bluuebunny/crossref_metadata_2025 huggingface dataset:
What do healthcare workers need? A qualitative study on support strategies to protect mental health of healthcare workers during the SARS-CoV-2 pandemic
Authors: Halms Theresa , Strasser Martina , Papazova Irina , Reicherts Philipp , Zerbini Giulia , Grundey Svenja , Täumer Esther , Ohmer-Kluge Manuela , Kunz Miriam , Hasan Alkomiet
Published: March 2023

Background

To support healthcare workers (HCWs) during the increased burden caused by the SARS-CoV-2 pandemic, numerous recommendations for action and possible interventions have been developed. However, the actual protective factors, needs and desires of those affected, as well as potential barriers to implementing psychological interventions, have been insufficiently examined. This study addresses this research gap and captures HCWs’ experiences and views.

Methods

Medical personnel including nursing staff and physicians were recruited for a qualitative study regarding protective factors as well as barriers to the implementation of support services. We conducted 21 individual, semi-structured interviews with members of the medical staff at tertiary care center in Germany. The collected data were analyzed using a qualitative content analysis.

Results

The analyses showed that social interaction in the professional and private context was rated as helpful in coping with the challenges of everyday work amplified by the SARS-CoV-2 pandemic. The results also suggest that the available support services, despite being highly valued, were rarely accessed. Possible barriers included the fear of negative consequences when asking for support. It could be deduced that the fear and shame of admitting one’s own mistakes as well as the work-related tradition of showing no weakness could be the underlying factors for this fear.

Results

The results of this study suggest that medical staff need a more extensive range of low-threshold support services, which should be adapted to the respective needs of the professional groups. The study also provides indications that the norms and expectations represented in the hospital system require critical reflection.
Assessment of the underlying causes of adult deaths using a short version of verbal autopsy in Xaiyabouli Province, Lao People’s Democratic Republic
Authors: Thanavanh Bounbouly , Hamajima Nobuyuki , Sida Kaiyason , Duangdy Kene , Latsamy Lasavong , Senaphane Khounsavath , Louangpradith Viengsakhone , Sadettan Souphaphone , Inthaphatha Souphalak , Nishino Kimihiro , Yamamoto Eiko
Published: March 2023

Background

In developing countries, it is difficult to collect the data of the underlying cause of death (UCOD), especially when a death does not occur in a health facility. This study aimed to develop a short version of verbal autopsy (VA) and identify the UCOD of adults in Lao People’s Democratic Republic (Lao PDR).

Methods

A short version of VA for deaths outside health facilities was developed. This study included all deaths of people aged 15 years old or older in Xaiyabouli Province in 2020. Socio-demographic factors, place of death, and UCOD of the deceased were collected from health facilities or from family members using a questionnaire including the short VA form. UCOD was compared between home deaths and hospital deaths, between the age group of 15–59 years old and the age group ≥ 60 years old, and between males and females.

Results

Of all the 1,235 deaths included in this study, 1,012 deaths (81.9%) occured at home and 223 deaths (18.1%) at hospitals. The most common UCOD was senility (13.3%), followed by heart/renal failure (10.5%), pneumonia (9.6%) and traffic accident (7.1%). Compared to hospital deaths, home deaths had more people who were females, 75 years old or older, and Lao-Tai. Home deaths had more deaths than hospital deaths due to accident/injury (16.0% vs. 8.1%), tumor (4.7% vs. 1.8%), and senility (16.2% vs. 0%); fewer deaths due to heart/renal disease (15.1% vs. 32.3%), respiratory disease (12.2% vs. 18.8%), liver/gastro-intestine disease (5.3% vs. 9.0%), and infection (3.1% vs. 14.3%). The age group of 15–59 years had more deaths in the categories of accident/injury (28.1% vs. 4.4%), liver/gastro-intestine disease (8.1% vs. 4.4%), infection (7.2% vs. 3.5%), and tumor (6.0% vs. 2.8%). Males had more deaths due to tumor (5.2% vs. 3.0%) and fewer natural deaths (11.2% vs. 15.9%) than females.

Conclusions

The major UCOD category was heart/renal disease in the adult generation in Xaiyabouli Province. Cost-effective interventions based on the multisectoral noncommunicable disease prevention plan should be appropriately implemented. Mortality surveillance using the short VA tool should be conducted for all home deaths in Lao PDR.
Implementation, barriers, and recommendations for further development of advance care planning for the last phase of life in nursing homes in Germany (Gut-Leben): protocol for a mixed-methods study
Authors: Stiel Stephanie , Brütt Anna Levke , Stahmeyer Jona T , Bockelmann Anne W E , Schleef Tanja , Völkel Anna , Hoffmann Falk
Published: March 2023

Background

Nursing home entry often marks the transition into the end-of-life. In 2018, Germany legally introduced reimbursement for advance care planning (ACP according to § 132 g SGB V) in nursing homes that applied for ACP approval to improve end-of-life care. The Gut-Leben project aims to evaluate the implementation and barriers of ACP in nursing homes in Germany, with a special focus on the federal state of Lower Saxony, and provide practical recommendations for further development of end-of-life care.

Methods

This mixed-methods study spreads across five work packages (WP) over a three-year period. WP 1 will explore the approval process, implementation, and barriers to ACP in nursing homes. Data will be collected through a national postal survey in a random sample of n = 600. WP 2 will explore whether documented ACP reports are applicable as a data source for research (expecting up to 500 available ACP reports). In WP 3a and 3b, data on the ACP process will be collected in n = 15 approved nursing homes in Lower Saxony over a 12-months period. For WP 3a and WP 3b, data on ACP conversations (n = 600) and on end-of-life care paths (n = 300) will be collected by facilitators and nurses of the respective nursing homes. In WP 4, residents’ characteristics upon entry and changes in these characteristics over the length of stay are analyzed, utilizing claims data from the AOK Lower Saxony (expected sample of about 100,000 people entering nursing homes over a 10-years period). WP 5 connects, interprets, and reflects on the findings from WP 1–4 through focus groups and individual interviews with facilitators, nursing staff, residents, relatives, and care providers. Within a participatory approach, a practice advisory board will be set up existing of personal of nursing homes and will be closely involved in the whole research process.

Discussion

In summary, the Gut-Leben project provides insight into the implementation and barriers of ACP in nursing homes according to German legislation for the first time, including practitioners’ and residents’ perspectives. Insights will help the further development of ACP in Germany through practical recommendations based on quantitative and qualitative data.
Effect of group education and person-centered support in primary health care on mental health and quality of life in women aged 45–60 years with symptoms commonly associated with stress: a randomized controlled trial
Authors: Rindner Lena , Nordeman Lena , Strömme Gunilla , Hange Dominique , Gunnarsson Ronny , Rembeck Gun
Published: March 2023

Background

Mental illness and somatic symptoms are common causes of long-term sick leave for women during menopause, which usually occurs between the ages of 45 and 55. Many women experience a lack of knowledge about menopause and its associated symptoms. This study evaluates the effect of group education and person-centered individual support in primary health care (PHC) on mental health and quality of life for women in menopause with symptoms that are usually associated with stress.

Methods

The randomized controlled clinical trial (RCT) with a two-factor design was conducted in PHC in southwestern Sweden, from 2018 to 2019. A total of 370 women aged 45–60 were allocated in four groups: 1, group education (GE) 2, GE and person-centered individual support (PCS) 3, PCS and 4, control group. GE comprised four weekly sessions and PCS included five sessions with topics related to menopause. The effect of the interventions were followed up at 6 and 12 months. Linear and ordinal regression were used to analyse the effect of the intervention, either group education or person-centred individual support.

Results

The main findings: Improved quality of life and physical, psychological, and urogenital symptoms. GE and PCS resulted in improvement of the quality of life at six months. At the 12-month follow-up these results were significantly strengthened for PCS and improved health-related quality of life, and reduced mental, urogenital, and stress-related symptoms with an effect lasting at least 12 months. These results suggest that this intervention could be an effective intervention in PHC for improving women’s health in menopause.

Conclusions

PCS can be an effective intervention in PHC for improving women’s health in menopause and possibly also prevent the development of exhaustion syndrome.

Trial registration: Universal trial number is U1111-1219-6542 and the registration number in ClinicalTrials.gov is NCT03663075, date of registration 10/09/2018.
Uptake of prevention of mother-to-child transmission cascade services in Burkina Faso between 2013 and 2020: are we on the right track?
Authors: Fassinou Lucresse Corine , Ouoba Joël , Ngwasiri Calypse , Romba Issa , Zoungrana-Yameogo Wedminere Noëlie , Bakiono Fidèle , Traoré Isidore Tiandiogo , Hien Hervé , Nagot Nicolas , Kirakoya-Samadoulougou Fati
Published: March 2023

Background

The use of services to prevent mother-to-child transmission (PMTCT) of the human immunodeficiency virus (HIV) remains a serious challenge in sub-Saharan Africa. In the last decade, Burkina Faso has implemented numerous policies to increase the use of PMTCT services by pregnant women and their partners, as well as children. This study assesses trends in the uptake of PMTCT services in Burkina Faso from 2013 to 2020 in order to study the progress and gaps in achieving the national and international targets set for 2020.

Methods

A repeated cross-sectional analysis was performed using data extracted from district health information software version 2. Percentages were computed for each PMTCT indicator and comparisons between the years were made using a chi-square test for trends with a significance threshold of 5%. Regions were not compared with each other.

Results

The proportion of pregnant women who were tested and received their results significantly increased from 47.9% in 2013 to 84.6% in 2020 (p value < 0.001). Of the 13 regions in the country, only 1 region met the 95% national targets whereas, 6 regions met the 90% international targets for this indicator. The proportions of HIV-positive women receiving antiretroviral therapy (ART) increased from 90.8% in 2013 to 100% in 2020. In the same period, the proportion of exposed infants who received antiretroviral prophylaxis increased from 64.3% in 2013 to 86.8% in 2020. Only 3 regions reached the national and international targets for this indicator. A positive trend was also observed for the indicator related to screening at 2 months or later of exposed infants using Polymerase Chain Reaction (PCR) technic; with the rate rising from 7.4% in 2013 to 75.7% in 2020. However, for this indicator, the national and international targets were not achieved considering the national and regional settings. Concerning the women’s partners, the proportion of those who tested for HIV increased from 0.9% in 2013 to 4.5% in 2020, with only 1 region that fully met the national target of 10% in 2020. The prevalence of HIV in this particular group was 0.5% in 2020.

Conclusions

PMTCT indicators show an increase from 2013 to 2020 but with a strong disparity between regions. National and international targets have not been achieved for any indicator; except for those related to women receiving ART. Strengthening strategies to effectively engage women and their partners on the use of PMTCT cascade services could help reduce mother-to-child transmission in Burkina Faso.
Systolic blood pressure reduction with tirzepatide in patients with type 2 diabetes: insights from SURPASS clinical program
Authors: Lingvay Ildiko , Mosenzon Ofri , Brown Katelyn , Cui Xuewei , O’Neill Ciara , Fernández Landó Laura , Patel Hiren
Published: March 2023

Background

Tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide/ glucagon-like peptide-1 receptor agonist, is approved in the United States, Europe and Japan for the treatment of type 2 diabetes. Across the SURPASS-1 to -5 clinical studies, tirzepatide 5, 10 and 15 mg demonstrated significant improvements in glycated haemoglobin A1c (HbA1c) (− 1.9 to − 2.6%), body weight (− 6.6 to − 13.9%) and systolic blood pressure (SBP) (− 2.8 to − 12.6 mmHg) at the end of study treatment.

Methods

Post-hoc mediation analyses were conducted to evaluate weight-loss dependent and weight-loss independent effects of tirzepatide on SBP reductions across the 5 SURPASS studies. The safety population (all randomized patients who took at least 1 dose of study drug) of each study was analyzed. Additional analyses were conducted at individual study level or pooled across 5 SURPASS trials.

Results

The difference in mean SBP change from baseline at 40 weeks (total effect) between the tirzepatide and comparator groups was − 1.3 to − 5.1 mmHg (tirzepatide 5 mg), − 1.7 to − 6.5 mmHg (tirzepatide 10 mg) and − 3.1 to − 11.5 mmHg (tirzepatide 15 mg). These SBP reductions were primarily mediated through weight loss, with different degrees of contributions from weight-loss independent effects across the different trials. In the SURPASS-4 study, which enrolled patients with established cardiovascular disease, weight-loss independent effects explained 33% to 57% of difference in SBP change between tirzepatide and insulin glargine groups. In a pooled analysis of the SURPASS-1 to -5 studies, there was a significant (p < 0.001) but weak correlation (r = 0.18 to 0.22) between change in body weight and SBP. Reductions in SBP with tirzepatide were not dependent on concomitant antihypertensive medications at baseline as similar reductions were observed whether participants were receiving them or not (interaction p = 0.77). The largest SBP reductions were observed in the highest baseline category (> 140 mmHg), while those in the first quartile of baseline SBP category (< 122 mmHg) observed no further decrease in SBP.

Conclusions

Tirzepatide-induced SBP reduction was primarily mediated through weight loss, with different degrees of contributions from weight-loss independent effects across the different trials. SBP reduction was not dependent on antihypertensive medication use but dependent on baseline SBP value, alleviating theoretical concerns of hypotension.
Rational design of GDP‑d‑mannose mannosyl hydrolase for microbial l‑fucose production
Authors: Fu Cong , Xu Xuexia , Xie Yukang , Liu Yufei , Liu Min , Chen Ai , Blamey Jenny M. , Shi Jiping , Zhao Suwen , Sun Junsong
Published: March 2023

Background

l‑Fucose is a rare sugar that has beneficial biological activities, and its industrial production is mainly achieved with brown algae through acidic/enzymatic fucoidan hydrolysis and a cumbersome purification process. Fucoidan is synthesized through the condensation of a key substance, guanosine 5′‑diphosphate (GDP)‑l‑fucose. Therefore, a more direct approach for biomanufacturing l‑fucose could be the enzymatic degradation of GDP‑l‑fucose. However, no native enzyme is known to efficiently catalyze this reaction. Therefore, it would be a feasible solution to engineering an enzyme with similar function to hydrolyze GDP‑l‑fucose.

Results

Herein, we constructed a de novo l‑fucose synthetic route in Bacillus subtilis by introducing heterologous GDP‑l‑fucose synthesis pathway and engineering GDP‑mannose mannosyl hydrolase (WcaH). WcaH displays a high binding affinity but low catalytic activity for GDP‑l‑fucose, therefore, a substrate simulation‑based structural analysis of the catalytic center was employed for the rational design and mutagenesis of selected positions on WcaH to enhance its GDP‑l‑fucose‑splitting efficiency. Enzyme mutants were evaluated in vivo by inserting them into an artificial metabolic pathway that enabled B. subtilis to yield l‑fucose. WcaHR36Y/N38R was found to produce 1.6 g/L l‑fucose during shake‑flask growth, which was 67.3% higher than that achieved by wild‑type WcaH. The accumulated l‑fucose concentration in a 5 L bioreactor reached 6.4 g/L.

Conclusions

In this study, we established a novel microbial engineering platform for the fermentation production of l‑fucose. Additionally, we found an efficient GDP‑mannose mannosyl hydrolase mutant for L‑fucose biosynthesis that directly hydrolyzes GDP‑l‑fucose. The engineered strain system established in this study is expected to provide new solutions for l‑fucose or its high value‑added derivatives production.
Effects of branched-chain amino acids on Shiraia perylenequinone production in mycelium cultures
Authors: Shen Wen Hao , Cong Rui Peng , Li Xin Ping , Huang Qun Yan , Zheng Li Ping , Wang Jian Wen
Published: March 2023

Background

Perylenequinones from Shiraia fruiting bodies are excellent photosensitizers and widely used for anti-cancer photodynamic therapy (PDT). The lower yield of Shiraia perylenequinones becomes a significant bottleneck for their medical application. Branched-chain amino acids (BCAAs) not only serve as important precursors for protein synthesis, but also are involved in signaling pathway in cell growth and development. However, there are few reports concerning their regulation of fungal secondary metabolism. In present study, the eliciting effects of BCAAs including l-isoleucine (l-Ile), l-leucine (l-Leu) and l-valine (l-Val) on Shiraia perylenequinone production were investigated.

Results

Based on the analysis of the transcriptome and amino acid contents of Shiraia in the production medium, we revealed the involvement of BCAAs in perylenequinone biosynthesis. The fungal conidiation was promoted by l-Val treatment at 1.5 g/L, but inhibited by l-Leu. The spore germination was promoted by both. The production of fungal perylenequinones including hypocrellins A (HA), HC and elsinochromes A-C (EA–EC) was stimulated significantly by l-Val at 1.5 g/L, but sharply suppressed by l-Leu. After l-Val treatment (1.5 g/L) in Shiraia mycelium cultures, HA, one of the main bioactive perylenequinones reached highest production 237.92 mg/L, about 2.12-fold than that of the control. Simultaneously, we found that the expression levels of key genes involved in the central carbon metabolism and in the late steps for perylenequinone biosynthesis were up-regulated significantly by l-Val, but most of them were down-regulated by l-Leu.

Conclusions

Our transcriptome analysis demonstrated that BCAA metabolism was involved in Shiraia perylenequinone biosynthesis. Exogenous BCAAs exhibit contrasting effects on Shiraia growth and perylenequinones production. l-Val could promote perylenequinone biosynthesis via not only enhancing the central carbon metabolism for more precursors, but also eliciting perylenequinone biosynthetic gene expressions. This is the first report on the regulation of BCAAs on fungal perylenequinone production. These findings provided a basis for understanding physiological roles of BCAAs and a new avenue for increasing perylenequinone production in Shiraia mycelium cultures.

Graphical Abstract
Opioid overdose prevention education in Texas during the COVID-19 pandemic
Authors: Mathias Charles W. , Cavazos Diana M. , McGlothen-Bell Kelly , Crawford Allison D. , Flowers-Joseph Brieanna , Wang Zhan , Cleveland Lisa M.
Published: March 2023

Background

Distribution of naloxone and training on its proper use are evidence-based strategies for preventing opioid overdose deaths. In-person naloxone training was conducted in major metropolitan areas and urban centers across Texas as part of a state-wide targeted opioid response program. The training program transitioned to a live, virtual format during the COVID-19 public health emergency declaration. This manuscript describes the impact of this transition through analyses of the characteristics of communities reached using the new virtual training format.

Case presentation

Training participant addresses were compared to county rates of opioid overdose deaths and broadband internet access, and census block comparison to health services shortages, rural designation, and race/ethnicity community characteristics.

Conclusions

The virtual training format reached more learners than the in-person events. Training reached nearly half of the counties in Texas, including all with recent opioid overdose deaths. Most participants lived in communities with a shortage of health service providers, and training reached rural areas, those with limited broadband internet availability, and majority Hispanic communities. In the context of restrictions on in-person gathering, the training program successfully shifted to a live, online format. This transition increased participation above rates observed pre-pandemic and reached communities with the need for equipping those most likely to witness an opioid overdose with the proper use of naloxone.
Adaptation and multicentre validation of a patient-centred outcome scale for people severely ill with COVID (IPOS-COV)
Authors: Hocaoglu Mevhibe B. , Murtagh Fliss E. M. , Walshe Catherine , Chambers Rachel L. , Maddocks Matthew , Sleeman Katherine E. , Oluyase Adejoke O. , Dunleavy Lesley , Bradshaw Andy , Bajwah Sabrina , Fraser Lorna K. , Preston Nancy , Higginson Irene J. ,   the CovPall study team, Bradshaw Andrew
Published: March 2023

Background

Patient-centred measures to capture symptoms and concerns have rarely been reported in severe COVID. We adapted and tested the measurement properties of the proxy version of the Integrated Palliative care Outcome Scale–IPOS-COV for severe COVID using psychometric approach.

Methods

We consulted experts and followed consensus-based standards for the selection of health status measurement instruments and United States Food and Drug Administration guidance for adaptation and analysis. Exploratory Factor Analysis and clinical perspective informed subscales. We tested the internal consistency reliability, calculated item total correlations, examined re-test reliability in stable patients, and also evaluated inter-rater reproducibility. We examined convergent and divergent validity of IPOS-COV with the Australia-modified Karnofsky Performance Scale and evaluated known-groups validity. Ability to detect change was examined.

Results

In the adaptation phase, 6 new items were added, 7 items were removed from the original measure. The recall period was revised to be the last 12–24 h to capture fast deterioration in COVID. General format and response options of the original Integrated Palliative care Outcome Scale were preserved. Data from 572 patients with COVID from across England and Wales seen by palliative care services were included. Four subscales were supported by the 4-factor solution explaining 53.5% of total variance. Breathlessness-Agitation and Gastro-intestinal subscales demonstrated good reliability with high to moderate (a = 0.70 and a = 0.67) internal consistency, and item–total correlations (0.62–0.21). All except the Flu subscale discriminated well between patients with differing disease severity. Inter-rater reliability was fair with ICC of 0.40 (0.3–0.5, 95% CI, n = 324). Correlations between the subscales and AKPS as predicted were weak (r = 0.13–0.26) but significant (p < 0.01). Breathlessness-Agitation and Drowsiness-Delirium subscales demonstrated good divergent validity. Patients with low oxygen saturation had higher mean Breathlessness-Agitation scores (M = 5.3) than those with normal levels (M = 3.4), t = 6.4 (186), p < 0.001. Change in Drowsiness-Delirium subscale correctly classified patients who died.

Conclusions

IPOS-COV is the first patient-centred measure adapted for severe COVID to support timely management. Future studies could further evaluate its responsiveness and clinical utility with clinimetric approaches.
Risk factors for subsequent lupus nephritis in patients with juvenile-onset systemic lupus erythematosus: a retrospective cohort study
Authors: Hsu Tzu-Chuan , Yang Yao-Hsu , Wang Li-Chieh , Lee Jyh-Hong , Yu Hsin-Hui , Lin Yu-Tsan , Hu Ya-Chiao , Chiang Bor-Luen
Published: March 2023

Background

Lupus nephritis (LN) is a crucial organ involvement in systemic lupus erythematosus (SLE). Patients with LN have higher morbidity and mortality rates than those without. Among all patients with LN, 20–40% had delayed onset, but the data for patients with juvenile-onset SLE (jSLE), who have a higher percentage of LN than patients with adult-onset SLE (aSLE), were limited. This study aimed to determine the risk factors for subsequent LN in patients with jSLE.

Methods

A retrospective cohort study was conducted between 2008 and 2018 in a single tertiary medical centre. Patients with diagnosed jSLE were reviewed. We investigated those without LN at diagnosis and whether they developed LN afterward. The primary outcome was the development of subsequent LN. Clinical manifestations at diagnosis, serial laboratory data, and treatments were reviewed during follow-up periods.

Results

Among the 48 patients with jSLE without initial LN, 20 developed subsequent LN later (Group 1), whereas 28 remained free of LN (Group 2). There was no difference in the percentage of initial manifestations except for more discoid rashes in Group 2 patients. In the Cox regression model, elevated average anti-double-stranded DNA (dsDNA) antibody, low average serum complements, and high average erythrocyte sedimentation rate (ESR) levels during follow-up were predictors of subsequent LN. After adjusting for these factors in multivariable analyses, only high average anti-dsDNA antibody and high average ESR levels remained predictive of subsequent LN. For every 100 IU/ml increase in anti-dsDNA antibody, the risk for subsequent LN in jSLE increases by 1.29 times (hazard ratio = 1.29, 95% confidence interval 1.055–1.573).

Conclusion

Persistently high anti-dsDNA antibody and ESR levels during the follow-up period were risk factors for subsequent LN in patients with jSLE.
The economic and humanistic burden of bipolar disorder in adults in the United States
Authors: Dembek Carole , Mackie deMauri , Modi Kushal , Zhu Yingying , Niu Xiaoli , Grinnell Todd
Published: March 2023

Background

Bipolar disorder is associated with functional impairment and diminished health-related quality of life (HRQoL). The purpose of this study was to estimate the annual per patient direct healthcare costs, indirect costs, and HRQoL of patients with bipolar disorder by depressive symptom severity and overall compared to the general population in the US.

Methods

This cross-sectional study used self-reported data from the 2020 US National Health and Wellness Survey. Adult respondents who reported bipolar disorder symptoms in the past 12 months and/or a diagnosis of bipolar disorder were identified (bipolar disorder cohort) and were further classified by depressive symptom severity based on Patient Health Questionnaire (PHQ-9) scores (none/mild = 0–9, moderate = 10–14, severe = 15–27). Annualized direct healthcare costs and indirect costs were calculated from 6-month healthcare resource utilization and work productivity, respectively. A general population cohort was constructed using 2:1 propensity score matching. Multivariate regression models of all-cause hospitalizations in the past 6 months, annualized direct healthcare costs, annualized indirect costs, and HRQoL (eg, EuroQol 5-Dimension Health Questionnaire (EQ-5D)) controlled for confounders (demographic and clinical characteristics).

Results

Of 3583 adults meeting pre-specified criteria for bipolar disorder, 1401 (39.1%) reported none/mild, 889 (24.8%) moderate, and 1293 (36.1%) severe depressive symptom severity. Additionally, 3285 (91.7%) were matched to 6570 adults in the general population. Compared to the general population, adjusted mean hospitalizations (0.53 vs. 0.30), annualized per patient direct healthcare costs ($20,846 vs. $11,391), and indirect costs ($14,795 vs. $9274) were significantly greater for the bipolar disorder cohort (all p < 0.001); adjusted HRQoL (EQ-5D: 0.69 vs. 0.79) was significantly worse (p < 0.001). By depressive symptom severity, adjusted mean hospitalizations (none/mild = 0.30, moderate = 0.50, severe = 0.46), direct healthcare costs ($14,389, $22,302, $21,341), and indirect costs ($10,799, $17,109, $18,470) were significantly greater for moderate and severe compared to none/mild depressive symptom severity (all p < 0.01); adjusted HRQoL (EQ-5D: 0.77, 0.67, 0.59) was significantly worse (p < 0.001).

Conclusions

Among respondents with bipolar disorder, those with moderate to severe depression had greater direct healthcare costs and indirect costs as well as worse HRQoL than those with mild or no depressive symptoms. Treatment targeting reduction in depressive symptoms may reduce the economic and humanistic burden of bipolar disorder.
Emergent hybrid surgical approaches for non-dissecting ruptured Kommerell's aneurysm: a case report series
Authors: Velandia-Sánchez Alejandro , Gómez-Galán Sebastián , Gallo-Bernal Sebastian , Polania-Sandoval Camilo A. , Pineda-Rodríguez Ivonne G. , Florez-Amaya Paula , Sanabria-Arévalo Lina M. , Senosiain-González Julián , Barrera-Carvajal Juan G. , Umana Juan P. , Camacho-Mackenzie Jaime
Published: March 2023

Background

Kommerell’s aneurysm is a saccular or fusiform dilatation found in 3–8% of Kommerell’s diverticulum cases. A non-dissecting rupture rate of 6% has been reported. If ruptured, emergent surgical correction is usually granted. However, evidence regarding the optimal surgical approach in this acute setting is scarce. In this case report series, we aim to describe our experience managing type-1 non-dissecting ruptured Kommerell's aneurysm with hybrid emergent surgical approaches.

Cases presentation

From January 2005 to December 2020, three cases of type-1 non-dissecting ruptured Kommerell's aneurysm requiring emergent surgical repair were identified. The mean age was 66.67 ± 7.76 years, and 3/3 were male. The most common symptoms were atypical chest pain, dyspnoea, and headache (2/3). The mean aneurysm’s diameter was 63.67 ± 5.69 mm. Frozen Elephant Trunk was the preferred surgical approach (2/3). The Non-Frozen Elephant Trunk patient underwent a hybrid procedure consisting of a supra-aortic debranching and a zone-2 stent-graft deployment. We found a mean clamp time of 140 ± 60.75 min, cardiac arrest time of 51.33 ± 3.06 min, and a hospital stay of 13.67 ± 5.51 days. The most common complications were surgical-site infection and shock (2/3). Only one patient died (1/3).

Conclusion

Evidence of management for non-dissecting ruptured Kommerell's aneurysms is scarce. Additional, robust, and more extensive studies are required. The selection of the appropriate surgical approach is challenging, and each patient should be individualized. Frozen Elephant Trunk was feasible for patients requiring emergent surgical repair in our centre. However, other hybrid or open procedures can be performed.
Serial prophylactic exchange blood transfusion in pregnant women with sickle cell disease (TAPS-2): statistical and qualitative analysis plan for a randomised controlled feasibility trial
Authors: Seed Paul T. , Brien Sarah B. , Oakley Laura L. , Robinson Vicky , Sharif Joseph , Thompson Hilary , Joseph Jeannine , Oteng-Ntim Eugene
Published: March 2023

Background

There are significant knowledge gaps regarding the effectiveness of serial prophylactic exchange blood transfusion (SPEBT) for pregnant women with sickle cell disease (SCD). The protocol for the randomised feasibility trial assessing SPEBT versus usual care in women with SCD (TAPS2 trial) has previously been published. This publication outlines the statistical and qualitative analysis plan for the study.

Methods and design

TAPS2 is a randomised two-arm phase 2 feasibility trial with a nested qualitative study and health economic evaluation. Up to 50 pregnant women with SCD and a singleton pregnancy will be recruited and individually randomised to either SPEBT approximately every 6–10 weeks until delivery (intervention arm) or to usual care (control arm). Information will be collected on a range of feasibility and clinical outcomes.

Results

Due to the impact of COVID-19 on study recruitment, the initial study period of 24 months was extended to 48 months. Other protocol updates designed to mitigate the impact of COVID-19-related disruption included allowing for remote consent and conducting all qualitative interviews by telephone. The primary outcome for the trial is the overall recruitment rate. The number of women screened, eligible, consented, randomised and withdrawn will be summarised as a CONSORT flow diagram. Differences in clinical outcomes will additionally be presented as an initial assessment of efficacy and to inform sample size calculations for a future definitive trial. Qualitative interviews with trial participants and clinicians will be analysed using reflexive thematic analysis; data from interviews with participants who declined to participate in the trial will be extracted and incorporated into summary tables to report key findings. The health economic analysis plan is not covered by this update.

Conclusion

The publication of this analysis plan is designed to aid transparency and to reduce the potential for reporting bias.

Trial registration

NIH registry (www.clinicaltrials.gov), registration number NCT03975894 (registered 05/06/19); ISRCTN (www.isrctn.com), registration number ISRCTN52684446 (retrospectively registered 02/08/19).
Efficacy of carbapenem vs non carbapenem β-lactam therapy as empiric antimicrobial therapy in patients with extended-spectrum β-lactamase-producing Enterobacterales urinary septic shock: a propensity-weighted multicenter cohort study
Authors: Cariou Erwann , Griffier Romain , Orieux Arthur , Silva Stein , Faguer Stanislas , Seguin Thierry , Nseir Saad , Canet Emmanuel , Desclaux Arnaud , Souweine Bertrand , Klouche Kada , Guisset Olivier , Pillot Jerome , Picard Walter , Saghi Tahar , Delobel Pierre , Gruson Didier , Prevel Renaud , Boyer Alexandre
Published: March 2023

Background

The rise in antimicrobial resistance is a global threat responsible for about 33,000 deaths in 2015 with a particular concern for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) and has led to a major increase in the use of carbapenems, last-resort antibiotics.

Methods

In this retrospective propensity-weighted multicenter observational study conducted in 11 ICUs, the purpose was to assess the efficacy of non carbapenem regimen (piperacillin–tazobactam (PTZ) + aminoglycosides or 3rd-generation cephalosporin (3GC) + aminoglycosides) as empiric therapy in comparison with carbapenem in extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) urinary septic shock. The primary outcome was Day-30 mortality.

Results

Among 156 patients included in this study, 69 received a carbapenem and 87 received non carbapenem antibiotics as empiric treatment. Baseline clinical characteristics were similar between the two groups. Patients who received carbapenem had similar Day-30 mortality (10/69 (15%) vs 6/87 (7%), OR = 1.99 [0.55; 5.34] p = 0.16), illness severity, resolution of septic shock, and ESBL-E infection recurrence rates than patients who received an empiric non carbapenem therapy. The rates of secondary infection with C. difficile were comparable.

Conclusions

In ESBL-E urinary septic shock, empiric treatment with a non carbapenem regimen, including systematically aminoglycosides, was not associated with higher mortality, compared to a carbapenem regimen.
Antipsychotic drugs and their effects on cognitive function: protocol for a systematic review, pairwise, and network meta-analysis
Authors: Feber Lena , Peter Natalie , Schneider-Thoma Johannes , Siafis Spyridon , Bighelli Irene , Hansen Wulf-Peter , Prates Baldez Daniel , Salanti Georgia , Keefe Richard S. E. , Engel Rolf R. , Leucht Stefan
Published: March 2023

Background

There is evidence that antipsychotic drugs differ in their effect on the cognitive symptoms of schizophrenia. So far, there is no comprehensive systematic review available that would enable providers and patients to make informed choices regarding this important aspect of treatment. With a large number of substances available, conventional pairwise meta-analyses will not be sufficient to inform this choice. To fill this gap, we will conduct a network meta-analysis (NMA), integrating direct and indirect comparisons from randomized controlled trials (RCTs) to rank antipsychotics according to their effect on cognitive functioning.

Methods

In our NMA, we will include RCTs in patients with schizophrenia or schizophrenia-like psychoses comparing one antipsychotic agent with another antipsychotic agent or placebo that measures cognitive function. We will include studies on patients of every age group, in any phase of illness (e.g., acute or stable, first episode or chronic schizophrenia, in- or outpatients) with an intervention time of at least 3 weeks. The primary outcome will be the composite score of cognitive functioning, preferentially measured with the test battery developed by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative. The secondary outcomes include the seven cognitive domains that the composite score is composed of, as well as functioning and quality of life. Study selection and data extraction will be conducted by at least two independent reviewers. We will use the Cochrane Risk of Bias tool 2 to determine the risk of bias in studies, and we will evaluate the confidence in the results using Confidence in Network Meta-Analysis (CINeMA). We will perform NMA using R (package netmeta). We will conduct subgroup and sensitivity analyses to explore the heterogeneity and assess the robustness of our findings.

Discussion

This systematic review and network meta-analysis aims to inform evidence-based antipsychotic treatment choice for cognitive deficits in schizophrenia patients by analyzing existing RCTs on this subject. The results have the potential to support patients’ and physicians’ decision-making processes based on the latest available evidence.

Systematic review registration

PROSPERO CRD42022312483
A half-discrete Hilbert-type inequality in the whole plane with the constant factor related to a cotangent function
Authors: You Minghui
Published: March 2023

In this work, by the introduction of some parameters, a new half-discrete kernel function in the whole plane is defined, which involves both the homogeneous and the nonhomogeneous cases. By employing some techniques of real analysis, especially the method of a weight function, a new half-discrete Hilbert-type inequality with the new kernel function, as well as its equivalent Hardy-type inequalities are established. Moreover, it is proved that the constant factors of the newly obtained inequalities are the best possible. Finally, assigning special values to the parameters, some new half-discrete Hilbert-type inequalities with special kernels are presented at the end of the paper.
On Toeplitz operators between different Fock–Sobolev-type spaces
Authors: Chen Jianjun , Xu Guangxia
Published: March 2023

In this paper, we characterize those positive Borel measurable symbols μ on $\mathbb{C}^{n}$

C
n

that induce the Toeplitz operators $T^{\alpha}_{\mu}$

T
μ
α

to be bounded or compact between different Fock–Sobolev–type spaces $F^{p}_{\alpha}$

F
α
p

and $F^{\infty}_{\alpha}$

F
α
∞

with $0< p\leq \infty $
0
<
p
≤
∞
.
Effect of complex hydraulic variables and physicochemical factors on freshwater mussel density in the largest floodplain lake, China
Authors: Jia Chenchen , Wu Chenhuizi , Huang Xiaochen , Zhou Chunhua , Ouyang Shan , Liu Xiongjun , Wu Xiaoping
Published: March 2023

Background

Habitat degradation and flow regime alterations are two of the most prominent and common impact factors to freshwater mussel populations. Knowledge of the correlation between freshwater mussel distribution, density and habitat characteristics is important for maintaining and restoring their biodiversity and ecological functions. Information on predicting habitat suitability of freshwater mussels is lacking in China. Here, we aimed to analyze the correlation between freshwater mussel density and complex hydraulic and physicochemical variables to predict habitat suitability.

Results

The results showed that four complex hydraulic variables (boundary Reynolds number, critical shear stress, bed roughness and mean sediment particle size) and four physicochemical variables (water temperature, chlorophyll-a, transparency and pH) were key factors for predicting habitat suitability of freshwater mussels. Freshwater mussel density was significantly correlated with Froude number, water temperature and chlorophyll-a.

Conclusions

Our results confirmed that higher freshwater mussel density would be associated with areas that are stable in complex hydraulic and physicochemical variables. These results provide an important insight into the conservation of freshwater mussel diversity and their habitat restoration in China and globally.
Development of analytical method for veterinary antibiotics and monitoring of residuals in agricultural environment
Authors: Kim Jin-Wook , Hong Young-Kyu , Ryu Song-Hee , Kwon Oh-Kyung , Lee Yong-Bok , Kim Sung Chul
Published: March 2023

Veterinary antibiotics (VAs) administered to livestock are introduced into the soil through livestock manure and compost. These antibiotics can run off to surface water or leach into groundwater during rainfall, causing problems such as antibiotic contamination or the occurrence of antibiotic-resistant bacteria. In this study, an analytical method for detecting four classes of VAs (penicillin, tetracyclines, macrolides, and sulfonamides) in river water and soil was developed, and the occurrence of residual antibiotics in the agricultural environment was monitored. Soil samples were extracted with the McIlvain buffer solution and pretreatment was conducted using solid-phase extraction, followed by liquid chromatography-tandem mass spectrometry to quantify target VAs. The results of this study showed that the recovery ranged from 62 to 121% in river water and 40.2–149.3% in soil. Among the other VAs, amoxicillin and spiramycin were observed to have low recoveries in all the samples. The method detection limit (MDL) was calculated in the range of 2.1–12.3 ng L−1 in river water and 1.2–13.2 ng kg−1 in soil, and the limit of quantification was 6.6–39.2 ng L−1 and 4.0–42.0 ng kg−1, respectively. This optimal method was then applied to measure the residual concentrations of VAs in river water, sediment, and soil samples around the Muhan watershed in Korea. A total of seven antibiotics were detected, and their concentrations ranged from 0.014 to 0.309 μg L−1in river water, and 1.45–9.04 μg kg−1 in sediment and arable soil. This method can be used to screen VAs in river water and soil and is expected to be used as primary data for examining the occurrence and fate of antibiotics in agricultural environments.
Mechanisms of Lactation-induced Infertility in Female Mice
Authors: Hackwell Eleni C R , Ladyman Sharon R , Brown Rosemary S E , Grattan David R
Published: March 2023

Lactation in mammals is associated with a period of infertility, which serves to direct maternal metabolic resources toward caring for the newborn offspring rather than supporting another pregnancy. This lactational infertility is characterized by reduced pulsatile luteinizing hormone (LH) secretion and lack of ovulation. The mechanisms mediating suppression of LH secretion during lactation are unclear. There are potential roles for both hormonal cues such as prolactin and progesterone, and pup-derived cues such as suckling, on the inhibition of reproduction. To enable future studies using transgenic animals to investigate these mechanisms, in the present study our aim was to characterize lactational infertility in mice, and to investigate the effect of removing pup-derived cues on LH secretion, time to ovulation, and kisspeptin immunoreactivity. We first confirmed that C57BL/6J mice experience prolonged anestrus during lactation, which is dependent on establishment of lactation, as removal of pups the day of parturition led to immediate resumption of pulsatile LH secretion and normal estrous cycles. Once lactation is established, however, the lactational anestrus persisted for several days even after premature removal of pups. Pharmacological suppression of prolactin following premature weaning significantly reduced this period of lactational infertility. Progesterone does not appear to play a significant role in the suppression of fertility during lactation in mice, as levels measured during lactation were not different from nonpregnant mice. These data suggest that prolactin plays a key role in mediating anestrus during early lactation in mice, even in the absence of the suckling stimulus.
The alpha7 integrin subunit in astrocytes promotes endothelial blood–brain barrier integrity
Authors: Chen Zhihua , Kelly Jack R. , Morales John E. , Sun Raymond C. , De Arpan , Burkin Dean J. , McCarty Joseph H.
Published: March 2023

The blood–brain barrier (BBB) is a vascular endothelial cell boundary that partitions the circulation from the central nervous system to promote normal brain health. We have a limited understanding of how the BBB is formed during development and maintained in adulthood. We used quantitative transcriptional profiling to investigate whether specific adhesion molecules are involved in BBB functions, with an emphasis on understanding how astrocytes interact with endothelial cells. Our results reveal a striking enrichment of multiple genes encoding laminin subunits as well as the laminin receptor gene Itga7, which encodes the alpha7 integrin subunit, in astrocytes. Genetic ablation of Itga7 in mice led to aberrant BBB permeability and progressive neurological pathologies. Itga7−/− mice also showed a reduction in laminin protein expression in parenchymal basement membranes. Blood vessels in the Itga7−/− brain showed separation from surrounding astrocytes and had reduced expression of the tight junction proteins claudin 5 and ZO-1. We propose that the alpha7 integrin subunit in astrocytes via adhesion to laminins promotes endothelial cell junction integrity, all of which is required to properly form and maintain a functional BBB.
The role of mitochondrial dynamics in mtDNA maintenance
Authors: Sabouny Rasha , Shutt Timothy E.
Published: March 2023

The dynamic nature of mitochondria, which can fuse, divide and move throughout the cell, allows these critical organelles to adapt their function in response to cellular demands, and is also important for regulating mitochondrial DNA (mtDNA). While it is established that impairments in mitochondrial fusion and fission impact the mitochondrial genome and can lead to mtDNA depletion, abnormal nucleoid organization or accumulation of deletions, it is not entirely clear how or why remodeling mitochondrial network morphology affects mtDNA. Here, we focus on recent advances in our understanding of how mitochondrial dynamics contribute to the regulation of mtDNA and discuss links to human disease.