bluuebunny/crossref_metadata_2025 huggingface dataset:
Reporting to police by intimate partner violence victim-survivors during the COVID-19 pandemic
Authors: Morgan Anthony , Boxall Hayley , Payne Jason L
Published: April 2022

There is evidence from around the world that rates of intimate partner violence (IPV) recorded by police have been impacted by the COVID-19 pandemic. However, not all studies or data sources have shown a consistent increase, and it is not clear how these observed trends may have been influenced by changes in the propensity of victim-survivors to contact police during the pandemic. We use data from a large survey of women in Australia drawn from a national online research panel to examine correlates of police reporting and barriers to help-seeking among a subset of respondents who had experienced physical or sexual IPV during the period of the first national lockdown. Victim-survivors were less likely to have contacted police following the most recent incident if the time spent at home with their partner had increased. They were also more likely to say they were unable to safely seek advice or support on at least one occasion. Police were more likely to be contacted by the victim-survivor if they or their partner had lost their job or taken a pay cut, but there was no relationship with changes in financial stress. Results suggest containment measures introduced in response to COVID-19 may have influenced help-seeking behavior among IPV victim-survivors. This needs to be considered when conducting or interpreting studies on the impact of the pandemic on IPV using police data. Proactive responses to support IPV victim-survivors are needed during current and future restrictions and periods of reduced mobility.
Mutated SETBP1 activates transcription of Myc programs to accelerate CSF3R-driven myeloproliferative neoplasms
Authors: Carratt Sarah A. , Kong Garth L. , Curtiss Brittany M. , Schonrock Zachary , Maloney Lauren , Maniaci Breanna N. , Blaylock Hunter Z. , Baris Adrian , Druker Brian J. , Braun Theodore P. , Maxson Julia E.
Published: April 2022

Colony stimulating factor 3 receptor (CSF3R) mutations lead to JAK pathway activation and are the molecular hallmark of chronic neutrophilic leukemia (CNL). Approximately half of patients with CNL also have mutations in SET binding protein 1 (SETBP1). In this study, we developed models of SETBP1-mutated leukemia to understand the role that SETBP1 plays in CNL. SETBP1 mutations promote self-renewal of CSF3R-mutated hematopoietic progenitors in vitro and prevent cells from undergoing terminal differentiation. In vivo, SETBP1 mutations accelerate leukemia progression, leading to the rapid development of hepatosplenomegaly and granulocytosis. Through transcriptomic and epigenomic profiling, we found that SETBP1 enhances progenitor-associated programs, most strongly upregulating Myc and Myc target genes. This upregulation of Myc can be reversed by LSD1 inhibitors. In summary, we found that SETBP1 mutations promote aggressive hematopoietic cell expansion when expressed with mutated CSF3R through the upregulation of Myc-associated gene expression programs.
There and back again: the once and current developments in donor-derived platelet products for hemostatic therapy
Authors: Kogler Valery J. , Stolla Moritz
Published: April 2022

More than 100 years ago, Duke transfused whole blood to a patient with thrombocytopenia to raise the platelet count and prevent bleeding. Since then, platelet transfusions have undergone numerous modifications from whole blood–derived platelet-rich plasma to apheresis-derived platelet concentrates. The storage time and temperature have also changed. The mandate to store platelets for a maximum of 5 to 7 days at room temperature has been challenged by recent clinical trial data, ongoing difficulties with transfusion-transmitted infections, and recurring periods of shortages that were further exacerbated by the COVID-19 pandemic. Alternative platelet storage approaches are as old as the first platelet transfusions. Cold-stored platelets may offer increased storage times (days) and improved hemostatic potential at the expense of reduced circulation time. Frozen (cryopreserved) platelets extend the storage time to years but require storage at −80°C and thawing before transfusion. Lyophilized platelets can be powder-stored for years at room temperature and reconstituted within minutes in sterile water but are probably the least explored alternative platelet product to date. Finally, whole blood offers the hemostatic spectrum of all blood components but has challenges such as ABO incompatibility. We know more than ever before about the in vitro properties of these products, and clinical trial data are accumulating. The purpose of this review is to summarize the findings of recent preclinical and clinical studies on alternative, donor-derived platelet products.
Loss of METTL3 attenuates blastic plasmacytoid dendritic cell neoplasm response to PRMT5 inhibition via IFN signaling
Authors: Rethnam Malini , Tan Darren Qiancheng , Tan Shi Hao , Li Jia , Yokomori Rui , Li Ying , Yang Henry , Sanda Takaomi , Suda Toshio
Published: April 2022

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy with poor clinical outcomes. Dysregulated MYC expression, which is associated with protein arginine methyltransferase 5 (PRMT5) dependency, is a recurrent feature of BPDCN. Although recent studies have reported a PRMT5 gene signature in BPDCN patient samples, the role of PRMT5 in BPDCN remains unexplored. Here, we demonstrate that BPDCN is highly sensitive to PRMT5 inhibition. Consistent with the upregulation of PRMT5 in BPDCN, we show that pharmacological inhibition (GSK3326595) of PRMT5 inhibits the growth of the patient-derived BPDCN cell line CAL-1 in vitro and mitigated tumor progression in our mouse xenograft model. Interestingly, RNA-sequencing (RNA-seq) analysis revealed that PRMT5 inhibition increases intron retention in several key RNA methylation genes, including METTL3, which was accompanied by a dose-dependent decrease in METTL3 expression. Notably, the function of cellular m6A RNA modification of METTL3 was also affected by PRMT5 inhibition in CAL-1 cells. Intriguingly, METTL3 depletion in CAL-1 caused a significant increase in interferon (IFN) signaling, which was further elevated upon PRMT5 inhibition. Importantly, we discovered that this increase in IFN signaling attenuated the sensitivity of METTL3-depleted CAL-1 cells to PRMT5 inhibition. Correspondingly, stimulation of IFN signaling via TLR7 agonists weakened CAL-1 cell sensitivity to PRMT5 inhibition. Overall, our findings implicate PRMT5 as a therapeutic target in BPDCN and provide insight into the involvement of METTL3 and the IFN pathway in regulating the response to PRMT5 inhibition.
Distinct clinical and genetic features of hepatitis B virus–associated follicular lymphoma in Chinese patients
Authors: Ren Weicheng , Wang Xianhuo , Yang Mingyu , Wan Hui , Li Xiaobo , Ye Xiaofei , Meng Bing , Li Wei , Yu Jingwei , Lei Mengyue , Xie Fanfan , Jiang Wenqi , Kimby Eva , Huang Huiqiang , Liu Dongbing , Li Zhi-Ming , Wu Kui , Zhang Huilai , Pan-Hammarström Qiang
Published: April 2022

Hepatitis B virus (HBV) infection has been associated with an increased risk for B-cell lymphomas. We previously showed that 20% of diffuse large B-cell lymphoma (DLBCL) patients from China, an endemic area of HBV infection, have chronic HBV infection (surface antigen–positive, HBsAg+) and are characterized by distinct clinical and genetic features. Here, we showed that 24% of follicular lymphoma (FL) Chinese patients are HBsAg+. Compared with the HBsAg− FL patients, HBsAg+ patients are younger, have a higher histological grade at diagnosis, and have a higher incidence of disease progression within 24 months. Moreover, by sequencing the genomes of 109 FL tumors, we observed enhanced mutagenesis and distinct genetic profile in HBsAg+ FLs, with a unique set of preferentially mutated genes (TNFAIP3, FAS, HIST1H1C, KLF2, TP53, PIM1, TMSB4X, DUSP2, TAGAP, LYN, and SETD2) but lack of the hallmark of HBsAg− FLs (ie, IGH/BCL2 translocations and CREBBP mutations). Transcriptomic analyses further showed that HBsAg+ FLs displayed gene-expression signatures resembling the activated B-cell–like subtype of diffuse large B-cell lymphoma, involving IRF4-targeted genes and NF-κB/MYD88 signaling pathways. Finally, we identified an increased infiltration of CD8+ memory T cells, CD4+ Th1 cells, and M1 macrophages and higher T-cell exhaustion gene signature in HBsAg+ FL samples. Taken together, we present new genetic/epigenetic evidence that links chronic HBV infection to B-cell lymphomagenesis, and HBV-associated FL is likely to have a distinct cell-of-origin and represent as a separate subtype of FL. Targetable genetic/epigenetic alterations identified in tumors and their associated tumor microenvironment may provide potential novel therapeutic approaches for this subgroup of patients.
Preinfusion factors impacting relapse immunophenotype following CD19 CAR T cells
Authors: Lamble Adam J. , Myers Regina M. , Taraseviciute Agne , John Samuel , Yates Bonnie , Steinberg Seth M. , Sheppard Jennifer , Kovach Alexandra E. , Wood Brent , Borowitz Michael J. , Stetler-Stevenson Maryalice , Yuan Constance M. , Pillai Vinodh , Foley Toni , Chung Perry , Chen Lee , Lee Daniel W. , Annesley Colleen , DiNofia Amanda , Grupp Stephan A. , Verneris Michael R. , Gore Lia , Laetsch Theodore W. , Bhojwani Deepa , Brown Patrick A. , Pulsipher Michael A. , Rheingold Susan R. , Gardner Rebecca A. , Shah Nirali N.
Published: April 2022

Relapse following chimeric antigen receptor (CAR) T-cell therapy directed against CD19 for relapsed/refractory B-acute lymphoblastic leukemia (r/r B-ALL) remains a significant challenge. Three main patterns of relapse predominate: CD19 positive (CD19pos) relapse, CD19 negative (CD19neg) relapse, and lineage switch (LS). Development and validation of risk factors that predict relapse phenotype could help define potential pre- or post-CAR T-cell infusion interventions aimed at decreasing relapse. Our group sought to extensively characterize preinfusion risk factors associated with the development of each relapse pattern via a multicenter, retrospective review of children and young adults with r/r B-ALL treated with a murine-based CD19-CAR construct. Of 420 patients treated with CAR, 166 (39.5%) relapsed, including 83 (50%) CD19pos, 68 (41%) CD19neg, and 12 (7.2%) LS relapses. A greater cumulative number of prior complete remissions was associated with CD19pos relapses, whereas high preinfusion disease burden, prior blinatumomab nonresponse, older age, and 4-1BB CAR construct were associated with CD19neg relapses. The presence of a KMT2A rearrangement was the only preinfusion risk factor associated with LS. The median overall survival following a post-CAR relapse was 11.9 months (95% CI, 9-17) and was particularly dismal in patients experiencing an LS, with no long-term survivors following this pattern of relapse. Given the poor outcomes for those with post-CAR relapse, study of relapse prevention strategies, such as consolidative hematopoietic stem cell transplantation, is critical and warrants further investigation on prospective clinical trials.
Optimal reperfusion strategy in acute high-risk pulmonary embolism requiring extracorporeal membrane oxygenation support: a systematic review and meta-analysis
Authors: Chopard Romain , Nielsen Peter , Ius Fabio , Cebotari Serghei , Ecarnot Fiona , Pilichowski Hugo , Schmidt Matthieu , Kjaergaard Benedict , Sousa-Casasnovas Iago , Ghoreishi Mehrdad , Narayan Rajeev L. , Lee Su Nam , Piazza Gregory , Meneveau Nicolas
Published: April 2022

Background

The optimal pulmonary revascularisation strategy in high-risk pulmonary embolism (PE) requiring implantation of extracorporeal membrane oxygenation (ECMO) remains controversial.

Methods

We conducted a systematic review and meta-analysis of evidence comparing mechanical embolectomy and other strategies, including systemic thrombolysis, catheter-directed thrombolysis or ECMO as stand-alone therapy, with regard to mortality and bleeding outcomes.

Results

We identified 835 studies, 17 of which were included, comprising 327 PE patients. Overall, 32.4% were treated with mechanical pulmonary reperfusion (of whom 85.9% had surgical embolectomy), while 67.6% received other strategies. The mortality rate was 22.6% in the mechanical reperfusion group and 42.8% in the “other strategies” group. The pooled odds ratio for mortality with mechanical reperfusion was 0.439 (95% CI 0.237–0.816) (p=0.009; I2=35.2%)versusother reperfusion strategies and 0.368 (95% CI 0.185–0.733) (p=0.004; I2=32.9%) for surgical embolectomyversusthrombolysis. The rate of bleeding in patients under ECMO was 22.2% in the mechanical reperfusion group and 19.1% in the “other strategies” group (OR 1.27, 95% CI 0.54–2.96; I2=7.7%). The meta-regression model did not identify any relationship between the covariates “more than one pulmonary reperfusion therapy”, “ECMO implantation before pulmonary reperfusion therapy”, “clinical presentation of PE” or “cancer-associated PE” and the associated outcomes.

Conclusions

The results of the present meta-analysis and meta-regression suggest that mechanical reperfusion, notably by surgical embolectomy, may yield favourable results regardless of the timing of ECMO implantation in the reperfusion timeline, independent of thrombolysis administration or cardiac arrest presentation.
Recurrence of primary disease following lung transplantation
Authors: Rama Esendagli Dorina , Ntiamoah Prince , Kupeli Elif , Bhardwaj Abhishek , Ghosh Subha , Mukhopadhyay Sanjay , Mehta Atul C.
Published: April 2022

Lung transplant has become definitive treatment for patients with several end-stage lung diseases. Since the first attempted lung transplantation in 1963, survival has significantly improved due to advancement in immunosuppression, organ procurement,ex vivolung perfusion, surgical techniques, prevention of chronic lung allograft dysfunction and bridging to transplant using extracorporeal membrane oxygenation. Despite a steady increase in number of lung transplantations each year, there is still a huge gap between demand and supply of organs available, and work continues to select recipients with potential for best outcomes. According to review of the literature, there are some rare primary diseases that may recur following transplantation. As the number of lung transplants increase, we continue to identify disease processes at highest risk for recurrence, thus shaping our future approaches. While the aim of lung transplantation is improving survival and quality of life, choosing the best recipients is crucial due to a shortage of donated organs. Here we discuss the common disease processes that recur and highlight its impact on overall outcome following lung transplantation.
Predictors of chronic obstructive pulmonary disease in women who have never smoked: a cohort study
Authors: Engel Roger M. , de Luca Katie , Graham Petra L. , Kaboli Farshchi Masoumeh , Vemulpad Subramanyam , Byles Julie
Published: April 2022

COPD is responsible for an increasing number of deaths worldwide. Smoking is the most reliable predictor for developing COPD later in life. However, women make up the majority of patients with COPD who have never smoked. There is therefore a need to identify other factors that can predict COPD in women. The aim of this study is to identify factors associated with increasing the risk of developing COPD later in life in women who have never smoked.

Data from the Australian Longitudinal Study on Women's Health (ALSWH) cohort born between 1946 and 1951 were used to investigate potential predictors of COPD. Retrospective analyses were performed on data from two of the ALSWH surveys: wave 1 (1996) and wave 9 (2019).

There were 3584 women who self-reported as being never-smokers (at waves 1 and 9) and did not have COPD at baseline, of which 109 had developed COPD at wave 9. Logistic regression showed a significant relationship between COPD at wave 9 and baseline breathing difficulties (p<0.001), asthma (p<0.001) and allergies (p=0.026), though significance of asthma and allergies disappeared when included together in a single model, implying that women with these symptoms earlier in life were more likely to be diagnosed with COPD later in life compared to women without these symptoms.

Our study supports the inclusion of lung function testing in primary care settings for women over the age of 45 years who have never smoked and have a history of breathing difficulties, asthma or allergies.
Physical activity and sedentary behavior trajectories and their associations with quality of life, disability, and all-cause mortality
Authors: Salinas-Rodríguez Aarón , Manrique-Espinoza Betty , Palazuelos-González Rosa , Rivera-Almaraz Ana , Jáuregui Alejandra
Published: April 2022

Background

Physical activity (PA) and sedentary behavior (SB) are not stable conditions but change over time and among individuals, and both could have deleterious effects on health-related outcomes among older adults. This study aimed to identify the longitudinal trajectories of PA and SB and estimate their association with quality of life, disability, and all-cause mortality in a national sample of older Mexican adults.

Methods

Data comes from three waves of the WHO Study on global AGEing and adult health (SAGE) in Mexico (2009, 2014, 2017). In total, 3209 older adults ages 50 and above were included. PA and SB were determined by using the Global Physical Activity Questionnaire (GPAQ). Disability was measured using the WHO Disability Assessment Schedule (WHODAS 2.0), quality of life using the WHOQOL (WHO Quality of Life) instrument, and all-cause mortality using a verbal autopsy. We used growth mixture modeling (GMM) to investigate the longitudinal trajectories of PA and SB. Three-level linear mixed effect models were used to estimate the associations of PA and SB with quality of life and disability and the Cox model for the association with all-cause mortality.

Results

Three longitudinal trajectories of PA and SB were found: low-PA-decreasers, moderate-PA-decreasers, and high-PA-decreasers for PA; and low-maintainers, steep-decreasers, and steep-increasers for SB. Decreased quality of life, increased disability, and all-cause mortality were all consistently associated with worse PA and SB trajectories.

Conclusions

Our results highlight the need for health policies and prevention strategies that promote PA and limit SB in middle-aged adults. Further studies should consider these activities/behaviors as exposures that vary throughout life and work to identify vulnerable groups of older adults for whom physical activation interventions and programs would be most impactful.
Development and consensus of entrustable professional activities for final-year medical students in anaesthesiology
Authors: Weissenbacher Andreas , Bolz Robert , Stehr Sebastian N. , Hempel Gunther
Published: April 2022

Background

The transfer of classic concepts of competency-based medical education into clinical practice has been proven to be difficult in the past, being described as partially fragmented, misleading and inadequate. At the beginning of training, novice doctors commonly feel overwhelmed, overloaded and exposed to extreme time pressure. The discrepancy between expected and actual clinical competence of doctors at the start of their speciality training jeopardizes patient safety. The framework of Entrustable Professional Activities (EPAs) is a promising instrument to effectively integrate competency-based training into clinical practice and may help to close this gap and consequently to improve patient safety.

Methods

For anaesthesiology, we developed 5 EPAs for final-year medical students. The EPAs comprised the following seven categories: 1. Title, 2. Specifications, 3. Limitations, 4. Competency domains, 5. Knowledge, abilities and skills, professional attitudes, 6. Assessment and 7. Entrustment. Based on a modified, online-based Delphi study, we further developed and refined these EPAs. Education experts were recruited from the alumni network of the Master of Medical Education (MME) degree course from the University of Heidelberg, Germany.

Results

28 data sets were evaluated in three Delphi rounds. 82% of study participants had previous experience with EPAs. Qualitative and quantitative data formed the basis during the iterative process and resulted in complete descriptions of 5 EPAs for final-year medical students in anaesthesiology.

Conclusions

Our study including the associated description of 5 EPAs represent a further step and starting point for EPA-based curricula in medical training in Germany linking undergraduate training, to residency training and continuous medical education.
Desflurane improves lung collapse more than propofol during one-lung ventilation and reduces operation time in lobectomy by video-assisted thoracic surgery: a randomized controlled trial
Authors: Kawanishi Ryosuke , Kakuta Nami , Sakai Yoko , Hari Yuki , Sasaki Hideto , Sekiguchi Ryo , Tanaka Katsuya
Published: April 2022

Background

This study evaluated whether desflurane improved lung collapse during one-lung ventilation (OLV) more than propofol, and whether it could reduce the operation time of video-assisted thoracic surgery.

Methods

Sixty patients undergoing lobectomy by video-assisted thoracic surgery (VATS) were randomly assigned to general anesthesia with desflurane or propofol. Lungs were inspected by thoracoscope at 10, 30, and 60 min after initiation of OLV. After surgery, the Lung Collapse Score, a composite of lung color and volume assessments, was assigned by two clinicians blinded to the anesthetic regimen. The primary outcome was operation time. The secondary outcome included the complication rate.

Results

Of the 60 participants, 50 completed the study, 26 in Desflurane group and 24 in Propofol group. The Lung Collapse Scores at 30 and 60 min after OLV initiation were significantly better in Desflurane group than in Propofol group, and operation time was significantly shorter in Desflurane group (214 (57) min vs. 262 (72) min [mean (SD)], difference in means, -48; 95% CI, -85 to -11; P = 0.01). The incidence of multiple complications was 1/26 (3%) and 6/24 (25%) in Desflurane and Propofol group, respectively (relative risk, 0.1; 95% CI, 0.02 to 1.18; P = 0.04).

Conclusions

Desflurane improved lung collapse during OLV and significantly shortened VATS lobectomy operation time compared to propofol in our studied patients. Desflurane resulted in fewer postoperative complications. Thus, desflurane may be an appropriate anesthetic during lobectomy by VATS requiring OLV.

Trial registration

The study was registered with the University Hospital Medical Information Network (UMIN000009412). The date of disclosure of this study information is 27/11/2012. On this date, we registered the study into UMIN; patients were included from 2013 to 2014. However, on 11/27/2015, the UMIN system administrator suggested a detailed description. Thereafter, we added it to the Randomization Unit. Despite being prospective, it was retrospectively registered on UMIN for the above reasons.
Admission vital signs as predictors of COVID-19 mortality: a retrospective cross-sectional study
Authors: Ikram Ahmed Sameer , Pillay Somasundram
Published: April 2022

Background

COVID-19 remains a major healthcare concern. Vital signs are routinely measured on admission and may provide an early, cost-effective indicator of outcome – more so in developing countries where such data is scarce. We sought to describe the association between six routinely measured admission vital signs and COVID-19 mortality, and secondarily to derive potential applications for resource-limited settings.

Methods

Retrospective analysis of consecutive patients admitted to King Edward VIII Hospital, South Africa, with COVID-19 during June–September 2020 was undertaken. The sample was subdivided into survivors and non-survivors and comparisons made in terms of demographics and admission vital signs. Univariate and multivariate analysis of predictor variables identified associations with in-hospital mortality, with the resulting multivariate regression model evaluated for its predictive ability with receiver operating characteristic (ROC) curve analysis.

Results

The 236 participants enrolled comprised 153(77.54%) survivors and 53(22.46%) non-survivors. Most participants were Black African(87.71%) and female(59.75%) with a mean age of 53.08(16.96) years. The non-survivor group demonstrated a significantly lower median/mean for admission oxygen saturation (%) [87(78–95) vs. 96(90–98)] and diastolic BP (mmHg) [70.79(14.66) vs. 76.3(12.07)], and higher median for admission respiratory rate (breaths/minute) [24(20–28) vs. 20(20–23)] and glucose (mmol/l) [10.2(6.95–16.25) vs. 7.4(5.5–9.8)]. Age, oxygen saturation, respiratory rate, glucose and diastolic BP were found to be significantly associated with mortality on univariate analysis. A log rank test revealed significantly lower survival rates in patients with an admission oxygen saturation < 90% compared with ≥90% (p = 0.001). Multivariate logistic regression revealed a significant relationship between age and oxygen saturation with in-hospital mortality (OR 1.047; 95% CI 1.016–1.080; p = 0.003 and OR 0.922; 95% CI 0.880–0.965; p = 0.001 respectively). A ROC curve analysis generated an area under the curve (AUC) of 0.778 (p < 0.001) when evaluating the predictive ability of oxygen saturation, respiratory rate, glucose and diastolic BP for in-hospital death. This improved to an AUC of 0.832 (p < 0.001) with the inclusion of age.

Conclusion

A multivariate regression model comprising admission oxygen saturation, respiratory rate, glucose and diastolic BP (with/without age) demonstrated promising predictive capacity, and may provide a cost-effective means for early prognostication of patients admitted with COVID-19 in resource-limited settings.
Minimal important difference and patient acceptable symptom state for the Numerical Rating Scale (NRS) for pain and the Patient-Rated Wrist/Hand Evaluation (PRWHE) for patients with osteoarthritis at the base of thumb
Authors: Stjernberg-Salmela Susanna , Karjalainen Teemu , Juurakko Joona , Toivonen Pirjo , Waris Eero , Taimela Simo , Ardern Clare L. , Järvinen Teppo L. N. , Jokihaara Jarkko
Published: April 2022

Background

The Numerical Rating Scale (NRS) and Patient-rated wrist/hand evaluation (PRWHE) are patient-reported outcomes frequently used for evaluating pain and function of the wrist and hand. The aim of this study was to determine thresholds for minimal important difference (MID) and patient acceptable symptom state (PASS) for NRS pain and PRWHE instruments in patients with base of thumb osteoarthritis.

Methods

Fifty-two patients with symptomatic base of thumb osteoarthritis wore a splint for six weeks before undergoing trapeziectomy. NRS pain (0 to 10) and PRWHE (0 to 100) were collected at the time of recruitment (baseline), after splint immobilization prior to surgery, and at 3, 6, 9 and 12 months after surgery. Four anchor-based methods were used to determine MID for NRS pain and PRWHE: the receiver operating characteristics (ROC) curve, the mean difference of change (MDC), the mean change (MC) and the predictive modelling methods. Two approaches were used to determine PASS for NRS pain and PRWHE: the 75th percentile and the ROC curve methods. The anchor question for MID was the change perceived by the patient compared with baseline; the anchor question for PASS was whether the patient would be satisfied if the condition were to stay similar. The correlation between the transition anchor at baseline and the outcome at all time points combined was calculated using the Spearman’s rho analysis.

Results

The MID for NRS pain was 2.5 using the ROC curve method, 2.0 using the MDC method, 2.8 using the MC method, and 2.5 using the predictive modelling method. The corresponding MIDs for PRWHE were 22, 24, 10, and 20. The PASS values for NRS pain and PRWHE were 2.5 and 30 using the ROC curve method, and 2.0 and 22 using the 75th percentile method, respectively. The area under curve (AUC) analyses showed excellent discrimination for all measures.

Conclusion

We found credible MID estimates for NRS and PRWHE (including its subscales), although the MID estimates varied depending on the method used. The estimates were 20-30% of the range of scores of the instruments. The cut-offs for MID and PASS showed good or excellent discrimination, lending support for their use in future studies.

Trial registration

This clinimetrics study was approved by the Helsinki University ethical review board (HUS1525/2017).
Learning from COVID-19 related trial adaptations to inform efficient trial design—a sequential mixed methods study
Authors: Chatters Robin , Cooper Cindy L. , O’Cathain Alicia , Murphy Caroline , Lane Athene , Sutherland Katie , Burton Christopher , Cape Angela , Tunnicliffe Louis
Published: April 2022

Background

Many clinical trial procedures were often undertaken in-person prior to the COVID-19 pandemic, which has resulted in adaptations to these procedures to enable trials to continue. The aim of this study was to understand whether the adaptations made to clinical trials by UK Clinical Trials Units (CTUs) during the pandemic have the potential to improve the efficiency of trials post-pandemic.

Methods

This was a mixed methods study, initially involving an online survey administered to all registered UK CTUs to identify studies that had made adaptations due to the pandemic. Representatives from selected studies were qualitatively interviewed to explore the adaptations made and their potential to improve the efficiency of future trials. A literature review was undertaken to locate published evidence concerning the investigated adaptations. The findings from the interviews were reviewed by a group of CTU and patient representatives within a workshop, where discussions focused on the potential of the adaptations to improve the efficiency of future trials.

Results

Forty studies were identified by the survey. Fourteen studies were selected and fifteen CTU staff were interviewed about the adaptations. The workshop included 15 CTU and 3 patient representatives. Adaptations were not seen as leading to direct efficiency savings for CTUs. However, three adaptations may have the potential to directly improve efficiencies for trial sites and participants beyond the pandemic: a split remote-first eligibility assessment, recruitment outside the NHS via a charity, and remote consent. There was a lack of published evidence to support the former two adaptations, however, remote consent is widely supported in the literature. Other identified adaptations may benefit by improving flexibility for the participant. Barriers to using these adaptations include the impact on scientific validity, limitations in the role of the CTU, and participant’s access to technology.

Conclusions

Three adaptations (a split remote-first eligibility assessment, recruitment outside the NHS via a charity, and remote consent) have the potential to improve clinical trials but only one (remote consent) is supported by evidence. These adaptations could be tested in future co-ordinated ‘studies within a trial’ (SWAT).
Attachment and patient activation as predictors of the interest and use of telemedical health applications –results of an observational study in primary health care
Authors: Brenk-Franz Katja , Leonhardt Leo Johannes , Strauß Bernhard
Published: April 2022

Background

Telemedicine applications are becoming more accepted and offer great potential to support physicians and patients. However, there is an increasing need for research, especially in personal predictors that determine the interest and use of telemedicine and e-health applications. This study aims to identify if attachment and patient activation are potential predictors of the interest in and the use of e-health applications in primary care patients.

Methods

We used data from the cross-sectional observational Weimar TelMed study on 192 patients treated by general practitioners from a practice of family medicine in Thuringia, the middle of Germany. The adult attachment was measured using the ECR-RD12 and patient activation with the PAM-13D. Multiple regression analysis by the General Linear Model was used to evaluate the association between attachment, patient activation, and interest in and use of e-health applications.

Results

Patient activation was associated with a higher interest in e-health care. The attachment dimension avoidance was a potential predictor of interest in e-health and e-health-care use.

Conclusion

Adult attachment is an essential predictor of different ways of healthcare use. While avoidant patients evade contact with general practitioners, self-determined access via e-health seems to improve the health care of these patients. A personalized view might be a basis for the evaluation of individual approaches in Primary Care.
Robustness analysis for quantitative assessment of vaccination effects and SARS-CoV-2 lineages in Italy
Authors: Antonini Chiara , Calandrini Sara , Bianconi Fortunato
Published: April 2022

Background

In Italy, the beginning of 2021 was characterized by the emergence of new variants of SARS-CoV-2 and by the availability of effective vaccines that contributed to the mitigation of non-pharmaceutical interventions and to the avoidance of hospital collapse.

Methods

We analyzed the COVID-19 propagation in Italy starting from September 2021 with a Susceptible-Exposed-Infected-Recovered (SEIR) model that takes into account SARS-CoV-2 lineages, intervention measures and efficacious vaccines. The model was calibrated with the Bayesian method Conditional Robust Calibration (CRC) using COVID-19 data from September 2020 to May 2021. Here, we apply the Conditional Robustness Analysis (CRA) algorithm to the calibrated model in order to identify model parameters that most affect the epidemic diffusion in the long-term scenario. We focus our attention on vaccination and intervention parameters, which are the key parameters for long-term solutions for epidemic control.

Results

Our model successfully describes the presence of new variants and the impact of vaccinations and non-pharmaceutical interventions in the Italian scenario. The CRA analysis reveals that vaccine efficacy and waning immunity play a crucial role for pandemic control, together with asymptomatic transmission. Moreover, even though the presence of variants may impair vaccine effectiveness, virus transmission can be kept low with a constant vaccination rate and low restriction levels.

Conclusions

In the long term, a policy of booster vaccinations together with contact tracing and testing will be key strategies for the containment of SARS-CoV-2 spread.
Risk factors of white matter hyperintensities in migraine patients
Authors: Al-Hashel Jasem Yousef , Alroughani Raed , Gad Khaled , Al-Sarraf Lamiaa , Ahmed Samar Farouk
Published: April 2022

Background

Migraine frequently is associated with White Matter Hyperintensities (WMHs). We aimed to assess the frequency of WMHs in migraine and to assess their risk factors.

Methods

This is cross-sectional study included 60 migraine patients of both genders, aged between 18 and 55 years. Patients with vascular risk factors were excluded. We also included a matched healthy control group with no migraine. Demographic, clinical data, and serum level of homocysteine were recorded. All subjects underwent brain MRI (3 Tesla).

Results

The mean age was 38.65 years and most of our cohort were female (83.3). A total of 24 migraine patients (40%) had WMHs versus (10%) in the control group, (P < 0.013). Patients with WMHs were significantly older (43.50 + 8.71 versus. 35.92+ 8.55 years, P < 0.001), have a longer disease duration (14.54+ 7.76versus 8.58+ 6.89 years, P < 0.002), higher monthly migraine attacks (9.27+ 4. 31 versus 7.78 + 2.41 P < 0.020) and high serum homocysteine level (11.05+ 5.63 versus 6.36 + 6.27, P < 0.006) compared to those without WMHs. WMHs were more frequent in chronic migraine compared to episodic migraine (75% versus 34.6%; P < 0.030) and migraine with aura compared to those without aura (38.3% versus 29,2; P < 0.001). WMHs were mostly situated in the frontal lobes (83.4%), both hemispheres (70.8%), and mainly subcortically (83.3%).

Conclusion

Older age, longer disease duration, frequent attacks, and high serum homocysteine level are main the risk factors for WMHs in this cohort. The severity or duration of migraine attacks did not increase the frequency of WMHs. The number of WMHs was significantly higher in chronic compared to episodic migraineurs.
Predicting self-harm and suicide ideation during the COVID-19 pandemic in Indonesia: a nationwide survey report
Authors: Liem Andrian , Prawira Benny , Magdalena Selvi , Siandita Monica Jenifer , Hudiyana Joevarian
Published: April 2022

Background

It is estimated that 77.0% of suicide cases occurred in low-and-middle-income countries (LMICs), which would increase because of the COVID-19 pandemic and socioeconomic inequity. However, there is lack of reports on this topic from LMICs, especially during the pandemic. Therefore, this nationwide study aimed to explore self-harm and suicide ideation and its predictive variables during the pandemic in Indonesia as a MIC with the highest COVID-19 fatality rate in Asia.

Methods

Non-random sampling online survey was conducted nationwide between 25 May and 16 June 2021. The collected data were demographic variables (i.e. age group), loneliness from social isolation using The UCLA Loneliness Scale Six Items (ULS-6), and self-harm and suicide ideation using item 9 of The Patient Health Questionnaire-9 (PHQ-9). Predictive model was analyzed using hierarchical logistic regression.

Results

A total of 5211 participants from all 34 provinces in Indonesia completed the survey. Among 39.3% of them reported self-harm and suicide ideation during the pandemic, which significantly correlated with loneliness. The predictive variables associated with the likelihood of self-harm and suicide ideation were age, residence, job, religion, sex-gender, sexual orientation, HIV status, disability status, and loneliness. The predictive model showed a significant goodness-of-fit to the observed data (x2 [ (15)] = 1803.46, p < .001), RN2 = .40.

Conclusion

Four out of 10 Indonesians experienced self-harm and suicide ideation during the COVID-19 pandemic, particularly people within the age range of 18–24, living in the Java Island, unemployed/student/retired and freelancer, women, members of minority and marginalized communities, and experience of loneliness during the pandemic.
Projecting years in good health between age 50–69 by education in the Netherlands until 2030 using several health indicators - an application in the context of a changing pension age
Authors: Rubio Valverde Jose R. , Mackenbach Johan P. , De Waegenaere Anja M. B. , Melenberg Bertrand , Lyu Pintao , Nusselder Wilma J.
Published: April 2022

Objective

We investigate whether there are changes over time in years in good health people can expect to live above (surplus) or below (deficit) the pension age, by level of attained education, for the past (2006), present (2018) and future (2030) in the Netherlands.

Methods

We used regression analysis to estimate linear trends in prevalence of four health indicators: self-assessed health (SAH), the Organization for Economic Co-operation and Development (OECD) functional limitation indicator, the OECD indicator without hearing and seeing, and the activities-of-daily-living (ADL) disability indicator, for individuals between 50 and 69 years of age, by age category, gender and education using the Dutch National Health Survey (1989–2018). We combined these prevalence estimates with past and projected mortality data to obtain estimates of years lived in good health. We calculated how many years individuals are expected to live in good health above (surplus) or below (deficit) the pension age for the three points in time. The pension ages used were 65 years for 2006, 66 years for 2018 and 67.25 years for 2030.

Results

Both for low educated men and women, our analyses show an increasing deficit of years in good health relative to the pension age for most outcomes, particularly for the SAH and OECD indicator. For high educated we find a decreasing surplus of years lived in good health for all indicators with the exception of SAH. For women, absolute inequalities in the deficit or surplus of years in good health between low and high educated appear to be increasing over time.

Conclusions

Socio-economic inequalities in trends of mortality and the prevalence of ill-health, combined with increasing statutory pension age, impact the low educated more adversely than the high educated. Policies are needed to mitigate the increasing deficit of years in good health relative to the pension age, particularly among the low educated.
High risks of HIV transmission for men sex worker — a comparison of profile and risk factors of HIV infection between MSM and MSW in China
Authors: Yu Maohe , Song Desheng , Zhang Tiantian , Yao Tingting , Chen Yang , Liu Yuanyuan , Peixoto Elissa , Xu Jie , Li Zhijun , Yang Jie , Li Changping , Cui Zhuang
Published: April 2022

Background

Although men who have sex with men (MSM) and male sex workers (MSWs) both represent the high-risk groups for the transmission of HIV/AIDS and syphilis, the comparison between them have not yet been well studied in China. We aimed to evaluate the prevalence of HIV among MSM and MSW, and then identify the difference of risk factors of HIV infection.

Methods

A snowball sampling was employed to recruit patrons attending the Tianjin bathhouse from March 2011 to October 2018. A questionnaire covering sociodemographic characteristics, sexual behaviors, HIV-related and HIV awareness was completed by 5166 patrons from all parts of China. Bivariate analyses were done using the Chi-square test to investigate the association between factors and HIV infection among MSM and MSWs. Subsequently, we studied the different impact of risk factors on HIV infections among the two groups using multiple logistic regression with the adjusted odds ratio (aOR) being derived.

Results

From 2011 to 2018, 235 MSWs and 4931 MSM were included into our study. HIV prevalence among the MSWs was 17.8% (95%CI: 13.2% ~ 23.4%) while 6.5% (95%CI: 5.8% ~ 7.2%) for MSM (P < 0.01). MSWs tends to be younger (26.50% in MSWs vs. 8.64% in MSM, P < 0.05), live alone (84.68% in MSWs vs. 47.98 in MSM, P < 0.05), get poor education (41.28% in MSWs vs. 28.45 in MSM, P < 0.05), use drug (8.09% in MSWs vs. 0.89% in MSM, P < 0.05), have more proportion of always use condom during anal sex (56.50% in MSWs vs. 41.95% in MSM, P < 0.05) but less proportion during commercial sex (81.28% in MSWs vs. 98.48% in MSM, P < 0.05), access HIV-related health services (65.96% in MSWs vs. 47.80% in MSM, P < 0.05) and have a HIV test last year(60.85% in MSWs vs. 41.27% in MSM, P < 0.05). The significant associations between risk factors with HIV infection in MSM were not observed in MSWs and vice versa.

Conclusions

High HIV prevalence needs urgent intervention targeting MSWs as a higher susceptible to HIV in comparison to MSM owing to their unique characteristics. The discrepancies of profiles and risk factors between MSM and MSWs should be consider in design and development of strategies.
Fractures of the lateral malleolus – a retrospective before-and-after study of treatment and resource utilization following the implementation of a structured treatment algorithm
Authors: Rydberg Emilia Möller , Skoglund Jonas , Brezicka Hampus , Ekelund Jan , Sundfeldt Mikael , Möller Michael , Wennergren David
Published: April 2022

Background

In 2015 a study of isolated lateral malleolar fractures (AO/OTA44-B1) treated at Sahlgrenska University hospital (SU) during two consecutive years revealed large-scale variation in the choice of treatment and planned follow-up. The study resulted in the development of a structured treatment algorithm (TA) for ankle fractures. We investigated the effects of this well-implemented TA on the classification, treatment and follow-up of lateral malleolar fractures.

Methods

The current study is an uncontrolled, non-randomized, retrospective before-and-after study comparing a group of AO/OTA44-B1 fractures treated at SU before the introduction of the TA for ankle fractures (1 April 2012 to 31 March 2014) with a group treated after the introduction of the TA (1 September 2017 to 31 August 2019).

Results

In all the studied parameters regarding treatment for AO/OTA44-B1 fractures, a statistically significant change was seen after the introduction of the TA. Surgical treatment reduced from 32% (95% CI 27.5 – 36.5) pre-TA to 10% (95% CI 6.9 – 13.1) post-TA, while the number of patients permitted full weight-bearing increased from 41% (95% CI 36.3 – 45.7) to 84% (95% CI 80.1 – 87.9).

Conclusions

A thoroughly implemented treatment algorithm can reduce the number of surgical treatments for stable ankle fractures. The current study demonstrates that a structured treatment algorithm can standardize the management of ankle fractures and make decisions less dependent on the surgeon’s discretion.
Circular stapling anastomosis with indocyanine green fluorescence imaging for cervical esophagogastric anastomosis after thoracoscopic esophagectomy: a propensity score-matched analysis
Authors: Shishido Yuji , Matsunaga Tomoyuki , Makinoya Masahiro , Miyauchi Wataru , Shimizu Shota , Miyatani Kozo , Uejima Chihiro , Morimoto Masaki , Murakami Yuki , Hanaki Takehiko , Kihara Kyoichi , Yamamoto Manabu , Tokuyasu Naruo , Takano Shuichi , Sakamoto Teruhisa , Saito Hiroaki , Hasegawa Toshimichi , Fujiwara Yoshiyuki
Published: April 2022

Background

Thoracoscopic esophagectomy has been extensively used worldwide as a curative surgery for patients with esophageal cancer; however, complications such as anastomotic leakage and stenosis remain a major concern. Therefore, the objective of this study was to evaluate the efficacy of circular stapling anastomosis with indocyanine green (ICG) fluorescence imaging, which was standardized for cervical esophagogastric anastomosis after thoracoscopic esophagectomy.

Methods

Altogether, 121 patients with esophageal cancer who underwent thoracoscopic esophagectomy with radical lymph node dissection and cervical esophagogastric anastomosis from November 2009 to December 2020 at Tottori University Hospital were enrolled in this study. Patients who underwent surgery before the anastomotic method was standardized were included in the classical group (n = 82) and patients who underwent surgery after the anastomotic method was standardized were included in the ICG circular group (n = 39). The short-term postoperative outcomes, including anastomotic complications, were compared between the two groups using propensity-matched analysis and the risk factors for anastomotic leakage were evaluated using logistic regression analyses.

Results

Of the 121 patients, 33 were included in each group after propensity score matching. The clinicopathological characteristics of patients did not differ between the two groups after propensity score matching. In terms of perioperative outcomes, a significantly higher proportion of patients who underwent surgery using the laparoscopic approach (P < 0.001) and narrow gastric tube (P = 0.003), as well as those who had a lower volume of blood loss (P = 0.009) in the ICG circular group were observed after matching. Moreover, the ICG circular group had a significantly lower incidence of anastomotic leakage (39% vs. 9%, P = 0.004) and anastomotic stenosis (46% vs. 21%, P = 0.037) and a shorter postoperative hospital stay (30 vs. 20 days, P < 0.001) than the classical group. According to the multivariate analysis, the anastomotic method was an independent risk factor for anastomotic leakage after thoracoscopic esophagectomy (P = 0.013).

Conclusions

Circular stapling anastomosis with ICG fluorescence imaging is effective in reducing complications such as anastomotic leakage and stenosis.