bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of LC3-associated phagocytosis in COPD and in response to cigarette smoke
Authors: Asare Patrick F. , Tran Hai B. , Hurtado Plinio R. , Perkins Griffith B. , Nguyen Phan , Jersmann Hubertus , Roscioli Eugene , Hodge Sandra
Published: December 2021

Introduction/Rationale:

In chronic obstructive pulmonary disease (COPD), defective macrophage phagocytic clearance of cells undergoing apoptosis by efferocytosis may lead to secondary necrosis of the uncleared cells and contribute to airway inflammation. The precise mechanisms for this phenomenon remain unknown. LC3-associated phagocytosis (LAP) is indispensable for effective efferocytosis. We hypothesized that cigarette smoke inhibits the regulators of LAP pathway, potentially contributing to the chronic airways inflammation associated with COPD.

Methods:

Bronchoalveolar (BAL)-derived alveolar macrophages, lung tissue macrophages obtained from lung resection surgery, and monocyte-derived macrophages (MDM) were prepared from COPD patients and control participants. Lung/airway samples from mice chronically exposed to cigarette smoke were also investigated. Differentiated THP-1 cells were exposed to cigarette smoke extract (CSE). The LAP pathway including Rubicon, as an essential regulator of LAP, efferocytosis and inflammation was examined using western blot, ELISA, flow cytometry, and/or immunofluorescence.

Results:

Rubicon was significantly depleted in COPD alveolar macrophages compared with non-COPD control macrophages. Rubicon protein in alveolar macrophages of cigarette smoke-exposed mice and cigarette smoke-exposed MDM and THP-1 was decreased with a concomitant impairment of efferocytosis. We also noted increased expression of LC3 which is critical for LAP pathway in COPD and THP-1 macrophages. Furthermore, THP-1 macrophages exposed to cigarette smoke extract exhibited higher levels of other key components of LAP pathway including Atg5 and TIM-4. There was a strong positive correlation between Rubicon protein expression and efferocytosis.

Conclusion:

LAP is a requisite for effective efferocytosis and an appropriate inflammatory response, which is impaired by Rubicon deficiency. Our findings suggest dysregulated LAP due to reduced Rubicon as a result of CSE exposure. This phenomenon could lead to a failure of macrophages to effectively process phagosomes containing apoptotic cells during efferocytosis. Restoring Rubicon protein expression has unrecognized therapeutic potential in the context of disease-related modifications caused by exposure to cigarette smoke.
Understanding cultural artefacts to ensure seamless transitions in the Early Years
Authors: Bobongie Fiona , Jackson Cathy
Published: December 2021

For Aboriginal and Torres Strait Islander Jarjums (children), the cultural and world views they bring from their home life can be very different to those in school, creating an additional layer of adjustments in the Early Years pathway. We describe an Early Years Transitions Framework that demonstrates how changing transition from a process to move Jarjums as quickly as possible into a Western system to one that acknowledges the beliefs and cultural artefacts Jarjums bring to the Early Years space builds smoother transitions. The Framework is underlain by a mesh of High-Expectations Relationships, which moves the educator from the position of ‘knowledge holder’ to one of deep listening to understand the cultural needs and aspirations of families. By bringing these different world views together and building relationships across the Early Years sectors, educators can create a third cultural space where transition becomes a process of interwoven spaces and incremental learning.
Assessing the Structural and Functional Similarity of Insulin Glargine Biosimilars
Authors: Vishwakarma Gayatri , Nupur Neh , Rathore Anurag S.
Published: December 2021

Background:

A biosimilar product is expected to exhibit similar safety, efficacy, and quality as that of the approved reference product. Only a few reports of thorough evaluation of the quality of insulin glargine biosimilars are available in literature. Here, we examine the structural and functional similarity of biosimilars of insulin glargine, the first basal long-acting insulin analogue with respect to its innovator product (Lantus® from Sanofi Aventis).

Methods:

Structural similarity was established using mass spectrometry, chromatographic, and spectroscopic techniques. Stability was compared by performing accelerated thermal stress studies. Functional similarity was established via in vitro assay.

Results:

Biosimilar 4 exhibited greater content of high molecular weight species (HMWs) (0.80%) and related substances (RS) (0.45±0.06%) vs others (HMWs of 0.04% and RS of 0.17%). Biosimilars 1 and 3 exhibited higher rate of impurity generation (0.78% and 0.73% per week, respectively), as compared with other drug products (0.02% to 0.43% per week). Furthermore, %aggregation at 14 days was found to statistically correlate ( R2= 0.99, root mean square error (RMSE) = 0.095) with %aggregation at 0 day (linearly) and the number of months from expiry (nonlinearly), highlighting the overpowering impact of the latter.

Conclusions:

While an overall structural and functional similarity was observed across insulin glargine biosimilars with respect to the innovator product, low amounts of product-related variants were seen in some biosimilars and these impact product stability. The %aggregation at 14 days exhibits statistical correlation with %aggregation at 0 day and the number of months from expiry. The order of biosimilarity was denoted as Lantus®>Biosimilar 2>Biosimilar 4>Biosimilar 1>Biosimilar 3.
Assessing the clinical impact and resource use of a 30-minute chlamydia and gonorrhoea point-of-care test at three sexual health services
Authors: Huntington Susie , Weston Georgie , Adams Elisabeth
Published: December 2021

Objectives:

To assess clinical metrics and resource use of a 30-minute point-of-care test (POCT) for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) compared to laboratory-based testing.

Methods:

Three English sexual health services (SHSs) were recruited as part of a study. Existing processes for CT/NG testing and treatment were assessed, and adaptions to incorporate the CT/NG POCT were developed during semi-structured interviews. Staff time and consumables data were collected by clinic staff prior to and following introduction of the POCT.

Results:

SHSs selected patient groups for whom the CT/NG POCT would be used. Testing and treatment process data were collected for 225 patients (n = 118 POC; n = 107 standard). The percentage of patients receiving unnecessary CT treatment was 5% (5/95) and 13% (12/93) for POC and standard care respectively. The average CT/NG pathway cost varied and was on average £61.55 for POC and £50.88 for standard care. For the two SHSs where the POCT was used during a patient’s visit, for standard and POC respectively, the average time to CT treatment was 10.0 and 0.0 days and to NG treatment, 0.3 and 0.0 days.

Conclusion:

Use of a 30-minute POCT at three SHSs yielded clinical benefits by reducing time to treatment and unnecessary CT treatment.
A Pilot Study Evaluating the Effects of a Technology-Based and Positive Psychological Training Intervention on Blood Pressure in African Americans With Hypertension
Authors: Still Carolyn H. , Margevicius Seunghee P. , Wright Jackson T. , Ruksakulpiwat Suebarn , Moore Shirley M.
Published: December 2021

Behavioral interventions consolidating technology are underutilized and do not reach diverse populations such as African Americans with hypertension. This pilot study aimed to evaluate the effects of a theoretically derived, technology-based intervention in African Americans with hypertension. African Americans with hypertension (N = 18; age range 25-85; 72.22% females) were randomized to the technology-based plus positive psychological training (PPT) experimental group (n = 10) or the comparison group (n = 8) for 12 weeks. The technology-based intervention included analytic components (web-based education, self-monitoring of blood pressure [BP], and medication management using a commercially free app-Medisafe) and an emotional component (comprised of skills and behaviors directed at engaging 1 in positive activities to help build increasing healthy behaviors). The comparison group received the technology-based intervention alone. Demographic information, self-management cognitive processes, self-management behaviors, and health status outcomes were assessed. After completing the 12-week intervention, the groups did not significantly differ in health outcomes, health behavior outcomes, and technology utilization outcomes. Mean systolic BP decrease 6.02 mmHg (standard deviation [SD] = 22.75) in the comparison group and 1.1 mmHg (SD = 20.64; P = .439) in the experimental group. Diastolic BP decreased 0.1 mmHg (SD = 11.78) in the comparison group and 1.5 mmHg (SD = 12.7; P = .757) in the experimental group. Our findings suggest that behavioral interventions using technology have the potential to improve self-management outcomes among African American populations. Further research is warranted in a larger sample size and a longer time frame to identify the intervention’s effectiveness.
Atypical Presentation of a Midline Nasal Dermoid with Intracranial Extension
Authors: Chocron Yehuda , Zammit Dino , Cugno Sabrina , Atkinson Jeffrey , Gilardino Mirko S.
Published: December 2021

Although rarer than their lateral orbital counterparts, dermoid cysts are part of any differential diagnosis of a midline nasal mass in the pediatric population. Here we present a case of a nasal dermoid with intracranial extension that presented as a mass appearing at the nasal-cheek junction. This atypical presentation for a nasal dermoid highlights the need for clinicians to remain vigilant and consider midline dermoid cyst as a diagnosis despite an off-midline position on the face.
Return-to-Sport Outcomes After Primary Ulnar Collateral Ligament Reconstruction With Palmaris Versus Hamstring Tendon Grafts: A Systematic Review
Authors: Trofa David P. , Constant Michael , Crutchfield Connor R. , Dantzker Nicholas J. , Saltzman Bryan M. , Lynch T. Sean , Ahmad Christopher S.
Published: December 2021

Background:

Ulnar collateral ligament (UCL) reconstruction is the current gold standard of treatment for overhead athletes with a symptomatic, deficient UCL of the elbow who have failed nonoperative treatment and wish to return to sport (RTS) at a high level. The palmaris longus and hamstring tendons are common graft choices, but no study has analyzed the existing literature to assess whether one graft is superior to the other.

Purpose:

To systematically report on the outcomes of UCL reconstruction using palmaris and hamstring autografts.

Study Design:

Systematic review; Level of evidence, 4.

Methods:

A combination of the terms “ulnar collateral ligament,” “valgus instability,” “Tommy John surgery,” “hamstring,” and “palmaris longus” were searched in PubMed, Embase, and the Cochrane Library. RTS and return-to-same-level (RSL) rates, patient-reported outcomes, and complications were included for analysis. We used the modified Coleman Methodology Score and risk-of-bias tool for nonrandomized studies to assess the quality of the included studies.

Results:

This review included 6 studies (combined total of 2154 elbows) that directly compared palmaris and hamstring graft use in UCL reconstruction. Follow-up ranged from 24 to 80.4 months, and the mean patient age across all studies was 21.8 years. The mean RSL across all studies and grafts was 79.0%, and the mean RTS was 84.1%, consistent with results previously reported in the literature. The mean RTS and RSL rates for the palmaris graft group were 84.6% and 82%, respectively; the hamstring graft group showed mean RTS and RSL rates of 80.8% and 80.8%. Meta-analysis revealed no significant difference in RSL between the 2 graft groups (odds ratio, 1.06; 95% CI, 0.77-1.46). The combined complication rate of the included studies was 18.2%, with failure rates ranging from 0% to 7.1%.

Conclusion:

Results of this review indicated that both palmaris and hamstring tendon grafts are viable options for primary UCL reconstruction. Graft choice should be determined by a combination of patient and surgeon preference.
Benefits and Drawbacks of Continuous Glucose Monitoring (CGM) Use in Young Children With Type 1 Diabetes: A Qualitative Study From a Country Where the CGM Is Not Reimbursed
Authors: Karakuş Kağan Ege , Sakarya Sibel , Yeşiltepe Mutlu Gül , Berkkan Metehan , Muradoğlu Serra , Can Ecem , Gökçe Tuğba , Eviz Elif , Hatun Şükrü
Published: December 2021

Investigating the daily life experiences of patients using Continuous Glucose Monitoring (CGM) can highlight the benefits and barriers in using this system for people with type 1 diabetes (T1D). Semi-structured qualitative interviews were conducted with the caregivers of 10 children aged <9 years, all of whom had been treated for T1D and had used CGM >6 months. These interviews were analyzed using the content analysis approach and from these interviews, four meta themes emerged: metabolic control, barriers to CGM use, CGM use in daily life, and comparison with fingersticks. Families reported the following as benefits of CGM: pain relief, better hypoglycemia and hyperglycemia management, increased control over diet and social life, reduced worries at school and during the night, and convenience in entrusting the child to the care of others. Cost, concerns related to accuracy and reliability of measurements, insertion, adhesion and removal issues all emerged as barriers to CGM use. The most prominent issue was the economic burden of CGM. Families accept this burden, even though it is challenging, as their experiences in using CGM are positive and they feel that CGM is necessary for T1D management.
Association of clonal hematopoiesis with chronic obstructive pulmonary disease
Authors: Miller Peter G. , Qiao Dandi , Rojas-Quintero Joselyn , Honigberg Michael C. , Sperling Adam S. , Gibson Christopher J. , Bick Alexander G. , Niroula Abhishek , McConkey Marie E. , Sandoval Brittany , Miller Brian C. , Shi Weiwei , Viswanathan Kaushik , Leventhal Matthew , Werner Lillian , Moll Matthew , Cade Brian E. , Barr R. Graham , Correa Adolfo , Cupples L. Adrienne , Gharib Sina A. , Jain Deepti , Gogarten Stephanie M. , Lange Leslie A. , London Stephanie J. , Manichaikul Ani , O’Connor George T. , Oelsner Elizabeth C. , Redline Susan , Rich Stephen S. , Rotter Jerome I. , Ramachandran Vasan , Yu Bing , Sholl Lynette , Neuberg Donna , Jaiswal Siddhartha , Levy Bruce D. , Owen Caroline A. , Natarajan Pradeep , Silverman Edwin K. , van Galen Peter , Tesfaigzi Yohannes , Cho Michael H. , Ebert Benjamin L. ,   for the COPDGene Study Investigators, National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine Consortium
Published: December 2021

Chronic obstructive pulmonary disease (COPD) is associated with age and smoking, but other determinants of the disease are incompletely understood. Clonal hematopoiesis of indeterminate potential (CHIP) is a common, age-related state in which somatic mutations in clonal blood populations induce aberrant inflammatory responses. Patients with CHIP have an elevated risk for cardiovascular disease, but the association of CHIP with COPD remains unclear. We analyzed whole-genome sequencing and whole-exome sequencing data to detect CHIP in 48 835 patients, of whom 8444 had moderate to very severe COPD, from four separate cohorts with COPD phenotyping and smoking history. We measured emphysema in murine models in which Tet2 was deleted in hematopoietic cells. In the COPDGene cohort, individuals with CHIP had risks of moderate-to-severe, severe, or very severe COPD that were 1.6 (adjusted 95% confidence interval [CI], 1.1-2.2) and 2.2 (adjusted 95% CI, 1.5-3.2) times greater than those for noncarriers. These findings were consistently observed in three additional cohorts and meta-analyses of all patients. CHIP was also associated with decreased FEV1% predicted in the COPDGene cohort (mean between-group differences, −5.7%; adjusted 95% CI, −8.8% to −2.6%), a finding replicated in additional cohorts. Smoke exposure was associated with a small but significant increased risk of having CHIP (odds ratio, 1.03 per 10 pack-years; 95% CI, 1.01-1.05 per 10 pack-years) in the meta-analysis of all patients. Inactivation of Tet2 in mouse hematopoietic cells exacerbated the development of emphysema and inflammation in models of cigarette smoke exposure. Somatic mutations in blood cells are associated with the development and severity of COPD, independent of age and cumulative smoke exposure.
Comorbid insomnia and sleep apnoea is associated with all-cause mortality
Authors: Lechat Bastien , Appleton Sarah , Melaku Yohannes Adama , Hansen Kristy , McEvoy R. Doug , Adams Robert , Catcheside Peter , Lack Leon , Eckert Danny J. , Sweetman Alexander
Published: December 2021

Background

Increased mortality has been reported in people with insomnia and in those with obstructive sleep apnoea (OSA). However, these conditions commonly co-occur and the combined effect of comorbid insomnia and sleep apnoea (COMISA) on mortality risk is unknown. This study used Sleep Heart Health Study (SHHS) data to assess associations between COMISA and all-cause mortality risk.

Methods

Insomnia was defined as difficulties falling asleep, maintaining sleep and/or early morning awakenings from sleep ≥16 times per month, and daytime impairments. OSA was defined as an apnoea–hypopnoea index ≥15 events·h−1. COMISA was defined if both conditions were present. Multivariable adjusted Cox proportional hazards models were used to determine the association between COMISA and all-cause mortality (n=1210) over 15 years of follow-up.

Results

5236 participants were included. 2708 (52%) did not have insomnia/OSA (reference group), 170 (3%) had insomnia-alone, 2221 (42%) had OSA-alone and 137 (3%) had COMISA. COMISA participants had a higher prevalence of hypertension (OR 2.00, 95% CI 1.39–2.90) and cardiovascular disease (CVD) (OR 1.70, 95% CI 1.11–2.61) compared with the reference group. Insomnia-alone and OSA-alone were associated with higher risk of hypertension but not CVD compared with the reference group. Compared with the reference group, COMISA was associated with a 47% (hazard ratio 1.47, 95% CI 1.06–2.07) increased risk of mortality. The association between COMISA and mortality was consistent across multiple definitions of OSA and insomnia.

Conclusions

COMISA was associated with higher rates of hypertension and CVD at baseline, and an increased risk of all-cause mortality compared with no insomnia/OSA.
An international survey on the use of intrapleural tissue plasminogen activator/DNase therapy for pleural infection
Authors: Lau Estee P.M. , Eshraghi Matin , Dootson Kirstie , Yeoh Cindy , Ywe Phu Wint , Lee Y.C. Gary , Popowicz Natalia D.
Published: December 2021

Introduction

Intrapleural tissue plasminogen activator (tPA) combined with human recombinant DNase (DNase) could be an effective alternative to surgery in managing pleural infection, as demonstrated in the Multi-centre Intrapleural Sepsis Trial (MIST)-2. However, the optimal delivery regimen is still unknown. The aim of this survey was to identify the current practice of tPA/DNase use by physicians with published interests in pleural infection, and their opinions on dose de-escalation of tPA/DNase therapy.

Methods

Potential participants were identified using four search strategies. Only practising physicians who were managing patients with pleural infections and either actively involved in pleural research and publications, or were members of relevant pleural disease guideline panels at the time of survey were included.

Results

An invitation email with the questionnaire was sent to 102 participants, of whom 49 (48%) responded. Most respondents (90%, n=44) have used tPA/DNase to manage pleural infection, but the dosing and delivery regimens employed varied. Many (86%, 38 out of 44) respondents have used 10 mg tPA, while 73% (n=32), 16% (n=7) and 9% (n=4) have used 5 mg, 2.5 mg and 1 mg doses, respectively. Most respondents instilled tPA/DNase concurrently (61%, n=27) and routinely administered six doses of tPA/DNase (52%, n=23) twice daily (82%, n=36). Respondents would consider using a lower starting dose of tPA (with the possibility of escalation if clinically needed) if a median 80% (interquartile range 50–80%) of patients could be successfully treated at that dose.

Conclusion

This survey observed a large variation in the current treatment protocol of intrapleural tPA/DNase therapy worldwide and the need for more data on this subject.
Breast-cancer detection using blood-based infrared molecular fingerprints
Authors: Kepesidis Kosmas V. , Bozic-Iven Masa , Huber Marinus , Abdel-Aziz Nashwa , Kullab Sharif , Abdelwarith Ahmed , Al Diab Abdulrahman , Al Ghamdi Mohammed , Hilal Muath Abu , Bahadoor Mohun R. K. , Sharma Abhishake , Dabouz Farida , Arafah Maria , Azzeer Abdallah M. , Krausz Ferenc , Alsaleh Khalid , Zigman Mihaela , Nabholtz Jean-Marc
Published: December 2021

Background

Breast cancer screening is currently predominantly based on mammography, tainted with the occurrence of both false positivity and false negativity, urging for innovative strategies, as effective detection of early-stage breast cancer bears the potential to reduce mortality. Here we report the results of a prospective pilot study on breast cancer detection using blood plasma analyzed by Fourier-transform infrared (FTIR) spectroscopy – a rapid, cost-effective technique with minimal sample volume requirements and potential to aid biomedical diagnostics. FTIR has the capacity to probe health phenotypes via the investigation of the full repertoire of molecular species within a sample at once, within a single measurement in a high-throughput manner. In this study, we take advantage of cross-molecular fingerprinting to probe for breast cancer detection.

Methods

We compare two groups: 26 patients diagnosed with breast cancer to a same-sized group of age-matched healthy, asymptomatic female participants. Training with support-vector machines (SVM), we derive classification models that we test in a repeated 10-fold cross-validation over 10 times. In addition, we investigate spectral information responsible for BC identification using statistical significance testing.

Results

Our models to detect breast cancer achieve an average overall performance of 0.79 in terms of area under the curve (AUC) of the receiver operating characteristic (ROC). In addition, we uncover a relationship between the effect size of the measured infrared fingerprints and the tumor progression.

Conclusion

This pilot study provides the foundation for further extending and evaluating blood-based infrared probing approach as a possible cross-molecular fingerprinting modality to tackle breast cancer detection and thus possibly contribute to the future of cancer screening.
A national population-based study of patients, bystanders and contextual factors associated with resuscitation in witnessed cardiac arrest: insight from the french RéAC registry
Authors: Reuter Paul-Georges , Baert Valentine , Colineaux Hélène , Escutnaire Joséphine , Javaud Nicolas , Delpierre Cyrille , Adnet Frédéric , Loeb Thomas , Charpentier Sandrine , Lapostolle Frédéric , Hubert Hervé , Lamy Sébastien
Published: December 2021

Background

In out-of-hospital cardiac arrest (OHCA), bystander initiated cardiopulmonary resuscitation (CPR) increases the chance of return of spontaneous circulation and survival with a favourable neurological status. Socioeconomic disparities have been highlighted in OHCA field. In areas with the lowest average socioeconomic status, OHCA incidence increased, and bystander CPR decreased. Evaluations were performed on restricted geographical area, and European evaluation is lacking. We aimed to analyse, at a national level, the impact of area-level social deprivation on the initiation of CPR in case of a witnessed OHCA.

Methods

We included all witnessed OHCA cases with age over 18 years from July 2011 to July 2018 form the OHCA French national registry. We excluded OHCA occurred in front of rescue teams or in nursing home, and patients with incomplete address or partial geocoding. We collected data from context, bystander and patient. The area-level social deprivation was estimated by the French version of the European Deprivation Index (in quintile) associated with the place where OHCA occurred. We assessed the associations between Utstein variables and social deprivation level using a mixed-effect logit model with bystander-initiated CPR.

Results

We included 23,979 witnessed OHCA of which 12,299 (51%) had a bystander-initiated CPR. More than one third of the OHCA (8,326 (35%)) occurred in an area from the highest quintile of social deprivation. The higher the area-level deprivation, the less the proportion of bystander-initiated CPR (56% in Quintile 1 versus 48% in Quintile 5). The In the multivariable analysis, bystander less often began CPR in areas with the highest deprivation level, compared to those with the lowest deprivation level (OR=0.69, IC95%: 0.63-0.75).

Conclusions

The level of social deprivation of the area where OHCA occurred was associated with bystander-initiated CPR. It decreased in the more deprived areas although these areas also concentrate more younger patients.
Serum interleukin-17 predicts severity and prognosis in patients with community acquired pneumonia: a prospective cohort study
Authors: Feng Chun-Mei , Wang Xin-Ming , Li Meng-Die , Xu Zheng , Hua Dong-Xu , Cheng Jia-Yi , Zheng Ling , Zhao Hui , Fu Lin
Published: December 2021

Background

Some studies previously demonstrated that interleukin-17 (IL-17) involves in pulmonary diseases progression. Nevertheless, the role of IL-17 in community-acquired pneumonia (CAP) remains unknown. This study aims to examine the correlations between serum IL-17 with the severity and prognosis in CAP patients through a prospective cohort study.

Methods

All 239 CAP patients were recruited. Serum IL-17 was detected by enzyme-linked immunosorbent assay (ELISA). The CAP severity was evaluated through CAP severity scores, including CURB-65, CRB-65, PSI, SMART-COP, CURXO and APACHE II.

Results

Serum IL-17 was gradually increased consistent with the severity of CAP. Correlative analysis suggested that serum IL-17 was associated with clinical physiologic indicators among CAP patients. Logistic regression indicated that serum IL-17 was positively related to CAP severity scores. Additionally, the prognostic outcomes were tracked among CAP patients. The levels of IL-17 on admission were significantly increased in CAP patients with ICU admission, mechanical ventilation, vasoactive agent, death and longer hospitalization days. Logistic regression analyses revealed serum higher IL-17 on admission elevated the risks of vasoactive agent usage and longer hospital stays in CAP patients. The cut-off concentrations of serum IL-17 for death, ICU admission, mechanical ventilation and ≥ 14 hospital stays were 86.80 ng/mL, 84.92 ng/mL, 84.92 ng/mL and 60.29 ng/mL respectively.

Conclusions

Serum IL-17 on admission is positively associated with the severity and poor prognosis among CAP patients, revealing that IL-17 may implicate in the pathological process of CAP. Therefore, serum IL-17 may become an effective biomarker for diagnosis, prognosis and therapy for CAP patients.
Risk factors of early periprosthetic femoral fracture after total knee arthroplasty
Authors: Pornrattanamaneewong Chaturong , Sitthitheerarut Akraporn , Ruangsomboon Pakpoom , Chareancholvanich Keerati , Narkbunnam Rapeepat
Published: December 2021

Background

Periprosthetic femoral fracture (PFF) is a serious complication after total knee arthroplasty (TKA). However, the risk factors of PFF in the early postoperative setting are not well documented. This study determines the risk factors of early PFF after primary TKA.

Methods

This study recruited 24 patients who had early PFF within postoperative 3 months and 96 control patients. Demographic data (age, gender, weight, height, body mass index, Deyo-Charlson comorbidity index, diagnosis, operated side, underlying diseases and history of steroid usage intraoperative outcomes), intraoperative outcomes (operative time, surgical approach, type and brand of the prosthesis), and radiographic outcomes (distal femoral width; DFW, prosthesis-distal femoral width ratio; PDFW ratio, anatomical lateral distal femoral angle; LDFA, the change of LDFA, femoral component flexion angle; FCFA and anterior femoral notching; AFN) were recorded and compared between groups. Details of PFF, including fracture pattern, preoperative deformity, and time to PFF were also documented.

Results

In univariate analysis, the PFF group had significantly older, right side injury, rheumatoid, dyslipidemia, Parkinson patients than the control group (p < 0.05). No cruciate-retaining design was used in PFF group (p = 0.004). Differences between the prosthetic brand used were found in this study (p = 0.049). For radiographic outcomes, PFF group had significantly lower DFW but higher PDFW ratio and postoperative LDFA than the control group (p < 0.05). While the change of LDFA, FCFA and AFN were similar between groups. The fracture patterns were medial condylar (45.8%), lateral condylar (25.0%) and supracondylar fracture (29.2%). The mean overall time to PFF was 37.2 ± 20.6 days (range 8–87 days). Preoperative deformity was significantly different among the three patterns (p < 0.05). When performed multivariate analysis using the logistic regression model, age was only an independent risk factor for early PFF. The cut-off point of age was > = 75 years, with a sensitivity of 75.0% and specificity of 78.1%.

Conclusion

This study determined that age was the independent risk factors for early PFF. However, further well-controlled studies with a larger sample size were needed to address this issue.
The influence of home care supply on delayed discharges from hospital in England
Authors: Allan Stephen , Roland Daniel , Malisauskaite Gintare , Jones Karen , Baxter Kate , Gridley Kate , Birks Yvonne
Published: December 2021

Background

Delayed transfers of care (DTOC) of patients from hospital to alternative care settings are a longstanding problem in England and elsewhere, having negative implications for patient outcomes and costs to health and social care systems. In England, a large proportion of DTOC are attributed to a delay in receiving suitable home care. We estimated the relationship between home care supply and delayed discharges in England from 2011 to 2016.

Methods

Reduced form fixed effects OLS models of annual DTOC attributed to social care at local authority (LA)-level from 2011 to 2016 were estimated, using both number of days and patients as the dependent variable. A count of home care providers at LA-level was utilised as the measure of home care supply. Demand (e.g. population, health, income) and alternative supply (e.g. care home places, local unemployment) measures were included as controls. Instrumental Variable (IV) methods were used to control for any simultaneity in the relationship between DTOC and home care supply. Models for DTOC attributed to NHS and awaiting a home care package were used to assess the adequacy of the main model.

Results

We found that home care supply significantly reduced DTOC. Each extra provider per 10 sq. km. in the average local authority decreased DTOC by 14.9% (equivalent to 449 days per year), with a per provider estimate of 1.6% (48 days per year). We estimated cost savings to the public sector over the period of analysis from reduced DTOC due to increased home care provision between £73 m and £274 m (95% CI: £0.24 m to £545.3 m), with a per provider estimate of savings per year of £12,600 (95% CI: £900 to £24,500).

Conclusion

DTOC are reduced in LAs with better supply of home care, and this reduces costs to the NHS. Further savings could be achieved through improved outcomes of people no longer delayed. Appropriate levels of social care supply are required to ensure efficiency in spending for the public sector overall.
Pregnant women’s experiences with the management of hypertensive disorders of pregnancy: a qualitative study
Authors: Helou Amyna , Stewart Kay , Ryan Kath , George Johnson
Published: December 2021

Background

Hypertensive disorders are a leading cause of mortality and morbidity during pregnancy. Despite multiple national and international clinical guidelines and a plethora of research in the field of optimising management, there has been limited research describing the perspectives and experiences of pregnant women with the management of hypertensive disorders of pregnancy (HDP). Understanding these perceptions and experiences is imperative to the optimisation of HDP management.

Methods

A qualitative study involving face-to-face, in-depth interviews were undertaken with 27 pregnant women diagnosed with and being treated for HDP to explore their perspectives of and experiences with clinical management. Written consent was obtained individually from each participant, and the interviews ranged from 16 to 54 min. Inductive codes were generated systematically for the entire data set. Line-by-line analysis was then performed and nodes were created within NVivo, a qualitative data management software. Data collection was continued until thematic saturation was reached. Thematic analysis was employed to interpret the data.

Results

Three major descriptive themes were discerned regarding the women’s perspectives on and experiences with the management of HDP: attitudes towards monitoring of HDP, attitudes and perceptions towards development and management of complications, and perceptions of pregnant women with chronic hypertension. Trust in the hospital system, positive attitudes towards close blood pressure monitoring as well as self-monitoring of blood pressure, and a realistic approach to emergency antenatal hospital admissions contributed to a positive attitude towards monitoring of HDP. Women with prior experiences of HDP complications, including pre-eclampsia, were more confident in their clinical management and knew what to expect. Those without prior experience were often in shock when they developed pre-eclampsia. Some women with chronic hypertension displayed limited understanding of the potential risks that they may experience during pregnancy and thus lacked comprehension of the seriousness of the condition.

Conclusions

The clinical management experiences of pregnant women with HDP were varied. Many women did not feel that they were well informed of management decisions and had a desire to be more informed and involved in decision-making. Clear, concise information about various facets of HDP management including blood pressure monitoring, prescription of the appropriate antihypertensive agent, and planning for potential early delivery are required.
COVID-19 pandemic modifies temperature and heat-related illness ambulance transport association in Japan: a nationwide observational study
Authors: Seposo Xerxes , Madaniyazi Lina , Ng Chris Fook Sheng , Hashizume Masahiro , Honda Yasushi
Published: December 2021

Background

During the COVID-19 pandemic, several illnesses were reduced. In Japan, heat-related illnesses were reduced by 22% compared to pre-pandemic period. However, it is uncertain as to what has led to this reduction. Here, we model the association of maximum temperature and heat-related illnesses in the 47 Japanese prefectures. We specifically examined how the exposure and lag associations varied before and during the pandemic.

Methods

We obtained the summer-specific, daily heat-related illness ambulance transport (HIAT), exposure variable (maximum temperature) and covariate data from relevant data sources. We utilized a stratified (pre-pandemic and pandemic), two-stage approach. In each stratified group, we estimated the 1) prefecture-level association using a quasi-Poisson regression coupled with a distributed lag non-linear model, which was 2) pooled using a random-effects meta-analysis. The difference between pooled pre-pandemic and pandemic associations was examined across the exposure and the lag dimensions.

Results

A total of 321,655 HIAT cases was recorded in Japan from 2016 to 2020. We found an overall reduction of heat-related risks for HIAT during the pandemic, with a wide range of reduction (10.85 to 57.47%) in the HIAT risk, across exposure levels ranging from 21.69 °C to 36.31 °C. On the contrary, we found an increment in the delayed heat-related risks during the pandemic at Lag 2 (16.33%; 95% CI: 1.00, 33.98%).

Conclusion

This study provides evidence of the impact of COVID-19, particularly on the possible roles of physical interventions and behavioral changes, in modifying the temperature-health association. These findings would have implications on subsequent policies or heat-related warning strategies in light of ongoing or future pandemics.
Hepatic metastasis from perianal Paget’s disease without identified underlying carcinoma: a case report
Authors: Cao Yi-Sheng , Wang Shu-Yan
Published: December 2021

Background

Perianal Paget’s disease (PPD) is a rare malignancy, often associated with an underlying adenocarcinoma and a poor prognosis.

Case presentation

A 69-year-old female was presented with a history of perianal pruritus for 6 months and enlarged inguinal lymph nodes in the left side. Paget cells were confirmed by pathology after a wide excision of perianal skin. Radiotherapy was performed covering the bilateral inguinal lymphatic drainage area. Hepatic metastasis was found 8 months after surgery. Hepatic artery embolization (HAE) and high-intensity focused ultrasound therapy (HIFU) were performed successively. However, hepatic metastasis happened again 3 months later. Ultrasound-guided percutaneous radiofrequency ablation (PRFA) was carried out and various means of inspection could not identify the primary tumor. In the case of rapid progression of the tumor, we gave the patient chemotherapy regimens of XELOX. After 4 cycles of chemotherapy, the tumor marker went down continuously and the hepatic metastasis stayed stable.

Conclusions

Hepatic metastasis from perianal Paget’s disease without identified underlying carcinoma may benefit from XELOX on the basis of adenocarcinoma.
Systemic inflammasome activation and pyroptosis associate with the progression of amnestic mild cognitive impairment and Alzheimer’s disease
Authors: Rui Wenjuan , Xiao Hong , Fan Yi , Ma Zhongxuan , Xiao Ming , Li Sheng , Shi Jingping
Published: December 2021

Background

Growing evidence indicates that inflammasome-mediated inflammation plays important roles in the pathophysiology of amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD). Pyroptosis induced by inflammasome, and Gasdermin D (GSDMD) is involved in several neurodegenerative disorders. However, it is not clear whether peripheral inflammasome and pyroptosis are activated in aMCI and AD patients, influencing on neuroinflammation. The aim of this study was to examine the association between systemic inflammasome-induced pyroptosis and clinical features in aMCI and AD.

Methods

A total of 86 participants, including 33 subjects with aMCI, 33 subjects with AD, and 20 cognitively normal controls, in this study. The Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) scale were used for cognitive assessment. Levels of inflammasome-related genes/proteins in peripheral blood mononuclear cells (PBMCs) were determined using quantitative polymerase chain reaction and Western blotting. The levels of IL-1β, Aβ1-42, Aβ1-40, p-tau, and t-tau in cerebrospinal fluid (CSF), as well as the plasma IL-1β level, were measured by enzyme-linked immunosorbent assay. Finally, lipopolysaccharides (LPS) were used to investigate the effects of systemic inflammasome-induced pyroptosis in an AD mice model.

Results

Several genes involved in the inflammatory response were enriched in PBMCs of AD patients. The mRNA and protein levels of NLRP3, caspase-1, GSDMD, and IL-1β were increased in PBMCs of aMCI and AD patients. The IL-1β level in plasma and CSF of aMCI and AD patients was significantly higher than that in controls and negatively correlated with the CSF Aβ1-42 level, as well as MMSE and MoCA scores. Furthermore, there was a positive correlation between the IL-1β level in plasma and CSF of aMCI or AD patients. In vivo experiments showed that systemic inflammasome-induced pyroptosis aggravated neuroinflammation in 5 × FAD mice.

Conclusions

Our findings showed that canonical inflammasome signaling and GSDMD-induced pyroptosis were activated in PBMCs of aMCI and AD patients. In addition, the proinflammatory cytokine IL-1β was strongly associated with the pathophysiology of aMCI and AD. As such, targeting inflammasome-induced pyroptosis may be a new approach to inhibit neuroinflammation in aMCI and AD patients.
Maximising the wealth of few at the expense of the health of many: a public health analysis of market power and corporate wealth and income distribution in the global soft drink market
Authors: Wood Benjamin , Baker Phil , Scrinis Gyorgy , McCoy David , Williams Owain , Sacks Gary
Published: December 2021

Background

Many of the harms created by the global soft drink industry that directly influence human and planetary health are well documented. However, some of the ways in which the industry indirectly affects population health, via various socio-economic pathways, have received less attention. This paper aimed to analyse the extent to which market power and corporate wealth and income distribution in the global soft drink market negatively impact public health and health equity. In doing so, the paper sought to contribute to the development of a broad-based public health approach to market analysis. A range of dimensions (e.g., market concentration; financial performance; corporate wealth and income distribution) and indicators (e.g., Herfindahl Hirschman Index; earnings relative to the industry average; effective tax rates; and shareholder value ratios) were descriptively analysed. Empirical focus was placed on the two dominant global soft drink manufacturers.

Results

Coca-Cola Co, and, to a lesser extent, PepsiCo, operate across an extensive patchwork of highly concentrated markets. Both corporations control vast amounts of wealth and resources, and are able to allocate relatively large amounts of money to potentially harmful practices, such as extensive marketing of unhealthy products. Over recent decades, the proportion of wealth and income transferred by these firms to their shareholders has increased substantially; whereas the proportion of wealth and income redistributed by these two firms to the public via income taxes has considerably decreased. Meanwhile, the distribution of soft drink consumption is becoming increasingly skewed towards population groups in low and middle-income countries (LMICs).

Conclusions

Market power and corporate wealth and income distribution in the global soft drink market likely compound the market’s maldistribution of harms, and indirectly influence health by contributing to social and economic inequalities. Indeed, a ‘double burden of maldistribution’ pattern can be seen, wherein the wealth of the shareholders of the market’s dominant corporations, a group over-represented by a small and wealthy elite, is maximised largely at the expense of the welfare of LMICs and lower socioeconomic groups in high-income countries. If this pattern continues, the appropriate role of the global soft drink market as part of sustainable economic development will require rethinking.
Clinical and cost-effectiveness of a New psychosocial intervention to support Independence in Dementia (NIDUS-family) for family carers and people living with dementia in their own homes: a randomised controlled trial
Authors: Burton Alexandra , Rapaport Penny , Palomo Marina , Lord Kathryn , Budgett Jessica , Barber Julie , Hunter Rachael , Butler Laurie , Vickerstaff Victoria , Rockwood Kenneth , Ogden Margaret , Smith Debs , Lang Iain , Livingston Gill , Dow Briony , Kales Helen , Manthorpe Jill , Walters Kate , Hoe Juanita , Orgeta Vasiliki , Samus Quincy , Cooper Claudia ,   on behalf of the NIDUS study team
Published: December 2021

Background

Most people living with dementia want to remain living in their own homes and are supported to do so by family carers. No interventions have consistently demonstrated improvements to people with dementia’s life quality, functioning, or other indices of living as well as possible with dementia. We have co-produced, with health and social care professionals and family carers of people with dementia, a new intervention (NIDUS-family). To our knowledge, NIDUS-family is the first manualised intervention that can be tailored to personal goals of people living with dementia and their families and is delivered by facilitators without clinical training. The intervention utilizes components of behavioural management, carer support, psychoeducation, communication and coping skills training, enablement, and environmental adaptations, with modules selected to address dyads’ selected goals. We will evaluate the effect of NIDUS-family and usual care on goal attainment, as measured by Goal Attainment Scaling (GAS) rated by family carers, compared to usual care alone at 12-month follow-up. We will also determine whether NIDUS-family and usual care is more cost-effective than usual care alone over 12 months.

Methods

A randomised, two-arm, single-masked, multi-site clinical trial involving 297 people living with dementia-family carer dyads. Dyads will be randomised 2:1 to receive the NIDUS-family intervention with usual care (n = 199) or usual care alone (n = 98). The intervention group will be offered, over 1 year, via 6–8 video call or telephone sessions (or face to face if COVID-19 restrictions allow in the recruitment period) in the initial 6 months, followed by telephone follow-ups every 1–2 months to support implementation, with a trained facilitator.

Discussion

Increasing the time lived at home by people living with dementia is likely to benefit lives now and in the future. Our intervention, which we adapted to include remote delivery prior to trial commencement due to the COVID-19 pandemic, aims to address barriers to living as well and as independently as possible that distress people living with dementia, exacerbate family carer(s) stress, negatively affect relationships, lead to safety risks, and frequently precipitate avoidable moves to a care home.

Trial registration

International Standard Randomised Controlled Trials Number ISRCTN11425138. Registered on 7 October 2019