bluuebunny/crossref_metadata_2025 huggingface dataset:
Fibula Nail Outcomes in Soft Tissue Compromised Ankle Fractures
Authors: Ahmed Maryam , Barrie Andrew , Kozhikunnath Arun , Thimmegowda Abliash , Ho Sebastian , Kunasingam Kumar , Guryel Enis ,   MEFNO Collaborative
Published: November 2022

Category:

Trauma; Ankle

Introduction/Purpose:

Lower limb fractures account for a third of all orthopaedic injuries of which 22% are ankle fractures. With a gradual move toward minimally invasive surgery for ankle fractures, intramedullary implants have evolved over the years to dedicated fixation devices for fibula fractures. The aim of this study was to determine the clinical outcomes following fibula nail fixation and to identify the indication for the use of fibula nails in ankle fractures.

Methods:

A retrospective study of adult patients from 2 major trauma centers (MTCs) and 9 trauma units (TUs) who underwent fibula nail fixation for AO/OTA 44 fractures between January 1, 2018, and October 31, 2020 was conducted. Fracture were classified based on the Weber or AO/OTA classification. Operative fixation was performed using the Acumed Fibula Rod (Acumend Fibula Rod System, Hilsboro, OR, USA) and a minimally invasive direct approach to the lateral malleolsus with radiography-guided percutaneous screw insertion was used in all patients. The outcome measures included infection, metalwork complications, nonunion or malunion, time to union, and length of inpatient hospital stay.

Results:

Ninety-five patients were included, with a mean age of 66 years; 57.9% of patients were female. The average body mass index was 30. Sixty-nine patients (72.6%) sustained a Weber B and 24 (27.4%) sustained a Weber C fracture. In addition, 26.3% were open fractures and all patients had soft tissue compromise affecting the lateral malleolus. The calculated infection rate for fibula nail was 4.2% and metalwork complication rate was 5.2%. The nonunion and malunion rate was 8.4% and rate of removal of hardware was 2.1%. The average time to union was 12.5 weeks, and length of inpatient stay was 9.4 days (SD 10).

Conclusion:

This is the largest multicenter to date which demonstrates that use of a fibula nail appears to be a safe approach to treating patients who have a physiologically higher risk of surgery, poor skin condition, and a complex fracture pattern. The risks of wound and metalwork complicatons appear relatively low following fibula nail fixation in comparison to ankle ORIF's.
Do Concomitant Posterior Malleolus Fractures Affect Mid-Term Functional Outcomes in Tibial Shaft Fractures?
Authors: Bastias Gonzalo F. , Ignacio Quezada Morales Jose , Gutierrez Paulina , Diaz Felipe G. , Melo Rodrigo , Cuchacovich Mikenberg Natalio R. , Munoz Gerardo , Filippi Jorge
Published: November 2022

Category:

Trauma; Ankle

Introduction/Purpose:

The association between diaphyseal tibial fractures and posterior malleolus fracture has been reported between 4 to 25% of cases. Early diagnosis requires a high level of suspicion and may change the surgical strategy. To our knowledge, no studies had compared the functional and quality of life results of tibial fractures with and without posterior malleolus extension.

Methods:

A retrospective comparative study including patients sustaining tibial shaft fractures classified by AO type 42, 43A, and 43B1.1, with a minimum one-year follow-up. Exclusion criteria included open fractures, pathological bone fractures and patients with a previous history of ipsilateral bone injury. Patients were divided into two groups, tibial shaft injuries with posterior malleolus fracture (PM) and fractures without posterior malleolus fracture (WPM) diagnosed using computed tomography (CT) preoperatively. The posterior malleolus fracture was fixed before the tibial fracture, either with 1 or 2 percutaneous anteroposterior or posteroanterior screws. Postoperative CT was used to assess the quality of reduction in all patients. Functional and quality of life results were evaluated using the Lower Extremity Function Score (LEFS), visual pain analog scale (VAS), and Short Form (SF12). We compared times of return to work/sports, complications and additional procedures during follow-up. Shapiro-Wilk test and Student t-test were used for statistical analysis.

Results:

Twenty patients in the PM group and 22 in the WPM group were included with a mean follow-up of 43 months (R:8-43). Groups were demographically comparable, with an average age of 47.6 and 43.3 years (p:0.34), respectively. All fractures healed, CT showed an anatomical articular reduction in all patients. Tibial shaft fracture was treated with intramedullary nailing in 15 patients of the WPM group and seven patients in the PM group. Percutaneous medial plating was used in the rest of the cases. At final follow-up, LEFS score in the PM group was 73.6 vs. 70.6 in the WPM group, with no significant difference (p:0.23). There were also no significant differences in VAS scale, time of return to work and sports in both groups. The PM group scored better in physical (p:0,02) and mental (p:0,01) SF-12.

Conclusion:

In this series of closed tibial shaft fractures, the presence of a posterior malleolus fracture did not affect functional results, time to return to work, or return to sports. Moreover, the SF-12 was superior in the PM group. All patients in the PM group had a timely diagnosis and anatomical reduction, which probably influenced the good clinical results. There were no additional procedures or degenerative complications in the PM group.
A Scoping Survey of BOFAS Membership: What are the Perceived Barriers and Facilitators of Day- Case Surgery for Major Foot and Ankle Procedures in the UK?
Authors: Berry Amber L. , Houchen-Wolloff Linzy , Mangwani Jitendra , Clayton Robert A.
Published: November 2022

Category:

Ankle

Introduction/Purpose:

Recent advances in minimally invasive surgery and improved post-operative pain management make it possible to perform major foot/ ankle operations as day-case. This could have significant impact on length of stay, saving resources and is in keeping with government policy. However there is no consensus of barriers reducing foot/ankle operations being performed as day-case.The aim of this survey was to scope the practice of UK foot and ankle surgeons in terms of perceived barriers and facilitators to performing day-case surgery for major foot/ankle procedures.

Methods:

An online survey (19 questions) was sent to UK foot and ankle surgeons via BOFAS (British Orthopaedic Foot & Ankle Society) membership list in August 2021. Major foot/ankle procedures are defined as surgery that is usually performed as an inpatient and day-case as same day discharge, with day surgery as the intended treatment pathway.

Results:

A total of 132 respondents: 80% working in Acute NHS Trusts. 78% of respondents thought that more procedures could be performed as day-case at their centre (currently 45% of respondents perform less than 100 day-case surgeries per year for these procedures). The top 2 perceived barriers to performing more major foot and ankle procedures as day-case were: no physiotherapy provision pre/ post-operatively 23%, no out of hours support for patients 21%.

Conclusion:

There is consensus among surgeons to do more major foot/ ankle procedures as day-case. Despite theoretical concerns about post-operative pain and satisfaction this was only measured by a third of those surveyed. Out of hours support and physiotherapy input pre/post-op were perceived as the main barriers to increasing the number day-case procedures. There is a need for nationally agreed protocols to optimise the delivery of care for this patient group and to scope the provision of physiotherapy pre/post-operatively at sites where this is a perceived barrier.
Does a 1st Metatarsophalangeal Fusion in a Patient with Pes Planus Improve the Pes Planus Deformity? A Retrospective Case Series
Authors: Chapman James , Jenkinson Hollie , Dalal Neel , Airey Grace L. , Molloy Andrew P. , Singh Anjani K. , Sirikonda Siva , Mason Lyndon W.
Published: November 2022

Category:

Midfoot/Forefoot; Bunion

Introduction/Purpose:

A pes planus deformity is a pathology relating to the loss of normality of the complex interaction of the bones and joints of the foot resulting in a flattening of the medial longitudinal arch with or without abduction of the midfoot. The distal aspect of the medial longitudinal arch can be a feature of the deformity. The fusion of the 1st metatarsophalangeal joint (MTPJ) is a common operation. In patients with concomitant pes planus deformity, it is unknown if reducing and stabilising the distal aspect of the medial ray through a 1st MTPJ fusion can subsequently improve the pes planus deformity. We sought to analyse the pes planus deformity pre and post 1st MTPJ fusion with the null hypothesis that there was no difference.

Methods:

We identified patients who had undergone 1st MTPJ fusion using our electronic database from January 2011 to October 2021. To meet the inclusion criteria, cases required pre- and post-operative weightbearing plain radiographs, with a Meary's angle of >4 degrees on pre-operative imaging. Routine pes planus measurements were undertaken by 2 independent observers. Pre- and post-operative measurements were tested for significant change using Wilcoxon Signed Rank Test or Paired T-Test depending on the normality testing of the data. Routine demographic data was also collected. Data was analysed using IBM SPSS v.27.

Results:

Following radiographic analysis, 25 feet fitted the inclusion criteria. The mean patient age was 63 years. There was no pre-operative correlation between Meary's angle and the hallux valgus angle (Kendall's tau p=.441). Pre-operatively, Meary's line broke at the talo-navicular and navicular-cuneiform joints in 12 cases each; the remaining case broke at the tarsal-metatarsal joint. A statistically significant improvement between the pre- and post-operative measurements was identified in Meary's angle, calcaneal pitch angle, talo-navicular coverage angle, intermetatarsal angle and talo-navicular angle (see table). Significant changes were also noted in the medial cuneiform height (mean increase of 2.74mm; p=.022). A post-operative Meary's angle of <4°was only achieved in 4/25 (16%) of cases. Of the remaining 21 cases, the point at which Meary's line broke moved proximally one joint in 4 and distally one joint in 3 cases; it remained at the same joint in 14 cases.

Conclusion:

Our results suggest that 1st MTPJ fusion improves axial alignment of the foot as well as reducing Meary's angle by a statistically significant amount, although diagnostic criteria for pes planus remained in most cases.
Treatment Strategy for Posterior Malleolar Fractures: Different Operative Strategies are Needed for Each Morphological Type
Authors: Choi Seung-myung
Published: November 2022

Category:

Trauma; Ankle

Introduction/Purpose:

The operative indication for posterior malleolar fracture (PMF) remains controversial. This study aimed to assess the midterm outcomes of PMF treatment for developing a treatment strategy for each morphological type.

Methods:

In this retrospective analysis, 472 patients undergoing operative treatment for an unstable ankle fracture involving PMF were included after at least 3 years of follow-up. PMFs were classified by fracture morphology, according to the Haraguchi classification, and the outcomes of the groups wherein PMF was either fixed through a posterior approach or unfixed were compared (PMF fixation and nonfixation groups, respectively). The radiographic evaluation included the development of posttraumatic osteoarthritis. The clinical evaluation included the AOFAS score and postoperative complications.

Results:

The mean patient age was 45.8 years, and the mean follow-up was 51 months. The intercalary fragment (ICF) was more frequently observed for type 1 PMFs preoperatively in the fixation group (P < .001). The postoperative outcomes of the two groups showed no significant differences. For type 2 PMFs, the radiological and clinical outcomes of the PMF fixation group were statistically superior to those of the nonfixation group (both P < .001). Overall, postoperative complications occurred more frequently in the fixation group (40.4% vs. 24.4%, P < .001). Compared with the patients with and without syndesmotic stabilization in type 3 PMF, no significant differences in the postoperative outcomes were observed. The radiological and clinical parameters showed no significant intergroup differences, including the postoperative complications when comparing PMF fixation using a plate and posterior screw.

Conclusion:

Different treatment strategies are required for each PMF morphological subtype. The operative treatment might not lead to favorable outcomes for all PMF subtypes: potential indicators for operation are the presence of an ICF preventing the reduction of the posterior malleolus in type 1 and all type 2 PMFs.
Management, Complications, and Radiographic Follow-Up of Total Ankle Arthroplasty in the Setting of Talar Bone Loss
Authors: Cornelius Canon C. , Duncan Leslie A. , Wetzig Alex , Gauvain Taggart T. , Greaser Michael C. , McGarvey William C.
Published: November 2022

Category:

Ankle Arthritis; Ankle

Introduction/Purpose:

As the incidence and indications for total ankle arthroplasty (TAA) continue to expand the need to better understand the properative risk factors becomes increasingly important. Talar bone loss whether from avascular necrosis, osteoarthritis, or post traumatic arthritis can be a challenging problem to deal with in TAA. The aim of this study is to report the operative characteristics, clinical complications, and radiographic changes in patients’ status post TAA in the setting of talar bone loss.

Methods:

A retrospective review using CPT codes for four surgeons over a three year period at an academic institution was performed. A single surgeon reviewed the immediate preoperative plain radiographs for 200 consecutive patients captured by the CPT codes for talar bone loss. The mortise and lateral views were used to measure the lesions and an example measurement is shown in Figure 1. 38 patients were identified as having talar bone defects of greater than 20 percent when the two measurements were averaged and the depth of the penetrance was categorized by dividing the talus into thirds. A chart review was then performed that included demographic information, additional procedures at the primary procedure, use of adjuvants, reoperation rates and, subsidence rates.

Results:

The average patient age and follow up were 59 years and 23 months respectively. The average defect was 44 percent with a range of 20 to 100 percent. 16 out of 38 defects were contained to the upper third of the talus and 17 had a corresponding tibial lesion. Overall the reoperation rate was 34 percent with the plurality being I&Ds of both superficial and deep infections. Two patients ended up with below knee amputations. Subsidence of talar components occurred at a rate of 43 percent with about half of these having a reoperation. 68 percent of the patients had additional procedures such as tendo achilles lengthening, lateral ligament reconstruction, and various osteotomies. 35 percent of talar components were cemented and there was an intra operative complication rate of 14 percent with the most common being intra operative fracture.

Conclusion:

While TAA for patients with talar bone loss can be a good option for both the patient and surgeon it has a higher complication rate in our series than previously described. Careful surgical strategy including implant choice is paramount and the need for additional procedures should be considered.
Epidemiology of Lower Leg Fractures at a Colorado Ski Resort
Authors: Hunt Kenneth J. , Cogburn Jennifer , Pierpoint Lauren , Kordell Jennifer R. , Saeedi Anahita , Spittler Jack , Khodaee Morteza
Published: November 2022

Category:

Trauma; Ankle; Sports

Introduction/Purpose:

Lower extremity fractures are relatively common among winter sports participants. The purpose of this study is to evaluate the demographics, injury mechanisms and environmental features among patients evaluated for lower leg fractures at a high-volume Colorado ski resort during five consecutive ski seasons.

Methods:

We conducted a retrospective descriptive analysis of patients with lower leg fractures at the Denver Health Winter Park Medical Center during the 2012/13 to 2016/17 ski seasons. We included all fractures below the knee (excluding tibial plateau and isolated fibular head fractures) sustained by skiing or snowboarding. Chart review was performed on the patient cohort, confirming diagnosis and evaluating factors associated with these fractures.

Results:

There were 346 lower leg, ankle, and/or foot fractures (5.4% of all clinic visits) during the study period. The average age was 33.1 years (range 4-74) with the majority being male (60.7%) and mainly as a result of skiing (84.7%). The majority of fractures were sustained among skiers and snowboarders who self-identified as beginner or intermediate skill level (64.8%), and on easy (green) or intermediate (blue) runs (64.9%). The most common fractures sustained were complete tibia-fibula fractures (30.9%) and lateral malleolus fractures (27.5%). More than half (57.0%) of complete tibia-fibula fractures were classified and boot top (mid- shaft just above the ski boot) fractures. The most common type of lateral malleolus fractures was Danis-Weber B (72.0%) with only 5.4% being Weber C fractures. Foot fractures were rare with only 12 total cases (3.5%).

Conclusion:

Skiers are much more likely to sustain lower leg fractures compared to snowboarders. Men were much more likely than women to sustain lower leg fractures. Most fractures occurred in mild or moderately difficult ski runs relative to advanced runs. Fractures appear to be more common with advancing age. Complete tibia-fibula fractures were the most common fractures sustained in all riders with lateral malleolus fractures being the second most common. Foot fractures are very rare in this population. Given the frequency of these injuries, additional education around prevention may be warranted.
Horizontal Cleavage Meniscus Tear Repaired Using a Cerclage Technique
Authors: MacLean Ian S. , Diduch David R.
Published: November 2022

Background:

Horizontal meniscal cleavage tears often occur in older individuals and have a degenerative component. Commonly, these are managed with partial meniscectomy. However, this results in significantly decreased contact area and increased peek contact forces. Arthroscopic repair has shown comparable results with repairs of other tear types.

Indications:

Cerclage repair is performed for a horizontal cleavage tear in individuals without significant arthritis and in whom partial meniscectomy would remove an unacceptably large portion of meniscal tissue.

Technique Description:

Using standard arthroscopy portals, a self-retrieving suture passing device is used to pass a #0 high-strength suture through the periphery of the meniscus. Arthroscopic knots are tied on the superior surface of the meniscus and pushed as far posteriorly as possible. A small 1-cm incision is made just through skin on the proximal, posteromedial border of the tibia. Through this a spinal needle is placed percutaneously to pass a Chia into the joint just posterior to the knot. A curved spinal needle from an outside-in meniscal repair kit may be used as this provides a better trajectory to tears closer to the root attachment. The Chia and suture limbs are retrieved out the front of the knee, and then the suture tails are shuttled out the back of the knee. This is repeated until the repair is complete. The suture limbs are then cut below skin.

Results:

After arthroscopic all-inside repair of horizontal cleavage tears, patients do well. Outcomes are similar to repairs of other meniscal tear types. In all, 80% of patients are satisfied with their results, and there is an 11% to 12% failure rate which is comparable to other types of tear repairs.

Discussion:

All-inside cerclage repair should be considered for individuals sustaining a horizontal cleavage tear. This preserves meniscal tissue compared to partial meniscectomy and yields good healing rates and outcomes. The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.
Low toxicity and excellent outcomes in patients with DLBCL without residual lymphoma at the time of CD19 CAR T-cell therapy
Authors: Wudhikarn Kitsada , Tomas Ana Alarcon , Flynn Jessica R. , Devlin Sean M. , Brower Jamie , Bachanova Veronika , Nastoupil Loretta J. , McGuirk Joseph P. , Maziarz Richard T. , Oluwole Olalekan O. , Schuster Stephen J. , Porter David L. , Bishop Michael R. , Riedell Peter A. , Perales Miguel-Angel
Published: November 2022

CD19 chimeric antigen receptor (CAR) T-cell therapy represents a breakthrough for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), inducing sustained remissions in these patients. However, CAR T cells can result in significant toxicities. Preinfusion disease burden is associated with toxicities and outcomes after CAR T-cell therapy. We identified 33 patients with R/R DLBCL treated at 8 academic centers who had no detectable disease at the time of CAR T-cell therapy. The median time from leukapheresis to CAR T-cell infusion was 48 (19-193) days. Nine patients received axicabtagene ciloleucel, and 24 received tisagenlecleucel. There was no severe (grade ≥3) cytokine release syndrome, and only 1 patient developed severe neurotoxicity (grade 4). After a median follow-up of 16 months, 13 patients relapsed (39.4%) and 6 died (18.1%). One-year event-free survival and overall survival were 59.6% and 81.3%, respectively. Our findings suggest that, in patients with R/R DLBCL who have an indication for CAR T-cell therapy, treating patients in complete remission at the time of infusion is feasible, safe, and associated with favorable disease control. Further exploration in a larger clinical trial setting is warranted.
Respective roles of non-pharmaceutical interventions in bronchiolitis outbreaks: an interrupted time-series analysis based on a multinational surveillance system
Authors: Lenglart Lea , Ouldali Naim , Honeyford Kate , Bognar Zsolt , Bressan Silvia , Buonsenso Danilo , Da Dalt Liviana , De Tisham , Farrugia Ruth , Maconochie Ian K. , Moll Henriette A. , Oostenbrink Rianne , Parri Niccolo , Roland Damian , Rose Katy , Akyüz Özkan Esra , Angoulvant François , Aupiais Camille , Barber Clarissa , Barrett Michael , Basmaci Romain , Castanhinha Susana , Chiaretti Antonio , Durnin Sheena , Fitzpatrick Patrick , Fodor Laszlo , Gomez Borja , Greber-Platzer Susanne , Guedj Romain , Hey Florian , Jankauskaite Lina , Kohlfuerst Daniela , Mascarenhas Ines , Musolino Anna Maria , Pučuka Zanda , Reis Sofia , Rybak Alexis , Salamon Petra , Schaffert Matthias , Shahar-Nissan Keren , Supino Maria Chiara , Teksam Ozlem , Turan Caner , Velasco Roberto , Nijman Ruud G. , Titomanlio Luigi ,   the EPISODES Study Group
Published: November 2022

Background

Bronchiolitis is a major source of morbimortality among young children worldwide. Non-pharmaceutical interventions (NPIs) implemented to reduce the spread of severe acute respiratory syndrome coronavirus 2 may have had an important impact on bronchiolitis outbreaks, as well as major societal consequences. Discriminating between their respective impacts would help define optimal public health strategies against bronchiolitis. We aimed to assess the respective impact of each NPI on bronchiolitis outbreaks in 14 European countries.

Methods

We conducted a quasi-experimental interrupted time-series analysis based on a multicentre international study. All children diagnosed with bronchiolitis presenting to the paediatric emergency department of one of 27 centres from January 2018 to March 2021 were included. We assessed the association between each NPI and change in the bronchiolitis trend over time by seasonally adjusted multivariable quasi-Poisson regression modelling.

Results

In total, 42 916 children were included. We observed an overall cumulative 78% (95% CI −100– −54%; p<0.0001) reduction in bronchiolitis cases following NPI implementation. The decrease varied between countries from −97% (95% CI −100– −47%; p=0.0005) to −36% (95% CI −79–7%; p=0.105). Full lockdown (incidence rate ratio (IRR) 0.21 (95% CI 0.14–0.30); p<0.001), secondary school closure (IRR 0.33 (95% CI 0.20–0.52); p<0.0001), wearing a mask indoors (IRR 0.49 (95% CI 0.25–0.94); p=0.034) and teleworking (IRR 0.55 (95% CI 0.31–0.97); p=0.038) were independently associated with reducing bronchiolitis.

Conclusions

Several NPIs were associated with a reduction of bronchiolitis outbreaks, including full lockdown, school closure, teleworking and facial masking. Some of these public health interventions may be considered to further reduce the global burden of bronchiolitis.
Single-cell RNA-seq uncovers cellular heterogeneity and provides a signature for paediatric sleep apnoea
Authors: Cortese Rene , Adams Taylor S. , Cataldo Kylie H. , Hummel Justin , Kaminski Naftali , Kheirandish-Gozal Leila , Gozal David
Published: November 2022

Background

Obstructive sleep apnoea (OSA) is a highly prevalent disease and a major cause of systemic inflammation leading to neurocognitive, behavioural, metabolic and cardiovascular dysfunction in children and adults. However, the impact of OSA on the heterogeneity of circulating immune cells remains to be determined.

Methods

We applied single-cell transcriptomics analysis (scRNA-seq) to identify OSA-induced changes in transcriptional landscape in peripheral blood mononuclear cell (PBMC) composition, which uncovered severity-dependent differences in several cell lineages. Furthermore, a machine-learning approach was used to combine scRNAs-seq cell-specific markers with those differentially expressed in OSA.

Results

scRNA-seq demonstrated OSA-induced heterogeneity in cellular composition and enabled the identification of previously undescribed cell types in PBMCs. We identified a molecular signature consisting of 32 genes, which distinguished OSA patients from various controls with high precision (area under the curve 0.96) and accuracy (93% positive predictive value and 95% negative predictive value) in an independent PBMC bulk RNA expression dataset.

Conclusion

OSA deregulates systemic immune function and displays a molecular signature that can be assessed in standard cellular RNA without the need for pre-analytical cell separation, thereby making the assay amenable to application in a molecular diagnostic setting.
Nontuberculous mycobacterial infections during cancer therapy with immune checkpoint inhibitors: a systematic review
Authors: Lombardi Andrea , Gramegna Andrea , Ori Margherita , Azzarà Cecilia , Blasi Francesco , Gori Andrea
Published: November 2022

Immune checkpoint inhibitors (ICIs) are drugs growingly employed in the treatment of cancers, but there are still uncertainties about their possible role in the risk of developing nontuberculous mycobacteria (NTM) infections. To understand this, we performed a systematic review of the literature including studies published between 20 June 2012 and 20 June 2022 which described the occurrence of NTM infections among patients treated with ICIs. Overall, we included seven studies describing nine patients with NTM infection occurring during ICIs therapy.

NTM infections occurring during ICIs therapy are mainly caused by germs belonging to theMycobacterium avium complex, involve primarily the lungs, on average 1 year after the start of treatment, and are not associated with immunosuppressive treatments.
AV-101, a novel inhaled dry-powder formulation of imatinib, in healthy adult participants: a phase 1 single and multiple ascending dose study
Authors: Gillies Hunter , Niven Ralph , Dake Benjamin T. , Chakinala Murali M. , Feldman Jeremy P. , Hill Nicholas S. , Hoeper Marius M. , Humbert Marc , McLaughlin Vallerie V. , Kankam Martin
Published: November 2022

Background

Oral imatinib has been shown to be effective, but poorly tolerated, in patients with advanced pulmonary arterial hypertension (PAH). To maintain efficacy while improving tolerability, AV-101, a dry powder inhaled formulation of imatinib, was developed to deliver imatinib directly to the lungs.

Methods

This phase 1, placebo-controlled, randomised single ascending dose (SAD) and multiple ascending dose (MAD) study evaluated the safety/tolerability and pharmacokinetics of AV-101 in healthy adults. The SAD study included five AV-101 cohorts (1 mg, 3 mg, 10 mg, 30 mg, 90 mg) and placebo, and a single-dose oral imatinib 400-mg cohort. The MAD study included three AV-101 cohorts (10 mg, 30 mg, 90 mg) and placebo; dosing occurred twice daily for 7 days.

Results

82 participants (SAD n=48, MAD n=34) were enrolled. For the SAD study, peak plasma concentrations of imatinib occurred within 3 h of dosing with lower systemic exposure compared to oral imatinib (p<0.001). For the MAD study, systemic exposure of imatinib was higher after multiple doses of AV-101 compared to a single dose, but steady-state plasma concentrations were lower for the highest AV-101 cohort (90 mg) compared to simulated steady-state oral imatinib at day 7 (p=0.0002). Across AV-101 MAD dose cohorts, the most common treatment-emergent adverse events were cough (n=7, 27%) and headache (n=4, 15%).

Conclusions

AV-101 was well tolerated in healthy adults, and targeted doses of AV-101 significantly reduced the systemic exposure of imatinib compared with oral imatinib. An ongoing phase 2b/phase 3 study (IMPAHCT; clinicaltrials.gov identifierNCT05036135) will evaluate the safety/tolerability and clinical benefit of AV-101 for PAH.
Molecular assessment of mycobacterial burden in the treatment of nontuberculous mycobacterial disease
Authors: Ellis Huw C. , Moffatt Miriam F. , Churchward Colin , Cuthbertson Leah , Cookson William O.C. , Loebinger Michael R.
Published: November 2022

Introduction

Nontuberculous pulmonary disease causes significant morbidity and mortality. Efforts to tackle infections are hampered by the lack of reliable biomarkers for diagnosis, assessment and prognostication. The aim of this study was to develop molecular assays capable of identifying and quantifying multiple nontuberculous mycobacterial (NTM) species and to examine their utility in following individual patients’ clinical courses.

Methods

DNA was extracted from 410 sputum samples obtained longitudinally from a cohort of 38 patients who were commencing treatment for eitherMycobacterium abscessusorMycobacterium aviumcomplex or who were patients with bronchiectasis who had never had positive cultures for mycobacteria. NTM quantification was performed with quantitative PCR assays developed in-house.

Results

The molecular assays had highin vitrosensitivity and specificity for the detection and accurate quantification of NTM species. The assays successfully identified NTM DNA from human sputum samples (in vivosensitivity: 0.86–0.87%; specificity: 0.62–0.95%; area under the curve: 0.74–0.92). A notable association between NTM copy number and treatment (Friedman ANOVA (df)=22.8 (3), p≤0.01 forM. abscessustreatment group) was also demonstrated.

Conclusion

The quantitative PCR assays developed in this study provide affordable, real-time and rapid measurement of NTM burden, with significant implications for prompt management decisions.
Association between metabolic syndrome and colorectal cancer incidence and all-cause mortality: a hospital-based observational study
Authors: Chung Kuan-Chih , Juang Sin-Ei , Chen Hong-Hwa , Cheng Kung-Chuan , Wu Kuen-Lin , Song Ling-Chiao , Lee Ko-Chao
Published: November 2022

Background

Metabolic syndrome (MetS) is a worldwide pandemic and complex disorder associated with colorectal cancer (CRC). This study aims to identify the influence of number of MetS components on CRC incidence and mortality, using a national, longitudinal dataset of hospital care in Taiwan.

Methods

Patient data from the Taiwan National Health Insurance Research Database (NHIRD) from 2001 to 2008 were extracted. Individuals with at least one inpatient diagnosis or 2 outpatient visits with any MetS component found within one year were identified and included. Subjects died within 12 months after the presence of MetS components or had any prior cancer were excluded. The study cohort were then divided into two groups: subjects who had more (i.e., 3 to 4) MetS components and those who had fewer (i.e., 1 to 2) MetS components. An 2:1 propensity score (PS) matching were performed to balance the baseline characteristics between the groups. Cox regression analyses were conducted to compare the CRC incidence and all-cause mortality at follow-up between subjects with more MetS components versus fewer components.

Results

After matching, a total of 119,843 subjects (78,274 with 1–2 and 41,569 with 3–4 MetS components) were analyzed. After adjusting for confounders, subjects with 3–4 MetS components had a significantly higher risk of CRC [adjusted hazard ratio (aHR), 1.28; 95% confidence interval (CI), 1.15–1.43, p < 0.001) and all-cause mortality (aHR, 1.13; 95% CI, 1.08–1.17, p < 0.001) than those with only 1–2 MetS components. In stratified analyses, the greatest increased risk of CRC incidence that 3–4 MetS components posed as compared to 1–2 MetS components was seen in subjects without CHD history (aHR, 1.41, 95% CI, 1.23–1.62, p < 0.001). In addition, 3–4 MetS components (vs. 1–2) led to greater all-cause mortality among the subjects < 65y, both genders, with or without CHD, subjects without CKD hisotry, both aspirin users and non-users, users of nonsteroidal anti-inflammatory drugs (NSAIDs), and users of statin.

Conclusion

Compared with 1–2 components, subjects with 3–4 MetS components are at greater risk of CRC and death at follow-up. This study also demonstrates the risks for CRC and all-cause mortality in certain subgroups of individuals with 3–4 MetS components compared to 1–2 components. These findings may help clinicians on the CRC risk stratification according to individuals’ characteristics, as well as to optimize the strategy of MetS surveillance and control in order to prevent CRC.
Professional and academic profile of the Brazilian research ethics committees
Authors: de Veras Santos Eugênio Pacelli , Guerriero Iara Coelho Zito
Published: November 2022

Background

Brazil is among the sixteen countries that conducts the most clinical trials in the world. It has a system to review research ethics with human beings made up by the National Commission on Research Ethics (CONEP) and 779 Research Ethics Committees (RECs), in 2017. The RECs are supposed to follow the same rules regarding their membership, although the RECs that review Social Science and Humanities (SSH) researches must respect Resolution 510/16. There are Brazilian RECs that review SSH and clinical trials. This study aimed to analyze the academic professional profile of the members of the CONEP and Brazilian RECs, their adequacy to the norms, and the challenges faced by the REC’s Chairs to compose their membership.

Methods

All 779 Brazilian RECs’ chairs are invited to fill in a questionnaire informing academic and professional background of the RECs members, and 92 answered. However, eight were excluded for having sent an incomplete questionnaire, leaving a total of 84 participants. The variables were described by absolute and relative frequency. The Chi-square test and ANOVA was used to analyze regional differences related difficulties to compose the committee. The significance level was 95%.

Results

The results showed a predominance of members from the biomedical area (57%), while 33% were members of the Social Sciences and Humanities and 5.5% were community representatives. As for the academic degree, there were (45.2%) PhD and (27.9%) masters. The divergences in relation to the guidelines result from the difficulties of having participants in some areas and the little interest in the work carried out by the committees.

Conclusion

The RECs are partially adequate to the norms and their performance may be compromised by the low participation of community representatives. The organization of REC’s specifics to review biomedical research could improve the ethical review process, ensuring a membership more qualified for these protocols.
Polish immigrants’ access to colorectal cancer screening in Norway – a qualitative study
Authors: Bhargava Sameer , Czapka Elżbieta , Hofvind Solveig , Kristiansen Maria , Diaz Esperanza , Berstad Paula
Published: November 2022

Background

The Norwegian colorectal cancer (CRC) screening programme started in May 2022. Inequities in uptake of CRC screening is a concern, and we expect that immigrants are at risk of non-uptake. Immigrants from Poland are the most populous immigrant group in Norway. The purpose of this study was to identify and explore factors that may facilitate Polish immigrants’ access to the Norwegian CRC screening programme.

Material and methods

This study was based on qualitative interviews with ten Polish immigrants in Norway. The participants represented a convenience sample that varied in terms of gender, education, employment, time in Norway, place of residence, Norwegian language skills and ties to the Norwegian-Polish community. We performed thematic content analysis to understand CRC screening from the perspective of Polish immigrants, using transnationalism and Levesque’s conceptualization of accessibility as theoretical frameworks.

Results

We grouped our findings into three themes; “understanding of CRC development and the need to access health care”, “binationalism” and “improving accessibility through information”. Within these themes, various factors influenced the participants’ accessibility to CRC screening, namely knowledge about the screening and about causes, development and prevention of the disease, language, choice of screening country, trust in health personnel’s competence, information needs, methods and sources, as well as participants’ perception of the faecal immunochemical test screening user manual. These factors were further influenced by communication between the Polish community in Norway and Poland, as well as travel between the countries.

Conclusion

We identified several factors that can be targeted with an aim to increase Polish immigrants’ access to the Norwegian CRC screening programme. Effective measures could include increasing cultural competence among health care providers and providing information in Polish through Polish-speaking health care professionals, general practitioners and internet portals used by the Polish-speaking community. Focusing on accessibility in a transnational setting, our findings may be of interest for policy makers and service providers planning preventive health measures for immigrants.
Validity and reliability of the Chinese version of the Normalization MeAsure Development(NoMAD)
Authors: Jiang Mengyao , Wang Qing , Finch Tracy , She Dongli , Zhou Yujun , Chung Yuet Foon , Chen Jie , Han Lin
Published: November 2022

Background

The Normalization MeAsure Development (NoMAD) is a brief quantitative tool based on the Normalization Process Theory (NPT), which can measure the implementation process of new technologies and complex interventions. The aim of our study was to translate and culturally adapt the NoMAD into Chinese, and to evaluate the psychometric properties of the Chinese version of NoMAD.

Methods

According to the NoMAD translation guideline, we undertook forward translation, backward translation, and compared these translations to get a satisfactory result, then we performed cognitive interviews to achieve cross-culture adaptation. And the psychometric properties of the final version were evaluated among clinical nurses who used the pressure injuries management system via WeChat mini-program at a tertiary hospital in northwestern China.

Results

A total of 258 nurses were enrolled in our study, and the response rate was 92.1%. The Cronbach’s alpha of four dimensions were as follow: Coherence (0.768), Cognitive Participation (0.904), Collective Action (0.820), and Reflexive Monitoring (0.808). The overall internal consistency was 0.941. The confirmatory factor analysis results showed a good fit for its theoretical structure (CFI = 0.924, TLI = 0.910, RMSEA = 0.0079, SRMSR = 0.046, χ2/df = 2.61). The item-level content validity index ranged from 0.857 to 1, and the scale-level content validity index was 0.95. There were positive correlations between four constructs scores and three general normalization scores.

Conclusions

The Chinese version of NoMAD is a reliable and valid tool to evaluate the implementation process of innovations.
Assessment of competencies in the prevention and control of chronic diseases and their influencing factors among health assistants in Bhutan: a cross-sectional study
Authors: Lhadon Tshewang , Kitreerawutiwong Nithra
Published: November 2022

Background

The morbidity and mortality of chronic diseases are increasing worldwide. The literature confirms that the prevention and control of chronic disease necessitates a robust primary health care system with a competent health care workforce. Studies on competencies in the prevention and control of chronic diseases and their determinants among health assistants (HAs) in Bhutan are scarce. This cross-sectional survey aimed to examine the level of competencies and investigate the factors influencing competencies in the prevention and control of chronic diseases among HAs.

Methods

The sample consisted of 330 HAs who were recruited through simple random sampling. A validated and reliable self-administered questionnaire was used to collect data through a web-based Google Form. Data were analysed using descriptive statistics and multiple regression analysis.

Results

The findings showed that the mean summed competency score was 191 (SD = 25.7). Approximately 96% of the participants perceived that they were competent in the prevention and control of chronic diseases. The multiple regression analysis indicated that work environment (β = 0.473), sex (β = 0.126), location of the health facility (β = − 0.114), and organizational support (β = 0.117) affected competencies in the prevention and control of chronic diseases by 31.4% with statistical significance (R2 = 0.314) (p < 0.05).

Conclusions

This study suggested that improving the number of staff and availability of learning resources, considering training for both sexes, especially female primary health care workers, enhancing mentorship and supervision in rural areas, and establishing the recognition and encouragement of primary health care workers are needed.
Education-related inequalities in beliefs and behaviors pertaining to COVID-19 non-pharmaceutical interventions
Authors: Kirkby Katherine , Bergen Nicole , Vidal Fuertes Cecilia , Schlotheuber Anne , Hosseinpoor Ahmad Reza
Published: November 2022

Background

The coronavirus pandemic has exposed existing social inequalities in relation to disease preventive behaviors, risk of exposure, testing and healthcare access, and consequences as a result of illness and containment measures across different population groups. However, due to a lack of data, to date there has been limited evidence of the extent of such within-country inequalities globally.

Methods

We examined education-related inequalities in four COVID-19 prevention and testing indicators within 90 countries, using data from the University of Maryland Social Data Science Center Global COVID-19 Trends and Impact Survey, in partnership with Facebook, over the period 1 June 2021 to 31 December 2021. The overall level of education-related inequalities, as well as how they differ across country income groups and how they have changed over time were analyzed using the Slope Index of Inequality (SII) and the Relative Index of Inequality (RII). We also assessed whether these education-related inequalities were associated with government policies and responses.

Results

Education-related inequalities in beliefs, mask wearing, social distancing and testing varied across the study countries. Mask wearing and beliefs in the effectiveness of social distancing and mask wearing were overall more common among people with a higher level of education. Even after controlling for other sociodemographic and health-related factors, social distancing practice was higher among the most educated in low/lower middle income countries, but was higher overall among the least educated in high income countries. Overall there were low education-related inequalities in COVID-19 testing, though there was variation across countries.

Conclusions

The study highlights important within-country education-related differences in COVID-19 beliefs, preventive behaviors and testing, as well as differing trends across country income groups. This has implications for considering and targeting specific population groups when designing public health interventions and messaging during the COVID-19 pandemic and future health emergencies.
Effect size quantification for interrupted time series analysis: implementation in R and analysis for Covid-19 research
Authors: Travis-Lumer Yael , Goldberg Yair , Levine Stephen Z.
Published: November 2022

Background

Interrupted time series (ITS) analysis is a time series regression model that aims to evaluate the effect of an intervention on an outcome of interest. ITS analysis is a quasi-experimental study design instrumental in situations where natural experiments occur, gaining popularity, particularly due to the Covid-19 pandemic. However, challenges, including the lack of a control group, have impeded the quantification of the effect size in ITS. The current paper proposes a method and develops a user-friendly R package to quantify the effect size of an ITS regression model for continuous and count outcomes, with or without seasonal adjustment.

Results

The effect size presented in this work, together with its corresponding 95% confidence interval (CI) and P-value, is based on the ITS model-based fitted values and the predicted counterfactual (the exposed period had the intervention not occurred) values. A user-friendly R package to fit an ITS and estimate the effect size was developed and accompanies this paper. To illustrate, we implemented a nation population-based ITS study from January 2001 to May 2021 covering the all-cause mortality of Israel (n = 9,350 thousand) to quantify the effect size of Covid-19 exposure on mortality rates. In the period unexposed to the Covid-19 pandemic, the mortality rate decreased over time and was expected to continue decreasing had Covid-19 not occurred. In contrast, the period exposed to the Covid-19 pandemic was associated with an increased all-cause mortality rate (relative risk = 1.11, 95% CI = 1.04, 1.18, P < 0.001).

Conclusion

For the first time, the effect size in ITS: was quantified, can be estimated by end-users with an R package we developed, and was demonstrated with data showing an increase in mortality following the Covid-19 pandemic. ITS effect size reporting can assist public health policy makers in assessing the magnitude of the entire intervention effect using a single, readily understood measure.
Retraction Note: MicroRNA-15b shuttled by bone marrow mesenchymal stem cell-derived extracellular vesicles binds to WWP1 and promotes osteogenic differentiation
Authors: Li Yanhong , Wang Jing , Ma Yanchao , Du Wenjia , Feng Haijun , Feng Kai , Li Guangjie , Wang Shuanke
Published: November 2022

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13075-022-02950-3.