bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical characteristics and risk factors of 47 cases with ruptured neuroblastoma in children
Authors: Qin Hong , Yang Shen , Cai Siyu , Ren Qinghua , Han Wei , Yang Wei , Cheng Haiyan , Ma Xiaoli , Wang Huanmin
Published: March 2020

Background

Neuroblastoma (NB) tumor rupture is a rare oncology emergency with a poor prognosis. We aimed to evaluate patient clinical characteristics and risk factors for ruptured NB.

Methods

A retrospective study of 47 patients with confirmed NB rupture between January 2009 and January 2019 at Beijing Children’s Hospital was conducted. To identify tumor rupture risk factors in high-risk NB patients, we included 93 consecutive non-ruptured high-risk NB patients from January 2017 to January 2019.

Results

The median age at presentation was 29 months (adrenal and retroperitoneum origin) for 47 ruptured NB patients. Spontaneous tumor rupture occurred in 22 cases; 18 cases occurred during or after the first chemotherapy cycle, and 7 occurred after core needle biopsy. Five patients died of tumor rupture, and 17 patients’ parents refused further antitumor therapy. Among the 25 remaining patients, 6 survived without disease, 5 received ongoing treatment and achieved stable disease, and 14 died. According to multivariate logistic regression analysis, a maximum primary tumor diameter > 13.20 cm and MYCN gene amplification were independent risk factors for tumor rupture within high-risk NB.

Conclusions

Tumor rupture is an uncommon, life-threatening event for NB patients; these patients are most likely to have poor outcomes due to tumor recurrence or rapid progression. Several treatment modalities, including symptomatic support therapy and chemotherapy, are important for saving lives and for developing NB risk-based treatment in the future.
Challenges in the cultural adaptation of the German Myeloma Patient Outcome Scale (MyPOS): an outcome measure to support routine symptom assessment in myeloma care
Authors: Gerlach Christina , Taylor Katherine , Ferner Marion , Munder Markus , Weber Martin , Ramsenthaler Christina
Published: March 2020

Background

Patients with multiple myeloma report more problems with quality of life (QoL) than other haematological malignancies over the course of their incurable illness. The patient-centred Myeloma Patient Outcome Scale (MyPOS) was developed to assess and monitor symptoms and supportive care factors in routine care. Our aim was to translate and culturally adapt the outcome measure to the German context, and to explore its face and content validity.

Methods

Translation and cultural adaptation following established guidelines used an exploratory, sequential mixed method study design. Steps included: (1) forward translation to German; (2) backward translation to English; (3) expert review; (4) focus groups with the target population (patients, family members, healthcare professionals) to achieve conceptual equivalence; (5) cognitive interviews using Tourangeau’s model with think-aloud technique to evaluate comprehension and acceptability; (6) final review. Results were analysed using thematic analysis.

Results

Cultural and linguistic differences were noted between the German and English original version. The focus groups (n = 11) and cognitive interviews (n = 9) both highlighted the need for adapting individual items and their answer options to the German healthcare context. Greater individuality regarding need for information with the right to not be informed was elaborated by patients. While the comprehensive nature of the tool was appreciated, item wording regarding satisfaction with healthcare was deemed not appropriate in the German context. Before implementation into routine care, patients’ concerns about keeping their MyPOS data confidential need to be addressed as a barrier, whereas the MyPOS itself was perceived as a facilitator/prompt for a patient-centred discussion of QoL issues.

Conclusion

With adaptations to answer options and certain items, the German version of the MyPOS can help monitor symptoms and problems afflicting myeloma patients over the course of the disease trajectory. It can help promote a model of comprehensive supportive and patient-centred care for these patients.
Intraocular endoscopy for the evaluation and treatment of hypotony due to a traumatic cyclodialysis: a case report
Authors: Bair Henry , Lin Chun-Ju , Lai Chun-Ting , Hsia Ning-Yi , Tsai Yi-Yu
Published: March 2020

Background

A cyclodialysis cleft often leads to direct communication between the anterior chamber and the suprachoroidal space. It is a rare condition that is encountered with blunt trauma, and less commonly, after surgery. Hypotony is the major sequelae that may lead to hypotonous maculopathy, optic disc edema, corneal folds, and astigmatism. These may cumulatively lead to visual loss. We describe how endoscopy in a cyclodialysis repair allowed us to accurately locate the cleft and guided its appropriate management avoiding unnecessary cryopexy.

Case presentation

A 41-year-old male experienced a traumatic cyclodialysis cleft, which resulted in persistent hypotony. Pars plana vitrectomy was performed to treat vitreous hemorrhage. Scleral indentation was attempted to visualize the cyclodialysis cleft. However, the depression distorted the visualization. Intraocular endoscopy was therefore used to evaluate the cleft. Guided by this assessment, only intraocular gas tamponade was used to reposition the ciliary body. The patient’s intraocular pressure was restored to 13 mmHg 3 days after the operation, and OCT confirmed cleft closure 1 month after the operation.

Conclusion

Endoscopy-assisted repair of cyclodialysis is an approach that enhances visualization and can guard against common causes of persistent cleft and hypotony, as well as reveal the causes of recurrent failure. Hence, it can eliminate unnecessary cryopexy that might worsen the hypotonous state. In our case, intraocular endoscopy was effective for the evaluation of a cyclodialysis cleft and the subsequent selection of an appropriate management technique, gas tamponade, that was more conservative than other approaches initially considered.
A case of severe malnutrition infant with neonatal onset intractable diarrhea
Authors: Fang Youhong , Luo Youyou , Yu Jindan , Chen Jie
Published: March 2020

Background

Congenital tufting enteropathy (CTE) is a rare disease that manifests as intractable diarrhea during the neonatal period which is associated with mutations of the epithelial cell adhesion molecule (EpCAM) gene.

Case presentation

A male infant who presented with vomiting, diarrhea, abdominal distention, malnutrition and growth failure was admitted to our department when he was 2 months old. His parents were healthy and nonconsanguineous. Etiologic examinations of stool, inflammatory markers, blood gas and electrolytes levels, serum albumin level, serum immunoglobin levels were all normal. And there was no indication for metabolic diseases. Additionally, gastrointestinal contrast did not reveal abnormality of gastrointestinal. The patient was diagnosed with intestinal malabsorptive syndrome and severe malnutrition without definite cause. He was on supportive treatment and nutritional therapy for 13 months. However, he did not gain weight obviously. He was discharged at the age of 15 months and was fed with partial hydrolyzed formula and rice paste at home. Three months later he developed hypoglycemia and severe respiratory infection. Finally, he died due to sepsis and multiple organs failure. The next generation sequencing revealed one homozygous mutation ofEpCAMgene and one complex heterozygous mutation ofTTC7Agene. He was diagnosed CTE according to the genetic results and clinical manifestations.

Conclusions

CTE is rarely reported in Asia. Patients present with congenital diarrhea, poor weight gain and growth failure are recommended to perform endoscopy examination with proper immunohistochemistry study as early as possible, and genetic testing is necessary when suspecting congenital diarrhea and enteropathy.
Water, sanitation and hygiene practices associated with improved height-for-age, weight-for-height and weight-for-age z-scores among under-five children in Nepal
Authors: Shrestha Som Kumar , Vicendese Don , Erbas Bircan
Published: March 2020

Background

Evidence of the influence of water, sanitation and hygiene (WASH) behaviors on childhood nutritional status is inconsistent. Few studies have examined their interactive effects. This study aimed to examine associations and interactions between WASH variables and preschool child undernutrition.

Methods

Data from a nationally representative sample of 2352 children assessed during the 2016 Nepal Demographic and Health Survey were analyzed by multi-variable linear regression to understand the association between height-for-age (HAZ), weight-for-height (WHZ) and weight-for-age (WAZ) z-scores and WASH variables. Interactions between WASH variables, sex and area of residence on childhood nutritional status were also examined.

Results

The mean z-score [standard deviation] for children’s WAZ, HAZ and WHZ scores were − 1.33 [1.1], − 1.52 [1.3] and − 0.65 [1.1], respectively. A unit increase in cluster sanitation coverage was associated with an increase of 0.30 (95%CI: 0.12 to 0.48) for WAZ and 0.28 (95%CI: 0.001 to 0.56) for HAZ scores. Household water purification practice was associated with an increase of 0.24 (95%CI: 0.07 to 0.41) in WHZ score. Handwashing practice with water and soap was associated with an increase of 0.15 (95%CI: 0.04 to 0.25) in WAZ and 0.13 (95%CI: 0.01 to 0.24) in WHZ scores. The effect of water purification practice was higher for rural areas compared to urban settings for HAZ scores (p-value for interaction = 0.02).

Conclusions

Consistent with findings from other countries in the South Asian region, findings of this study highlight the potential importance of good WASH practices, and therefore the potential of WASH interventions, to contribute to improved nutritional status in rural Nepal.
Correction to: Dimensions of leisure-time physical activity and risk of depression in the “Seguimiento Universidad de Navarra” (SUN) prospective cohort
Authors: Fernandez-Montero Alejandro , Moreno-Galarraga Laura , Sánchez-Villegas Almudena , Lahortiga-Ramos Francisca , Ruiz-Canela Miguel , Martínez-González Miguel Ángel , Molero Patricio
Published: March 2020

After publication of our article [1] we have been notified that Table 2 was incorrectly formatted.
Time trends in smoking in Russia in the light of recent tobacco control measures: synthesis of evidence from multiple sources
Authors: Shkolnikov Vladimir M. , Churilova Elena , Jdanov Dmitry A. , Shalnova Svetlana A. , Nilssen Odd , Kudryavtsev Alexander , Cook Sarah , Malyutina Sofia , McKee Martin , Leon David A.
Published: March 2020

Background

The study aims at identifying long-term trends and patterns of current smoking by age, gender, and education in Russia, including the most recent period from 2008 during which tobacco control policies were implemented, and to estimate the impact on mortality of any reductions in prevalence. We present an in-depth analysis based on an unprecedentedly large array of survey data.

Methods

We examined pooled micro-data on smoking from 17 rounds of the Russian Longitudinal Monitoring Study of 1996–2016, 11 other surveys conducted in Russia in 1975–2017, and two comparator surveys from England and the USA. Standardization by age and education, regression and meta-analysis were used to estimate trends in the prevalence of current smoking by gender, age, and educational patterns.

Results

From the mid-1970s to the mid-2000s smoking prevalence among men was relatively stable at around 60%, after which time prevalence declined in every age and educational group. Among women, trends in smoking were more heterogeneous. Prevalence more than doubled above the age of 55 years from very low levels (< 5%). At younger ages, there were steep increases until the mid-2000s after which prevalence has declined. Trends differed by educational level, with women in the lowest educational category accounting for most of the long-term increase. We estimate that the decline in male smoking may have contributed 6.2% of the observed reduction in cardiovascular deaths among men in the period 2008–16.

Conclusions

The implementation of an effective tobacco control strategy in Russia starting in 2008 coincided with a decline in smoking prevalence among men from what had been stable, high levels over many decades regardless of age and education. Among women, the declines have been more uneven, with young women showing recent downturns, while the smoking prevalence in middle age has increased, particularly among those with minimal education. Among men, these positive changes will have made a small contribution to the reduction in mortality seen in Russia since 2005.
Combining national survey with facility-based HIV testing data to obtain more accurate estimate of HIV prevalence in districts in Uganda
Authors: Ouma Joseph , Jeffery Caroline , Valadez Joseph J. , Wanyenze Rhoda K. , Todd Jim , Levin Jonathan
Published: March 2020

Background

National or regional population-based HIV prevalence surveys have small sample sizes at district or sub-district levels; this leads to wide confidence intervals when estimating HIV prevalence at district level for programme monitoring and decision making. Health facility programme data, collected during service delivery is widely available, but since people self-select for HIV testing, HIV prevalence estimates based on it, is subject to selection bias. We present a statistical annealing technique, Hybrid Prevalence Estimation (HPE), that combines a small population-based survey sample with a facility-based sample to generate district level HIV prevalence estimates with associated confidence intervals.

Methods

We apply the HPE methodology to combine the 2011 Uganda AIDS indicator survey with the 2011 health facility HIV testing data to obtain HIV prevalence estimates for districts in Uganda. Multilevel logistic regression was used to obtain the propensity of testing for HIV in a health facility, and the propensity to test was used to combine the population survey and health facility HIV testing data to obtain the HPEs. We assessed comparability of the HPEs and survey-based estimates using Bland Altman analysis.

Results

The estimates ranged from 0.012 to 0.178 and had narrower confidence intervals compared to survey-based estimates. The average difference between HPEs and population survey estimates was 0.00 (95% CI: − 0.04, 0.04). The HPE standard errors were 28.9% (95% CI: 23.4–34.4) reduced, compared to survey-based standard errors. Overall reduction in HPE standard errors compared survey-based standard errors ranged from 5.4 to 95%.

Conclusions

Facility data can be combined with population survey data to obtain more accurate HIV prevalence estimates for geographical areas with small population survey sample sizes. We recommend use of the methodology by district level managers to obtain more accurate HIV prevalence estimates to guide decision making without incurring additional data collection costs.
What have we learnt from measles outbreaks in 3 English cities? A qualitative exploration of factors influencing vaccination uptake in Romanian and Roma Romanian communities
Authors: Bell Sadie , Saliba Vanessa , Ramsay Mary , Mounier-Jack Sandra
Published: March 2020

Background

Since 2016, large scale measles outbreaks have heavily affected countries across Europe. In England, laboratory confirmed measles cases increased almost four-fold between 2017 and 2018, from 259 to 966 cases.

Several of the 2017–18 measles outbreaks in England particularly affected Romanian and Roma Romanian communities, with the first outbreaks in these communities occurring in Birmingham, Leeds and Liverpool. This study explored factors influencing vaccination behaviours amongst Romanian and Roma Romanian communities in these three cities.

Methods

Across Birmingham, Leeds and Liverpool, we conducted semi-structured interviews with 33 key providers to explore their experience in delivering vaccinations and managing the outbreak response. We also interviewed 9 Romanian women in one of the cities to explore their vaccination attitudes and behaviours. To categorise factors affecting vaccination we applied the 5As Taxonomy for Determinants of Vaccine Uptake (Access, Affordability, Awareness, Acceptance and Activation) during data analysis.

Results

Factors related to access and acceptance, such as language and literacy, ease of registering with a general practice, and trust in health services, were reported as the main barriers to vaccination amongst the communities. Concerns around vaccination safety and importance were reported but these appeared to be less dominant contributing factors to vaccination uptake. The active decline of vaccinations amongst interviewed community members was linked to distrust in healthcare services, which were partly rooted in negative experiences of healthcare in Romania and the UK.

Conclusion

Access and acceptance, dominant barriers to vaccination, can be improved through the building of trust with communities. To establish trust providers must find ways to connect with and develop a greater understanding of the communities they serve. To achieve this, cultural and linguistic barriers need to be addressed. Better provider-service user relationships are crucial to reducing vaccination inequalities and tackling broader disparities in health service access.
Risk of wheezing and asthma exacerbation in children treated with paracetamol versus ibuprofen: a systematic review and meta-analysis of randomised controlled trials
Authors: Sherbash Mohamed , Furuya-Kanamori Luis , Nader Joanne Daghfal , Thalib Lukman
Published: March 2020

Background

Paracetamol and ibuprofen are the most commonly used medications for fever and pain management in children. While the efficacy appears similar with both drugs, there are contradictory findings related to adverse events. In particular, incidence of wheezing and asthma among children taking paracetamol compared to ibuprofen, remain unsettled.

Methods

We conducted a meta-analysis of randomized controlled trials (RCTs) that compared wheezing and asthma exacerbations in children taking paracetamol versus ibuprofen. A comprehensive search was conducted in five databases. RCTs reporting on cases of wheezing or asthma exacerbations in infants or children after the administration of paracetamol or ibuprofen were included. The pooled effect size was estimated using the Peto’s odds ratio.

Results

Five RCTs with 85,095 children were included in the analysis. The pooled estimate (OR 1.05; 95%CI 0.76–1.46) revealed no difference in the odds of developing asthma or presenting an exacerbation of asthma in children who received paracetamol compared to ibuprofen. When the analysis was restricted to RCTs that examined the incidence of asthma exacerbation or wheezing, the pooled estimate remained similar (OR 1.01; 95%CI 0.63–1.64). Additional bias adjusted quality effect sensitivity model yielded similar results (RR 1.03; 95%CI 0.84–1.28).

Conclusion

Although, Ibuprofen and paracetamol appear to have similar tolerance and safety profiles in terms of incidence of asthma exacerbations in children, we suggest high quality trials with clear definition of asthma outcomes after receiving ibuprofen or paracetamol at varying doses with longer follow-up are warranted for any conclusive finding.
The rat model of COPD skeletal muscle dysfunction induced by progressive cigarette smoke exposure: a pilot study
Authors: Su Jianqing , Li Jian , Lu Yufan , Li Ning , Li Peijun , Wang Zhengrong , Wu Weibing , Liu Xiaodan
Published: March 2020

Background

Chronic obstructive pulmonary disease (COPD) skeletal muscle dysfunction is a prevalent malady that significantly affects patients’ prognosis and quality of life. Although the study of this disease has attracted considerable attention, a definite animal model is yet to be established. This study investigates whether smoke exposure could lead to the development of a COPD skeletal muscle dysfunction model in rats.

Methods

Sprague Dawley rats were randomly divided into model (MG, n = 8) and control groups (CG, n = 6). The MG was exposed to cigarette smoke for 16 weeks while the CG was not. The body weight and forelimb grip strength of rats were monitored monthly. The pulmonary function and the strength of tibialis anterior muscle were assessed in vitro and compared after establishing the model. The histological changes in lung and gastrocnemius muscles were observed. The expressions of interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α were detected by ELISA, while the expressions of Atrogin-1 and MuRF1 in the gastrocnemius muscle were determined by Western blotting.

Results

Smoke exposure slowly increases the body weight and forelimb grip strength of MG rats, compared to CG rats. However, it significantly decreases the pulmonary ventilation function and the skeletal muscle contractility of the MG in vitro. Histologically, the lung tissues of MG show typical pathological manifestations of emphysema, while the skeletal muscles present muscular atrophy. The expressions of IL-6, IL-8, and TNF-α in MG rats are significantly higher than those measured in CG rats. Increased levels of Atrogin-1 and MuRF1 were also detected in the gastrocnemius muscle tissue of MG.

Conclusion

Progressive smoking exposure decreases the contractile function of skeletal muscles, leading to muscular atrophy. It also increases the expressions of inflammatory and muscle protein degradation factors in COPD rats. This indicates that smoke exposure could be used to establish a COPD skeletal muscle dysfunction model in rats.
Validity of EQ-5D utility index and minimal clinically important difference estimation among patients with chronic obstructive pulmonary disease
Authors: Bae Eunmi , Choi Sang-Eun , Lee Haeyoung , Shin Gyeongseon , Kang Daewon
Published: March 2020

Background

The discriminatory ability of multi-attribute utility (MAU) measures compared to condition-specific measures (CSM) in assessing health-related quality of life (HRQoL) among patients with chronic obstructive pulmonary disease (COPD) is an unsettled issue. This study investigated the quality of life of patients with COPD with three different HRQoL instruments and examined whether they could differentiate between adjacent severity groups in a statistically and clinically meaningful manner. In the process, the minimal clinically important differences (MCID) of the EQ-5D utility index were estimated.

Methods

Cross-sectional survey data were collected from patients with mild to very severe COPD in South Korea. In addition to demographic and clinical information, the following HRQoL questionnaires were used: The three-level five-dimensional Euro-Quality of Life tool (EQ-5D-3L), the EQ-Visual Analog Scale (EQ-VAS), and the Chronic Obstructive Pulmonary Disease Assessment Test (CAT). Patients’ health-related quality of life was analyzed with reference to severity groups based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. To investigate the discriminatory ability of the HRQoL instruments between COPD severity groups, tests examining variance, covariance, and standardized mean difference were performed. After estimating the MCID of the EQ-5D utility index using the anchor-based method, we investigated whether the differences in the EQ-5D utility scores between groups exceeded the clinically meaningful minimum level.

Results

A total of 298 patients completed this study. All the quality of life scores showed statistically significant differences between the GOLD severity groups. The pooled MCID estimate for the EQ-5D utility index was 0.028 (range: 0.017–0.033). Even after adjusting for other factors affecting quality of life, the EQ-5D utility index differentiated the GOLD groups well.

Conclusions

We conclude that the EQ-5D utility index is a valid instrument for measuring the quality of life of patients with COPD, and the pooled MCID estimate for the EQ-5D utility index was 0.028.
Moral distress and burnout in caring for older adults during medical school training
Authors: Perni Subha , Pollack Lauren R. , Gonzalez Wendy C. , Dzeng Elizabeth , Baldwin Matthew R.
Published: March 2020

Background

Moral distress is a reason for burnout in healthcare professionals, but the clinical settings in which moral distress is most often experienced by medical students, and whether moral distress is associated with burnout and career choices in medical students is unknown. We assessed moral distress in medical students while caring for older patients, and examined associations with burnout and interest in geriatrics.

Methods

A cross-sectional survey study of second-, third-, and fourth-year medical students at an American medical school. The survey described 12 potentially morally distressing clinical scenarios involving older adult patients. Students reported if they encountered each scenario, and whether they experienced moral distress, graded on a 1–10 scale. We conducted a principal axis factor analysis to assess the dimensionality of the survey scenarios. A composite moral distress score was calculated as the sum of moral distress scores across all 12 scenarios. Burnout was assessed using the Maslach Abbreviated Burnout Inventory, and interest in geriatrics was rated on a 7-point Likert scale.

Results

Two-hundred and nine students responded (47%), of whom 90% (188/209) reported moral distress in response to ≥1 scenario with a median (IQR) score of 6 (4–7). Factor analysis suggested a unidimensional factor structure of the 12 survey questions that reliably measured individual distress (Cronbach alpha = 0.78). Those in the highest tertile of composite moral distress scores were more likely to be burnt out (51%) than those in the middle tertile of scores (34%), or lowest tertile of scores (31%) (p = 0.02). There was a trend towards greater interest in geriatrics among those in the higher tertiles of composite moral distress scores (16% lowest tertile, 20% middle tertile, 25% highest tertile,p-for-tend = 0.21). Respondents suggested that moral distress might be mitigated with didactic sessions in inpatient geriatric care, and debriefing sessions with peers and faculty on the inpatient clerkships on medicine, neurology, and surgery, where students most often reported experiencing moral distress.

Conclusions

Moral distress is highly prevalent among medical students while caring for older patients, and associated with burnout. Incorporating geriatrics education and debriefing sessions into inpatient clerkships could alleviate medical student moral distress and burnout.
Personal decision support for survivor engagement: formulation and feasibility evaluation of a conceptual framework for implementing online cancer survivorship care plans
Authors: Kapoor Akshat , Nambisan Priya
Published: March 2020

Background

Although cancer survivorship care plans have been in use for several years, they have been shown to not be effective in meeting the long-term needs of cancer survivors, in addition being generic and passive in nature. Interactive survivorship care plans in the form of a personal decision support aid could provide an opportunity to not only engage survivors in their health care, but also capture meaningful treatment-related outcomes to use as a rich data source as the basis for making informed decisions. The objective of this research is to formulate an evidence-based model framework for implementing breast cancer survivorship guidelines via an online breast cancer survivorship care plan (SCP).

Methods

The study was completed in three steps. In the first step, or the requirements gathering phase, we conducted personal interviews of breast cancer survivors to determine their use of the survivorship care plan (SCP) and related needs to determine core SCP functions and formulate an implementation framework for an online SCP. In the second step, we used the framework as a guide to design and develop the online SCP tool. Finally, in the third step, we conducted preliminary testing to determine the feasibility of the developed tool among online users.

Results

Fifteen breast cancer survivors were consulted, who reported several issues from their use of the traditional paper-based SCP. Four themes were identified that represent the SCP’s core desired functions. Eight features were matched to implement these core functions. Using a personal decision approach, an online SCP tool called ACESO that incorporates these features and functions was developed. Preliminary feasibility testing yielded overall positive responses from breast cancer survivors (n = 51).

Conclusion

Our study demonstrated that survivors face challenges from their use of a traditional paper-based SCP. The online SCP we developed is technically feasible and has the potential to effectively engage breast cancer survivors in self-management and shared decision-making with their clinicians and caregivers. Further testing is required to assess its usability and long-term impact.
A proportional rule for setting reimbursement prices of new drugs and its mathematical consistency
Authors: Gandjour Afschin
Published: March 2020

Background

Value-based pricing (VBP) of new drugs has been suggested both as a way to control health expenditures and to maximize health benefits based on the available resources. The purpose of this work is to present a simple mathematical proof showing that prices of new drugs are set in a mathematically consistent way when the sum of intervention and downstream costs is proportional to the size of health benefits. Such proportional relationship underlies the efficiency-frontier method used by the German Institute for Quality and Efficiency in Health Care (IQWiG).

Methods

A proof by contradiction is presented that is based upon the following three premises: 1) total costs (intervention plus downstream costs) of existing non-dominated drugs and interventions are acceptable to decision-making bodies; 2) new drugs with health benefits in-between those of the most and second most effective existing interventions are not automatically excluded from reimbursement and are acceptable if prices are sufficiently low; and 3) value is measured on a cardinal scale.

Result

The proof shows that a proportional rule sets reimbursement prices of new drugs in a mathematically consistent way.

Conclusion

Based on the proof and the underlying assumptions a proportional relationship between costs and health benefits ensures mathematical consistency in VBP of drugs.
Clinical-grade cryopreserved doxorubicin-loaded platelets: role of cancer cells and platelet extracellular vesicles activation loop
Authors: Wu Yu-Wen , Huang Cheng-Chain , Changou Chun Austin , Lu Long-Sheng , Goubran Hadi , Burnouf Thierry
Published: March 2020

Background

Human platelets (PLT) and PLT-extracellular vesicles (PEV) released upon thrombin activation express receptors that interact with tumour cells and, thus, can serve as a delivery platform of anti-cancer agents. Drug-loaded nanoparticles coated with PLT membranes were demonstrated to have improved targeting efficiency to tumours, but remain impractical for clinical translation. PLT and PEV targeted drug delivery vehicles should facilitate clinical developments if clinical-grade procedures can be developed.

Methods

PLT from therapeutic-grade PLT concentrate (PC; N > 50) were loaded with doxorubicin (DOX) and stored at − 80 °C (DOX-loaded PLT) with 6% dimethyl sulfoxide (cryopreserved DOX-loaded PLT). Surface markers and function of cryopreserved DOX-loaded PLT was confirmed by Western blot and thromboelastography, respectively. The morphology of fresh and cryopreserved naïve and DOX-loaded PLT was observed by scanning electron microscopy. The content of tissue factor-expressing cancer-derived extracellular vesicles (TF-EV) present in conditioned medium (CM) of breast cancer cells cultures was measured. The drug release by fresh and cryopreserved DOX-loaded PLT triggered by various pH and CM was determined by high performance liquid chromatography. The thrombin activated PEV was analyzed by nanoparticle tracking analysis. The cellular uptake of DOX from PLT was observed by deconvolution microscopy. The cytotoxicities of DOX-loaded PLT, cryopreserved DOX-loaded PLT, DOX and liposomal DOX on breast, lung and colon cancer cells were analyzed by CCK-8 assay.

Results

15~36 × 106 molecules of DOX could be loaded in each PLT within 3 to 9 days after collection. The characterization and bioreactivity of cryopreserved DOX-loaded PLT were preserved, as evidenced by (a) microscopic observations, (b) preservation of important PLT membrane markers CD41, CD61, protease activated receptor-1, (c) functional activity, (d) reactivity to TF-EV, and (e) efficient generation of PEV upon thrombin activation. The transfer of DOX from cryopreserved PLT to cancer cells was achieved within 90 min, and stimulated by TF-EV and low pH. The cryopreserved DOX-loaded PLT formulation was 7~23-times more toxic to three cancer cells than liposomal DOX.

Conclusions

Cryopreserved DOX-loaded PLT can be prepared under clinically compliant conditions preserving the membrane functionality for anti-cancer therapy. These findings open perspectives for translational applications of PLT-based drug delivery systems.
Long-term LVEF trajectories in patients with type 2 diabetes and heart failure: diabetic cardiomyopathy may underlie functional decline
Authors: Julián María Teresa , Alonso Núria , Lupón Josep , Gavidia-Bovadilla Giovana , Ferrer Elena , de Antonio Marta , López-Ayerbe Jorge , Domingo Mar , Santiago-Vacas Evelyn , Zamora Elisabet , Codina Pau , Moliner Pedro , Núñez Julio , Santesmases Javier , Puig-Domingo Manel , Bayes-Genis Antoni
Published: March 2020

Background

Left ventricular ejection fraction (LVEF) trajectories and functional recovery with current heart failure (HF) management is increasingly recognized. Type 2 diabetes mellitus (T2D) leads to a worse prognosis in HF patients. However, it is unknown whether T2D interferes with LVEF trajectories. The aim of this study was to prospectively assess very long-term (up to 15 years) LVEF trajectories in patients with and without T2D and underlying HF.

Methods

Ambulatory patients admitted to a multidisciplinary HF clinic were prospectively evaluated by scheduled two-dimensional echocardiography at baseline, 1 year, and then every 2 years afterwards, up to 15 years. Statistical analyses of LVEF change with time were performed using the linear mixed effects (LME) models, and locally weighted error sum of squares (Loess) curves were plotted.

Results

Of the 1921 patients, 461 diabetic and 699 non-diabetic patients with LVEF < 50% were included in the study. The mean number of echocardiography measurements performed in diabetic patients was 3.3 ± 1.6. Early LVEF recovery was similar in diabetic and non-diabetic patients, but Loess curves showed a more pronounced inverted U shape in diabetics with a more pronounced decline after 9 years. LME analysis showed a statistical interaction between T2D and LVEF trajectory over time (p = 0.009), which was statistically significant in patients with ischemic etiologies (p < 0.001). Other variables that showed an interaction between LVEF trajectories and T2D were male sex (p = 0.04) and HF duration (p = 0.008).

Conclusions

LVEF trajectories in T2D patients with depressed systolic function showed a pronounced inverted U shape with a marked decline after 9 years. Diabetic cardiomyopathy may underlie the functional decline observed.
Simultaneous determination of five essential amino acids in plasma of Hyperlipidemic subjects by UPLC-MS/MS
Authors: Chen Zhibin , Lin Feiyan , Ye Xuemei , Dong Yuqian , Hu Lufeng , Huang Aifang
Published: March 2020

Background

Millions of adults have been reported with hyperlipemia in the world. It is still unclear whether the plasma level of essential amino acids (AAs) will be influenced by the hyperlipemia. This study was aimed to investigate the AAs levels and the underlying metabolic relationship in hyperlipidemic subjects.

Methods

An ultra-high performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method was developed for the determination of phenylalanine (Phe), valine (Val), histidine (His), tryptophan (Trp), and methionine (Met). Plasma samples (100 μL) were precipitated by acetonitrile (300 μL) and analyzed on a BEH C18 (2.1 mm × 100 mm, 1.7 μm) column at 40 °C by gradient elution. The mobile phase composed of 0.1% formic acid and acetonitrile was used with flow rate at 0.2–0.4 ml/0-3 min. Five AAs were determined at positive electrospray ionization (ESI+) at m/z 118.1/72.1 (Val), 150.12/104.02(Met), 156.06/110.05(His), 166.1/120.1(Phe), and 205.2/188.02 (Trp). A total of 75 healthy subjects and 83 hyperlipidemic subjects, who had blood routine test and plasma lipid test were determined by developed UPLC-MS/MS.

Results

It was shown that there was good linearity for Val, Met, His, Phe, and Trp within 1–100 μg/mL. The relative standard deviations of precision and accuracy were all within 15%. The level of Val, Phe, Trp, His, and Met were 35.34 ± 15.64, 22.72 ± 9.13, 17.23 ± 4.94, 16.78 ± 13.64, and 6.24 ± 1.97 μg/mL in healthy subjects, while they were 38.04 ± 16.70, 22.41 ± 8.45, 15.62 ± 5.77, 18.35 ± 14.49, and 6.21 ± 1.97 μg/mL in hyperlipidemic subjects respectively. The Spearman’s correlations analysis showed that there were high correlations between Val, Phe, Trp, His, Met and triglyceride in healthy subjects. While, those correlations decreased in hyperlipemia cases.

Conclusion

A convenient and sensitive method for simultaneous determination of Val, Phe, Trp, His, and Met in human plasma was developed. There was a high correlation between Val, Phe, Trp, His, Met and triglyceride. Hyperlipemia influences the metabolic balance of His, Phe, Trp, Met and Val.
Evaluating networked drug checking services in Toronto, Ontario: study protocol and rationale
Authors:   Drug Checking Services in Toronto Working Group, Maghsoudi N. , McDonald K. , Stefan C. , Beriault D. R. , Mason K. , Barnaby L. , Altenberg J. , MacDonald R. D. , Caldwell J. , Nisenbaum R. , Leece P. , Watson T. M. , Tupper K. W. , Kufner L. , Scheim A. I. , Werb D.
Published: March 2020

Background

The increasing incidence of fatal opioid overdose is a public health crisis in Canada. Given growing consensus that this crisis is related to the presence of highly potent opioid adulterants (e.g., fentanyl) in the unregulated drug supply, drug checking services (DCS) have emerged as part of a comprehensive approach to overdose prevention. In Canada’s largest city, Toronto, a network of DCS launched in 2019 to prevent overdose and overdose-related risk behaviors. This network employs mass spectrometry technologies, with intake sites co-located with supervised consumption services (SCS) at three frontline harm reduction agencies. The protocol and rationale for assessing the impact of this multi-site DCS network in Toronto is described herein. The aims of this study are to (1) evaluate the impact of DCS access on changes in and factors influencing overdose and related risk behaviors, (2) investigate the perceived capacity of DCS to prevent overdose, and (3) identify composition (qualitative and quantitative) trends in Toronto’s unregulated drug supply.

Methods

We will use a parallel-mixed-methods design with complementary data sources (including data from chemical analysis of drug samples, quantitative intake and post-test surveys, SCS, coroners, paramedic services, and qualitative interviews), followed by a meta-inference process wherein results from analyses are synthesized.

Results

Whereas most DCS globally target “recreational drug users,” in Toronto, this networked DCS will primarily target marginalized people who use drugs accessing frontline services, many of whom use drugs regularly and by injection. This evolution in the application of DCS poses important questions that have not yet been explored, including optimal service delivery models and technologies, as well as unique barriers for this population. Increasing information on the unregulated drug supply may modify the risk environment for this population of people who use drugs.

Conclusions

This study addresses evidence gaps on the emerging continuum of overdose prevention responses and will generate critical evidence on a novel approach to reducing the ongoing high incidence of drug-related morbidity and mortality in Canada and elsewhere.
Importance of pediatric rheumatologists and transitional care for juvenile idiopathic arthritis-associated uveitis: a retrospective series of 9 cases
Authors: Yamazaki Susumu , Shimbo Asami , Akutsu Yuko , Takase Hiroshi , Morio Tomohiro , Mori Masaaki
Published: March 2020

Background

Juvenile idiopathic arthritis-associated uveitis (JIA-U) is a serious condition associated with the risk of blindness. However, pediatric rheumatologists rarely encounter cases of blindness, because most patients reach adulthood during the course of follow-up before blindness occurs. Here, we report the progress of 9 patients with JIA-U, including 2 patients who became blind after the transition period. We aimed to highlight the importance of the role of pediatric rheumatologists and transitional care in preventing blindness associated with JIA-U.

Case presentation

We conducted a retrospective analysis of the case records of 9 JIA-U patients (1 male, 8 female; median age 16.8 years, range 5.5–19.8 years). All patients presented with oligo-juvenile idiopathic arthritis (oligo-JIA) (one presented with extended oligo-JIA); the median age of uveitis onset was 5.0 years (range 3.0–13.0 years), and the onset of uveitis preceded the onset of arthritis in 2 patients. The median disease duration was 12.5 years (range 3.5–24.7 years); 4 patients had anti-nuclear antibody (ANA) positivity (≧1:160) (all with a homogeneous and speckled-pattern subtype). All patients were negative for rheumatoid factor. Eight patients received methotrexate, 7 patients received one or more biologic drugs (etanercept, infliximab, adalimumab, and golimumab), and 6 patients required ophthalmic surgery at an early age (≦ 18 years).

Two patients developed blindness after the transition period. Medical examination by pediatric rheumatologists and use of biologics had been delayed in both patients. One patient developed depression after transition and interrupted her own treatment.

Conclusions

The reason for blindness in the 2 patients was thought to be the delay in the commencement of treatment and failure to provide transitional care. Inflammation is difficult to control in JIA-U even with appropriate treatment. Pediatric rheumatologists must be informed about the risk of JIA-U blindness, especially after transition. To ensure a good prognosis, the specialized treatment with the involvement of pediatric rheumatologists is necessary early on, and consideration for transitional medicine is essential. Therefore, this report reaffirms the importance of planned transitional care that has been advocated for globally.
Work related cardiovascular load in professional dance teachers – a pilot study
Authors: Wanke Eileen M. , Schmidt Mike , Oremek Gerhard , Groneberg David A.
Published: March 2020

Objective

There have been only a limited number of studies available on the physical requirements in dance teachers (DT), who are responsible for the training of recreational and/or professional dancers and/or dance students. First results provide indications that a consideration of physical work load (teaching load) of this occupational group is necessary.

Methods

HR measurements were done on a total of 21 DT (f:n = 18, m:n = 3) aged 48.2 ± 9.3 years during their lessons in three dance styles: ballet (B), jazz/modern dance (J/MD) and pre-school dance (CD). The HR data were objectified using the spiroergometrically measured maximum HR (HRmax). In addition, the rating of perceived exertion (RPE) was asked directly after the lesson using the Borg scale together with an additional questionnaire.

Results

Depending on the dance style, the average HR load during the lessons ranged between 56.7% ± 7.4%) (B) and 63.6% ± 9.8% (CD) of the individual HRmax. No significant differences could be found between the dance styles for the minimum, medium and maximum teaching loads. The DTs rated the average RPE of the teaching units according to BORG (11.4 ± 2.1). Correlations between the RPE and the mean and maximum cardiovascular loads (r = 0.376,p = 0.037 and r = 0.441,p = 0.013) could be shown for all dance units and for the mean loads in J/MD (r = 0.558,p = 0.044).

Conclusion

Most dance units do not represent a load in the sense of a endurance training unit. An increase in aerobic fitness and possible positive effects in the context of injury prevention is not to be expected. In J/MD, the use of RPEs for the rough estimation of cardiovascular stress is conceivable. The assessment of cardiovascular load in dance lessons requires further investigations for more precise assessments.
Potential mechanisms for lumbar spinal stiffness change following spinal manipulative therapy: a scoping review
Authors: Jun Peter , Pagé Isabelle , Vette Albert , Kawchuk Greg
Published: March 2020

Introduction

In individuals having low back pain, the application of spinal manipulative therapy (SMT) has been shown to reduce spinal stiffness in those who report improvements in post-SMT disability. The underlying mechanism for this rapid change in stiffness is not understood presently. As clinicians and patients may benefit from a better understanding of this mechanism in terms of optimizing care delivery, the objective of this scoping review of current literature was to identify if potential mechanisms that explain this clinical response have been previously described or could be elucidated from existing data.

Methods

Three literature databases were systematically searched (MEDLINE, CINAHL, and PubMed). Our search terms included subject headings and keywords relevant to SMT, spinal stiffness, lumbar spine, and mechanism. Inclusion criteria for candidate studies were publication in English, quantification of lumbar spinal stiffness before and after SMT, and publication between January 2000 and June 2019.

Results

The search identified 1931 articles. Of these studies, 10 were included following the application of the inclusion criteria. From these articles, 7 themes were identified with respect to potential mechanisms described or derived from data: 1) change in muscle activity; 2) increase in mobility; 3) decrease in pain; 4) increase in pressure pain threshold; 5) change in spinal tissue behavior; 6) change in the central nervous system or reflex pathways; and 7) correction of a vertebral dysfunction.

Conclusions

This scoping review identified 7 themes put forward by authors to explain changes in spinal stiffness following SMT. Unfortunately, none of the studies provided data which would support the promotion of one theme over another. As a result, this review suggests a need to develop a theoretical framework to explain rapid biomechanical changes following SMT to guide and prioritize future investigations in this important clinical area.