bluuebunny/crossref_metadata_2025 huggingface dataset:
Equivalency between the shock index and subtracting the systolic blood pressure from the heart rate: an observational cohort study
Authors: Kamikawa Yohei , Hayashi Hiroyuki
Published: October 2020

Background

Although the shock index is known to predict mortality and other severe outcomes, deriving it requires complex calculations. Subtracting the systolic blood pressure from the heart rate may produce a simple shock index that would be a clinically useful substitute for the shock index. In this study, we investigated whether the simple shock index was equivalent to the shock index.

Methods

This observational cohort study was conducted at 2 tertiary care hospitals. Patients who were transported by ambulance were recruited for this study and were excluded if they were aged < 15 years, had experienced prehospital cardiopulmonary arrest, or had undergone inter-hospital transfer. Pearson’s product-moment correlation coefficient and regression equation were calculated, and two one-sided tests were performed to examine their equivalency.

Results

Among 5429 eligible patients, the correlation coefficient between the shock index and simple shock index was extremely high (0.917, 95% confidence interval 0.912 to 0.921,P < .001). The regression equation was estimated as sSI = 258.55 log SI. The two one-sided tests revealed a very strong equivalency between the shock index and the index estimated by the above equation using the simple shock index (mean difference was 0.004, 90% confidence interval 0.003 to 0.005).

Conclusion

The simple shock index strongly correlated with the shock index.
Pharmacist and patient perspectives on recruitment strategies for randomized controlled trials: a qualitative analysis
Authors: Fletcher Jane M. , Saunders-Smith Terry , Manns Braden J. , Tsuyuki Ross , Hemmelgarn Brenda R. , Tonelli Marcello , Campbell David J. T.
Published: October 2020

Background

Although recruitment is a major challenge for most randomized controlled trials, few report on the difficulties of recruitment, or how it might be enhanced. The objective of our study was to qualitatively explore the experiences of both patients and pharmacists related to recruitment for ACCESS, a large trial involving low-income seniors, given that two of our most successful recruitment strategies were direct patient recruitment materials and use of community pharmacists.

Methods

Using qualitative descriptive methods, we collected data from pharmacists and study participants. Pharmacists were asked about their impressions of the study, as well as challenges they faced and methods they used to recruit potential participants. Focus groups with trial participants centered on the patient recruitment materials. Interviews and focus groups were recorded, transcribed and analyzed using thematic analysis.

Results

Pharmacists noted that their first impressions of the study were positive as they described being enticed to help the study team by the potential benefit of copayment elimination for their patients and the low time commitment. Pharmacists noted they were more likely to recruit if they were well informed on the study, as they could answer their patients’ questions. Participants noted that their primary motivations for participating were the tangible benefits of free medications and the intrinsic value of participating in research.

Conclusions

We noted that recruitment through pharmacies was an effective method as most patients have trusting relationships with their pharmacist. To optimize recruitment through pharmacies, study procedures should be straightforward, and pharmacists need to be equipped with good knowledge of the study. When promoting a study to potential participants, messaging should ensure the individuals are aware of the tangible benefits of participation while still presenting a full overview of the trial.

Trial registration

Trial Registration Number:NCT02579655– initially registered Oct 19, 2015.
Retrospective analysis of a dedicated care pathway for nonalcoholic fatty liver disease in an integrated US healthcare system demonstrates support of weight management and improved ALT
Authors: Patton Heather , Burchette Raoul , Tovar Stephanie , Pio Jose , Shi Jiaxiao , Nyberg Lisa M.
Published: October 2020

Background

A care pathway for nonalcoholic fatty liver disease (NAFLD) in Kaiser Permanente San Diego, California was instituted in August 2017 to improve efficiency of disease staging and promote lifestyle modification.

Methods

The NAFLD Care Pathway includes: (1) patient education (2) vibration controlled transient elastography (VCTE) examination (3) hepatology consultation for VCTE ≥ 8 kPa and (4) referral to weight management (WM). Patients referred to the pathway during the first 6 months of its implementation were studied for adherence to its components and impact on weight change and ALT values in the 12 months following referral. Retrospective assessment of WM participation, change in weight, and change in ALT were evaluated in the 12-months following referral and compared to changes 12-months prior. Student’s t-test or Wilcoxon signed rank test were used as appropriate (p < 0.05).

Results

632 patients were included. 575 (91.0%) completed VCTE examination with mean liver stiffness 8.5 kPa (SD 9.2). 52 patients had mean liver stiffness ≥ 15 kPa. 180/632 (28.5%) attended NAFLD education. 153/632 (24.2%) were offered hepatology clinic and 136/153 (88.9%) completed at least 1 appointment. Participation in WM was 24/632 (3.8%) prior to referral and 67/632 (10.6%) after referral and increased among patients who attended NAFLD education. Mean weight change following referral was − 0.69 kg (SD 6.58 kg) among patients without WM and − 7.78 kg (SD 13.43 kg) with WM. Overall, 44.2% of participants experienced weight gain after referral, 40.8% had weight loss < 5% and 15% had weight loss ≥ 5%. Variables associated with weight loss included WM (p < 0.0001) and higher liver stiffness (p = 0.0066). Mean ALT change was − 15.2 (SD 38.5) U/L without WM and − 28.8 (SD 29.6) U/L with WM.

Conclusions

A care pathway for NAFLD within a large, integrated healthcare system provides non-invasive disease staging and minimizes hepatology clinic utilization to those with more advanced disease. Referral was associated with increased enrollment in WM, weight loss, and decreased ALT. Given its impact on healthcare resources, strategies to improve NAFLD identification, staging, and promotion of lifestyle modification are imperative.
Changes in plasma bile acids are associated with gallbladder stones and polyps
Authors: Wu Linshi , Wang Yinping , Zhu Sibo , Bao Xunxia , Fu Zhiliang , Zhen Timing , Yuan Zhiqing , Li Qiwei , Deng Zheng , Sun Jianhua , Chen Tao
Published: October 2020

Background

The development of gallbladder disease (GBD) is related to bile acid (BA) metabolism, and the rate of BA circulation increases the risk of biliary cancer. However, it is unclear whether patterns of circulating bile acids (BAs) change in patients with benign GBDs such as gallbladder stones and polyps. Herein, we compared and characterised plasma BA profiles in patients with cholecystolithiasis and non-neoplastic polyps with healthy controls, and explored relationships between plasma BA profiles, demographics, and laboratory test indices.

Methods

A total of 330 subjects (13 healthy controls, 292 cholecystolithiasis and 25 non-neoplastic polyps) were recruited and plasma BA profiles including 14 metabolites from patients with pathologically confirmed cholecystolithiasis and non-neoplastic polyps were compared with controls. BAs were quantitated by liquid chromatography and mass spectrometry, and statistical and regression analyses of demographics and laboratory test indices were performed.

Results

Females displayed a higher burden of GBD than males (63.36% cholecystolithiasis, 60% non-neoplastic polyps). Cholecystolithiasis and non-neoplastic polyps were associated with increased plasma total secondary BAs, while levels of primary BAs were lower than in healthy controls. Plasma ursodeoxycholic acid (UDCA), tauroursodeoxycholic acid (TUDCA), glycyurdeoxycholic acid (GUDCA), taurochenodeoxycholic acid (TCDCA) and glycochenodeoxycholic acid (GCDCA) were decreased significantly in GBDs, and ursodeoxycholic acid (UDCA) was negatively correlated with white blood cell count and neutrophil percentage.

Conclusions

Secondary BA levels were higher in patients with cholecystolithiasis and non-neoplastic polyps. White blood cell count and percentage of neutrophil in peripheral blood were negatively correlated with UDCA, indicating an anti-inflammation effect of UDCA.
Changes in the provision of instrumental support by older adults in nine European countries during 2004—2015: a panel data analysis
Authors: Lestari S. K. , de Luna X. , Eriksson M. , Malmberg G. , Ng N.
Published: October 2020

Background

Providing support to others has been shown to be beneficial to older adults. As people age, their health and social relationships change. These changes may also relate to changes in social support provision. We examined the trajectory of instrumental support provision by older people in three European regions throughout 11 years of follow-up. We then examined the extent to which age at baseline, sex, and region (representing welfare state regime) influenced the variations in the trajectory.

Methods

Data collected from 8354 respondents who had completed at least waves 1 and 6 of the Survey of Health, Ageing and Retirement in Europe (SHARE) was analysed. Instrumental support provision was determined from asking a single question regarding whether the respondent provided help personally for people outside their household. Region, sex, and age at baseline were the main predictors tested. We used growth modelling to address the aims of this study.

Results

The northern European region (Sweden and Denmark) had the highest odds ratio of instrumental support provision. The likelihood of being involved in providing instrumental support decreased by 8% annually (OR: 0.916, 95%CI: 0.893,0.940) over the 11 years of follow-up. Older respondents were less likely to provide instrumental support and their trajectories declined faster than those of the younger respondents. Sex difference in instrumental support provision was more apparent among younger-older people in the southern European region.

Conclusions

Older European adults are an important source of instrumental support, especially for their families. The probability of instrumental support provision by European older adults declines over time. Age, sex, and welfare state regime predict this trajectory.
What do older adults with multimorbidity and polypharmacy think about deprescribing? The LESS study - a primary care-based survey
Authors: Rozsnyai Zsofia , Jungo Katharina Tabea , Reeve Emily , Poortvliet Rosalinde K. E. , Rodondi Nicolas , Gussekloo Jacobijn , Streit Sven
Published: October 2020

Background

Multimorbidity and polypharmacy are very common in older adults in primary care. Ideally, general practitioners (GPs), should regularly review medication lists to identify inappropriate medication(s) and, where appropriate, deprescribe. However, it remains challenging to deprescribe given time constraints and few recommendations from guidelines. Further, patient related barriers and enablers to deprescribing have to be accounted for. The aim of this study was to identify barriers and enablers to deprescribing as reported by older adults with polypharmacy and multimorbidity.

Methods

We conducted a survey among participants aged ≥70 years, with multimorbidity (≥3 chronic conditions) and polypharmacy (≥5 chronic medications). We invited Swiss GPs, to recruit eligible patients who then completed a paper-based survey on demographics, medications and chronic conditions. We used the revised Patients’ Attitudes Towards Deprescribing (rPATD) questionnaire and added twelve additional Likert scale questions and two open-ended questions to assess barriers and enablers towards deprescribing, which we coded and categorized into meaningful themes.

Result

Sixty four Swiss GPs consented to recruit 5–6 patients each and returned 300 participant responses. Participants were 79.1 years (SD 5.7), 47% female, 34% lived alone, and 86% managed their medications themselves. Sixty-seven percent of participants took 5–9 regular medicines and 24% took ≥10 medicines. The majority of participants (77%) were willing to deprescribe one or more of their medicines if their doctor said it was possible. There was no association with sex, age or the number of medicines and willingness to deprescribe. After adjustment for baseline characteristics, there was a strong positive association between willingness to deprescribe and saying that because they have a good relationship with their GP, they would feel that deprescribing was safe OR 11.3 (95% CI: 4.64–27.3) and agreeing that they would be willing to deprescribe if new studies showed an avoidable risk OR 8.0 (95% CI 3.79–16.9). From the open questions, the most mentioned barriers towards deprescribing were patients feeling well on their current medicines and being convinced that they need all their medicines.

Conclusions

Most older adults with polypharmacy are willing to deprescribe. GPs may be able to increase deprescribing by building trust with their patients and communicating evidence about the risks of medication use.
Novel variants of ABCA4 in Han Chinese families with Stargardt disease
Authors: Hu Fang-Yuan , Gao Feng-Juan , Li Jian-kang , Xu Ping , Wang Dan-Dan , Zhang Sheng-Hai , Wu Ji-Hong
Published: October 2020

Background

Stargardt disease (STGD1) is a common recessive hereditary macular dystrophy in early adulthood or childhood, with an estimated prevalence of 1:8000 to 1:10,000. ABCA4 is the causative gene for STGD1. The current study aims at identifying the novel disease-related ABCA4 variants in Han Chinese families with STGD1 using next-generation sequencing (NGS).

Methods

In the present study, 12 unrelated Han Chinese families (19 males and 17 females) with STGD1 were tested by panel-based NGS. In order to capture the coding exons and the untranslated regions (UTRs) plus 30 bp of intronic flanking sequences of 792 genes, which were closely associated with usual ophthalmic genetic disease, we designed a customized panel, namely, Target_Eye_792_V2 chip. STGD1 patients were clinically diagnosed by experienced ophthalmologists. All the detected variants were filtered and analyzed through the public databases and in silico programs to assess potential pathogenicity.

Results

Twenty-one ABCA4 mutant variants were detected in 12 unrelated Han Chinese families with STGD1, containing 14 missense, three splicing, two frameshift, one small deletion, and one nonsense variants. Base on the American College of Medical Genetics (ACMG) guidelines, 8 likely pathogenic and 13 pathogenic variants were determined. The functional consequences of these mutant variants were predicted through in silico programs. Of the 21 mutant variants in ABCA4, two novel coding variants c.3017G > A and c.5167 T > C and one novel null variant c.3051-1G > A were detected in three unrelated probands.

Conclusions

By panel-based NGS, 21 ABCA4 variants were confirmed in 12 unrelated Han Chinese families. Among them, 3 novel mutant variants were found, which further expanded the ABCA4 mutation spectrum in STGD1 patients.
Differential effects of different delivery methods on progression to severe postpartum hemorrhage between Chinese nulliparous and multiparous women: a retrospective cohort study
Authors: Xu Chang , Zhong Wanting , Fu Qiang , Yi Li , Deng Yuqing , Cheng Zhaohui , Lin Xiaojun , Cai Miao , Zhong Shilin , Wang Manli , Tao Hongbing , Xiong Haoling , Jiang Xin , Chen Yun
Published: October 2020

Background

Delivery methods are associated with postpartum hemorrhage (PPH) both in nulliparous and multiparous women. However, few studies have examined the difference in this association between nulliparous and multiparous women. This study aimed to explore the difference of maternal and neonatal characteristics and delivery methods between Chinese nulliparous and multiparous women, and then examine the differential effects of different delivery methods on PPH between these two-type women.

Methods

Totally 151,333 medical records of women who gave birth between April 2013 to May 2016 were obtained from the electronic health records (EHR) in a northern province, China. The severity of PPH was estimated and classified into blood loss at the level of < 900 ml, 900–1500 ml, 1500–2100 ml, and > 2100 ml. Neonatal and maternal characteristics related to PPH were derived from the same database. Multiple ordinal logistic regression was used to estimate associations.

Results

Medical comorbidities, placenta previa and accreta were higher in the nulliparous group and the episiotomy rate was higher in the multiparous group. Compared with spontaneous vaginal delivery (SVD), the adjusted odds (aOR) for progression to severe PPH due to the forceps-assisted delivery was much higher in multiparous women (aOR: 9.32; 95% CI: 3.66–23.71) than in nulliparous women (aOR: 1.70; 95% CI: 0.91–3.18). The (aOR) for progression to severe PPH due to cesarean section (CS) compared to SVD was twice as high in the multiparous women (aOR: 4.32; 95% CI: 3.03–6.14) as in the nulliparous women (aOR: 2.04; 95% CI: 1.40–2.97). However, the (aOR) for progression to severe PPH due to episiotomy compared to SVD between multiparous (aOR: 1.24; 95% CI: 0.96–1.62) and nulliparous women (aOR: 1.55; 95% CI: 0.92–2.60) was not significantly different. The (aOR) for progression to severe PPH due to vacuum-assisted delivery compared to SVD in multiparous women (aOR: 2.41; 95% CI: 0.36–16.29) was not significantly different from the nulliparous women (aOR: 1.05; 95% CI: 0.40–2.73).

Conclusions

Forceps-assisted delivery and CS methods were found to increase the risk of severity of the PPH. The adverse effects were even greater for multiparous women. Episiotomy and the vacuum-assisted delivery, and SVD were similar to the risk of progression to severe PPH in either nulliparous or multiparous women. Our findings have implications for the obstetric decision on the choice of delivery methods, maternal and neonatal health care, and obstetric quality control.
Multimodal imaging of Hurler syndrome-related keratopathy treated with deep anterior lamellar keratoplasty
Authors: Da Cunha Elodie , Georgeon Cristina , Bouheraoua Nacim , Putterman Marc , Brignole-Baudouin Françoise , Borderie Vincent M.
Published: October 2020

Background

Hurler syndrome-associated keratopathy is an exceedingly rare corneal disorder that requires corneal transplantation in advanced stages. Precise assessment of the corneal condition is necessary for deciding which type of keratoplasty (i.e., deep anterior lamellar or penetrating) should be proposed. We aimed to confront the results of multimodal imaging with those of histology in a case of Hurler syndrome-associated keratopathy.

Case presentation

A 16-year-old patient with Hurler’s syndrome treated with hematopoietic stem cell transplantation was referred for decreased vision related to advanced keratopathy. The patient was treated with deep anterior lamellar keratoplasty (DALK) in both eyes with uncomplicated outcome. Visual acuity improved from 0.1 (20/200) preoperatively to 0.32 (20/63) and 0.63 (20/32) after transplantation. The corneal endothelial cell density was 2400 cells/mm2 in both eyes 3 years after transplantation. In vivo confocal microscopy (IVCM) and spectral domain optical coherence tomography (SD-OCT) were performed preoperatively. The corneal buttons retrieved during keratoplasty were processed for histology. In SD-OCT scans, corneal opacities appeared as diffuse stromal hyperreflectivity associated with increased corneal thickness. IVCM showed diffuse cytoplasmic granular hyperreflectivity and rounded/ellipsoid aspects of keratocytes, presence of small intracellular vacuoles, and hyperreflective epithelial intercellular spaces. Bowman’s layer was thin and irregular. The corneal endothelium was poorly visualized but no endothelial damage was observed. Histology showed irregular orientation and organization of stromal lamellae, with the presence of macrophages whose cytoplasm appeared clear and granular. A perinuclear clear halo was visible within the epithelial basal cells. Bowman’s layer featured breaks and irregularities.

Conclusions

The observed corneal multimodal imaging features in mucopolysaccharidosis-related keratopathy were concordant with histology. Compared with standard histology, multimodal imaging allowed additional keratocyte features to be observed. It revealed both morphological and structural changes of all corneal layers but the endothelium. This information is essential for therapeutic management which should include DALK as the first-choice treatment in case of impaired visual acuity.
Primary pure angiosarcoma of the testis: a vanishingly rare malignancy. Case report and literature review
Authors: Walravens-Evans J. , Yao M. , Grannò S. , Arul D. , Chitale S.
Published: October 2020

Background

Primary pure angiosarcoma of the testis is an exceptionally rare testicular malignancy, which is poorly understood. We present the fifth and youngest case in the current medical literature. Additionally, all cases of angiosarcoma of the testicle, both occurring with associated germ cell tumour and without, were compared in an extended tabular format.

Case presentation

A 56-year old man presented with unilateral scrotal pain, swelling and erythema. Ultrasonography revealed two testicular lesions with a high suspicion of malignancy but serum tumour markers were negative. A radical orchidectomy was performed with clear surgical margins. Diagnosis of primary pure angiosarcoma of the testis was confirmed on subsequent histopathology.

Conclusions

Primary pure angiosarcoma is a rare testicular neoplasm. We present the fifth case in the literature. Clinical and radiological features are non-specific. The diagnosis is purely histological, with the pathologist choosing immunohistochemistry based on abnormal morphology. Local invasiveness is variable but metastatic sites are typical for extra-gonadal angiosarcomas. Primary pure testicular angiosarcoma diagnosis confers a relatively better prognosis compared to angiosarcoma arising in the context of a testicular germ cell tumour. While extra-gonadal angiosarcomas are associated with high rates of local recurrence following resection, in all cases of testicular angiosarcoma there were no local recurrences following radical orchidectomy. Surgical resection remains the most effective treatment for both subtypes of testicular angiosarcoma.
How and why do French medical students choose the specialty of infectious and tropical diseases? A national cross-sectional study
Authors: Peiffer-Smadja Nathan , Ardellier François-Daniel , Thill Pauline , Beaumont Anne-Lise , Catho Gaud , Osei Lindsay , Dubée Vincent , Bleibtreu Alexandre , Lemaignen Adrien , Thy Michaël
Published: October 2020

Background

Infectious and tropical diseases (ID) physicians are needed now more than ever to tackle existing and emerging global threats. However, in many countries, ID is not recognized as a qualifying specialty. The creation of ID residency in 2017 in France offers the opportunity to know how and why the specialty is chosen by medical students.

Methods

We first analyzed the choice of specialty of all French medical students in 2017 and 2018 according to their rank at the national exam that ends medical studies. A web questionnaire was then sent in January 2019 to all ID residents in France (n = 100) to assess the factors influencing their choice of specialty and their career plan.

Results

We analyzed the choice of 17,087 medical students. ID was the first-chosen specialty with a median national rank of 526/8539, followed by plastic surgery and ophthalmology. The questionnaire was completed by 90% of the French ID residents (n = 100). The most encouraging factors to choose ID were the multi-system approach of the specialty, the importance of diagnostic medicine and having done an internship in ID during medical school. The potential deterrents were the work-life balance, the workload and the salary.

Conclusions

The recent recognition of ID as a qualifying specialty in France can be considered a success insofar as the specialty is the most popular among all medical and surgical specialties. Individuals who choose ID are attracted by the intellectual stimulation of the specialty but express concerns about the working conditions and salaries.
Personality and learning styles in relation to attitudes towards interprofessional education: a cross-sectional study on undergraduate medical students during their clinical courses
Authors: Olsson Caroline , Lachmann Hanna , Kalén Susanne , Ponzer Sari , Mellstrand Navarro Cecilia
Published: October 2020

Background

Interprofessional Education (IPE) is now included in curricula in universities worldwide. It is known that there are differences in attitudes towards IPE among students, but less is known regarding how students’ personalities and learnings styles correspond with those attitudes. The aim of this study was to investigate whether personality traits and learning styles have any impact on medical students’ attitudes towards IPE.

Methods

Seventy nine medical students in their 9th term (63% females, mean age 29 years) were questioned regarding their attitudes towards IPE according to the Interdisciplinary Education Perception Scale questionnaire, the Kolb’s learning style and Big Five Inventory questionnaires. For all three instruments we used the Swedish translated versions.

Results

When investigated with a logistic regression, adjusting for age and gender, there were no significant associations between Big Five inventory, Kolb’s learning style and IEPS, except for the Reflective-Pragmatic learning style that was moderately associated with a higher IEPS score.

Conclusion

There was no clear correlation between personality, learning style and attitude towards IPE as measured by the IEPS among medical students in our study population. Further investigations would benefit from a combination of qualitative and quantitative design.
A critical realist evaluation of an integrated care project for vulnerable families in Sydney, Australia
Authors: Tennant E. , Miller E. , Costantino K. , De Souza D. , Coupland H. , Fotheringham P. , Eastwood J.
Published: October 2020

Background

Healthy Homes and Neighbourhoods (HHAN) Integrated Care Initiative was established to improve the care of families with complex health and social needs who reside in Sydney Local Health District. HHAN seeks to provide long-term multi-disciplinary care coordination as well as enhance capacity building and promote integrated care. The critical realist study reported here is part of the longitudinal development and evaluation of complex integrated health and social care interventions in Sydney, Australia.

Methods

We describe the qualitative component of a critical realist pilot case study aimed at exploring, explaining and refining emerging HHAN programme theories in relation to care coordination. Qualitative interviews were undertaken with HHAN clients (n = 12), staff and other stakeholders (n = 21). Interviews and coding used a context (C), mechanism (M) and outcome (O) framework. Inductive, deductive, retroductive and abductive modes of reasoning were used with the CMO heuristic tool to inform the developing programme theory.

Results

The mechanisms underpinning effective engagement of clients by care coordinators included: building trust, leveraging other family, social and organisational relationships, meeting clients on their own terms, demonstrating staff effectiveness as quickly as possible, and client empowerment. Mechanisms for enhancing care integration included knowledge transfer activities and shared learning among collaborators, structural and cultural changes, enhancing mutual respect, co-location of multidisciplinary and/or interagency staff and cultivating faith in positive change among staff.

Conclusions

Use of a critical realism case study approach served to elucidate the varied influences of contexts and mechanisms on programme outcomes, to highlight what works for whom and in what context. Findings supported the initial programme theory that engagement and trust building with clients, alongside enhanced collaboration and integration of services, improved outcomes for vulnerable families with complex needs. Further research is needed to explore the cost-effectiveness of integrated care initiatives, in view of the long term nature of service provision and the risk of staff burnout.
Describing the characteristics and healthcare use of high-cost acute care users at the end of life: a pan-Canadian population-based study
Authors: Qureshi Danial , Isenberg Sarina , Tanuseputro Peter , Moineddin Rahim , Quinn Kieran , Meaney Christopher , McGrail Kimberlyn , Seow Hsien , Webber Colleen , Fowler Robert , Hsu Amy
Published: October 2020

Background

A minority of individuals use a large portion of health system resources, incurring considerable costs, especially in acute-care hospitals where a significant proportion of deaths occur. We sought to describe and contrast the characteristics, acute-care use and cost in the last year of life among high users and non-high users who died in hospitals across Canada.

Methods

We conducted a population-based retrospective-cohort study of Canadian adults aged ≥18 who died in hospitals across Canada between fiscal years 2011/12–2014/15. High users were defined as patients within the top 10% of highest cumulative acute-care costs in each fiscal year. Patients were categorized as: persistent high users (high-cost in death year and year prior), non-persistent high users (high-cost in death year only) and non-high users (never high-cost). Discharge abstracts were used to measure characteristics and acute-care use, including number of hospitalizations, admissions to intensive-care-unit (ICU), and alternate-level-of-care (ALC).

Results

We identified 191,310 decedents, among which 6% were persistent high users, 41% were non-persistent high users, and 46% were non-high users. A larger proportion of high users were male, younger, and had multimorbidity than non-high users. In the last year of life, persistent high users had multiple hospitalizations more often than other groups. Twenty-eight percent of persistent high users had ≥2 ICU admissions, compared to 8% of non-persistent high users and only 1% of non-high users. Eleven percent of persistent high users had ≥2 ALC admissions, compared to only 2% of non-persistent high users and < 1% of non-high users. High users received an in-hospital intervention more often than non-high users (36% vs. 19%). Despite representing only 47% of the cohort, persistent and non-persistent high users accounted for 83% of acute-care costs.

Conclusions

High users – persistent and non-persistent – are medically complex and use a disproportionate amount of acute-care resources at the end of life. A greater understanding of the characteristics and circumstances that lead to persistently high use of inpatient services may help inform strategies to prevent hospitalizations and off-set current healthcare costs while improving patient outcomes.
Composition of gut and oropharynx bacterial communities in Rattus norvegicus and Suncus murinus in China
Authors: He Wen-qiao , Xiong Yi-quan , Ge Jing , Chen Yan-xia , Chen Xue-jiao , Zhong Xue-shan , Ou Ze-jin , Gao Yu-han , Cheng Ming-ji , Mo Yun , Wen Yu-qi , Qiu Min , Huo Shu-ting , Chen Shao-wei , Zheng Xue-yan , He Huan , Li Yong-zhi , You Fang-fei , Zhang Min-yi , Chen Qing
Published: October 2020

Background

Rattus norvegicus and Suncus murinus are important reservoirs of zoonotic bacterial diseases. An understanding of the composition of gut and oropharynx bacteria in these animals is important for monitoring and preventing such diseases. We therefore examined gut and oropharynx bacterial composition in these animals in China.

Results

Proteobacteria, Firmicutes and Bacteroidetes were the most abundant phyla in faecal and throat swab samples of both animals. However, the composition of the bacterial community differed significantly between sample types and animal species. Firmicutes exhibited the highest relative abundance in throat swab samples of R. norvegicus, followed by Proteobacteria and Bacteroidetes. In throat swab specimens of S. murinus, Proteobacteria was the predominant phylum, followed by Firmicutes and Bacteroidetes. Firmicutes showed the highest relative abundance in faecal specimens of R. norvegicus, followed by Bacteroidetes and Proteobacteria. Firmicutes and Proteobacteria had almost equal abundance in faecal specimens of S. murinus, with Bacteroidetes accounting for only 3.07%. The family Streptococcaceae was most common in throat swab samples of R. norvegicus, while Prevotellaceae was most common in its faecal samples. Pseudomonadaceae was the predominant family in throat swab samples of S. murinus, while Enterobacteriaceae was most common in faecal samples. We annotated 33.28% sequences from faecal samples of S. murinus as potential human pathogenic bacteria, approximately 3.06-fold those in R. norvegicus. Potential pathogenic bacteria annotated in throat swab samples of S. murinus were 1.35-fold those in R. norvegicus.

Conclusions

Bacterial composition of throat swabs and faecal samples from R. norvegicus differed from those of S. murinus. Both species carried various pathogenic bacteria, therefore both should be closely monitored in the future, especially for S. murinus.
Characterization of WWOX expression and function in canine mast cell tumors and malignant mast cell lines
Authors: Makii Rebecca , Cook Hanna , Louke Darian , Breitbach Justin , Jennings Ryan , Premanandan Christopher , Green Eric M. , Fenger Joelle M.
Published: October 2020

Background

The WW domain-containing oxidoreductase (WWOX) tumor suppressor gene is frequently lost in a variety of solid and hematopoietic malignancies in humans. Dysregulation of WWOX has been implicated as playing a key role in tumor cell survival, DNA damage repair, and genomic stability. The purpose of this study was to characterize WWOX expression in spontaneous canine mast cell tumors (MCTs) and malignant cell lines and investigate the potential contribution of WWOX loss on malignant mast cell behavior.

Methods/results

WWOX expression is decreased in primary canine MCTs and malignant mast cell lines compared to normal canine bone marrow-cultured mast cells. In transformed canine mastocytoma cell lines, overexpression of WWOX or WWOX knockdown had no effect on mast cell viability. Inhibition of WWOX enhanced clonogenic survival following treatment with ionizing radiation in the C2 mast cell line. Lastly, immunohistochemistry for WWOX was performed using a canine MCT tissue microarray, demonstrating that WWOX staining intensity and percent of cells staining for WWOX is decreased in high-grade MCTs compared to low-grade MCTs.

Conclusions

These data suggest that WWOX expression is attenuated or lost in primary canine MCTs and malignant mast cell lines. Given the observed increase in clonogenic survival in WWOX-deficient C2 mast cells treated with ionizing radiation, further investigation of WWOX and its role in mediating the DNA damage response in malignant mast cells is warranted.
Physiologically variable ventilation reduces regional lung inflammation in a pediatric model of acute respiratory distress syndrome
Authors: Dos Santos Rocha Andre , Fodor Gergely H. , Kassai Miklos , Degrugilliers Loic , Bayat Sam , Petak Ferenc , Habre Walid
Published: October 2020

Background

Benefits of variable mechanical ventilation based on the physiological breathing pattern have been observed both in healthy and injured lungs. These benefits have not been characterized in pediatric models and the effect of this ventilation mode on regional distribution of lung inflammation also remains controversial. Here, we compare structural, molecular and functional outcomes reflecting regional inflammation between PVV and conventional pressure-controlled ventilation (PCV) in a pediatric model of healthy lungs and acute respiratory distress syndrome (ARDS).

Methods

New-Zealand White rabbit pups (n = 36, 670 ± 20 g [half-width 95% confidence interval]), with healthy lungs or after induction of ARDS, were randomized to five hours of mechanical ventilation with PCV or PVV. Regional lung aeration, inflammation and perfusion were assessed using x-ray computed tomography, positron-emission tomography and single-photon emission computed tomography, respectively. Ventilation parameters, blood gases and respiratory tissue elastance were recorded hourly.

Results

Mechanical ventilation worsened respiratory elastance in healthy and ARDS animals ventilated with PCV (11 ± 8%, 6 ± 3%, p < 0.04), however, this trend was improved by PVV (1 ± 4%, − 6 ± 2%). Animals receiving PVV presented reduced inflammation as assessed by lung normalized [18F]fluorodeoxyglucose uptake in healthy (1.49 ± 0.62 standardized uptake value, SUV) and ARDS animals (1.86 ± 0.47 SUV) compared to PCV (2.33 ± 0.775 and 2.28 ± 0.3 SUV, respectively, p < 0.05), particularly in the well and poorly aerated lung zones. No benefit of PVV could be detected on regional blood perfusion or blood gas parameters.

Conclusions

Variable ventilation based on a physiological respiratory pattern, compared to conventional pressure-controlled ventilation, reduced global and regional inflammation in both healthy and injured lungs of juvenile rabbits.
The role of improved housing and living environments in malaria control and elimination
Authors: Carter Richard , Karunaweera Nadira D.
Published: October 2020

Malaria risk and endemicity is often associated with the nature of human habitation and living environment. The disappearance of malaria from regions where it had been endemic for centuries, such as coastal areas of southern England, has been attributed, at least in part, to improvement in the quality of housing. Moreover, indigenous malaria transmission ceased throughout England without the necessity to eliminate the vector mosquitoes. The principles of malaria transmission, as formulated following the thinking of the pioneers of malaria epidemiology, Ronald Ross and George Macdonald, show how this may happen. Malaria ceases to be sustainable where its reproduction number, R0, the number of new cases generated on average for each existing case of malaria, falls below 1. In the terms of a Ross/Macdonald analysis the reduced contact between humans and blood-feeding mosquitoes that is achieved through housing that is secure against mosquito entry can have a powerful effect in reducing malaria R0. The island of Sri Lanka, where malaria had been endemic probably for centuries previously, has reported no indigenous cases of malaria since 2012. The disappearance of malaria from Sri Lanka followed an effective attack upon malaria transmission by the Sri Lanka Anti Malaria Campaign. The targeted and enhanced efforts of this campaign launched in 1999, drove the malaria R0 below 1 for most of the period up to 2012, leading to a nearly continuous decline in malaria cases until their extinction. The decades leading up to the launch of these efforts were ones of general improvement of living environment and notably in the quality of housing stock. Studies in the late 1980s had shown that quality of housing in a highly malarious district of Sri Lanka was a strong determinant of malaria risk. Through its effects on malaria R0, improved housing is likely to have facilitated the malaria control and cessation of indigenous malaria transmission in Sri Lanka and that it will help reduce the risk of the re-introduction of malaria to the island.
Prognostic value of 18F-FDG PET and PET/CT for assessment of treatment response to neoadjuvant chemotherapy in breast cancer: a systematic review and meta-analysis
Authors: Han Sangwon , Choi Joon Young
Published: October 2020

Background

We performed a systematic review and meta-analysis to evaluate the prognostic significance of 18F-FDG PET and PET/CT for evaluation of responses to neoadjuvant chemotherapy (NAC) in breast cancer patients.

Methods

We searched PubMed, Embase, and the Cochrane Library databases until June 2020 to identify studies that assessed the prognostic value of 18F-FDG PET scans during or after NAC with regard to overall (OS) and disease-free survival (DFS). Hazard ratios (HRs) and their 95% confidence intervals (CIs) were pooled meta-analytically using a random-effects model.

Results

Twenty-one studies consisting of 1630 patients were included in the qualitative synthesis. Twelve studies investigated the use of PET scans for interim response evaluation (during NAC) and 10 studies assessed post-treatment PET evaluation (after NAC). The most widely evaluated parameter distinguishing metabolic responders from poor responders on interim or post-treatment PET scans was %ΔSUVmax, defined as the percent reduction of SUVmax compared to baseline PET, followed by SUVmax and complete metabolic response (CMR). For the 17 studies included in the meta-analysis, the pooled HR of metabolic responses on DFS was 0.21 (95% confidence interval [CI], 0.14–0.32) for interim PET scans and 0.31 (95% CI, 0.21–0.46) for post-treatment PET scans. Regarding the influence of metabolic responses on OS, the pooled HRs for interim and post-treatment PET scans were 0.20 (95% CI, 0.09–0.44) and 0.26 (95% CI, 0.14–0.51), respectively.

Conclusions

The currently available literature suggests that the use of 18F-FDG PET or PET/CT for evaluation of response to NAC provides significant predictive value for disease recurrence and survival in breast cancer patients and might allow risk stratification and guide rational management.
First-line support for assistance in breathing in children: statistical and health economic analysis plan for the FIRST-ABC trial
Authors: Orzechowska Izabella , Sadique M. Zia , Thomas Karen , Davis Peter , Morris Kevin P. , Mouncey Paul R. , Peters Mark J. , Richards-Belle Alvin , Tume Lyvonne N. , Ramnarayan Padmanabhan , Harrison David A.
Published: October 2020

Background

The FIRST-ABC trial comprises of two pragmatic, multicentre, parallel groups, non-inferiority randomised clinical trials designed to evaluate the clinical non-inferiority of first-line use of high flow nasal cannula (HFNC) to continuous positive airway pressure (CPAP) in critically ill children who require non-invasive respiratory support (NRS).

Objectives

To describe the pre-specified statistical and health economic analysis for the FIRST-ABC trial before completion of patient recruitment and data collection.

Methods

The statistical analysis plan was designed by the chief investigators and statisticians. We define the primary and secondary outcomes, summarise methods for data collection and safety monitoring, and present a detailed description of the planned statistical and health economic analysis.

Results

The primary clinical outcome is time to liberation from respiratory support. The primary effect estimate will be the adjusted hazard ratio, reported with a 95% confidence interval. As a sensitivity analysis, the primary analysis will be repeated using time to start weaning of NRS. Subgroup analyses will be performed to test for interactions between the effect of allocated treatment group and pre-specified baseline covariates. The health economic analysis will follow the intention-to-treat principle and report the mean (95% confidence interval) incremental costs, quality-adjusted life years (QALYs) and cost-effectiveness up to 6 months. All analyses will be performed separately for each of the two trials, and any results will not be combined.

Conclusion

The FIRST-ABC trial will assess the non-inferiority of HFNC compared to CPAP in two parallel trials with shared infrastructure (step-up RCT and step-down RCT). We have developed a pre-specified statistical and health economics analysis plan for the FIRST-ABC study before trial completion to minimise analytical bias.

Trial registration

ISRCTN ISRCTN60048867. Registered on 19 June 2019.
Comparative analysis of some bioactive compounds in leaves of different Aloe species
Authors: Andrea Bunea , Dumitrița Rugină , Florina Copaciu , Francisc Dulf , Anastasia Veres , Socaci Sonia , Adela Pintea
Published: October 2020

Although a vast number ofAloespecies are known, only theAloe veraandAloe arborescensspecies are currently used by cosmetic and pharmaceutical industries. Therefore, the current study aims to complete the existent literature data with new information on the phytochemical composition of some lesser-knownAloespecies, with the main focus on carotenoids and fatty acids. Among the analyzed species,Aloe aculeataandAloe feroxhad the highest content in carotenoids, the major pigments being lutein and β-carotene (according to HPLC analysis). The fatty acid profile of eachAloespecies was analysed by GC–MS. Linolenic and linoleic acids were the major polyunsaturated fatty acids found in higher percent inAloe ferox,Aloe spectabilisandAloe marlothii. Instead,Aloe aculeataproved to have a distinct fatty acid profile, rich in monounsaturated fatty acids. Species such asAloe arborescensandAloe marlothiiproved to have the highest antioxidant potential according to data of DPPH, ORAC, HPS assays, even if the richest one in vitamin C was found to beAloe spectabilis.Though the scientific research is mainly focused on the common speciesAloe barbadensis, the current data suggests that otherAloespecies could receive more attention from industry part, being great sources of bioactive compounds.
Adherence to veterinary recommendations for ectoparasiticides purchased by cat owners in the USA
Authors: Lavan Robert , Armstrong Rob , Normile Dorothy , Vaala Wendy
Published: October 2020

Background

Safe and effective flea and tick treatment options for cats are important in companion animal practice because of feline ectoparasite infestation prevalence and the potential for parasitic disease transmission. Retrospective cat owner purchasing transactions at United States of America (USA) veterinary clinics were obtained for three topical feline flea and tick ectoparasiticides. One medication, fluralaner, had a 12-week redosing interval, while two other medications (fipronil/s-methoprene/pyriproxyfen; imidacloprid/pyriproxyfen) were approved for monthly redosing. The annual number of doses purchased by cat owners was determined for each of the three medications and then compared between medications. The objective was to evaluate whether 12-week retreatment intervals resulted in a different duration of coverage compared to monthly treatments for ectoparasiticide products.

Methods

Study results were obtained by analyzing the transactional records from a commercial database derived from veterinary practice management software. The study database consisted of cat owner purchasing records from January 2017 through June 2019 from 671 veterinary practices representing 41,630 cats.

Results

Cat owners purchased an average of 1.5 doses of fluralaner per year which, based on a 12-week redosing interval, provides 4.2 months of treatment coverage. Cat owners who used monthly flea and tick medications respectively purchased 3.6 months (fipronil/s-methoprene/pyriproxyfen combination) and 2.8 months (imidacloprid/pyriproxyfen) annually of each of the two medications. Average yearly cat owner purchases of fluralaner provide a significantly longer duration of coverage than for cat owners purchasing fipronil/s-methoprene/pyriproxyfen (17% more) or imidacloprid/pyriproxyfen (50% more).

Conclusions

Cat owners who obtained a flea and tick treatment with a 12-week redosing interval (fluralaner) protected their cats for up to 17% or 50% longer duration each year, respectively, compared to the duration of protection obtained by cat owners who used a medication re-dosed monthly. Cat owners should increase their duration of flea and tick coverage to come closer to achieving veterinary recommendations.