bluuebunny/crossref_metadata_2025 huggingface dataset:
Left ventricular hypertrophy in a contemporary cohort of autosomal dominant polycystic kidney disease patients
Authors: Chen Huanwen , Watnick Terry , Hong Susie N. , Daly Barry , Li Yongfang , Seliger Stephen L.
Published: October 2019

Background

Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD) often develop hypertension in childhood or early adulthood. Although this could result in left ventricular hypertrophy (LVH), a major risk factor for cardiovascular morbidity and mortality, prior studies of LVH in ADPKD have yielded conflicting results. We estimated the prevalence of LVH using consensus echocardiography criteria and examined the independent association of ADPKD severity with LV mass in a contemporary cohort of ADPKD patients.

Methods

Adults with ADPKD and eGFR> 15 ml/min/1.73m2were enrolled in a single-center study. Left Ventricular Mass (LVM) was quantified using 2D echocardiography, and LVH was defined using gender-specific cut-points of LVM and LVM indexed to body surface area (LVMI) from consensus guidelines. Total Kidney Volume (TKV) was quantified using Magnetic Resonance Imaging, and GFR was estimated from serum creatinine using the CKD-Epi equation. Multiple linear regression was used to estimate the association of TKV and eGFR with LVM and LVMI, adjusting for potential confounders.

Results

Among 126 participants (78% with hypertension), median age was 46 years, median eGFR 63 ml/min/1.73 m2, and median [IQR] systolic blood pressure was 125 [116–133] mmHg. Prevalence of LVH was 21.4% as defined by LVMI and was not significantly different (p = 0.8) between those with and without HTN, and was similar (21.4%) after excluding those (N = 21) with known cardiac disease. Greater TKV and lower eGFR were directly correlated with greater LVMI (p = .016 andp < .001, respectively). In multiple linear regression models accounting for potential confounders including blood pressure, greater TKV was positively associated with LVM ($$ \hat{\beta} $$β̂=0.19,p = 0.04).

Conclusions

In a contemporary cohort of ADPKD patients with well-controlled blood pressure, the prevalence of LVH is high, and ADPKD severity as reflected by TKV is independently associated with greater LV mass. These results may suggest a relationship between ADPKD pathophysiology and increased LV mass.
Thermal imaging applications in neonatal care: a scoping review
Authors: Topalidou Anastasia , Ali Nazmin , Sekulic Slobodan , Downe Soo
Published: October 2019

Background

In neonatal care, assessment of the temperature of the neonate is essential to confirm on-going health, and as an early signal of potential pathology. However, some methods of temperature assessment involve disturbing the baby, disrupting essential sleep patterns, and interrupting maternal/infant interaction. Thermal imaging is a completely non-invasive and non-contact method of assessing emitted temperature, but it is not a standard method for neonatal thermal monitoring. To examine the potential utility of using thermal imaging in neonatal care, we conducted a comprehensive systematic scoping review of thermal imaging applications in this context.

Methods

We searched EMBASE, MEDLINE and MIDIRS.

Results

From 442 hits, 21 met the inclusion criteria and were included in the review. A significant number (n = 9) were published in the last 8 years. All the studies were observational studies, with 20 out of 21 undertaken in North America or Europe. Most of them had small cohorts (range 4–29 participants). The findings were analysed narratively, to establish the issues identified in the included studies. Five broad themes emerged for future examination. These were: general thermal physiology; heat loss and respiratory monitoring; identification of internal pathologies, including necrotising enterocolitis; other uses of thermal imaging; and technical concerns. The findings suggest that thermal imaging is a reliable and non-invasive method for continuous monitoring of the emitted temperature of the neonates, with potential for contributing to the assurance of wellbeing, and to the diagnosis of pathologies, including internal abnormalities. However, the introduction of thermal imaging into everyday neonatology practice has several methodological challenges, including environmental parameters, especially when infants are placed in incubators or open radiant warmers.

Conclusion

In conclusion, although the first attempt at using thermal imaging in neonatal care started in the early-1970s, with promising results, and subsequent small cohort studies have recently reinforced this potential, there have not been any large prospective studies in this area that examine both the benefits and the barriers to its use in practice.
Repurposing mechanistic insight of PDE-5 inhibitor in cancer chemoprevention through mitochondrial-oxidative stress intervention and blockade of DuCLOX signalling
Authors: Singh Manjari , Kasna Sweta , Roy Subhadeep , Aldosary Sara , Saeedan Abdulaziz S. , Ansari Mohd. Nazam , Kaithwas Gaurav
Published: October 2019

Background

This study evaluates the anti-cancer effects of Tadalafil (potent PDE-5 inhibitor) in female albino wistar rats against n-methyl n-nitrosourea induced mammary gland carcinogenesis.

Methods

The animals were selected and randomly divided among four groups and each group contains six animals per group. The animal tissue and serum samples were evaluated for the presence of antioxidant parameters and the cellular morphology was studied using carminic staining, haematoxylin staining and scanning electron microscopy followed by immunoblotting analysis.

Results

On the grounds of hemodynamic recordings and morphology, n-methyl n-nitrosourea treated group showed distorted changes along with distorted morphological parameters. For morphological analysis, the mammary gland tissues were evaluated using scanning electron microscopy, whole mount carmine staining, haematoxylin and eosin staining. The serum samples were evaluated for the evaluation of oxidative stress markers and inflammatory markers. The level of caspase 3 and 8 were also evaluated for the estimation of apoptosis. The fatty acid profiling of mammary gland tissue was evaluated using fatty acid methyl esters formation. The mitochondrial mediated apoptosis and inflammatory markers were evaluated using immunoblotting assay.

Conclusion

The results confirm that Tadalafil treatment restored all the biological markers to the normal and its involvement in mitochondrial mediated death apoptosis pathway along with inhibition of inflammatory markers.
Publication statuses of clinical trials supporting FDA-approved immune checkpoint inhibitors: a meta-epidemiological investigation
Authors: Omae Kenji , Kataoka Yuki , Tsujimoto Yasushi , Tsutsumi Yusuke , Yamamoto Yosuke , Fukuhara Shunichi , Furukawa Toshi A.
Published: October 2019

Background

The low data publication rate for Food and Drug Administration (FDA)-approved drugs, and discrepancies between FDA-submitted versus published data, remain a concern. We investigated the publication statuses of sponsor-submitted clinical trials supporting recent anticancer drugs approved by the FDA, with a focus on immune checkpoint inhibitors (ICPis).

Methods

We identified all ICPis approved between 2011 and 2014, thereby obtaining 3 years of follow-up data. We assessed the clinical trials performed for each drug indication and matched each trial with publications in the literature. The primary benchmark was the publication status 2 years post-approval. We examined the association between time to publication and drug type using a multilevel Cox regression model that was adjusted for clustering within drug indications and individual covariates.

Results

Between 2011 and 2014, 36 anticancer drugs including 3 ICPis were newly approved by the FDA. Of 19 trials investigating the 3 ICPis, 11 (58%) were published within 2 years post-approval. We randomly selected 10 of the 33 remaining anticancer drugs; 68 of 101 trials investigating these drugs (67%) were published. Overall, the publication rate was 66% at 2 years post-approval with a median time to publication of 2.3 years. There was no significant difference in the time to trial publication between ICPis and other anticancer drugs (adjusted hazard ratio [HR], 1.1; 95% confidence interval [CI], 0.8–1.7; P = 0.55). However, findings related to non-ICPis investigated specifically in randomized phase 2 or phase 3 trials were significantly more likely to be published earlier than those related to ICPis (adjusted HR, 7.4; 95% CI, 1.8–29.5; P = 0.005).

Conclusion

One in 3 sponsor-submitted trials of the most recently approved anticancer drugs remained unpublished 2 years post-FDA approval. We found no evidence that the drug type was associated with the time to overall trial publication.
The value of GRASP on DCE-MRI for assessing response to neoadjuvant chemotherapy in patients with esophageal cancer
Authors: Lu Yanan , Ma Ling , Qin Jianjun , Wang Zhaoqi , Guo Jia , Zhao Yan , Zhang Hongkai , Yan Xu , Liu Hui , Li Hailiang , Kamel Ihab R. , Qu Jinrong
Published: October 2019

Background

To compare the value of two dynamic contrast-enhanced Magnetic Resonance Images (DCE-MRI) reconstruction approaches, namely golden-angle radial sparse parallel (GRASP) and view-sharing with golden-angle radial profile (VS-GR) reconstruction, and evaluate their values in assessing response to neoadjuvant chemotherapy (nCT) in patients with esophageal cancer (EC).

Methods

EC patients receiving nCT before surgery were enrolled prospectively. DCE-MRI scanning was performed after nCT and within 1 week before surgery. Tumor Regression Grade (TRG) was used for chemotherapy response evaluation, and patients were stratified into a responsive group (TRG1 + 2) and a non-responsive group (TRG3 + 4 + 5). Wilcoxon test was utilized for comparing GRASP and VS-GR reconstruction, Kruskal-Wallis and Mann-Whitney test was performed for each parameter to assess response, and Spearman test was performed for analyzing correlation between parameters and TRGs, as well as responder and non-responder. The receiver operating characteristic (ROC) was utilized for each significant parameter to assess its accuracy between responders and non-responders.

Results

Among the 64 patients included in this cohort (52 male, 12 female; average age of 59.1 ± 7.9 years), 4 patients showed TRG1, 4 patients were TRG2, 7 patients were TRG3, 11 patients were TRG4, and 38 patients were TRG5. They were stratified into 8 responders and 56 non-responders.

A total of 15 parameters were calculated from each tumor. With VS-GR, 10/15 parameters significantly correlated with TRG and response groups. Of these, only AUCmax showed moderate correlation with TRG, 7 showed low correlation and 2 showed negligible correlation with TRG. 8 showed low correlation and 2 showed negligible correlation with response groups. With GRASP, 13/15 parameters significantly correlated with TRG and response groups. Of these, 10 showed low correlation and 3 showed negligible correlation with TRG. 11 showed low correlation and 2 showed negligible correlation with TRG. Seven parameters (AUC* > 0.70, P < 0.05) showed good performance in response groups.

Conclusions

In patients with esophageal cancer on neoadjuvant chemotherapy, several parameters can differentiate responders from non-responders, using both GRASP and VS-GR techniques. GRASP may be able to better differentiate these two groups compared to VS-GR.

Trial registration for this prospective study: ChiCTR, ChiCTR-DOD-14005308. Registered 2 October 2014.
Weight management among school-aged children and adolescents: a quantitative assessment in a Ghanaian municipality
Authors: Gyamfi Daniel , Obirikorang Christian , Acheampong Emmanuel , Asamoah Evans Adu , Sampong Bernard Berko , Batu Emmanuella Nsenbah , Anto Enoch Odame
Published: October 2019

Background

Childhood and adolescent overweight, obesity and underweight have become an issue of grave concern to both the developed and developing countries in context of global burden of non-communicable diseases. Unhealthy weight status is a significant public health issue for developing countries, of which Ghana is not excluded. This study evaluated the prevalence of overweight, obesity and underweight and its related factors among school-aged children and adolescents.

Methods

A total of 1004 participants were randomly selected from six schools. A structured questionnaire on demography and socioeconomic status of students’ parents/guardians was completed by the selected students. Anthropometric parameters were measured, and body mass index (BMI) and waist-to-height ratio (WHtR) were calculated. BMI-for-age z-scores were used to categorize anthropometric data of the children as underweight, normal, overweight or obese. A cut-off value of > 0.50 was used to define obesity by WHtR.

Results

Overweight prevalence of 13.8% and 12.6 was observed among basic school and high school students respectively based on BMI classification. Obesity prevalence of 8.8% was found in basic school students and 8.9% among high school students. Underweight was observed in 114 (11.3%) basic school students and 86 (8.6%) high school students. There was a difference in sex prevalence in unhealthy weight-behaviours; with more girls being overweight (19.4% vs 7.6%, p < 0.001) and obese (10.2% vs. 7.3%, p = 0.177) compared to boys. High WHtR found in 10.5% of basic students and 5.0% of high school students, with a statistical difference. Overweight/obesity was significantly associated with taking snacks before bed among basic school students [aOR = 10.45(5.95–18)] and high school students [aOR = 10.23(5.95–18.37)] respectively. Watching TV [aOR = 0.39(0.22–0.70)], sleeping during leisure periods [aOR = 0.43(0.23–0.81)] and bicycling as a means of transport [aOR = 0.37(0.19–0.72)] to school was protective of obesity among basic school students.

Conclusion

High prevalence of unhealthy weight-related behaviours was observed among school-aged children in the Bekwai Municipality. Snacking before bed was a major factor promoting obesity among school-aged children while leisure behaviours such as TV watching, and sleeping were protective of obesity. Therefore, it is recommended to promote and support healthy eating habits among school-aged children which are likely beneficial in reducing the risk of childhood unhealthy weight-related behaviours.
Air pollutants and outpatient visits for cardiovascular disease in a severe haze-fog city: Shijiazhuang, China
Authors: Tan Fengzhu , Wang Weijie , Qi Sufen , Kan Haidong , Yu Xinpei , Liu Yi , Wu Duanyang , Xu Bin , Meng Fan , Liu Sicen
Published: October 2019

Background

Many studies have reported the impact of air pollution on cardiovascular disease (CVD), but few of these studies were conducted in severe haze-fog areas. The present study focuses on the impact of different air pollutant concentrations on daily CVD outpatient visits in a severe haze-fog city.

Methods

Data regarding daily air pollutants and outpatient visits for CVD in 2013 were collected, and the association between six pollutants and CVD outpatient visits was explored using the least squares mean (LSmeans) and logistic regression. Adjustments were made for days of the week, months, air temperature and relative humidity.

Results

The daily CVD outpatient visits for particulate matter (PM10 and PM2.5), sulphur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) in the 90th-quantile group were increased by 30.01, 29.42, 17.68, 14.98, 29.34%, and − 19.87%, respectively, compared to those in the <10th-quantile group. Odds ratios (ORs) and 95% confidence intervals (CIs) for the increase in daily CVD outpatient visits in PM10 300- and 500-μg/m3, PM2.5 100- and 300-μg/m3 and CO 3-mg/m3 groups were 2.538 (1.070–6.020), 7.781 (1.681–36.024), 3.298 (1.559–6.976), 8.72 (1.523–49.934), and 5.808 (1.016–33.217), respectively, and their corresponding attributable risk percentages (AR%) were 60.6, 87.15, 69.68, 88.53 and 82.78%, respectively. The strongest associations for PM10, PM2.5 and CO were found only in lag 0 and lag 1. The ORs for the increase in CVD outpatient visits per increase in different units of the six pollutants were also analysed.

Conclusions

All five air pollutants except O3 were positively associated with the increase in daily CVD outpatient visits in lag 0. The high concentrations of PM10, PM2.5 and CO heightened not only the percentage but also the risk of increased daily CVD outpatient visits. PM10, PM2.5 and CO may be the main factors of CVD outpatient visits.
Isolating the impact of specific gambling activities and modes on problem gambling and psychological distress in internet gamblers
Authors: Gainsbury Sally M. , Angus Douglas J. , Blaszczynski Alex
Published: October 2019

Background

Gambling disorder is related to high overall gambling engagement; however specific activities and modalities are thought to have stronger relationships with gambling problems. This study aimed to isolate the relationship between specific gambling activities and modalities (Internet and venue/land-based) to gambling disorder and general psychological distress. Past-month Internet gamblers were the focus of this investigation because this modality may be associated with gambling disorders in a unique way that needs to be separated from overall gambling intensity.

Methods

Australians who had gambled online in the prior 30 days (N = 998, 57% male) were recruited through a market research company to complete an online survey measuring self-reported gambling participation, problem gambling severity, and psychological distress.

Results

When controlling for overall gambling frequency, problem gambling was significantly positively associated with the frequency of online and venue-based gambling using electronic gaming machines (EGMs) and venue-based sports betting. Psychological distress was uniquely associated with higher frequency of venue gambling using EGMs, sports betting, and casino card/table games.

Conclusions

This study advances our understanding of how specific gambling activities are associated with disordered gambling and psychological distress in users of Internet gambling services. Our results suggest that among Internet gamblers, online and land-based EGMs are strongly associated with gambling disorder severity. High overall gambling engagement is an important predictor of gambling-related harms, nonetheless, venue-based EGMs, sports betting and casinos warrant specific attention to address gambling-related harms and psychological distress among gamblers.
Diffuse alveolar haemorrhage associated with subsequent development of ANCA positivity and emphysema in three young adults
Authors: Stainer Anna , Rice Alex , Devaraj Anand , Barnett Joseph Luke , Donovan Jacqueline , Kokosi Maria , Nicholson Andrew Gordon , Cairns Tom , Wells Athol Umfrey , Renzoni Elisabetta Augusta
Published: October 2019

Background

Diffuse alveolar haemorrhage (DAH) is characterized by the diffuse accumulation of red blood cells within the alveoli, presence of ground glass opacities and/or consolidation on computed tomography (CT). Aside from identifiable non-immune causes, DAH is classically subdivided into idiopathic (idiopathic pulmonary haemosiderosis, IPH) and autoimmune DAH. Here we describe three cases presenting with recurrent pulmonary haemorrhage, initially classified as IPH, who, several years after first presentation, develop anti myeloperoxidase antibodies (MPO) positivity, emphysema on CT and, in one case, renal involvement.

Case presentation

Patient 1 was diagnosed with IPH aged 14. Her disease remained poorly controlled despite immunosuppression, although ANCA remained negative over the years. Nineteen years from initial presentation, she developed MPO-ANCA positive antibodies and mild renal impairment. She was treated with Rituximab with good response. From first presentation, the chest CT was consistently characterized by diffuse ground-glass opacities and interlobular septal thickening. Ten years later, cystic opacities consistent with emphysema, with a striking peribronchovascular distribution, developed. Patient 2 was diagnosed with IPH aged 32. He was treated with corticosteroids and methotrexate, with fluctuating response. At 11 years from initial presentation, MPO-ANCA positivity was identified, and emphysema with a peribronchovascular distribution was observed on CT, with subsequent significant increase in extent. Patient 3 was diagnosed with IPH at the age of seven, and had recurrent episodes of haemoptysis of varying degree of severity, treated with intermittent courses of corticosteroids until age 11, when he was intubated due to severe DAH. Eight years after the diagnosis emphysematous changes were noted on CT and MPO-ANCA positivity developed for the first time 11 years after initial diagnosis.

Conclusions

We believe these three cases highlight: 1) the possibility of development of ANCA positivity several years down the line from first DAH presentation 2) the possibility that DAH may lead to cystic/emphysematous changes with peribronchovascular distribution on CT. Moreover, the need for ongoing immunosuppressive treatment and the development of emphysema, emphasize a possible role played by autoimmune phenomena, even when DAH is initially diagnosed as “idiopathic”. Further studies are required to better understand the relationship between DAH, ANCA positivity and development of emphysema.
Metallic versus biodegradable suture anchors for rotator cuff repair: a case control study
Authors: Longo Umile Giuseppe , Petrillo Stefano , Loppini Mattia , Candela Vincenzo , Rizzello Giacomo , Maffulli Nicola , Denaro Vincenzo
Published: October 2019

Backgrounds

Repair of full-thickness rotator cuff (RC) tears is routinely performed using suture anchors, which produce secure and effective soft tissue fixation to bone. The aim of this prospective study is to compare the long-term outcomes of single row arthroscopic rotator cuff repair (RCR) performed using metal or biodegradable suture anchors. The null hypothesis is that there is no difference in shoulder function using metal or biodegradable suture anchors as evaluated by UCLA shoulder score, Wolfgang criteria, and Oxford shoulder score.

Methods

Arthroscopic RCR was performed in 110 patients included in this case control study. They were divided into 2 groups of 51 and 59 patients respectively. Metal suture anchors were used in group 1, and biodegradable suture anchors in group 2. Results were obtained at a mean follow up of 4.05 + 2 years. Clinical outcomes and functional outcomes were evaluated.

Results

The mean modified UCLA shoulder score was 26.9 + 7.1 in group 1, and 27.7 + 6.5 in group 2 (P = 0.5); the mean Wolfgang score was 13.3 + 3.3 in group 1, and 14 + 2.6 in group 2 (P = 0.3); the mean OSS was 23.7 + 11.4 in group 1, and 20.7 + 9.2 points in group 2 (P = 0.1). The mean active anterior elevation was 163.5° + 28.2° in group 1 and 163.6° + 26.9 in group 2 (P = 0.9); the mean active external rotation was 46° + 19.7° in group 1 and 44.6° + 16.3° in group 2 (P = 0.7). The mean strength in anterior elevation was 4.8.02 + 23.52 N in group 1, and 43.12 + 17.64 N in group 2 (P = 0.2); the mean strength in external rotation was 48.02 + 22.54 N in group 1 and 46.06 + 17.64 N in group 2 (P = 0.6); the mean strength in internal rotation was 67.62 + 29.4 N in group 1, and 68.6 + 25.48 N in group 2 (P = 0.9).

Conclusions

There are no statistically significant differences at a mean follow-up of 4.05 + 2 years in clinical and functional outcomes of single row arthroscopic RCR using metallic or biodegradable suture anchors for RC < 5 cm.
Comparison of microendoscopic selective laminectomy versus conventional laminoplasty in patients with degenerative cervcical myelopathy: a minimum 2-year follow-up study
Authors: Oshima Yasushi , Kato So , Doi Toru , Matsubayashi Yoshitaka , Taniguchi Yuki , Tanaka Sakae
Published: October 2019

Background

Although microendoscopic partial laminectomy for patients with degenerative cervical myelopathy (DCM) has been reported and demonstrated good results, a detailed comparison of its mid-term surgical results with those of laminoplasty (LP) has not been reported. The aim of this study was to compare the surgical outcomes, complications, and imaging parameters of cervical microendoscopic interlaminar decompression (CMID) via a midline approach versus conventional laminoplasty, with a minimum follow-up period of 2 years.

Methods

Two hundred and fifty-four patients who underwent either LP or CMID for DCM between May 2008 and April 2015 were enrolled. All patients routinely underwent LP (C3–6 or C3–7) before December 2011, whereas CMID was performed at the one or two affected level(s) only in patients with single- or two-level spinal cord compression after 2012.

Surgical procedure (CMID): For single-level patients (e.g., C5–6), partial laminectomy of C5 and C6 was performed under a microendoscope. For two-level patients (e.g., C5–6-7), decompression was completed by performing a C6 laminectomy.

We compared surgical outcomes and radiographic parameters between the CMID and LP groups.

Results

Of the 232 patients followed up for > 2 years, 87 patients with single- or two-level spinal cord compression, 46 that underwent CMID, and 41 that underwent LP were identified. There were no differences in the baseline demographic data of the patients between the groups. CMID showed better outcomes in terms of postoperative axial pain and quality of life, although both procedures showed good neurological improvement. Two and one patient complained of C5 palsy and hematoma, respectively, only in the LP group. The postoperative range of motion was worse and the degree of postoperative posterior spinal cord shift was larger in the LP group.

Conclusion

Selective decompression by CMID demonstrated surgical outcomes equivalent to those of conventional LP, which raises a question regarding the requirement of extensive posterior spinal cord shift in such patients. Although the indications of CMID are limited and comparison with anterior surgery is mandatory, it can be a minimally invasive procedure for DCM.
Impaired awareness of hypoglycemia in children and adolescents with type 1 diabetes mellitus in north of Jordan
Authors: Alkhatatbeh Mohammad J. , Abdalqader Nedaa A. , Alqudah Mohammad A. Y.
Published: October 2019

Background

Hypoglycemia is a common complication of insulin therapy in patients with Type 1 Diabetes Mellitus (DM). Awareness of hypoglycemic symptoms helps patients to recognize hypoglycemia and initiate self-treatment. Impaired Awareness of Hypoglycemia (IAH) exposes patients to severe hypoglycemia, which could be associated with seizures and unconsciousness. This study aimed to assess IAH, frequency of hypoglycemia, severe hypoglycemia and intensity of hypoglycemic symptoms among children and adolescents with Type 1 DM in North of Jordan.

Methods

Data were collected from 94 children and adolescents with Type 1 DM. Clarke’s and Edinburgh surveys were used to assess IAH and individual symptoms of hypoglycemia, respectively. Frequency of hypoglycemia and other related information were obtained by self-reporting or from medical records.

Results

16.0% of participants were having IAH, 66.0% of participants reported recurrent hypoglycemia (>once/month) and 18.0% of participants developed ≥1 severe hypoglycemia during the previous year. IAH was not associated with age, gender, duration of DM, HbA1c, insulin regimen, adherence to insulin or development of severe hypoglycemia (p-values> 0.05). Instead, IAH was associated with frequency of hypoglycemia during the previous 6 months (p-value< 0.01). Hunger, tiredness, dizziness, drowsiness, inability to concentrate, trembling and weakness were the most common symptoms felt by participants when they develop hypoglycemia. Hunger was the only common symptom that was significantly higher in children compared to adolescent (p-value < 0.01).

Conclusions

This study has reported low prevalence of IAH in children and adolescents with Type 1 DM in North of Jordan. IAH was more common in subjects with more frequent hypoglycemia.
The effect of psychosocial support on caregivers’ perceived criticism and emotional over-involvement of persons with dementia: an assessor-blinded randomized controlled trial
Authors: Bjørge Heidi , Kvaal Kari , Ulstein Ingun
Published: October 2019

Background

Many relatives of close family members suffering from dementia have taken on the caregiver role. While intervention studies have revealed promising results on caregiver burden, distress, and depression, there is a lack of knowledge about how caregivers’ perceived relationship with their ill family member influences the burden of care.

This study examined whether a psychosocial intervention influenced this perceived relationship from the caregivers’ perspective. We also explored whether the caregivers’ perception of the care receiver’s attitude and behavior changed over time, and whether caregiver stress and mood differed following the intervention.

Methods

The participating caregivers and care receivers were randomly assigned to a psychosocial intervention comprising education about dementia, counselling and group sessions, or to treatment as usual. The study investigated caregivers’ experience of expressed emotion using the Felt Expressed Emotion Rating Scale (FEERS), a self-report questionnaire that captures caregivers’ perception of criticism (CC) and emotional over-involvement (EOI) exhibited by the family members with dementia.

Results

A total of 208 dyads were enrolled in the study. There were no significant differences between the intervention and control groups in the studied variables. Caregivers’ perception of CC and EOI was low but fluctuated somewhat, whereas their mood and stress level were stable during the follow-up period.

Conclusions

According to the FEERS, the intervention did not influence caregivers’ perception of CC and EOI, and there was no difference between the intervention and control groups regarding caregivers’ perceived relationship. Despite the increased symptoms of dementia, caregivers’ level of distress and mood remained stable, and they seemed to maintain a positive perception of the quality of their relationship with the care receiver.

Trial registration

Clinical.Trials.gov Sept. 2009, NCT 01287767.
Collaborative governance in the Quebec Cancer Network: a realist evaluation of emerging mechanisms of institutionalization, multi-level governance, and value creation using a longitudinal multiple case study design
Authors: Tremblay Dominique , Touati Nassera , Poder Thomas , Vasiliadis Helen-Maria , Bilodeau Karine , Berbiche Djamal , Denis Jean-Louis , Pomey Marie-Pascale , Hébert Johanne , Roch Geneviève , Prady Catherine , Lévesque Lise
Published: October 2019

Background

People living with and beyond cancer (PLC) receive various forms of specialty care at different locations and many interventions concurrently or over time. They are affected by the operation of professional and organizational silos. This results in undue delays in access, unmet needs, sub-optimal care experiences and clinical outcomes, and human and financial costs for PLCs and healthcare systems.

National cancer control programs advocate organizing in a network to coordinate actions, solve fragmentation problems, and thus improve clinical outcomes and care experiences for every dollar invested. The variable outcomes of such networks and factors explaining them have been documented. Governance is the “missing link” for understanding outcomes. Governance refers to the coordination of collective action by a body in a position of authority in pursuit of a common goal. The Quebec Cancer Network (QCN) offers the opportunity to study in a natural environment how, why, by whom, for whom, and under what conditions collaborative governance contributes to practices that produce value-added outcomes for PLCs, healthcare providers, and the healthcare system.

Methods/design

The study design consists of a longitudinal case study, with multiple nested cases (4 local networks nested in the QCN), mobilizing qualitative and quantitative data and mixed data from various sources and collected using different methods, using the realist evaluation approach. Qualitative data will be used for a thematic analysis of collaborative governance. Quantitative data from validated questionnaires will be analyzed to measure relational coordination and teamwork, care experience, clinical outcomes, and health-related health-related quality of life, as well as a cost analysis of service utilization. Associations between context, governance mechanisms, and outcomes will be sought. Robust data will be produced to support decision-makers to guide network governance towards optimized clinical outcomes and the reduction of the economic toxicity of cancer for PLCs and health systems.
Longitudinal clinical outcomes in a real-world population of patients with idiopathic pulmonary fibrosis: the PROOF registry
Authors: Wuyts Wim A. , Dahlqvist Caroline , Slabbynck Hans , Schlesser Marc , Gusbin Natacha , Compere Christophe , Maddens Sofie , Lee Yuan-Chi , Kirchgaessler Klaus-Uwe , Bartley Karen , Bondue Benjamin
Published: October 2019

Background

The PROOF registry is an observational study initiated in October 2013 with the aim to monitor disease progression in a real-world population of patients with idiopathic pulmonary fibrosis (IPF). Here, we present longitudinal clinical outcomes from the PROOF registry.

Methods

Patients with IPF were enrolled across eight centers in Belgium and Luxembourg. For all patients, clinical outcomes data were collected, including mortality, lung transplant, acute exacerbations, and pulmonary hypertension. For patients treated with pirfenidone at any time during follow-up (2013–2017), for any duration of treatment (the pirfenidone-treated population): pirfenidone treatment patterns were collected; changes in pulmonary function (forced vital capacity [FVC] and carbon monoxide diffusing capacity [DLco]) were reviewed up to 24 months post-inclusion; and time-to-event analyses from the time of registry inclusion were performed.

Results

The PROOF registry enrolled a total of 277 patients. During follow-up, 23.1% of patients died, 5.1% received a lung transplant, 5.4% experienced an acute exacerbation, and 6.1% had comorbid pulmonary hypertension. In the pirfenidone-treated population (N = 233, 84.1%), 12.9% of patients had a temporary dose discontinuation and 31.8% had a temporary dose reduction; 4.3% of patients permanently discontinued pirfenidone due to an adverse drug reaction. Mean percent predicted FVC was 81.2% (standard deviation [SD] 19.0) at Month 0 and 78.3% (SD 25.0) at Month 24, and mean percent predicted DLco was 47.0% (SD 13.2) and 45.0% (SD 16.5), respectively. Rates of ≥ 10% absolute decline in percent predicted FVC and ≥ 15% absolute decline in percent predicted DLco over 24 months were 31.0% and 23.2%, respectively. Mean times from registry inclusion to categorical absolute decline in percent predicted FVC and percent predicted DLco were 20.1 (standard error [SE] 0.6) months and 23.4 (SE 0.5) months, respectively; mean time from registry inclusion to death was 31.0 (SE 0.9) months.

Conclusions

The PROOF registry is a source of European data characterizing longitudinal clinical outcomes of patients with IPF. Over 12 months of follow-up, pulmonary function remained largely stable in patients with IPF who received pirfenidone for any duration of treatment. Pulmonary function remained similar at 24 months of follow-up, although patient numbers were lower.

Trial registration

PROOF is registered with the relevant authorities in Belgium and Luxembourg, with registration to Comité National d’Éthique et de Recherche (CNER) N201309/03–12 September 2013 and a notification to Comité National de Protection des Données (CNDP) for Luxembourg.
Unraveling proteome changes and potential regulatory proteins of bovine follicular Granulosa cells by mass spectrometry and multi-omics analysis
Authors: Hou Shuning , Hao Qingling , Zhu Zhiwei , Xu Dongmei , Liu Wenzhong , Lyu Lihua , Li Pengfei
Published: October 2019

Background

In previous study, we performed next-gene sequencing to investigate the differentially expressed transcripts of bovine follicular granulosa cells (GCs) at dominant follicle (DF) and subordinate follicle (SF) stages during first follicular wave. Present study is designed to further identify the key regulatory proteins and signaling pathways associated with follicular development using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) and multi-omics data analysis approach.

Methods

DF and SF from three cattle were collected by daily ultrasonography. The GCs were isolated from each follicle, total proteins were digested by trypsin, and then proteomic analyzed via LC-MS/MS, respectively. Proteins identified were retrieved from Uniprot-COW fasta database, and differentially expressed proteins were used to functional enrichment and KEGG pathway analysis. Proteome data and transcriptome data obtained from previous studies were integrated.

Results

Total 3409 proteins were identified from 30,321 peptides (FDR ≤0.01) obtained from LC-MS/MS analysis and 259 of them were found to be differentially expressed at different stage of follicular development (fold Change > 2, P < 0.05). KEGG pathway analysis of proteome data revealed important signaling pathways associated with follicular development, multi-omics data analysis results showed 13 proteins were identified as being differentially expressed in DF versus SF.

Conclusions

This study represents the first investigation of transcriptome and proteome of bovine follicles and offers essential information for future investigation of DF and SF in cattle. It also will enrich the theory of animal follicular development.
Quality of life of patients on treatment for latent tuberculosis infection: a mixed-method study in Stockholm, Sweden
Authors: Shedrawy Jad , Jansson Lena , Röhl Isac , Kulane Asli , Bruchfeld Judith , Lönnroth Knut
Published: October 2019

Background

Unlike active tuberculosis, latent tuberculosis infection (LTBI) is asymptomatic and often considered not to affect the health-related quality of life (HRQoL) of patients. However, being diagnosed with and treated for LTBI can be associated with adverse clinical evens such side effects of treatment as well as psychosocial challenges. Therefore, the aims of this study were to qualitatively explore patients’ experiences during diagnosis and treatment of LTBI in Stockholm measure their HRQoL, and contrast and merge the results to better understand how the HRQoL of these patients is affected.

Methods

LTBI patients who were treated in Stockholm during September 2017 and June 2018and who fulfilled the inclusion criteria were invited to fill a survey that included a HRQoL instrument, EQ-5D-3 L, and a mental health screening instrument, RHS-15. After filling the survey, a subset of these patients was asked to participate in an interview with open-ended questions that focused on their experiences during the diagnosis and treatment.

Results

In total 108 participants filled that survey and interviews were conducted with 20 patients. Patients scored relatively high on EQ-5D: the scores of utility and VAS scale are similar to those reported by the general population of Stockholm. Very few patients reported problems on the physical health domains of EQ-5D which was supported by the quantitative data that showed no effect on physical health and usual activity. Thirty-eight percent screened positive for RHS-15 and 27.8% reported problems with anxiety/depression domain of EQ-5D which could be related to many stressing factors mentioned in the interviews such as: fear and distress related to lack of clarity about LTBI diagnosis, perceived risk of infecting others and uncertainties about the future.

Conclusion

The quantified HRQoL of LTBI patients in Stockholm is similar to the general population and there is thus no HRQoL decrements that is detectable with EQ-5D. However, the study reinforces the importance of tackling anxiety and fear and ensuring good health information for persons diagnosed with and treated for LTBI.
High expression of FABP4 and FABP6 in patients with colorectal cancer
Authors: Zhang Yaqin , Zhao Xiaotong , Deng Lili , Li Xueting , Wang Ganbiao , Li Yongxing , Chen Mingwei
Published: October 2019

Objective

To explore the relationship between FABP4 and FABP6 expression and the pathogenesis of colorectal cancer (CRC) and their potential as biomarkers in the diagnosis of CRC.

Methods

In total, 100 CRC patients and 100 controls were enrolled. The serum levels of FABP4 and FABP6 were detected by enzyme-linked immunosorbent assay (ELISA) before and 2 weeks after radical resection of CRC. The protein expressions of FABP4 and FABP6 were observed in colorectal tumor tissues and adjacent tissues by immunohistochemistry and western blot, respectively. The diagnostic performance of FABP4 and FABP6 in patients with CRC was evaluated by receiver operating characteristic (ROC) curve analysis.

Results

The serum levels of FABP4 and FABP6 in patients with CRC were higher than the levels in the controls before surgery (P < 0.001), and significantly decreased at 2 weeks after operation (P < 0.001). Immunohistochemistry showed that FABP4 and FABP6 were mainly distributed in the cytoplasm of human colorectal tumor tissues, and only a small amount distributed in adjacent tissues. Western blot revealed that the protein expressions of FABP4 and FABP6 were significantly higher in tumor tissues than in adjacent tissues (P < 0.001, P = 0.002, respectively). Tumors with high and low FABP4 and FABP6 expression have no significant correlation in tumor size, tumor site, distant organ and lymph node metastasis, histologic grade, lymphatic permeation, neurological invasion, vascular invasion, and Duke’s and TNM classification. Multivariate logistic regression analysis showed that FABP4 and FABP6 were independent risk factors for CRC (adjusted odds ratio 1.916; 95%CI 1.340–2.492; P < 0.001; adjusted odds ratio 2.162; 95%CI 1.046, 1.078); P < 0.001, respectively). In discriminating CRC from the normal control, the optimal sensitivity of FABP4 and FABP6 were 93.20% (95%CI 87.8–96.7) and 83.70% (95%CI 76.7–89.3), respectively, while the optimal specificity of FABP4 and FABP6 were 48.8% (95%CI 39.8–57.9) and 58.4% (95%CI 49.2–67.1), respectively. When combined detection of serum carcinoembryonic (CEA) and FABP4 and FABP6, the optimal sensitivity and specificity were 61.33% (95%CI 53.0–69.2) and 79.82% (95%CI 71.3–86.8), respectively.

Conclusion

Increased expression of FABP4 and FABP6 not only were strong risk factors for the development of CRC but could also represent a potential biomarker for CRC diagnosis in Chinese patients. Combined detection of CEA with FABP4 and FABP6 could improve the diagnostic efficacy of CRC.
Case study of a method of development of a selection process for community health workers in sub-Saharan Africa
Authors: Brown Celia , Lilford Richard , Griffiths Frances , Oppong-Darko Prince , Ndambo Myness , Okoh-Owusu Marion , Wroe Emily
Published: October 2019

Background

Choosingwhoshould be recruited as a community health worker (CHW) is an important task, for their future performance partly depends on their ability to learn the required knowledge and skills, and their personal attributes. Developing a fair and effective selection process for CHWs is a challenging task, and reports of attempts to do so are rare. This paper describes a five-stage process of development and initial testing of a CHW selection process in two CHW programmes, one in Malawi and one in Ghana, highlighting the lessons learned at each stage and offering recommendations to other CHW programme providers seeking to develop their own selection processes.

Case presentation

The five stages of selection process development were as follows: (1) review an existing selection process, (2) conduct a job analysis, (3) elicit stakeholder opinions, (4) co-design the selection process and (5) test the selection process. Good practice in selection process development from the human resource literature and the principles of co-design were considered throughout. Validity, reliability, fairness, acceptability and feasibility—the determinants of selection process utility—were considered as appropriate during stages 1 to 4 and used to guide the testing in stage 5. The selection methods used by each local team were a written test and a short interview.

Conclusions

Working with stakeholders, including CHWs, helped to ensure the acceptability of the selection processes developed. Expectations of intensiveness—in particular the number of interviewers—needed to be managed as resources for selection are limited, and CHWs reported that any form of interview may be stressful. Testing highlighted the importance of piloting with CHWs to ensure clarity of wording of questions, interviewer training to maximise inter-rater reliability and the provision of guidance to applicants in advance of any selection events. Trade-offs between the different components of selection process utility are also likely to be required. Further refinements and evaluation of predictive validity (i.e. a sixth stage of development) would be recommended before roll-out.
The multi-site docking protein Grb2-associated binder 1 (Gab1) enhances interleukin-6-induced MAPK-pathway activation in an SHP2-, Grb2-, and time-dependent manner
Authors: Bongartz Hannes , Gille Karen , Hessenkemper Wiebke , Mandel Katharina , Lewitzky Marc , Feller Stephan M. , Schaper Fred
Published: October 2019

Background

Cytokine-dependent activation of signalling pathways is tightly orchestrated. The spatiotemporal activation of signalling pathways dictates the specific physiological responses to cytokines. Dysregulated signalling accounts for neoplastic, developmental, and inflammatory diseases. Grb2-associated binder (Gab) family proteins are multi-site docking proteins, which expand cytokine-induced signal transduction in a spatial- and time-dependent manner by coordinating the recruitment of proteins involved in mitogen activated protein kinase (MAPK)/extracellular-signal regulated kinase (ERK) and phosphatidyl-inositol-3-kinase (PI3K) signalling. Interaction of Gab family proteins with these signalling proteins determines strength, duration and localization of active signalling cascades. However, the underlying molecular mechanisms of signal orchestration by Gab family proteins in IL-6-induced signalling are only scarcely understood.

Methods

We performed kinetic analyses of interleukin-6 (IL-6)-induced MAPK activation and analysed downstream responses. We compared signalling in wild-type cells, Gab1 knock-out cells, those reconstituted to express Gab1 mutants, and cells expressing gp130 receptors or receptor mutants.

Results

Interleukin-6-induced MAPK pathway activation can be sub-divided into an early Gab1-independent and a subsequent Gab1-dependent phase. Early Gab1-independent MAPK activation is critical for the subsequent initiation of Gab1-dependent amplification of MAPK pathway activation and requires binding of SH2 domain-containing phosphatase 2 (SHP2) to the interleukin-6 receptor complex. Subsequent and coordinated recruitment of Grb2 and SHP2 to Gab1 is essential for Gab1-dependent amplification of IL-6-induced late MAPK pathway activation and subsequent gene expression.

Conclusions

Overall, we elaborated the molecular requirements for Gab1-dependent, spatiotemporal orchestration of interleukin-6-dependent MAPK signalling. We discriminated IL-6-induced Gab1-independent, early activation of MAPK signalling and Gab1-dependent, sustained activation of MAPK signalling.