation antipsychotics live with many side effects, including activating and sedating side effects, sexual side effects, and weight gain. Presence of these side effects is associated with substantial impacts across all aspects of daily functioning and lower quality of life and satisfaction.