bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic diagnostic features after failure of initial treatment with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors among non-small-cell lung cancer patients harboring EGFR mutations
Authors: Takeda Yuichiro , Naka Go , Yamaguchi Yoh , Hashimoto Masao , Suzuki Manabu , Izumi Shinyu , Sugiyama Haruhito
Published: October 2020

Background

Osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), can be used as second-line treatment for lung cancer patients harboring the T790M substitution. Although osimertinib is more effective than the first-generation EGFR-TKIs used for first-line treatment, its efficacy with respect to long-term patient survival remains unclear even upon the administration of a complete sequence of EGFR-TKI therapy. Moreover, limited information is available regarding genetic diagnostic approaches after the treatment of EGFR-TKI–naïve patients. This study investigated the clinical characteristics of EGFR-mutated lung cancer patients harboring the T790M substitution resistant to EGFR-TKIs, as well as the advantages of rebiopsy and liquid biopsy for these patients.

Methods

The medical records of patients screened for EGFR mutations were reviewed. Upon failure of naïve treatment with EGFR-TKIs, except for osimertinib, single-plexus cobas version 2 was repeatedly used to detect the T790M substitution in EGFR via tissue or liquid biopsy.

Results

From April 2016 through May 2019, 113 patients were found to harbor EGFR mutations. Sixty patients were treated with EGFR-TKIs, among whom 46 underwent tissue or liquid biopsy. Twenty-nine of these 46 (63%) patients harbored the T790M substitution. In total, 141 rebiopsies were performed. The T790M substitution was detected in 24 of 43 tissue biopsies and 11 of 98 liquid biopsies. If patients displayed an EGFR exon 19 deletion, had a new lesion, and were administered gefitinib as first-line therapy, they were suspected to harbor the T790M substitution. Furthermore, the T790M substitution was detected through rebiopsy in patients with coexisting original mutations, brain metastases, tumor enlargement by ≥12 mm, or metastases at minor sites.

Conclusion

Among patients with positive factors associated with the T790M mutation, repeated tissue or liquid biopsies are useful to maximize the detection rate of the T790M substitution. Furthermore, these biopsies need to be repeated numerous times in order to reduce “detection overlook” among such patients.
Genetically-regulated transcriptomics & copy number variation of proctitis points to altered mitochondrial and DNA repair mechanisms in individuals of European ancestry
Authors: Pathak Gita A. , Polimanti Renato , Silzer Talisa K. , Wendt Frank R. , Chakraborty Ranajit , Phillips Nicole R.
Published: October 2020

Background

Proctitis is an inflammation of the rectum and may be induced by radiation treatment for cancer. The genetic heritability of developing radiotoxicity and prior role of genetic variants as being associated with side-effects of radiotherapy necessitates further investigation for underlying molecular mechanisms. In this study, we investigated gene expression regulated by genetic variants, and copy number variation in prostate cancer survivors with radiotoxicity.

Methods

We investigated proctitis as a radiotoxic endpoint in prostate cancer patients who received radiotherapy (n = 222). We analyzed the copy number variation and genetically regulated gene expression profiles of whole-blood and prostate tissue associated with proctitis. The SNP and copy number data were genotyped on Affymetrix® Genome-wide Human SNP Array 6.0. Following QC measures, the genotypes were used to obtain gene expression by leveraging GTEx, a reference dataset for gene expression association based on genotype and RNA-seq information for prostate (n = 132) and whole-blood tissue (n = 369).

Results

In prostate tissue, 62 genes were significantly associated with proctitis, and 98 genes in whole-blood tissue. Six genes - CABLES2, ATP6AP1L, IFIT5, ATRIP, TELO2, and PARD6G were common to both tissues. The copy number analysis identified seven regions associated with proctitis, one of which (ALG1L2) was also associated with proctitis based on transcriptomic profiles in the whole-blood tissue. The genes identified via transcriptomics and copy number variation association were further investigated for enriched pathways and gene ontology. Some of the enriched processes were DNA repair, mitochondrial apoptosis regulation, cell-to-cell signaling interaction processes for renal and urological system, and organismal injury.

Conclusions

We report gene expression changes based on genetic polymorphisms. Integrating gene-network information identified these genes to relate to canonical DNA repair genes and processes. This investigation highlights genes involved in DNA repair processes and mitochondrial malfunction possibly via inflammation. Therefore, it is suggested that larger studies will provide more power to infer the extent of underlying genetic contribution for an individual’s susceptibility to developing radiotoxicity.
In vivo optical cellular diagnosis for uterine cervical or vaginal intraepithelial neoplasia using flexible gastrointestinal endocytoscopy -a prospective pilot study-
Authors: Ono Shoko , Nozaki Ayako , Matsuda Kana , Takakuwa Emi , Sakamoto Naoya , Watari Hidemichi
Published: October 2020

Backgrouund

For patients with any kind of atypical squamous intraepithelial lesion of the uterine cervix or vagina, colposcopy and punch biopsy are common procedures for histological determination following cytology. However, colposcopy-guided biopsy does not provide a high level of diagnostic accuracy. The aim of this study was to determine the usefulness of optical biopsy in vivo using endocytoscopy compared with conventional procedures using colposcopy.

Methods

Between May 2018 and March 2019, patients who were scheduled for cervical conization or mapping biopsies of the vagina were prospectively enrolled. Endocytoscopy was performed by senior endoscopists prior to scheduled procedures, and endocytoscopic images and biopsy samples were taken from the most prominent site and surrounding area of the cervical or vaginal lesions. The collection process of images was randomized and anonymous, and three doctors separately evaluated the images according to the ECA classification. ECA 4 and 5 are indicative of endoscopic malignancy. The primary endpoint was diagnostic accuracy (benign or malignant: cervical intraepithelial neoplasia (CIN) 3 or vaginal intraepithelial neoplasia (VAIN) 3 or worse) of cell images at the most prominent site in each patient.

Results

A total of 28 consecutive patients were enrolled. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of endocytoscopic images were 95.0% (84.8–98.6%), 87.5% (61.9–96.5%), 95.0% (84.8–98.6%), 87.5% (61.9–96.5%) and 92.9% (78.2–98.0%), respectively. Inter-observer agreement among three reviewers was 0.78 (0.08–9.88, P < 0.01). On the other hand, the accuracy of colposcopy-guided biopsy was 74.1% (64.0–84.0%).

Conclusions

Optical cell diagnosis of cervical or vaginal intraepithelial neoplasia using endocytoscopy provides a high level of diagnostic accuracy.

Trial registration

The study was registered with the UMIN database (ID: 000031712).

UMIN000031712. Registered 16 March 2017,
KIAA0101 and UbcH10 interact to regulate non-small cell lung cancer cell proliferation by disrupting the function of the spindle assembly checkpoint
Authors: Lei Han , Wang Kun , Jiang Tongying , Lu Jingjing , Dong Xue , Wang Feilong , Li Qiang , Zhao Liming
Published: October 2020

Background

Chromosome mis-segregation caused by spindle assembly checkpoint (SAC) dysfunction during mitosis is an important pathogenic factor in cancer, and modulating SAC function has emerged as a potential novel therapy for non-small cell lung cancer (NSCLC). UbcH10 is considered to be associated with SAC function and the pathological types and clinical grades of NSCLC. KIAA0101, which contains a highly conserved proliferating cell nuclear antigen (PCNA)-binding motif that is involved in DNA repair in cancer cells, plays an important role in the regulation of SAC function in NSCLC cells, and bioinformatics predictions showed that this regulatory role is related to UbcH10. We hypothesized KIAA0101 and UbcH10 interact to mediate SAC dysfunction and neoplastic transformation during the development of USCLC.

Methods

NSCLC cell lines were used to investigate the spatial-temporal correlation between UbcH10 and KIAA0101 expression and the downstream effects of modulating their expression were evaluated. Further immunoprecipitation assays were used to investigate the possible mechanism underlying the correlation between UbcH10 and KIAA0101. Eventually, the effect of modulating UbcH10 and KIAA010 on tumor growth and its possible mechanisms were explored through in vivo tumor-bearing models.

Results

In this study, we demonstrated that both UbcH10 and KIAA0101 were upregulated in NSCLC tissues and cells and that their expression levels were correlated in a spatial and temporal manner. Importantly, UbcH10 and KIAA0101 coordinated to mediate the premature degradation of various SAC components to cause further SAC dysfunction and neoplastic proliferation. Moreover, tumor growth in vivo was significantly inhibited by silencing UbcH10 and KIAA0101 expression.

Conclusions

KIAA0101 and UbcH10 interact to cause SAC dysfunction, chromosomal instability and malignant proliferation in NSCLC, suggesting that UbcH10 and KIAA0101 are potential therapeutic targets for the treatment of NSCLC by ameliorating SAC function.
Integrated analysis identifies a pathway-related competing endogenous RNA network in the progression of pancreatic cancer
Authors: Zu Fuqiang , Liu Peng , Wang Huaitao , Zhu Ting , Sun Jian , Sheng Weiwei , Tan Xiaodong
Published: October 2020

Background

It is well acknowledged that cancer-related pathways play pivotal roles in the progression of pancreatic cancer (PC). Employing Integrated analysis, we aim to identify the pathway-related ceRNA network associated with PC progression.

Methods

We divided eight GEO datasets into three groups according to their platform, and combined TCGA and GTEx databases as a group. Additionally, we screened out the differentially expressed genes (DEGs) and performed functional enrichment analysis in each group, and recognized the top hub genes in the most enriched pathway. Furthermore, the upstream of miRNAs and lncRNAs were predicted and validated according to their expression and prognostic roles. Finally, the co-expression analysis was applied to identify a pathway-related ceRNA network in the progression of PC.

Results

A total of 51 significant pathways that common enriched in all groups were spotted. Enrichment analysis indicated that pathway in cancer was greatly linked with tumor formation and progression. Next, the top 20 hug genes in this pathway were recognized, and stepwise prediction and validation from mRNA to lncRNA, including 11 hub genes, 4 key miRNAs, and 2 key lncRNAs, were applied to identify a meaningful ceRNA network according to ceRNA rules. Ultimately, we identified the PVT1/miR-20b/CCND1 axis as a promising pathway-related ceRNA axis in the progression of PC.

Conclusion

Overall, we elucidate the pathway-related ceRNA regulatory network of PVT1/miR-20b/CCND1 in the progression of PC, which can be considered as therapeutic targets and encouraging prognostic biomarkers for PC.
Intermediate outcomes of ab externo circumferential trabeculotomy and canaloplasty in POAG patients with prior incisional glaucoma surgery
Authors: Wang Huaizhou , Xin Chen , Han Ying , Shi Yan , Ziaei Sarah , Wang Ningli
Published: October 2020

Background

To compare the efficacy and safety of ab externo circumferential trabeculotomy (ECT) and canaloplasty on primary open angle glaucoma (POAG) patients with failed filtering surgery and intact schlemm’s canal (SC).

Methods

We conducted a retrospective chart review of POAG patients with failed filtering surgery and intact SC, who further received ECT and canaloplasty. The primary outcome measures were intraocular pressure (IOP) and the number of topical medications at each follow-up point. The secondary outcome compared the quantified success rate at1-year follow-up between the groups.

Results

Twenty-nine eyes were recruited in the ECT group and 19 eyes in canaloplasty group. The postoperative IOP and the number of topical medications decreased significantly in both groups (p < 0.001). The IOP at 3-month and 6-monthwas significantly lower in the ECT group (p = 0.039, p = 0.001) than in the canaloplasty group. Although the IOP at 12-mon was similar between the two groups, the number of topical medications was less in the ECT group (p = 0.040). Hyphema (72.4%) and ciliary body detachment (27.6%), which mainly resolve spontaneously, were two leading complications in the ECT group. The prevalence of hyphema was higher in ECT than in canaloplasty group (p < 0.001).

Conclusion

For POAG with failed filtering surgery and intact SC, canaloplasty may be safer, whereas ECT presented better IOP control.

Translational Relevance: Suggestions for surgical choice for POAG with failed filtering surgery.
Epstein–Barr virus-related hemophagocytic lymphohistiocytosis complicated with coronary artery dilation and acute renal injury in a boy with a novel X-linked inhibitor of apoptosis protein (XIAP) variant: a case report
Authors: Chen Ru-Yue , Li Xiao-Zhong , Lin Qiang , Zhu Yun , Shen Yun-Yan , Xu Qin-Ying , Zhu Xue-Ming , Bai Zhen-Jiang , Li Ying
Published: October 2020

Background

X-linked lymphoproliferative disease (XLP) is a rare inherited X-linked primary immunodeficiency diseases (PID). One such disease, X-linked inhibitor of apoptosis protein (XIAP) deficiency, is characterized by Epstein–Barr virus-related hemophagocytic lymphohistiocytosis (EBV-HLH). However, EBV-HLH with coronary artery dilation and acute renal injury (AKI) in children is unusual.

Case presentation

We report the case of a young boy aged 17 months with a novel XIAP variant. He was initially diagnosed with EBV-HLH based on the HLH-2004 diagnostic criteria and the condition was accompanied by coronary artery dilation and acute renal injury. The comprehensive genetic analysis of peripheral blood-derived DNA revealed a hemizygous variant of the XIAP gene [c.116G > C(p.G39A)], which was inherited from his mother (heterozygous condition). After combined treatment with rituximab, intravenous immunoglobulin, corticosteroids, antiviral drugs, and mycophenolate mofetil (MMF) in addition to supportive therapy, his clinical manifestations and laboratory indexes were improved. The patient achieved complete remission with MMF treatment in the 8-month follow-up.

Conclusions

We report the [c.116G > C(p.G39A)] variant in the XIAP gene for the first time in a case of XLP-2 associated with EBV-HLH. For male patients with severe EBV-HLH, the possibility of XLP should be considered and molecular genetic testing should be used early in auxiliary diagnosis. Reports of EBV-HLH with coronary artery dilation and AKI in children are rare. In the patients with EBV-HLH, color Doppler echocardiography and urine tests should be monitored regularly. If necessary, renal biopsy can be performed to clarify the pathology. Treatment with rituximab, immunosuppressors and supportive therapy achieved a good effect, but long-term follow-up is required.
Promotion of mental health in young adults via mobile phone app: study protocol of the ECoWeB (emotional competence for well-being in Young adults) cohort multiple randomised trials
Authors: Newbold A. , Warren F. C. , Taylor R. S. , Hulme C. , Burnett S. , Aas B. , Botella C. , Burkhardt F. , Ehring T. , Fontaine J. R. J. , Frost M. , Garcia-Palacios A. , Greimel E. , Hoessle C. , Hovasapian A. , Huyghe VEI , Lochner J. , Molinari G. , Pekrun R. , Platt B. , Rosenkranz T. , Scherer K. R. , Schlegel K. , Schulte-Korne G. , Suso C. , Voigt V. , Watkins E. R.
Published: October 2020

Background

Promoting well-being and preventing poor mental health in young people is a major global priority. Building emotional competence (EC) skills via a mobile app may be an effective, scalable and acceptable way to do this. However, few large-scale controlled trials have examined the efficacy of mobile apps in promoting mental health in young people; none have tailored the app to individual profiles.

Method/design

The Emotional Competence for Well-Being in Young Adults cohort multiple randomised controlled trial (cmRCT) involves a longitudinal prospective cohort to examine well-being, mental health and EC in 16–22 year olds across 12 months. Within the cohort, eligible participants are entered to either the PREVENT trial (if selected EC scores at baseline within worst-performing quartile) or to the PROMOTE trial (if selected EC scores not within worst-performing quartile). In both trials, participants are randomised (i) to continue with usual practice, repeated assessments and a self-monitoring app; (ii) to additionally receive generic cognitive-behavioural therapy self-help in app; (iii) to additionally receive personalised EC self-help in app. In total, 2142 participants aged 16 to 22 years, with no current or past history of major depression, bipolar disorder or psychosis will be recruited across UK, Germany, Spain, and Belgium. Assessments take place at baseline (pre-randomisation), 1, 3 and 12 months post-randomisation. Primary endpoint and outcome for PREVENT is level of depression symptoms on the Patient Health Questionnaire-9 at 3 months; primary endpoint and outcome for PROMOTE is emotional well-being assessed on the Warwick-Edinburgh Mental Wellbeing Scale at 3 months. Depressive symptoms, anxiety, well-being, health-related quality of life, functioning and cost-effectiveness are secondary outcomes. Compliance, adverse events and potentially mediating variables will be carefully monitored.

Conclusions

The trial aims to provide a better understanding of the causal role of learning EC skills using interventions delivered via mobile phone apps with respect to promoting well-being and preventing poor mental health in young people. This knowledge will be used to develop and disseminate innovative evidence-based, feasible, and effective Mobile-health public health strategies for preventing poor mental health and promoting well-being.

Trial registration

ClinicalTrials.gov (www.clinicaltrials.org). Number of identification: NCT04148508 November 2019.
Association of ocular diseases with schizophrenia, bipolar disorder, and major depressive disorder: a retrospective case-control, population-based study
Authors: Liu Chun-Hao , Kang Eugene Yu-Chuan , Lin Yu-Hsiang , Wu Wei-Chi , Liu Zhuo-Hao , Kuo Chang-Fu , Lai Chi-Chun , Hwang Yih-Shiou
Published: October 2020

Background

Psychiatric disorders and ocular neurovascular diseases may share a similar pathophysiological route of vascular structures or neurological changes. The aim of this study is to investigate the association between ocular neurovascular diseases and the risk of major psychiatric disorders.

Methods

This was a retrospective case–control, population-based study including patients aged ≥20 and were diagnosed between 1997 and 2013. Ocular neurovascular diseases diagnosed between 1997 and 2006 and newly diagnosed psychiatric disorders including bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia between 2007 and 2013 were registered. Patients were propensity-score matched with control groups without psychiatric disorders in each cohort based on selected covariates.

Results

A total of one million sampled patients in the database were categorized based on their diagnoses; 2243 (37.4% men) were categorized into the BD group, 10,110 (35.2% men) into the MDD group, and 1623 (43.1% men) into the schizophrenia group. In the BD group, all glaucoma (OR 1.49, [1.18–1.89]), open-angle glaucoma (OR 2.08, [1.34–3.24]), and closed-angle glaucoma (OR 2.12, [1.36–3.33]) showed statistical significance of risk. In the MDD group, age-related macular degeneration (OR 1.33, [1.13–1.57]), all glaucoma (OR 1.24, [1.11–1.37]), open-angle glaucoma (OR 1.47, [1.21–1.80]), and dry eye syndrome (OR 1.22, [1.13–1.31]) were associated with a significantly higher risk. In the schizophrenia group, only all glaucoma (OR 1.47, [1.02–2.11]), glaucoma suspect (OR 1.88, [1.01–3.49]), and open-angle glaucoma (OR 2.19, [1.13–4.26]) showed statistical significance.

Conclusions

In this population-based study, ocular neurovascular diseases, especially glaucoma, were associated with increased risks of BD, MDD, and schizophrenia.
Australasian interstitial lung disease registry (AILDR): objectives, design and rationale of a bi-national prospective database
Authors: Moore Irene , Wrobel Jeremy , Rhodes Jessica , Lin Qi , Webster Susanne , Jo Helen , Troy Lauren , Grainge Christopher , Glaspole Ian , Corte Tamera J. ,   on behalf of the Australasian ILD Registry, Thien Frank , Kwan Ben , Jee Adelle , Erskine Odette , Teoh Alan , De Boer Sally , Wilsher Margaret , Gallagher Harry
Published: October 2020

Background

Interstitial Lung Disease (ILD) is a group of respiratory conditions affecting the lung interstitium often associated with progressive respiratory failure. There is increasing recognition of the need for improved epidemiological data to help determine best practice and improve standardisation of care. The Australasian ILD Registry (AILDR) is a bi-national registry of patients with all ILD subtypes designed to establish a clinically meaningful database reflecting real world practice in Australasia with an objective to improve diagnostic and treatment pathways through research and collaboration.

Methods

AILDR is a prospective observational registry recruiting patients attending ILD clinics at centres around Australia and New Zealand. Core and non-core data are stored on a secure server. The pilot phase was launched in 2016 consisting of four sites in Australia. Currently in its second phase a further 16 sites have been recruited, including three in New Zealand.

Results

A total of 1061 participants were consented during the pilot phase. Baseline data demonstrated a mean age 68.3 ± 12.5 (SD) years, mean FVC (%predicted) 79.1 ± 20.4 (SD), mean DLCO (%predicted) 58.5 ± 17.9 (SD) and nadir exertional SpO2 (%) 91 ± 6.9 (SD). Idiopathic pulmonary fibrosis (31%) and connective-tissue disease related ILD (21.7%) were the two most common subtypes. Baseline demographics and physiology were not significantly different across the four centres.

Conclusion

AILDR is an important clinical and research tool providing a platform for epidemiological data that will prove essential in promoting understanding of a rare cohort of lung disease and provide foundations for our aspiration to standardise investigation and treatment pathways of ILD across Australasia.
The fraction of sensitization among lung transplant recipients in a transplant center in Japan
Authors: Kumata Sakiko , Hirama Takashi , Watanabe Yui , Oishi Hisashi , Niikawa Hiromichi , Akiba Miki , Tikkanen Jussi , Okada Yoshinori
Published: October 2020

Background

Anti-human leukocyte antigen (HLA) antibody testing was approved by the Japanese government in 2018. As such, there was no longitudinal data regarding the HLA-sensitization of lung transplant (LTX) patients in Japan. We therefore set out to measure anti-HLA antibodies from all our LTX patients during their annual follow-up to characterize the sensitization status in the Japanese population.

Methods

The cross-sectional study was conducted for consecutive LTX recipients who underwent transplantation from January 2000 to January 2020 at Tohoku University Hospital (TUH). The serum from the recipients was screened for anti-HLA antibody with the panel-reactive assay (PRA) and the donor-specific antibodies (DSA).

Results

Sensitization was reviewed in 93 LTX recipients, showing 23 positive (24.7%) and 70 negative (75.3%) PRA. More sensitized recipients were found in recent transplantations (60.9% (14/23), ≤5 years post LTX) than in older transplantations (17.4% (4/23), 5–10 years or 21.7% (5/23), ≥10 years post LTX) (p = 0.04). Even fewer recipients had DSA (5.4%, 5/93), among whom 4/5 (80%) were recently transplanted.

Conclusion

The rate of PRA positive LTX recipients in our population was lower compared with those in previous reports from US and Europe. More sensitized LTRs were found in recent transplantations than the older cohort, and DSA was identified primarily in the recent recipients. Due to several limitations, it is still unclear whether the sensitization would be related the development of CLAD or survival, yet this study would be fundamental to the future anti-HLA body study in Japanese population.
Adolescents’ experiences of fluctuating pain in musculoskeletal disorders: a qualitative systematic review and thematic synthesis
Authors: Khanom Sonia , McDonagh Janet E. , Briggs Michelle , Bakir Ebru , McBeth John
Published: October 2020

Background

Adolescents with chronic musculoskeletal pain experience daily fluctuations in pain. Although not all fluctuations are bothersome, pain flares are a distinct type of symptom fluctuation with greater impact. Since literature on the experience of pain flares is non-existent, the aim of this review was to (i) synthesise the qualitative literature on adolescents’ experiences of fluctuating pain in musculoskeletal disorders in order to (ii) identify knowledge gaps to inform future research on pain flares.

Methods

Electronic databases (CINAHL, MEDLINE, EMBASE, PsycINFO), grey literature and reference lists were searched from inception to June 2018 for qualitative studies reporting adolescents’ experiences of pain. Comprehensiveness of reporting was assessed using the Consolidated Criteria for Reporting Qualitative Health Research. Studies were analysed using thematic synthesis.

Results

Of the 3787 records identified, 32 studies (n = 536) were included. Principal findings were synthesised under three key themes: 1) symptom experience, 2) disruption and loss, and 3) regaining control. The first theme (symptom experience) describes adolescent’s perception and interpretation of pain fluctuations. The second theme (disruption and loss) describes the physical, social and emotional constraints faced as a result of changes in pain. The third theme (regaining control) describes coping strategies used to resist and accommodate unpredictable phases of pain. Each theme was experienced differently depending on adolescents’ characteristics such as their developmental status, pain condition, and the duration of the pain experience.

Conclusions

Adolescents with chronic musculoskeletal pain live with a daily background level of symptoms which frequently fluctuate and are associated with functional and emotional difficulties. It was not clear whether these symptoms and challenges were experienced as part of ‘typical’ fluctuations in pain, or whether they reflect symptom exacerbations classified as ‘flares’. Further research is needed to explore the frequency and characteristics of pain flares, and how they differ from their typical fluctuations in pain. The review also highlights areas relating to the pain experience, symptom management and health service provision that require further exploration to support more personalised, tailored care for adolescents with chronic musculoskeletal pain.
Combined stomach and duodenal perforating injury following blunt abdominal trauma: a case report and literature review
Authors: Lai Chun-Chi , Huang Hung-Chang , Chen Ray-Jade
Published: October 2020

Background

Gastrointestinal injury following blunt abdominal trauma is uncommon; a combined stomach and duodenal perforating injury is even more rare. Because these two organs are located in different spaces in the abdomen, such injuries are difficult to identify.

Case presentation

A young woman involved in a motor vehicle crash presented to our emergency department with concerns of severe peritonitis. Contrast-enhanced computed tomography of the abdomen revealed pneumoperitoneum and retroperitoneal hematoma in zone 1. An emergency laparotomy was performed, revealing a stomach-perforating injury, which was resolved with primary repair. No obvious injury was observed on retroperitoneal exploration. However, peritonitis presented again on the second postoperative day, and a second laparotomy was performed, revealing a duodenum-perforating injury in its third portion. We performed primary repair with multi-tube-ostomy. The patient recovered well without permanent tube placement or internal bypass.

Conclusions

Assessing associated injuries in blunt abdominal trauma is crucial because they may be fatal if timely intervention is not undertaken. These types of complicated injuries require a feasible surgical strategy formulated by experienced surgeons, which gives the patient a better chance of survival.
Ambient sulfur dioxide could have an impact on testicular volume from a observational study on a population of infertile male
Authors: Chen Yu-An , Chang Yi-Kai , Su Yann-Rong , Chang Hong-Chiang
Published: October 2020

Background

The effect of ambient pollutants on the male reproductive system is controversial. This retrospective study investigated the effect of environmental pollutants on male reproductive health.

Methods

Male patients with primary infertility (n = 282) were identified from a single center between January 2016 and December 2017. Patients were physically examined for the presence of varicocele and for the volume of both testicles. Semen quality was measured in terms of the total sperm count, sperm concentration, and the percentage of sperm cells with motility and normal morphology. Data were acquired on the concentration of ambient pollutants, namely particulate matters of diameter < 2.5 μm, sulfur dioxide (SO2), nitrogen oxides (NOx), and ozone (O3), measured on daily and hourly basis, from the Environmental Protection Administration Executive Yuan, Taiwan. Individual exposure to pollutants was estimated based on the reported residential address of each participant. Statistical analysis indicated the effect of each pollutant on the testicular volume, sex hormone profile, and semen parameters.

Results

The mean ± standard deviation of age was 36.7 ± 7.3 years. The average sperm count and concentration were 41.9 million/mL and 34.1 million/mL, respectively. The mean levels of serum testosterone, follicle-stimulating hormone, and luteinizing hormone were 3.57 ± 1.68 ng/mL, 7.59 ± 6.3 IU/L, and 4.68 ± 3.49 IU/L, respectively. According to the multivariate linear regression model, NOx exposure was a risk factor for decreased sperm concentration and motility (p = 0.043 and 0.032). Furthermore, SO2 exposure was negatively associated and testicular volume (p < 0.01).

Conclusions

NO2 and SO2 exposure were negatively associated with the seminal parameter and decreased testicular volume, respectively, in a population of men with infertility. However, additional prospective studies are needed to ascertain the cause–effect relation of current results.
Prevalence and correlates of transactional sex among women of low socioeconomic status in Portland, OR
Authors: Menza Timothy W. , Lipira Lauren , Bhattarai Amisha , Leon Victoria Cali-De , Orellana E. Roberto
Published: October 2020

Background

Women who report transactional sex are at increased risk for HIV and other sexually transmitted infections (STIs). However, in the United States, social, behavioral, and trauma-related vulnerabilities associated with transactional sex are understudied and data on access to biomedical HIV prevention among women who report transactional sex are limited.

Methods

In 2016, we conducted a population-based, cross-sectional survey of women of low socioeconomic status recruited via respondent-driven sampling in Portland, Oregon. We calculated the prevalence and, assessed the correlates of, transactional sex using generalized linear models accounting for sampling design. We also compared health outcomes, HIV screening, and knowledge and uptake of HIV pre-exposure prophylaxis (PrEP) between women who did and did not report transactional sex.

Results

Of 334 women, 13.6% reported transactional sex (95% confidence interval [CI]: 6.8, 20.5%). Women who reported transactional sex were older, more likely to identify as black, to identify as lesbian or bisexual, to experience childhood trauma and recent sexual violence, and to have been homeless. Six percent (95% CI: 1.8, 10.5%) of women with no adverse childhood experiences (ACEs) reported transactional sex compared to 23.8% (95% CI: 13.0, 34.6%) of women who reported eleven ACEs (P <  0.001). Transactional sex was strongly associated with combination methamphetamine and opiate use as well as condomless sex. Women who reported transactional sex were more likely to report being diagnosed with a bacterial STI and hepatitis C; however, HIV screening and pre-exposure prophylaxis knowledge and use were low.

Conclusions

In a sample of women of low socioeconomic status in Portland, Oregon, transactional sex was characterized by marginalized identities, homelessness, childhood trauma, sexual violence, substance use, and sexual vulnerability to HIV/STI. Multi-level interventions that address these social, behavioral, and trauma-related factors and increase access to biomedical HIV prevention are critical to the sexual health of women who engage in transactional sex.
Subacute uterine inversion following an induced abortion in a teenage girl: a case report
Authors: Owaraganise Asiphas , Tibaijuka Leevan , Ngonzi Joseph
Published: October 2020

Background

Subacute uterine inversion is a very rare complication of mid-trimester termination of pregnancy that should be considered in a situation where unsafe abortion occurs.

Case presentation

We present a case of subacute uterine inversion complicated by hypovolemic shock following an unsafe abortion in a 17-year-old nulliparous unmarried girl. She presented with a history of collapse, mass protruding per vagina that followed Valsalva, and persistent lower abdominal pain but not vaginal bleeding. This followed her second attempt to secretly induce an abortion at 18 weeks amenorrhea. On examination, she was agitated, severely pale, cold on palpation, with an axillary temperature of 35.8 °C, a tachycardia of 143 beats per minute and unrecordable low blood pressure. The abdomen was soft and non-tender with no palpable masses; the uterine fundus was absent at its expected periumbilical position and cupping was felt instead. A fleshy mass with gangrenous patches protruding in the introitus was palpated with no cervical lip felt around it. We made a clinical diagnosis of subacute uterine inversion complicated with hypovolemic shock and initiated urgent resuscitation with crystalloid and blood transfusion. Non-operative reversal of the inversion failed. Surgery was done to correct the inversion followed by total abdominal hysterectomy due to uterine gangrene.

Conclusion

Our case highlights an unusual presentation of subacute uterine inversion following unsafe abortion. This case was managed successfully but resulted in significant and permanent morbidity.
Ethical and human rights considerations in public health in low and middle-income countries: an assessment using the case of Uganda’s responses to COVID-19 pandemic
Authors: Barugahare John , Nakwagala Fredrick Nelson , Sabakaki Erisa Mwaka , Ochieng Joseph , K Sewankambo Nelson
Published: October 2020

Background

In response to COVID-19 pandemic, the Government of Uganda adopted public health measures to contain its spread in the country. Some of the initial measures included refusal to repatriate citizens studying in China, mandatory institutional quarantine, and social distancing. Despite being a public health emergency, the measures adopted deserve critical appraisal using an ethics and human rights approach. The goal of this paper is to formulate an ethics and human rights criteria for evaluating public health measures and use it to reflect on the ethical propriety of those adopted by the government of Uganda to contain the spread of COVID-19.

Main body

We begin by illustrating the value of ethics and human rights considerations for public health measures including during emergencies. We then summarize Uganda’s social and economic circumstances and some of the measures adopted to contain the spread of COVID-19. After reviewing some of the ethics and human rights considerations for public health, we reflect upon the ethical propriety of some of Uganda’s responses to COVID-19. We use content analysis to identify the measures adopted by the government of Uganda to contain the spread of COVID-19, the ethics and human rights considerations commonly recommended for public health responses and their importance. Our study found that some of the measures adopted violate ethics and human rights principles. We argue that even though some human rights can sometimes be legitimately derogated and limited to meet public health goals during public health emergencies, measures that infringe on human rights should satisfy certain ethics and human rights criteria. Some of these criteria include being effective, strictly necessary, proportionate to the magnitude of the threat, reasonable in the circumstances, equitable, and least restrictive. We reflect on Uganda’s initial measures to combat the spread of COVID-19 and argue that many of them fell short of these criteria, and potentially limit their effectiveness.

Conclusion

The ethical legitimacy of public health measures is valuable in itself and for enhancing effectiveness of the measures. Such legitimacy depends on the extent to which they conform to ethics and human rights principles recommended for public health measures.
An ethics analysis of the rationale for publicly funded plastic surgery
Authors: Sandman Lars , Hansson Emma
Published: October 2020

Background

Healthcare systems are increasingly struggling with resource constraints, given demographic changes, technological development, and citizen expectations. The aim of this article is to normatively analyze different suggestions regarding how publicly financed plastic surgery should be delineated in order to identify a well-considered, normative rationale. The scope of the article is to discuss general principles and not define specific conditions or domains of plastic surgery that should be treated within the publicly financed system.

Methods

This analysis uses a reflective equilibrium approach, according to which considered normative judgements in one area should be logically and argumentatively coherent with considered normative judgements and background theories at large within a system.

Results and conclusions

In exploring functional versus non-function conditions, we argue that it is difficult to find a principled reason for an absolute priority of functional conditions over non-functional conditions. Nevertheless, functional conditions are relatively easier to establish objectively, and surgical intervention has a clear causal effect on treating a functional condition.

Considering non-functional conditions that require plastic surgery [i.e., those related to appearance or symptomatic conditions (not affecting function)], we argue that the patient needs to experience some degree of suffering (and not only a preference for plastic surgery), which must be ‘validated’ in some form by the healthcare system.

This validation is required for both functional and non-functional conditions. Functional conditions are validated by distinguishing between statistically normal and abnormal functioning. Similarly, for non-functional conditions, statistical normality represents a potential method for distinguishing between what should and should not be publicly funded. However, we acknowledge that such a concept requires further development.
Pharmacy preparedness and response for the prevention and control of coronavirus disease (COVID-19) in Aksum, Ethiopia; a qualitative exploration
Authors: Kasahun Gebremicheal Gebreslassie , Kahsay Gebremichael Mulu , Asayehegn Amha Teklu , Demoz Gebre Teklemariam , Desta Desilu Mahari , Gebretekle Gebremedhin Beedemariam
Published: October 2020

Background

Novel Coronavirus is a global pandemic affecting all walks of life and it significantly changed the health system practices. Pharmacists are at the front line and have long been involved in combating this public health emergency. Therefore, the study was aimed to explore pharmacy preparedness and response to prevent and control coronavirus disease 2019 (COVID-19).

Methods

A qualitative study was conducted in six pharmacies in Aksum, Ethiopia in May, 2020. We conducted six in-depth interviews with purposively selected key informants. Direct observation measures were made to assess the activities made in the medicine retail outlets for the prevention and control of the pandemic. Interview data were audio-recorded, translated and transcribed verbatim. Thematic analysis was employed to analyze the data and OpenCode version 4.02 software was used to facilitate the data analysis.

Results

The thematic analysis has resulted in seven major themes. Good preparedness measures were undertaken to control and prevent COVID-19. Study informants had good knowledge about the pandemic disease and reported they had used different resource materials to update themselves. Preparing of alcohol-based hand-rub, availing finished sanitizers and alcohol, and advising clients to maintain physical distancing were the major counseling information being delivered to prevent the disease. Some tendencies of irrational drug use and false claims of COVID-19 were observed at the beginning of the pandemic. Interview informants had reported they were working with relevant stakeholders and appropriate patient education and support were given to combat the pandemic.

Conclusion

The study revealed necessary pharmacy services has been rendered to all clients. However, availability of drugs and medical supplies were scarce which negatively affected the optimal delivery of pharmacy services. The government and other responsible bodies should work together to solve such problems and contain the pandemic.
Disseminated Scedosporium apiospermum infection in a Maremmano-Abruzzese sheepdog
Authors: Di Teodoro Giovanni , Averaimo Daniela , Primavera Miria , Santoleri Doriana , Giovannini Giorgia , Cocco Antonio , Di Francesco Gabriella , Malatesta Daniela , Defourny Sabrina , D’Alterio Nicola , Curini Valentina , Di Domenico Marco , Petrini Antonio
Published: October 2020

Background

Few cases of scedosporiosis have been reported in animals, but the true prevalence is probably underestimated due to a lack of awareness. Scedosporiosis in dogs has often been associated with localized infection (i.e., nasal infection, eumycetoma, or keratomycosis) or, in rare cases, disseminated infections.

Case presentation

This case report describes the clinical and pathological features and the diagnostic process of a rare systemic and fatal fungal infection in a dog caused byScedosporium apiospermum. A 10-month-old female Maremmano-Abruzzese sheepdog showing weakness, lethargy, lateral decubitus, miosis and muscular rigidity was presented. Rodenticide poisoning was clinically suspected for the differential diagnosis. However, postmortem examinations revealed the presence of a swollen and soft subcutaneous nodule located near the right inguinal breast, which was associated with massive enlargement of the inguinal lymph nodes and small disseminated, cream-colored nodules in the kidneys and mesentery. Multiple fungal pyogranulomas were observed upon histological examination. Fungal isolation from the kidneys, breast and inguinal lymph nodes was performed. The internal transcribed spacer (ITS) sequences from the fungal colony DNA were searched in BLAST in the NCBI GenBank for species identification. The sequences of the fungi isolated from the kidney and breast cultures showed 100% sequence identity with sequences fromScedosporium apiospermum.

Conclusions

This report shows thatScedosporium apiospermummay act as a primary pathogen in young and apparently healthy dogs and represents an important pathogen that should be considered during the diagnostic process, particularly when a fungal infection is suspected.
How useful are malaria risk maps at the country level? Perceptions of decision-makers in Kenya, Malawi and the Democratic Republic of Congo
Authors: Ghilardi Ludovica , Okello George , Nyondo-Mipando Linda , Chirambo Chawanangwa Mahebere , Malongo Fathy , Hoyt Jenna , Lee Jieun , Sedekia Yovitha , Parkhurst Justin , Lines Jo , Snow Robert W. , Lynch Caroline A. , Webster Jayne
Published: October 2020

Background

Declining malaria prevalence and pressure on external funding have increased the need for efficiency in malaria control in sub-Saharan Africa (SSA). Modelled Plasmodium falciparum parasite rate (PfPR) maps are increasingly becoming available and provide information on the epidemiological situation of countries. However, how these maps are understood or used for national malaria planning is rarely explored. In this study, the practices and perceptions of national decision-makers on the utility of malaria risk maps, showing prevalence of parasitaemia or incidence of illness, was investigated.

Methods

A document review of recent National Malaria Strategic Plans was combined with 64 in-depth interviews with stakeholders in Kenya, Malawi and the Democratic Republic of Congo (DRC). The document review focused on the type of epidemiological maps included and their use in prioritising and targeting interventions. Interviews (14 Kenya, 17 Malawi, 27 DRC, 6 global level) explored drivers of stakeholder perceptions of the utility, value and limitations of malaria risk maps.

Results

Three different types of maps were used to show malaria epidemiological strata: malaria prevalence using a PfPR modelled map (Kenya); malaria incidence using routine health system data (Malawi); and malaria prevalence using data from the most recent Demographic and Health Survey (DRC). In Kenya the map was used to target preventative interventions, including long-lasting insecticide-treated nets (LLINs) and intermittent preventive treatment in pregnancy (IPTp), whilst in Malawi and DRC the maps were used to target in-door residual spraying (IRS) and LLINs distributions in schools. Maps were also used for operational planning, supply quantification, financial justification and advocacy. Findings from the interviews suggested that decision-makers lacked trust in the modelled PfPR maps when based on only a few empirical data points (Malawi and DRC).

Conclusions

Maps were generally used to identify areas with high prevalence in order to implement specific interventions. Despite the availability of national level modelled PfPR maps in all three countries, they were only used in one country. Perceived utility of malaria risk maps was associated with the epidemiological structure of the country and use was driven by perceived need, understanding (quality and relevance), ownership and trust in the data used to develop the maps.