bluuebunny/crossref_metadata_2025 huggingface dataset:
αβ T-cell graft depletion for allogeneic HSCT in adults with hematological malignancies
Authors: de Witte Moniek A. , Janssen Anke , Nijssen Klaartje , Karaiskaki Froso , Swanenberg Luuk , van Rhenen Anna , Admiraal Rick , van der Wagen Lotte , Minnema Monique C. , Petersen Eefke , Raymakers Reinier A. P. , Westinga Kasper , Straetemans Trudy , Halkes Constantijn J. M. , Boelens Jaap-Jan , Kuball Jürgen
Published: January 2021

We conducted a multicenter prospective single-arm phase 1/2 study that assesses the outcome of αβ T-cell depleted allogeneic hematopoietic stem cell transplantation (allo-HSCT) of peripheral blood derived stem cells from matched related, or unrelated donors (10/10 and 9/10) in adults, with the incidence of acute graft-versus-host disease (aGVHD) as the primary end point at day 100. Thirty-five adults (median age, 59; range, 19-69 years) were enrolled. Conditioning consisted of antithymocyte globulin, busulfan, and fludarabine, followed by 28 days of mycophenolic acid after allo-HSCT. The minimal follow-up time was 24 months. The median number of infused CD34+ cells and αβ T cells were 6.1 × 106 and 16.3 × 103 cells per kg, respectively. The cumulative incidence (CI) of aGVHD grades 2-4 and 3-4 at day 100 was 26% and 14%. One secondary graft failure was observed. A prophylactic donor lymphocyte infusion (DLI) (1 × 105 CD3+ T cells per kg) was administered to 54% of the subjects, resulting in a CI of aGVHD grades 2-4 and 3-4 to 37% and 17% at 2 years. Immune monitoring revealed an early reconstitution of natural killer (NK) and γδ T cells. Cytomegalovirus reactivation associated with expansion of memory-like NK cells. The CI of relapse was 29%, and the nonrelapse mortality 32% at 2 years. The 2-year CI of chronic GVHD (cGVHD) was 23%, of which 17% was moderate. We conclude that only 26% of patients developed aGVHD 2-4 after αβ T-cell–depleted allo-HSCT within 100 days and was associated with a low incidence of cGVHD after 2 years. This trial was registered at www.trialregister.nl as #NL4767.
Hematologic indices in individuals with pathogenic germline DICER1 variants
Authors: Vasta Lauren M. , Khan Nicholas E. , Higgs Cecilia P. , Harney Laura A. , Carr Ann G. , Harris Anne K. , Schultz Kris Ann P. , McMaster Mary L. , Stewart Douglas R.
Published: January 2021

Pathogenic germline variants in DICER1 underlie an autosomal dominant, pleiotropic tumor-predisposition disorder. Murine models with the loss of DICER1 in hematopoietic stem cell progenitors demonstrate hematologic aberrations that include reductions in red and white blood cell counts, hemoglobin volume, and impaired maturation resulting in dysplasia. We investigated whether hematologic abnormalities such as those observed in DICER1-deficient mice were observed in humans with a pathogenic germline variant in DICER1. A natural history study of individuals with germline pathogenic DICER1 variants and family controls conducted through the National Cancer Institute (NCI) evaluated enrollees at the National Institutes of Health Clinical Center during a comprehensive clinical outpatient visit that included collecting routine clinical laboratory studies. These were compared against normative laboratory values and compared between the DICER1 carriers and controls. There were no statistical differences in routine clinical hematology laboratory studies observed in DICER1 carriers and family controls. A review of the medical history of DICER1 carriers showed that none of the individuals in the NCI cohort developed myelodysplastic syndrome or leukemia. Query of the International Pleuropulmonary Blastoma/DICER1 Registry revealed 1 DICER1 carrier who developed a secondary leukemia after treatment of pleuropulmonary blastoma. We found limited evidence that the hematologic abnormalities observed in murine DICER1 models developed in our cohort of DICER1 carriers. In addition, no cases of myelodysplastic syndrome were observed in either the NCI cohort or the International Pleuropulmonary Blastoma/DICER1 Registry; 1 case of presumed secondary leukemia was reported. Abnormalities in hematologic indices should not be solely attributed to DICER1. This trial was registered at www.clinicaltrials.gov as #NCT01247597.
Clinical predictors of poor outcomes in patients with sickle cell disease and COVID-19 infection
Authors: Minniti Caterina P. , Zaidi Ahmar U. , Nouraie Mehdi , Manwani Deepa , Crouch Gary D. , Crouch Andrew S. , Callaghan Michael U. , Carpenter Sarah , Jacobs Charleen , Han Jin , Simon Jena , Glassberg Jeffrey , Gordeuk Victor R. , Klings Elizabeth S.
Published: January 2021

We aimed to identify predictors of outcomes and survival in patients living in 4 major metropolitan areas who had sickle cell disease (SCD) and COVID-19 to inform best approaches to prevention and care. Data were collected at baseline and during the clinical course in SCD patients diagnosed with COVID-19 in four COVID-19 epicenters. Patients were followed up posthospital discharge for up to 3 months. Of sixty-six SCD patients with COVID-19, fifty patients (75%) required hospitalization, and seven died (10.6%). Patients with preexisting kidney disease (chronic kidney disease) were more likely to be hospitalized. The most common presenting symptom was vaso-occlusive pain. Acute chest syndrome occurred in 30 (60%) of the 50 hospitalized patients and in all who died. Older age and histories of pulmonary hypertension, congestive heart failure, chronic kidney disease, and stroke were more prevalent in patients who died, as were higher creatinine, lactate dehydrogenase, and D-dimer levels. Anticoagulation use while inpatient was twice less common in patients who died. All deaths occurred in individuals not taking hydroxyurea or any other SCD-modifying therapy. Patients with SCD and COVID-19 exhibited a broad range of disease severity. We cannot definitively state that the overall mortality is higher in patients with SCD, although our case fatality rate was ∼10% compared with ∼3% in the general population, despite a median age of 34 years. Individuals with SCD aged >50 years, with preexisting cardiopulmonary, renal disease, and/or stroke not receiving hydroxyurea, who present with high serum creatinine, lactate dehydrogenase, and D-dimer levels, are at higher risk of death, irrespective of genotype or sex.
The use of photogrammetric fossil models in palaeontology education
Authors: Cunningham John A.
Published: January 2021

Photogrammetry allows overlapping photographs of fossils to be taken and converted into photo-realistic three-dimensional (3-D) digital models. These models offer potential advantages in teaching palaeontology: they are cheap to produce, can be easily shared and allow the study of rare and delicate specimens. Here I describe approaches for using photogrammetric models in the teaching and learning of palaeontology. Little is known about how students perceive these models and whether they find them valuable in their learning. To address this, first-year university students taught using both fossil specimens and digital models were surveyed about their experience through an anonymous online survey. Most students found that the digital models were easy to use, helped them understand anatomy and were more useful than studying photographs. However, most did not see the models as a substitute for studying real fossils and felt they could learn more from physical models. Digital models are a useful addition to palaeontological education that can supplement real fossils and allow palaeontological education to take place in circumstances where handling of specimens is not possible.
Serum alanine aminotransferase activity and risk factors for cardiovascular disease in a Caucasian population: the Tromsø study
Authors: Bekkelund Svein Ivar
Published: January 2021

Background

High and low levels of serum alanine aminotransferase (ALT) are both associated with cardiovascular diseases (CVD) risks especially in elderly, but the mechanisms are less known. This study investigated associations between ALT and CVD risk factors including effects of sex and age in a Caucasian population.

Methods

Cross-sectional data were analysed sex-stratified in 2555 men (mean age 60.4 years) and 2858 women (mean age 60.0 years) from the population study Tromsø 6. Associations were assessed by variance analysis and multivariable logistic regression of odds to have abnormal ALT. Risk factors included body mass index (BMI), waist-to-hip-ratio, blood pressure, lipids, glucose, glycated haemoglobin and high-sensitive C-reactive protein (CRP).

Results

Abnormal elevated ALT was detected in 113 men (4.4%) and 188 women (6.6%). Most CVD risk factors associated positively with ALT in both sexes except systolic blood pressure and CRP (women only), while ALT was positively associated with age in men when adjusted for CVD risk factors, P < 0.001. BMI predicted ALT in men (OR 0.94; 95% CI 0.88–1.00, P = 0.047) and women (OR 0.90; 95% CI 0.86–0.95, P < 0.001). A linear inversed association between age and ALT in men and a non-linear inversed U-trend in women with maximum level between 60 and 64 years were found.

Conclusion

This study confirms a positive relationship between ALT and CVD risk factors, particularly BMI. Age is not a major confounder in the ALT-CVD relationship, but separate sex-analyses is recommended in such studies.
Increasing consultant-level staffing as a proportion of overall physician coverage improves emergency department length of stay targets
Authors: Jenkins Dominic , Thomas Sarah A. , Pathan Sameer A. , Thomas Stephen H.
Published: January 2021

Objectives

One goal of Emergency Department (ED) operations is achieving an overall length of stay (LOS) that is less than four hours. The goal of the current study was to assess for association between increasing number of on-duty EM Consultants and LOS, while adjusting for overall (all-grade) on-duty emergency doctors’ numbers and other operational factors.

Methods

This was a retrospective analysis of three years (2016–2019) of data, employing a unit of analysis of 3276 eight-hour ED shifts. The study was conducted using a prospectively populated ED database in a busy (annual census 420,000) Middle Eastern ED with staffing by Consultants and multiple non-Consultant grades (Specialists, fellows, and residents). Using logistic regression, the main predictor variable of “on-duty Consultantn” was assessed for association with the study’s primary (dichotomous) endpoint: whether a shift’s median LOS met the target of < 240 min. Linear regression was used to assess for association between on-duty Consultantnand the study’s secondary (continuous) endpoint: median LOS for the ED shift.

Results

Multivariate logistic regression adjusting for a number of operations factors (including total EP on-duty complement) identified an association between increasingnof on-duty Consultants and the likelihood of a shift’s meeting the 4-h ED LOS target (OR 1.27, 95% CI 1.20 to 1.34,p < .0001). Multiple linear regression, which also adjusted for total on-duty EPnand other operational factors, also indicated LOS benefit from more on-duty Consultants: each additional on-duty Consultant was associated with a shift’s median LOS improving by 5.4 min (95% CI 4.3 to 6.5,p < .0001).

Conclusions

At the study site, in models that adjusted for overall on-duty EP numbers as well as myriad other operational factors, increasing numbers of on-duty Consultants was associated with a statistically and operationally significant reduction in ED LOS.
Informing the research agenda for optimizing audit and feedback interventions: results of a prioritization exercise
Authors: Colquhoun Heather L. , Carroll Kelly , Eva Kevin W. , Grimshaw Jeremy M. , Ivers Noah , Michie Susan , Brehaut Jamie C.
Published: January 2021

Background

Audit and feedback (A&F) interventions are one of the most common approaches for implementing evidence-based practices. A key barrier to more effective A&F interventions is the lack of a theory-guided approach to the accumulation of evidence. Recent interviews with theory experts identified 313 theory-informed hypotheses, spread across 30 themes, about how to create more effective A&F interventions. In the current survey, we sought to elicit from stakeholders which hypotheses were most likely to advance the field if studied further.

Methods

From the list of 313, three members of the research team identified 216 that were clear and distinguishable enough for prioritization. A web-based survey was then sent to 211 A&F intervention stakeholders asking them to choose up to 50 ‘priority’ hypotheses following the header “A&F interventions will be more effective if…”. Analyses included frequencies of endorsement of the individual hypotheses and themes into which they were grouped.

Results

68 of the 211 invited participants responded to the survey. Seven hypotheses were chosen by > 50% of respondents, including A&F interventions will be more effective… “if feedback is provided by a trusted source”; “if recipients are involved in the design/development of the feedback intervention”; “if recommendations related to the feedback are based on good quality evidence”; “if the behaviour is under the control of the recipient”; “if it addresses barriers and facilitators (drivers) to behaviour change”; “if it suggests clear action plans”; and “if target/goal/optimal rates are clear and explicit”. The most endorsed theme was Recipient Priorities (four hypotheses were chosen 92 times as a ‘priority’ hypotheses).

Conclusions

This work determined a set of hypotheses thought by respondents to be to be most likely to advance the field through future A&F intervention research. This work can inform a coordinated research agenda that may more efficiently lead to more effective A&F interventions.
Acute effects of strength and endurance exercise on serum BDNF and IGF-1 levels in older men
Authors: Arazi Hamid , Babaei Parvin , Moghimi Makan , Asadi Abbas
Published: January 2021

Background

Regarding an important effects of physical exercise on brain function in elders, the aim of this study was to examine the effects of strength and endurance exercise on brain neurobiological factors in older men.

Methods

Thirty older men volunteered to participate in this study and were randomly assigned to strength, endurance and control groups. The subjects in strength group performed two circuits of resistance exercise (6 exercises with 10 repetition of 65–70% of one repetition maximum), while endurance group performed 30 min running with 65–70% of maximal heart rate. Blood was obtained pre and post-exercise to determine changes in serum BDNF, IGF-1 and platelets.

Results

After exercise, both the strength and endurance groups showed significant increases in serum BDNF and IGF-1 concentrations and platelets at post-exercise and in comparison to control group (p < 0.05). In addition, no statistically significant differences were detected between the strength and endurance groups at post-exercise.

Conclusion

Our findings indicate that both the strength and endurance interventions are effective in elevating BDNF, IGF-1, and platelets, without significant differences between them.
Translation and validation of the Korean version of the clinical frailty scale in older patients
Authors: Ko Ryoung-Eun , Moon Seong Mi , Kang Danbee , Cho Juhee , Chung Chi Ryang , Lee Yunhwan , Hong Yun Soo , Lee So Hee , Lee Jung Hee , Suh Gee Young
Published: January 2021

Background

Frailty is a multidimensional syndrome that leads to an increase in vulnerability. Previous studies have suggested that frailty is associated with poor health-related outcomes. For frailty screening, the Clinical Frailty Scale (CFS) is a simple tool that is widely used in various translated versions. We aimed to translate the CSF into Korean and evaluated its contents and concurrent validity.

Methods

Translations and back-translations of the CFS were conducted independently. A multidisciplinary team decided the final CFS-K. Between August 2019 and April 2020, a total of 100 outpatient and inpatient participants aged ≥65 years were enrolled prospectively. The clinical characteristics were evaluated using the CFS-K. The CFS-K scores were compared with those of other frailty screening tools using Pearson’s correlation coefficient and Spearman’s rank correlation. The area under curve (AUC) for identifying the Eastern Cooperative Oncology Group Performance Status (ECOG PS) grade 3 or more was calculated for the CFS-K and other screening tools.

Results

The mean age of the participants was 76.5 years (standard deviation [SD], 7.0), and 63 (63%) participants were male. The mean CFS-K was 4.8 (SD, 2.5). Low body mass index (p = 0.013) and low score on the Korean version of the Mini-Mental State Examination (p < 0.001) were significantly associated with high CFS-K scores, except for those assigned to scale 9 (terminally ill). The CFS-K showed a significant correlation with other frailty screening tools (R = 0.7742–0.9190; p < 0.01), except in the case of those assigned to scale 9 (terminally ill). In comparison with other scales, the CFS-K identified ECOG PS grade 3 or more with the best performance (AUC = 0.99). Patients assigned to scale 9 on the CFS-K (terminally ill) had similar frailty scores to those assigned to scale 4 (vulnerable) or 5 (mildly frail).

Conclusions

In conclusion, the CFS-K is a valid scale for measuring frailty in older Korean patients. The CFS-K scores were significantly correlated with the scores of other scales. To evaluate the predictive and prognostic value of this scale, further larger-scale studies in various clinical settings are warranted.
Evaluation of undetected cases during the COVID-19 epidemic in Austria
Authors: Rippinger C. , Bicher M. , Urach C. , Brunmeir D. , Weibrecht N. , Zauner G. , Sroczynski G. , Jahn B. , Mühlberger N. , Siebert U. , Popper N.
Published: January 2021

Background

Knowing the number of undetected cases of COVID-19 is important for a better understanding of the spread of the disease. This study analyses the temporal dynamic of detected vs. undetected cases to provide guidance for the interpretation of prevalence studies performed with PCR or antibody tests to estimate the detection rate.

Methods

We used an agent-based model to evaluate assumptions on the detection probability ranging from 0.1 to 0.9. For each general detection probability, we derived age-dependent detection probabilities and calibrated the model to reproduce the epidemic wave of COVID-19 in Austria from March 2020 to June 2020. We categorized infected individuals into presymptomatic, symptomatic unconfirmed, confirmed and never detected to observe the simulated dynamic of the detected and undetected cases.

Results

The calculation of the age-dependent detection probability ruled values lower than 0.4 as most likely. Furthermore, the proportion of undetected cases depends strongly on the dynamic of the epidemic wave: during the initial upswing, the undetected cases account for a major part of all infected individuals, whereas their share decreases around the peak of the confirmed cases.

Conclusions

The results of prevalence studies performed to determine the detection rate of COVID-19 patients should always be interpreted with regard to the current dynamic of the epidemic wave. Applying the method proposed in our analysis, the prevalence study performed in Austria in April 2020 could indicate a detection rate of 0.13, instead of the prevalent ratio of 0.29 between detected and estimated undetected cases at that time.
The HIV care cascade for adolescents initiated on antiretroviral therapy in a health district of South Africa: a retrospective cohort study
Authors: Haghighat Roxanna , Toska Elona , Bungane Nontuthuzelo , Cluver Lucie
Published: January 2021

Background

Little evidence exists to comprehensively estimate adolescent viral suppression after initiation on antiretroviral therapy in sub-Saharan Africa. This study examines adolescent progression along the HIV care cascade to viral suppression for adolescents initiated on antiretroviral therapy in South Africa.

Methods

All adolescents ever initiated on antiretroviral therapy (n=1080) by 2015 in a health district of the Eastern Cape, South Africa, were interviewed in 2014–2015. Clinical records were extracted from 52 healthcare facilities through January 2018 (including records in multiple facilities). Mortality and loss to follow-up rates were corrected for transfers. Predictors of progression through the HIV care cascade were tested using sequential multivariable logistic regressions. Predicted probabilities for the effects of significant predictors were estimated by sex and mode of infection.

Results

Corrected mortality and loss to follow-up rates were 3.3 and 16.9%, respectively. Among adolescents with clinical records, 92.3% had ≥1 viral load, but only 51.1% of viral loads were from the past 12 months. Adolescents on ART for ≥2 years (AOR 3.42 [95%CI 2.14–5.47], p< 0.001) and who experienced decentralised care (AOR 1.39 [95%CI 1.06–1.83], p=0.018) were more likely to have a recent viral load. The average effect of decentralised care on recent viral load was greater for female (AOR 2.39 [95%CI 1.29–4.43], p=0.006) and sexually infected adolescents (AOR 3.48 [95%CI 1.04–11.65], p=0.043). Of the total cohort, 47.5% were recorded as fully virally suppressed at most recent test. Only 23.2% were recorded as fully virally suppressed within the past 12 months. Younger adolescents (AOR 1.39 [95%CI 1.06–1.82], p=0.017) and those on ART for ≥2 years (AOR 1.70 [95%CI 1.12–2.58], p=0.013) were more likely to be fully viral suppressed.

Conclusions

Viral load recording and viral suppression rates remain low for ART-initiated adolescents in South Africa. Improved outcomes for this population require stronger engagement in care and viral load monitoring.
Demographic features of identified PLWHA infected through commercial and nonmarital noncommercial heterosexual contact in China from 2015 to 2018: a retrospective cross-sectional study
Authors: Dong Zhilong , Ma Liying , Cai Chang , Gao George Fu , Lyu Fan
Published: January 2021

Background

Understanding the demographic characteristics of people living with HIV/AIDS (PLWHA) infected through commercial heterosexual contact (CHC) or nonmarital noncommercial heterosexual contact (NMNCHC) is important for HIV/AIDS prevention and control.

Methods

Cases reported through the Chinese HIV/AIDS Case Reporting System (CRS) from 2015 to 2018 were analyzed. A descriptive and preliminary inferential analysis were performed for those demographic characteristics deemed of interest.

Results

Overall, 523,121 identified PLWHA between 2015 and 2018 in the CRS were analyzed. The constituent ratio of heterosexual transmission increased from 66.25% in 2015 to 71.48% in 2018. The proportion of CHC heterosexual transmission decreased from 40.18% in 2015 to 37.99% in 2018, while that of NMNCHC increased from 46.33% in 2015 to 49.02% in 2018. PLWHA infected through NMNCHC were significantly younger than those who were infected through CHC (Student’s t test, P < 0.0001), with an average age gap ranging from 5.63 (2015) to 7.46 (2018) years, and the average age of both groups increased annually. The frequency of newly identified PLWHA who were infected through CHC had a remarkable increase among the ages of 65 and above. Gender distribution was significantly different between CHC and NMNCHC (χ2 = 8909.00(2015), 9941.90(2016), 11,004.00 (2017), 12,836.00(2018), all P < 0.0001), and the ratio of men to women in the NMCHC group was 1.50:1 (2015), 1.51:1 (2016), 1.54:1 (2017), and 1.52:1 (2018), while in the commercial heterosexual contact (CHC) group, these ratios were 11.45:1 (2015), 12.08:1 (2016), 12.53:1 (2017), and 13.28:1 (2018). Marital status was significantly different between CHC and NMNCHC (χ2 = 94.67 (2015), 109.88(2016), 58.18(2017), 152.38(2018), all P < 0.0001). As the educational level improved, the proportion of NMNCHC also increased (Cochran - Armitage test, P < 0.0001).

Conclusions

We found that heterosexual transmission was the primary mode of HIV transmission in China from 2015 to 2018. PLWHA infected through CHC and NMNCHC had different characteristics in age, gender, marital status, and educational level. The frequency of PLWHA infected through CHC increased substantially in the age group of 65 and above. This study provides useful baseline data for future studies on the heterosexual transmission of HIV in China.
Clinical physiological parameters for the prediction of gram-negative bacterial infection in the emergency department
Authors: Hsu Chan-Peng , Chen Hsin-Yu , Chen Wei-Lung , Chen Jiann-Hwa , Huang Chien-Cheng , Wu Po-Han , Chung Jui-Yuan
Published: January 2021

Background

Early detection and treatment of Gram-negative bacteria (GNB), major causative pathogens of sepsis (a potentially fatal condition caused by the body’s response to an infection), may benefit a patient’s outcome, since the mortality rate increases by 5–10% for each hour of delayed therapy. Unfortunately, GNB diagnosis is based on bacterial culture, which is time consuming. Therefore, an economic and effective GNB (defined as a positive blood, sputum, or urine culture) infection detection tool in the emergency department (ED) is warranted.

Methods

We conducted a retrospective cohort study in the ED of a university-affiliated medical center between January 01, 2014 and December 31, 2017. The inclusion criteria were as follows: (1) age ≥ 18; (2) clinical suspicion of bacterial infection; (3) bacterial culture from blood, sputum, or urine ordered and obtained in the ED. Descriptive statistics was performed on patient demographic characteristics, vital signs, laboratory data, infection sites, cultured microorganisms, and clinical outcomes. The accuracy of vital signs to predict GNB infection was identified via univariate logistic regression and receiver operating characteristic (ROC) curve analysis.

Results

A total of 797 patients were included in this study; the mean age was 71.8 years and 51.3% were male. The odds ratios of patients with body temperature ≥ 38.5 °C, heart rate ≥ 110 beats per minute, respiratory rate ≥ 20 breaths per minute, and Glasgow coma scale (GCS) < 14, in predicting GNB infection were found to be 2.3, 1.4, 1.9, and 1.6, respectively. The area under the curve values for ROC analysis of these measures were 0.70, 0.68, 0.69, and 0.67, respectively.

Conclusion

The four physiological parameters were rapid and reliable independent predictors for detection of GNB infection.
The physician as a success determining factor in CT-guided pain therapy
Authors: Stueckle Christoph A. , Hackert Benedikt , Talarczyk Sarah , Wawro Martin , Haage Patrick , Weger Ulrich
Published: January 2021

Background

Back pain is a common problem and a burden for the patient. MR-morphologically proven pain-causing changes of the spine is often successfully treated utilizing CT-guided pain therapy. The CT-guided execution enables a controlled and reproducible therapy. Nevertheless, treatment results can differ even with the same patient; the physician is a possible influencing factor of the outcome. Accordingly, the present study analyzes the different behaviors and forms of communication of the treating physicians during the course of the intervention as factors influencing the outcome of treatment.

Methods

67 patients suffering from specific back pain were included in this study. 5 treating physicians (2 female, 3 male) of different age (29–63 years), and experience and a total of 244 CT-guided treatments were included in this study. In every case a psychologist observed the treatment based on a standardized observation protocol. Observed were both the verbal and non-verbal interactions as well as the reaction of patient and physician. The success of the therapy was measured in the course of the treatment using the visual analogue pain scale. The technical comparability of the performed CT-guided periradicular therapy was ensured by the distribution of the drug mixture.

Results

The outcome is significantly better if the patient considers the treating physician to be competent (correlation coefficient: 0.24,p < 0.006) and feels understood (correlation coefficient: 0.29,p < 0.001). In addition, the outcome is better when the physician believes that the treatment brings a positive reduction of pain, underlining his belief with positive statements of affirmation before the intervention thus creating a positive atmosphere [correlation coefficient: 0.24 (p < 0.009)]. In contrast, the outcome is worse if the patient complains about pain during the intervention [average pain reduction M = 0.9 (pain group) vs. M = 2.0 (no-pain group)].

Conclusion

Our study shows that with comparable implementation of CT-guided periradicular therapy, the outcome of the patient with specific back pain can be significantly improved by certain behavioral patterns of the performing physician and this without side effects and without significant additional time expenditure. Our findings indicate that there is a non-negligible psychological factor linking confidence in therapy to actual therapy success.

Trial Registration: The study was designed as an observational study, therefore a trial registration was not necessary.
A qualitative study of women and partners from Lebanon and Quebec regarding an expanded scope of noninvasive prenatal testing
Authors: Haidar Hazar , Le Clerc-Blain Jessica , Vanstone Meredith , Laberge Anne-Marie , Bibeau Gilles , Ghulmiyyah Labib , Ravitsky Vardit
Published: January 2021

Background

In the near future, developments in non-invasive prenatal testing (NIPT) may offer couples the opportunity to expand the range of genetic conditions tested with this technology. This possibility raises a host of ethical and social concerns, such as the type of information (medical vs. non-medical information) that couples might be exposed to and how this might complicate their informed decision-making. Currently, only limited research, mainly carried out in western countries, was conducted on women’s and partners’ views regarding the potential expansion of NIPT.

Methods

This study used semi-structured interviews with pregnant women and their partners to explore their views on future potential NIPT applications such as non-medical sex selection and non-medical traits, paternity testing, and NIPT use for fetal whole genome sequencing (FWGS). It was conducted in Lebanon and Quebec, as case studies to explore the impact of cultural differences on these views.

Results

We found no differences and many similarities when comparing the perceptions of participants in both contexts. While couples in both settings disapproved of the use of NIPT for non-medical sex selection and non-medical traits such as physical characteristics, they were near-unanimous about their support for its use for paternity testing in specific cases, such as legal doubts or conflicts related to the identity of the father. Participants were more ambivalent about NIPT for Fetal Whole Genome Sequencing. They supported this use to detect conditions that would express at birth or early childhood, while objecting to testing for adult-onset conditions.

Conclusions

These results can further inform the debate on the future uses of NIPT and future policy related its implementation.
Optimal biological dose: a systematic review in cancer phase I clinical trials
Authors: Fraisse J. , Dinart D. , Tosi D. , Bellera C. , Mollevi C.
Published: January 2021

Background

Classical phase 1 dose-finding designs based on a single toxicity endpoint to assess the maximum tolerated dose were initially developed in the context of cytotoxic drugs. With the emergence of molecular targeted agents and immunotherapies, the concept of optimal biological dose (OBD) was subsequently introduced to account for efficacy in addition to toxicity. The objective was therefore to provide an overview of published phase 1 cancer clinical trials relying on the concept of OBD.

Methods

We performed a systematic review through a computerized search of the MEDLINE database to identify early phase cancer clinical trials that relied on OBD. Relevant publications were selected based on a two-step process by two independent readers. Relevant information (phase, type of therapeutic agents, objectives, endpoints and dose-finding design) were collected.

Results

We retrieved 37 articles. OBD was clearly mentioned as a trial objective (primary or secondary) for 22 articles and was traditionally defined as the smallest dose maximizing an efficacy criterion such as biological target: biological response, immune cells count for immunotherapies, or biological cell count for targeted therapies. Most trials considered a binary toxicity endpoint defined in terms of the proportion of patients who experienced a dose-limiting toxicity. Only two articles relied on an adaptive dose escalation design.

Conclusions

In practice, OBD should be a primary objective for the assessment of the recommended phase 2 dose (RP2D) for a targeted therapy or immunotherapy phase I cancer trial. Dose escalation designs have to be adapted accordingly to account for both efficacy and toxicity.
Identifying response and predictive biomarkers for Transcranial magnetic stimulation outcomes: protocol and rationale for a mechanistic study of functional neuroimaging and behavioral biomarkers in veterans with Pharmacoresistant depression
Authors: Williams Leanne M. , Coman John T. , Stetz Patrick C. , Walker Nicole C. , Kozel F. Andrew , George Mark S. , Yoon Jong , Hack Laura M. , Madore Michelle R. , Lim Kelvin O. , Philip Noah S. , Holtzheimer Paul E.
Published: January 2021

Background

Although repetitive transcranial magnetic stimulation (‘TMS’) is becoming a gold standard treatment for pharmacoresistant depression, we lack neural target biomarkers for identifying who is most likely to respond to TMS and why. To address this gap in knowledge we evaluate neural targets defined by activation and functional connectivity of the dorsolateral prefrontal cortex-anchored cognitive control circuit, regions of the default mode network and attention circuit, and interactions with the subgenual anterior cingulate. We evaluate whether these targets and interactions between them change in a dose-dependent manner, whether changes in these neural targets correspond to changes in cognitive behavioral performance, and whether baseline and early change in neural target and cognitive behavioral performance predict subsequent symptom severity, suicidality, and quality of life outcomes. This study is designed as a pragmatic, mechanistic trial partnering with the National Clinical TMS Program of the Veteran’s Health Administration.

Methods

Target enrollment consists of 100 veterans with pharmacoresistant Major Depressive Disorder (MDD). All veterans will receive a clinical course of TMS and will be assessed at ‘baseline’ pre-TMS commencement, ‘first week’ after initiation of TMS (targeting five sessions) and ‘post-treatment’ at the completion of TMS (targeting 30 sessions). Veterans will be assessed using functional magnetic resonance imaging (fMRI), a cognitive behavioral performance battery, and established questionnaires. Multivariate linear mixed models will be used to assess whether neural targets change with TMS as a function of dose (Aim 1), whether extent and change of neural target relates to and predicts extent of behavioral performance (Aim 3), and whether extent of neural target change predicts improvement in symptom severity, suicidality, and quality of life (Aim 3). For all three aims, we will also assess the contribution of baseline moderators such as biological sex and age.

Discussion

To our knowledge, our study will be the first pragmatic, mechanistic observational trial to use fMRI imaging and cognitive-behavioral performance as biomarkers of TMS treatment response in pharmacoresistant MDD. The results of this trial will allow providers to select suitable candidates for TMS treatment and better predict treatment response by assessing circuit connectivity and cognitive-behavioral performance at baseline and during early treatment.

Trial registration

ClinicalTrials.gov NCT04663481, December 5th, 2020, retrospectively registered. The first veteran was enrolled October 30th, 2020.
Metacognitive training: a useful complement to community-based rehabilitation for schizophrenia patients in China
Authors: Chen Qi , Sang Yueyun , Ren Lifang , Wu Jinping , Chen Yajun , Zheng Menglei , Bian Guolin , Sun Hanying
Published: January 2021

Background

The traditional general practitioner-based model (community-based rehabilitation [CBR]) for Chinese schizophrenia patients lacks sufficient content, usefulness, and theoretical basis for rehabilitation. Based on previous research, we postulate that Metacognitive Training (MCT) is effective in the community for schizophrenic patients.

Method

A randomized controlled, assessor-blinded trial was conducted. A total of 124 schizophrenia patients were recruited from Ningbo China and were randomly assigned to an intervention or a control group. A general practitioner (GP) training plan was carried out before intervention. Intervention and control groups received two CBR follow-ups once a month, while the intervention group, received an additional eight once-a-in-week session of MCT. The Positive and Negative Syndrome Scale (PANSS), and the Psychotic Symptom Rating Scales (PSYRATS) were the primary outcome instruments, while the Quality of Life Scale (SQLS) was the secondary outcome instrument.

Results

In the post-treatment between-groups assessment, the patients in the intervention group showed significantly more reductions on PSYRATS delusions, PSYRATS total, PANSS P6, PANSS core delusions, PANSS positive, PANSS negative, PANSS general and PANSS total, and a significant improvement in SQLS psychosocial aspect.

Conclusions

The study provides preliminary evidence for the usefulness of MCT as a complementary measure for community-based rehabilitation of schizophrenia patients.

Trial registration

ISRCTN, ISRCTN17333276. Registered 09 August 2020 - Retrospectively registered.
A randomized controlled trial of long-acting muscarinic antagonist and long-acting β2 agonist fixed-dose combinations in patients with chronic obstructive pulmonary disease
Authors: Muraki Masato , Kunita Yuki , Shirahase Ken , Yamazaki Ryo , Hanada Soichiro , Sawaguchi Hirochiyo , Tohda Yuji
Published: January 2021

Background

In chronic obstructive pulmonary disease (COPD) patients, combination treatment with long-acting muscarinic antagonist (LAMA) and long-acting β2 agonist (LABA) increases forced expiratory volume in one second and reduces symptoms compared to monotherapy. In Japan, three different once-daily fixed-dose combinations (FDCs) have been prescribed since 2015, although a direct comparison of these FDCs has never been performed. The objective of the present study was to compare the effectiveness, preference, and safety of three LAMA/LABA FDCs—glycopyrronium/indacaterol (Gly/Ind), umeclidinium/vilanterol (Ume/Vil), and tiotropium/olodaterol (Tio/Olo)—in patients with COPD.

Methods

We enrolled 75 COPD outpatients (male:female ratio, 69:6; 77.4 ± 6.9 years). A prospective, randomized, crossover study was conducted on three groups using three FDCs: Gly/Ind; Ume/Vil; and Tio/Olo. Each medication was administered for 4 weeks before crossover (total 12 weeks). After each FDC administration, a respiratory function test and questionnaire survey were conducted. A comparative questionnaire survey of all three LAMA/LABA FDCs was conducted after 12 weeks (following administration of final FDC).

Results

No significant differences in COPD Assessment Test or modified Medical Research Council dyspnea questionnaire were reported in the surveys completed after each FDC administration; no significant differences in spirometric items were observed. In the final comparative questionnaire survey, patients reported better actual feeling of being able to inhale following Gly/Ind administration compared with Tio/Olo, although no significant differences in adverse events or other evaluations were reported.

Conclusions

The three LAMA/LABA FDCs administered to COPD patients show similar effects and safety, although some minor individual preference was reported.

Trial registration This study retrospectively registered with the University Hospital Medical Information Network Clinical Trials Registry (number UMIN000041342, registered on August 6, 2020).
Factors associated with failure of bony union after conservative treatment of acute cases of unilateral lumbar spondylolysis
Authors: Tatsumura Masaki , Gamada Hisanori , Okuwaki Shun , Eto Fumihiko , Nagashima Katsuya , Ogawa Takeshi , Mammoto Takeo , Hirano Atsushi , Koda Masao , Yamazaki Masashi
Published: January 2021

Background

If bone union is expected, conservative treatment is generally selected for lumbar spondylolysis. However, sometimes conservative treatments are unsuccessful. We sought to determine the factors associated with failure of bony union in acute unilateral lumbar spondylolysis with bone marrow edema including contralateral pseudarthrosis.

Methods

This study targeted unilateral lumbar spondylolysis treated conservatively in high school or younger students. Conservative therapy was continued until the bone marrow edema disappeared on MRI and bone union was investigated by CT. We conducted a univariate analysis of sex, age, pathological stage, lesion level complicating the contralateral bone defect, lesion level, and intercurrent spina bifida occulta, and variables with p < 0.1 were considered in a logistic regression analysis. An item with p < 0.05 was defined as a factor associated with failure of bony union.

Results

We found 92 cases of unilateral spondylolysis with bone marrow edema and 66 cases were successfully treated conservatively. Failure of bony union in unilateral lumbar spondylolysis with bone marrow edema was associated with progressive pathological stage (p = 0.004), contralateral pseudarthrosis (p < 0.001), and L5 lesion level (p = 0.002). The odds ratio was 20.0 (95% CI 3.0–193.9) for progressive pathological stage, 78.8 (95% CI 13–846) for contralateral pseudarthrosis, and 175 (95% CI 8.5–8192) for L5 lesion level.

Conclusions

Conservative therapy aiming at bony union is contraindicated in cases of acute unilateral spondylolysis when the pathological stage is progressive, the lesion level is L5, or there is contralateral pseudarthrotic spondylolysis.
Eat Healthy, Be Active Community Workshops implemented with rural Hispanic women
Authors: Sanchez Janeth I. , Briant Katherine J. , Wu-Georges Samantha , Gonzalez Virginia , Galvan Avigail , Cole Sara , Thompson Beti
Published: January 2021

Background

In the U.S., obesity disproportionately affects some racial/ethnic groups more than others; 42.5% of Hispanic adults are obese, compared to 32.6% of non-Hispanic whites (NHW). Research also shows that Mexican American women are 40% more likely to be overweight, as compared to NHW women. With high obesity rates among Hispanics, improving healthier lifestyle practices is an important step for reducing health disparities. The Eat Healthy, Be Active (EHBA) community workshops were developed to assist individuals in translating national nutrition and physical activity recommendations into action.Promotora-ledEHBA workshops could be used to promote obesity-related health behavior lifestyle changes among Hispanics.

Methods

Hispanic women from rural communities in Washington state were recruited to participate in a six-weekPromotora-led workshop series. This pilot study used a pre- and post-test study design to examine differences in healthy lifestyle knowledge and practices.

Results

A total of 49 Hispanic women participated in the workshops, of whom 45% were obese. Six-weeks after implementation of EHBA, women had improvements in healthy lifestyle practices, including an increase in nutrition label literacy, decrease in consumption of food eaten in restaurants, and an increase in the number of times a woman performed physical activity long enough to make them sweat.

Conclusion

The findings from this pilot study indicate that delivering EHBA workshops throughpromotorasis a feasible culturally relevant approach to promoting healthier lifestyle practices among Hispanic women. Further, focusing on females, who do the food shopping and preparation in their homes, may help increase awareness among whole families.
Clinical relevance of routine transvaginal ultrasound in women referred with pelvic organ prolapse
Authors: Pedersen Lone , Glavind-Kristensen Marianne , Bor Pinar
Published: January 2021

Background

The aim of this study was to investigate the prevalence of incidental findings on transvaginal ultrasound scan in women referred with pelvic organ prolapse by a general practitioner and to investigate which further examinations and treatments were performed as a result of these findings.

Methods

This was a retrospective cohort study that investigated women with pelvic organ prolapse referred to the outpatient urogynaecological clinics at Randers Regional Hospital and Aarhus University Hospital, Denmark.

Results

A total of 521 women were included and all of them were examined with a routine transvaginal ultrasound scan and a gynaecological examination. Prolapse symptoms only and no specific indication for transvaginal ultrasound scan were seen in 507 women (97.3%), while 14 women (2.7%) received scans on indication. Among the latter women, five (35.7%) had cancer. In the women with solely prolapse symptoms, 59 (11.6%) had incidental findings on transvaginal ultrasound scan, but all were benign. However, two patients were later diagnosed with cancer unrelated to the initial ultrasound findings. The treatment was extended with further examinations not related to POP in 19 of the women (32.2%) with incidental ultrasound findings.

Conclusion

The prevalence of incidental ultrasound findings was not high in the women referred with pelvic organ prolapse and no additional symptoms, and all these findings were benign. However, it should be considered that these findings resulted in further investigations and changes to the patients’ initial treatment plans. A meticulous anamnesis and digital vaginal examination are crucial to rule out the need for vaginal ultrasound.
Factors associated with a clinically relevant reduction in menopausal symptoms of a standardized acupuncture approach for women with bothersome menopausal symptoms
Authors: Waldorff Frans Boch , Bang Christine Winther , Siersma Volkert , Brodersen John , Lund Kamma Sundgaard
Published: January 2021

Background

Little is known about factors associated with a clinically relevant reduction in menopausal symptoms through a brief acupuncture approach for women with moderate-to-severe menopausal symptoms.

Methods

Post hoc analysis of a randomized controlled trial where participants were allocated to early versus late standardized acupuncture. Both the early group and the late group are included in this study. The late group got an identical intervention parallel staged by 6 weeks. By means of the relative importance, the effect was evaluated for both early versus late women with a 6-week follow-up. We included four symptom subscales from the validated MenoScores Questionnaire: hot flushes, day and night sweats, general sweating, menopausal-specific sleeping problems, as well as an overall score, which is the sum of the four outcomes in the analysis.

Results

67 women with moderate to severe menopausal symptoms were included of whom 52 (77.6%) experienced a clinically relevant reduction in any of the four surveyed symptom subscales or overall score. 48 (71.6%) women experienced a clinically relevant reduction in any of the vasomotor symptom subscales: hot flushes, day and night sweats, general sweating.

Women with vocational education were most likely to experience improvement compared to women with higher education. Beyond education, other factors of some importance for a clinically relevant reduction were no alcohol consumption, two or more births and urinary incontinence.

Conclusions

Level of education was the most consistent factor associated with improvement. Beyond education, other factors of some importance were no alcohol consumption, two or more births and urinary incontinence.

Trial registration

This study was registered in ClinicalTrials.gov at April 21, 2016. The registration number is NCT02746497.