bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutation screening of germline TP53 mutations in high-risk Chinese breast cancer patients
Authors: Kwong Ava , Shin Vivian Yvonne , Ho Cecilia Y. S. , Au Chun Hang , Slavin Thomas P. , Weitzel Jeffrey N. , Chan Tsun-Leung , Ma Edmond S. K.
Published: November 2020

Background

Germline TP53 mutations are associated with Li-Fraumeni syndrome, a severe and rare hereditary cancer syndrome. Despite the rarity of germline TP53 mutations, the clinical implication for mutation carriers and their families is significant. The risk management of TP53 germline mutation carriers is more stringent than BRCA carriers, and radiotherapy should be avoided when possible.

Methods

TP53 gene mutation screening was performed in 2538 Chinese breast cancer patients who tested negative for BRCA mutations.

Results

Twenty TP53 mutations were identified with high next-generation sequencing concerning for germline mutations in Chinese breast cancer families. The majorities of the TP53 carriers had early-onset, hormone receptor-positive breast cancer, and had strong family history of cancer. Among all, 11 patients carried a germline mutation and 6 of which were likely de novo germline mutations. In addition, 1 case was suspected to be induced by chemotherapy or radiation, as this patient had no significant family history of cancer and aberrant clonal expansion can commonly include TP53 mutations. Furthermore, we have identified one mosaic LFS case. Two novel mutations (c.524_547dup and c.529_546del) were identified in patients with early-onset.

Conclusions

In view of the high lifetime risk of malignancy, identification of patients with germline TP53 mutations are important for clinicians to aid in accurate risk assessment and offer surveillance for patients and their families.
Covid-19 effects on the workload of Iranian healthcare workers
Authors: Shoja Esmail , Aghamohammadi Vahideh , Bazyar Hadi , Moghaddam Hamed Rezakhani , Nasiri Khadijeh , Dashti Mohammad , Choupani Ali , Garaee Masoumeh , Aliasgharzadeh Shafagh , Asgari Amin
Published: November 2020

Background

In this study, we aimed to evaluate the impact of the COVID-19 epidemic on the workload and mental health of Iranian medical staff using the General Health Questionnaire (GHQ-12) and NASA -Task Load Index (NASA-TLX) Questionnaire between March and April 2020, respectively.

Methods

The present cross-sectional study was conducted from March 5th to April 5th, 2020. To evaluate the workload and mental health of participants NASA-TLX and GHQ-12 online questionnaires were distributed. Data were entered into software SPSS (Version 23) and T-test, ANOVA, Regression methods were used for data analysis.

Results

Health workers who encountered COVID- 19 patients, were subjected to more task load compared to those who had no contact with COVID- 19 patients at the workplace (p <  0.001). In terms of the subscale score of NASA-TLX, nurses had more scores in mental pressure, physical pressure, time pressure (temporal), and frustration compared to the other jobs (p <  0.05). Moreover, nurses had significantly more workload compared to the other jobs.

Conclusions

Type of job, the shift of work, educational level, and facing COVID-19 affected the score of NASA-TLX. NASA-TLX scores were higher in nursing compared to the scores of other health staff groups. The results of this study indicate that the scores of NASA-TLX and GHQ-12 among staff who had contact with COVID-19 patients were significantly higher than those who did not face COVID-19 patients. We suggested that a comprehensive assistance should be provided to support the well-being of healthcare workers especially nurses and healthcare workers who treated COVID-19 patients.
OPTImising the implementation of pulMonary rehAbiLitation in people with chronic obstructive pulmonary disease (the OPTIMAL study): mixed methods study protocol
Authors: Hug Sarah , Cavalheri Vinicius , Gucciardi Daniel F. , Norman Richard , Hill Kylie
Published: November 2020

Background

Chronic obstructive pulmonary disease (COPD) is a common respiratory condition characterised by dyspnoea during daily life. As the disease progresses, people with COPD can experience poor quality of life, reduced exercise capacity, worsening of symptoms and increased hospital admissions. Pulmonary rehabilitation, which includes exercise training, optimises both psychological and physical function, reduces symptoms and mitigates healthcare utilisation in people with COPD. There is, however, a gap in implementation of pulmonary rehabilitation programs, with global access limited to a small fraction of people with COPD. The overall aim of this study is to gather evidence that will optimise the implementation of pulmonary rehabilitation in people with COPD living in Perth, Western Australia.

Methods

This is a mixed methods study protocol informed by a critical realist perspective. The study will comprise four phases. In Phase 1, we will quantify target behaviours of healthcare professionals and people with COPD which are related to the implementation of pulmonary rehabilitation at three tertiary hospitals. In Phase 2, we will conduct semi-structured interviews to explore the determinants of these target behaviours from the perspectives of healthcare professionals, people with COPD and their primary support person. In Phase 3, knowledge gained in Phases 1 and 2 will be used by healthcare professionals and people with COPD to co-create, field test and apply strategies that optimise these target behaviours. In Phase 4, we will re-quantify these target behaviours to determine the influence of co-created strategies. The cost effectiveness of implementing the co-created strategies will be explored by an economic analysis.

Discussion

Understanding current clinical practice and the determinants of target behaviours pertaining to the implementation of pulmonary rehabilitation is crucial when developing strategies that successfully bridge the pulmonary rehabilitation implementation gap. If co-created strategies are effective, more people with COPD living in Perth, Western Australia will have access to pulmonary rehabilitation enabling them to derive the health benefits associated with this intervention.
Talking about death and dying in a hospital setting - a qualitative study of the wishes for end-of-life conversations from the perspective of patients and spouses
Authors: Bergenholtz Heidi , Missel Malene , Timm Helle
Published: November 2020

Background

End-of-life (EOL) conversations are highly important for patients living with life-threatening diseases and for their relatives. Talking about the EOL is associated with reduced costs and better quality of care in the final weeks of life. However, there is therefore a need for further clarification of the actual wishes of patients and their relatives concerning EOL conversations in an acute hospital setting.

Aim

The purpose of this study was to explore the wishes of patients and their relatives with regard to talking about the EOL in an acute hospital setting when living with a life-threatening disease.

Methods

This study is a qualitative study using semi-structured in-depth interviews. A total of 17 respondents (11 patients and six spouses) participated. The patients were identified by the medical staff in a medical and surgical ward using SPICT™. The interview questions were focused on the respondents’ thoughts on and wishes about their future lives, as well as on their wishes regarding talking about the EOL in a hospital setting.

Results

This study revealed that the wish to talk about the EOL differed widely between respondents. Impairment to the patients’ everyday lives received the main focus, whereas talking about EOL was secondary. Conversations on EOL were an individual matter and ranged from not wanting to think about the EOL, to being ready to plan the funeral and expecting the healthcare professionals to be very open about the EOL. The conversations thus varied between superficial communication and crossing boundaries.

Conclusion

The wish to talk about the EOL in an acute hospital setting is an individual matter and great diversity exists. This individualistic stance requires the development of conversational tools that can assist both the patients and the relatives who wish to have an EOL conversation and those who do not. At the same time, staff should be trained in initiating and facilitating EOL discussions.
The cost-effectiveness of hypertonic saline inhalations for infant bronchiolitis
Authors: Buendía Jefferson Antonio , Acuña-Cordero Ranniery
Published: November 2020

Background

Pharmacological treatment for bronchiolitis is primarily supportive because bronchodilators, steroids, and antibiotics, show little benefit. Clinical studies have suggested that nebulized 3% hypertonic solution is useful for infants with bronchiolitis. This study aims to evaluate the cost-effectiveness of the HS inhalations in infant bronchiolitis in a tropical country.

Methods

Decision tree analysis was used to calculate the expected costs and QALYs. All cost and use of resources were collected directly from medical invoices of 193 patient hospitalized with diagnosis of bronchiolitis in tertiary centers, of Rionegro, Colombia. The utility values applied to QALYs calculations were collected from the literature. The economic analysis was carried out from a societal perspective.

Results

The model showed that nebulized 3% hypertonic solution, was associated with lower total cost than controls (US $200vs US $240 average cost per patient), and higher QALYs (0.92 vs 0.91 average per patient); showing dominance. A position of dominance negates the need to calculate an incremental cost-effectiveness ratio.

Conclusion

The nebulized 3% hypertonic solution was cost-effective in the inpatient treatment of infant bronchiolitis. Our study provides evidence that should be used by decision-makers to improve clinical practice guidelines and should be replicated to validate their results in other tropical countries.
How to assess the value of low-value care
Authors: Sacristán José Antonio
Published: November 2020

Background

Many of the strategies designed to reduce “low-value care” have been implemented without a consensus on the definition of the term “value”. Most “low value care” lists are based on the comparative effectiveness of the interventions.

Main text

Defining the value of an intervention based on its effectiveness may generate an inefficient use of resources, as a very effective intervention is not necessarily an efficient intervention, and a low effective intervention is not always an inefficient intervention. The cost-effectiveness plane may help to differentiate between high and low value care interventions. Reducing low value care should include three complementary strategies: eliminating ineffective interventions that entail a cost; eliminating interventions whose cost is higher and whose effectiveness is lower than that of other options (quadrant IV); and eliminating interventions whose incremental or decremental cost-effectiveness is unacceptable in quadrants I and III, respectively. Defining low-value care according to the efficiency of the interventions, ideally at the level of subgroups and individuals, will contribute to develop true value-based health care systems.

Conclusion

Cost-effectiveness rather than effectiveness should be the main criterion to assess the value of health care services and interventions. Payment-for-value strategies should be based on the definition of high and low value provided by the cost-effectiveness plane.
Association between antipsychotic use and acute ischemic heart disease in women but not in men: a retrospective cohort study of over one million primary care patients
Authors: Lai Francisco T. T. , Guthrie Bruce , Mercer Stewart W. , Smith Daniel J. , Yip Benjamin H. K. , Chung Gary K. K. , Lee Kam-Pui , Chung Roger Y. , Chau Patsy Y. K. , Wong Eliza L. Y. , Yeoh Eng-Kiong , Wong Samuel Y. S.
Published: November 2020

Background

Research comparing sex differences in the effects of antipsychotic medications on acute ischemic heart disease (IHD) is limited and the findings ambiguous. This study aimed to investigate these associations within a primary care setting.

Methods

Hong Kong public general outpatient electronic records of patients aged 45+ during 2007–2010 were extracted, with the last consultation date as the baseline for a 4-year follow-up period to observe acute IHD hospitalizations (2011–2014). Antipsychotic use was defined as any prescription over the previous 12 months from a list of 16 antipsychotics, while acute IHD was defined by ICD-9: 410.00–411.89. Both sex-specific and sex-combined (both sexes) mixed-effects Cox models (random intercept across 74 clinics) were implemented to examine the association and test the interaction between antipsychotics and sex.

Results

Among 1,043,236 included patients, 17,780 (1.7%) were prescribed antipsychotics, and 8342 (0.8%) developed IHD. In sex-specific analyses, antipsychotic prescription was associated with a 32% increased hazard rate of acute IHD among women (95% CI 1.05–1.67) but not among men. A likelihood ratio test comparing sex-combined models with and without the interaction between antipsychotic use and sex suggested significant interaction (χ2 = 4.72, P = 0.030). The association between antipsychotic use and IHD among women attenuated and became non-significant when haloperidol was omitted from the operationalization of antipsychotic use (HR = 1.23, 95% CI 0.95–1.60).

Conclusion

Our results suggest that antipsychotic prescription is moderately associated with an increased risk of acute IHD among women in primary care and this relationship may be explained by specific antipsychotics. Further research should observe and capture the potential intermediary mechanisms and the dose-response relationship of this association to provide more rigorous evidence to establish causality and inform clinical practices.
Enhancing the antibacterial activity of antimicrobial peptide PMAP-37(F34-R) by cholesterol modification
Authors: Chen Liangliang , Shen Tengfei , Liu Yongqing , Zhou Jiangfei , Shi Shuaibing , Wang Yang , Zhao Zhanqin , Yan Zhiling , Liao Chengshui , Wang Chen
Published: November 2020

Background

The problem of increasing resistance against conventional antibiotics has drawn people’s attention. Therefore, the development of novel antibacterial agents with effective and safe therapeutic effects is imminent. Antimicrobial peptides (AMPs) are considered a promising class of antibacterial agents due to their broad antibacterial spectrum.

Results

In this study, on the basis of our previously studied peptide PMAP-37(F34-R), a novel antimicrobial peptide Chol-37(F34-R) was developed by N-terminal cholesterol modification to increase hydrophobicity. We observed that the N-terminal cholesterol-modified Chol-37(F34-R) showed higher antimicrobial activity than PMAP-37(F34-R) in vitro. Chol-37(F34-R) also exhibited effective anti-biofilm activity and may kill bacteria by improving the permeability of their membranes. Chol-37(F34-R) exerted high stability in different pH, salt, serum, and boiling water environments. Chol-37(F34-R) also showed no hemolytic activity and substantially low toxicity. Furthermore, Chol-37(F34-R) exhibited good potency of bacteria eradication and promoted wound healing and abscess reduction in infected mice. Meanwhile, in S. aureus ATCC25923-infected peritonitis model, Chol-37(F34-R) exhibited an impressive therapeutic effect by reducing the decrease in systemic bacterial burden and alleviating organ damage.

Conclusions

Our findings suggested that the N-terminal cholesterol modification of PMAP-37(F34-R) could improve antibacterial activity. Chol-37(F34-R) displayed excellent bactericidal efficacy and impressive therapeutic effect in vivo. Thus, Chol-37(F34-R) may be a candidate for antimicrobial agents against microbial infection in the clinic.
Successful management of portal vein thrombosis in a Yorkshire Terrier with protein-losing enteropathy
Authors: Sakamoto Yumi , Ishigaki Kumiko , Ishikawa Chieko , Nakayama Tomohiro , Asano Kazushi , Sakai Manabu
Published: November 2020

Background

Portal vein thrombosis (PVT) is a rare presentation in dogs with protein-losing enteropathy (PLE). Rivaroxaban, an oral, selective, direct factor Xa inhibitor, has not been reported to be administrated for canine PVT and the effect is unclear in dogs with PLE.

Case presentation

An 11-year-old Yorkshire Terrier presented with moderate ascites. The dog had severe hypoalbuminemia (1.2 g/dL), and a portal vein thrombus was confirmed on computed tomographic angiography (CTA). On endoscopic examination, it became apparent that the hypoalbuminemia was caused by PLE, which was consequent of lymphatic dilation and lymphoplasmacytic enteritis. Therefore, the dog was initially treated with oral administrations of spironolactone and clopidogrel, with dietary fat restriction. However, a follow-up CTA showed no changes in the ascites, thrombus, and portal vein to aorta (PV/Ao) ratio. Therefore, the dog was additionally prescribed rivaroxaban and low-dose prednisolone for the portal vein thrombus and hypoalbuminemia due to lymphoplasmacytic enteritis, respectively. Following the treatment, the PV/Ao ratio decreased because of a decrease in the thrombus and the ascites disappeared completely with an elevation of albumin concentration (1.9 g/dL).

Conclusions

This case report demonstrated that oral administration of rivaroxaban combined with low-dose glucocorticoid was effective management for PVT in a dog with PLE.
Enhanced production of taxadiene in Saccharomyces cerevisiae
Authors: Nowrouzi Behnaz , Li Rachel A. , Walls Laura E. , d’Espaux Leo , Malcı Koray , Liang Lungang , Jonguitud-Borrego Nestor , Lerma-Escalera Albert I. , Morones-Ramirez Jose R. , Keasling Jay D. , Rios-Solis Leonardo
Published: November 2020

Background

Cost-effective production of the highly effective anti-cancer drug, paclitaxel (Taxol®), remains limited despite growing global demands. Low yields of the critical taxadiene precursor remains a key bottleneck in microbial production. In this study, the key challenge of poor taxadiene synthase (TASY) solubility in S. cerevisiae was revealed, and the strains were strategically engineered to relieve this bottleneck.

Results

Multi-copy chromosomal integration of TASY harbouring a selection of fusion solubility tags improved taxadiene titres 22-fold, up to 57 ± 3 mg/L at 30 °C at microscale, compared to expressing a single episomal copy of TASY. The scalability of the process was highlighted through achieving similar titres during scale up to 25 mL and 250 mL in shake flask and bioreactor cultivations, respectively at 20 and 30 °C. Maximum taxadiene titres of 129 ± 15 mg/L and 127 mg/L were achieved through shake flask and bioreactor cultivations, respectively, of the optimal strain at a reduced temperature of 20 °C.

Conclusions

The results of this study highlight the benefit of employing a combination of molecular biology and bioprocess tools during synthetic pathway development, with which TASY activity was successfully improved by 6.5-fold compared to the highest literature titre in S. cerevisiae cell factories.
Influence of community scorecards on maternal and newborn health service delivery and utilization
Authors: Kiracho Elizabeth Ekirapa , Namuhani Noel , Apolot Rebecca Racheal , Aanyu Christine , Mutebi Aloysuis , Tetui Moses , Kiwanuka Suzanne N. , Ayen Faith Adong , Mwesige Dennis , Bumbha Ahmed , Paina Ligia , Peters David H.
Published: November 2020

Introduction

The community score card (CSC) is a participatory monitoring and evaluation tool that has been employed to strengthen the mutual accountability of health system and community actors. In this paper we describe the influence of the CSC on selected maternal and newborn service delivery and utilization indicators.

Methods

This was a mixed methods study that used both quantitative and qualitative data collection methods. It was implemented in five sub-counties and one town council in Kibuku district in Uganda. Data was collected through 17 key informant interviews and 10 focus group discussions as well as CSC scoring and stakeholder meeting reports. The repeated measures ANOVA test was used to test for statistical significance. Qualitative data was analyzed manually using content analysis. The analysis about the change pathways was guided by the Wild and Harris dimensions of change framework.

Results

There was an overall improvement in the common indicators across sub-counties in the project area between the 1st and 5th round scores. Almost all the red scores had changed to green or yellow by round five except for availability of drugs and mothers attending Antenatal care (ANC) in the first trimester. There were statistically significant differences in mean scores for men escorting their wives for ante natal care (ANC) (F(4,20) = 5.45, P = 0.01), availability of midwives (F(4,16) =5.77, P < 0.01), availability of delivery beds (F(4,12) =9.00, P < 0.01) and mothers delivering from traditional birth attendants (TBAs), F(4,16) = 3.86, p = 0.02). The qualitative findings suggest that strengthening of citizens’ demand, availability of resources through collaborative problem solving, increased awareness about targeted maternal health services and increased top down performance pressure contributed to positive changes as perceived by community members and their leaders.

Conclusions and recommendations

The community score cards created opportunities for community leaders and communities to work together to identify innovative ways of dealing with the health service delivery and utilization challenges that they face.

Local leaders should encourage the availability of safe spaces for dialogue between communities, health workers and leaders where performance and utilization challenges can be identified and solutions proposed and implemented jointly.
Feasibility, acceptability and initial outcome of implementing community scorecard to monitor community level public health facilities: experience from rural Bangladesh
Authors: Mahmood Shehrin Shaila , Rasheed Sabrina , Chowdhury Asiful Haidar , Hossain Aazia , Selim Mohammad Abdus , Hoque Shahidul , Bhuiya Abbas
Published: November 2020

Background

Engaging communities in health facility management and monitoring is an effective strategy to increase health system responsiveness. Many developing countries have used community scorecard (CSC) to encourage community participation in health. However, the use of CSC in health in Bangladesh has been limited. In 2017, icddr,b initiated a CSC process to improve health service delivery at the community clinics (CC) providing primary healthcare in rural Bangladesh. The current study presents learnings around feasibility, acceptability, initial outcome and challenges of implementing CSC at community clinics.

Methods

A pilot study conducted between January’2018-December’2018 explored feasibility and acceptability of CSC using a thematic framework. The tool was implemented in purposively selected three CCs in Chakaria and one CC in Teknaf sub-district of Bangladesh. Qualitative data from 20 Key-Informant Interviews and four Focus Group Discussions with service users, healthcare providers, and government personnel, document reviews and meeting observations were used in analysis.

Results

The study showed that participants were enthusiastic and willing to take part in the CSC intervention. They perceived CSC to be useful in raising awareness about health in the community and facilitating structured monitoring of CC services. The process facilitated building stronger community ownership, enhancing accountability and stakeholder engagement. The participants identified issues around service provision, set SMART (specific, measurable, attainable, relevant and time-bound) targets and indicators on supplies, operations, logistics, environment, and patient satisfaction through CSC. However, some systematic and operational challenges of implementation were identified including time and resource constraint, understanding and facilitation of CSC, provider-user conflict, political influence, and lack of central level monitoring.

Conclusion

The findings suggest that CSC is a feasible and acceptable tool to engage community and healthcare providers in monitoring and managing health facilities. For countries with health systems faced with challenges around accountability, quality and coverage, CSC has the potential to improve community level health-service delivery. The findings are intended to inform program implementers, donors and other stakeholders about context, mechanisms, outcomes and challenges of CSC implementation in Bangladesh and other developing countries. However, proper contextualization, institutional capacity building and policy integration will be critical in establishing effectiveness of CSC at scale.
Maternal health challenges experienced by adolescents; could community score cards address them? A case study of Kibuku District– Uganda
Authors: Apolot Rebecca R. , Tetui Moses , Nyachwo Evelyne B. , Waldman Linda , Morgan Rosemary , Aanyu Christine , Mutebi Aloysius , Kiwanuka Suzanne N. , Ekirapa Elizabeth
Published: November 2020

Introduction

Approximately 34.8% of the Ugandan population is adolescents. The national teenage pregnancy rate is 25% and in Kibuku district, 17.6% of adolescents aged 12–19 years have begun child bearing. Adolescents mothers are vulnerable to many maternal health challenges including; stigma, unfriendly services and early marriages. The community score card (CSC) is a social accountability tool that can be used to point out challenges faced by the community in service delivery and utilization and ultimately address them. In this paper we aimed to document the challenges faced by adolescents during pregnancy, delivery and postnatal period and the extent to which the community score card could address these challenges.

Methods

This qualitative study utilized in-depth interviews conducted in August 2018 among 15 purposively selected adolescent women who had given birth 2 years prior to the study and had attended CSC meetings. The study was conducted in six sub counties of Kibuku district where the CSC intervention was implemented. Research assistants transcribed the audio-recorded interviews verbatim, and data was analyzed manually using the framework analysis approach.

Findings

This study found five major maternal health challenges faced by adolescents during pregnancy namely; psychosocial challenges, physical abuse, denial of basic human rights, unfriendly adolescent services, lack of legal and cultural protection, and lack of birth preparedness. The CSC addressed general maternal and new born health issues of the community as a whole rather than specific adolescent health related maternal health challenges.

Conclusion

The maternal health challenges faced by adolescents in Kibuku have a cultural, legal, social and health service dimension. There is therefore need to look at a multi-faceted approach to holistically address them. CSCs that are targeted at the entire community are unlikely to address specific needs of vulnerable groups such as adolescents. To address the maternal health challenges of adolescents, there is need to have separate meetings with adolescents, targeted mobilization for adolescents to attend meetings and deliberate inclusion of their maternal health challenges into the CSC.
Vaginal delivery in a patient with severe aortic stenosis under epidural analgesia, a case report
Authors: Driul Lorenza , Meroi Francesco , Sala Alessia , Delrio Silvia , Pavoni Daisy , Barbariol Federico , Londero Ambrogio , Dogareschi Teresa , Spasiano Alessandra , Vetrugno Luigi , Bove Tiziana
Published: November 2020

Background

A history of previous cardiac disease increases the maternal mortality risk by as much as 100%. There is no consensus on the absolute contraindications to vaginal delivery in valvular heart disease, but central regional anesthesia is traditionally considered contraindicated in patients with severe aortic stenosis.

Case presentation

A 29-year-old primigravid woman with severe aortic stenosis was admitted to the obstetrics department for programmed labor induction. With epidural anesthesia and mini-invasive hemodynamic monitoring labor and operative vaginal delivery were well tolerated, and hemodynamic stability was always maintained.

Conclusions

Epidural analgesia and oxytocin induction are possible for the labor management of parturients with severe aortic stenosis given that continuous non-invasive followed by invasive hemodynamic monitoring can be provided and given the absence of any obstetric or cardiologic contraindications and the strong will of the patient.
Health-related quality of life and work productivity in UK patients with HER2-positive breast cancer: a cross-sectional study evaluating the relationships between disease and treatment stage
Authors: Verrill Mark , Wardley Andrew M. , Retzler Jenny , Smith Adam B. , Bottomley Catherine , Ní Dhochartaigh Sorcha , Tran Irwin , Leslie Iain , Schmid Peter
Published: November 2020

Background

The impact of different disease stages and treatment for human epidermal growth factor 2 positive (HER2-positive) breast cancer (BC) on work productivity and health-related quality of life (HRQoL) is poorly understood.

Methods

This was a UK cross-sectional study of 299 adult patients with HER2-positive early or metastatic BC (NCT03099200). Productivity was assessed using the work productivity and activity impairment scale; HRQoL was measured using EuroQol-5 Dimensions-5 levels (EQ-5D-5L), and Functional Assessment of Cancer Therapy Breast (FACT-G and -B) instruments. Three balanced patient groups were recruited: (1) early BC on treatment post-surgery, (2) early BC after completion of adjuvant treatment, (3) during metastatic BC treatment. Between-group comparisons were performed using an analysis of variance.

Results

Group 1 comprised 89 patients, Group 2, 108 and Group 3, 102. Age, ethnicity and comorbidities were similar across groups. Patients in Group 3 reported more often being unable to work (significant Bonferroni adjusted p < 0.003). Proportions of employed patients were 50.6%, 50.9% and 27.5% in Groups 1, 2 and 3, respectively. For patients in part-time employment, the number of hours worked was significantly higher in Group 2 patients versus Group 3 (p = 0.002). Group 2 also had significantly lower levels of work absenteeism and overall work impairment compared with Group 1 (p < 0.001). Patients in Group 3 reported worse health utility scores (p ≤ 0.002), moderate or worse problems in the EQ-5D-5L self-care and usual activity domains (p ≤ 0.001), and lower HRQoL as assessed by FACT summary scores (p < 0.001 for FACT-B and -G) than Groups 1 and 2. Poorer HRQoL was significantly associated with higher work impairment (p < 0.001), with the strongest relationships being observed between activity impairment and HRQoL (Pearson’s r: 0.67).

Conclusions

Metastatic disease and treatment of HER2-positive BC adversely impacted on work productivity and HRQoL. The results of this study support the idea that being able to delay or prevent the metastatic recurrence of BC, for example by extending the time patients are in remission or at early stage of BC, has wider benefits in terms of patient productivity and HRQoL.
Detection of novel coronavirus (SARS-CoV-2) RNA in peripheral blood specimens
Authors: Azghandi Marjan , Kerachian Mohammad Amin
Published: November 2020

The latest outbreak of pneumonia caused by SARS-CoV-2 presents a significant challenge to global public health and has a major impact on clinical microbiology laboratories. In some situations, such as patients in coma condition, the oropharyngeal or nasopharyngeal sampling is seldom feasible, and blood sampling could be an alternative. In the current article, a comprehensive literature search has been conducted for detecting coronavirus disease 2019 (COVID-19) using plasma or serum samples. To date, twenty-six studies have used SARS-CoV-2 nucleic acid in plasma or serum (RNAaemia) to diagnose COVID-19. The pros and cons are discussed in this article. While the detection of SARS-CoV-2 viral load in respiratory specimens is commonly used to diagnose COVID-19, detecting SARS-CoV-2 RNA in plasma or serum should not lose sight and it could be considered as an alternative diagnostic approach.
In regards to Chu et al.: Patterns of brain metastasis immediately before prophylactic cranial irradiation (PCI): implications for PCI optimization in limited-stage small cell lung cancer
Authors: Käsmann Lukas , Eze Chukwuka , Taugner Julian , Manapov Farkhad
Published: November 2020

We read the article entitled “Patterns of brain metastasis immediately before prophylactic cranial irradiation (PCI): implications for PCI optimization in limited-stage small cell lung cancer” with great interest. In that study, the author reported about the importance of PCI timing in limited stage small cell lung cancer (LS-SCLC) in the era of MRI surveillance. In addition, the authors raise the issue of neurotoxicity of PCI. In this letter, we aimed to clarify the value of PCI in LS-SCLC and present ongoing trials regarding PCI and MRI surveillance in SCLC. As a result, we see the need for the development of a prediction tool to estimate the risk of intracranial relapse in LS-SCLC after chemoradiotherapy in order to support shared decision making through improved guidance.
Anxiety, depression and post-traumatic stress disorder management after critical illness: a UK multi-centre prospective cohort study
Authors: Hatch Robert , Young Duncan , Barber Vicki S. , Griffiths John , Harrison David A. , Watkinson Peter J.
Published: November 2020

Background

Survivors of critical illness have significant psychopathological comorbidity. The treatments offered by primary health care professionals to affected patients are unstudied.

Aim

To report the psychological interventions after GPs received notification of patients who showed severe symptoms of anxiety, depression or Post-Traumatic Stress Disorder.

Methods

Design: Multi-centre prospective cohort sub-study of the ICON study. Setting: NHS primary care in the United Kingdom. Participants: Adult patients, November 2006–October 2010 who had received at least 24 h of intensive care, where the general practitioner recorded notification that the patient had reported severe symptoms or caseness using the Hospital Anxiety and Depression Scale (HADS) or the Post-Traumatic Stress Disorder Check List-Civilian (PCL-C). Interventions: We notified general practitioners (GPs) by post if a patient reported severe symptoms or caseness and sent a postal questionnaire to determine interventions after notification. Main outcome measure: Primary or secondary healthcare interventions instigated by general practitioners following notification of a patient’s caseness.

Results

Of the 11,726 patients, sent questionnaire packs containing HADS and PCL-C, 4361 (37%) responded. A notification of severe symptoms was sent to their GP in 25% (1112) of cases. Of notified GPs, 65% (725) responded to our postal questionnaire. Of these 37% (266) had no record of receipt of the original notification. Of the 459 patients where GPs had record of notification (the study group for this analysis), 21% (98) had pre-existing psychopathology. Of those without a pre-existing diagnosis 45% (162) received further psychological assessment or treatment. GP screening or follow-up alone occurred in 18% (64) whilst 27% (98) were referred to mental health services or received drug therapy following notification.

Conclusions

Postal questionnaire identifies a burden of psychopathology in survivors of critical illness that have otherwise gone undiagnosed following discharge from an intensive care unit (ICU). After being alerted to the presence of psychological symptoms, GPs instigate treatment in 27% and augmented surveillance in 18% of cases.

Trial registration

ISRCTN69112866 (assigned 02/05/2006).
Effects of seasonality and land use on the diversity, relative abundance, and distribution of mosquitoes on St. Kitts, West Indies
Authors: Valentine Matthew J. , Ciraola Brenda , Jacobs Gregory R. , Arnot Charlie , Kelly Patrick J. , Murdock Courtney C.
Published: November 2020

Background

Mosquito surveys that collect local data on mosquito species’ abundances provide baseline data to help understand potential host-pathogen-mosquito relationships, predict disease transmission, and target mosquito control efforts.

Methods

We conducted an adult mosquito survey from November 2017 to March 2019 on St. Kitts, using Biogents Sentinel 2 traps, set monthly and run for 48-h intervals. We collected mosquitoes from a total of 30 sites distributed across agricultural, mangrove, rainforest, scrub and urban land covers. We investigated spatial variation in mosquito species richness across the island using a hierarchical Bayesian multi-species occupancy model. We developed a mixed effects negative binomial regression model to predict the effects of spatial variation in land cover, and seasonal variation in precipitation on observed counts of the most abundant mosquito species observed.

Results

There was high variation among sites in mosquito community structure, and variation in site level richness that correlated with scrub forest, agricultural, and urban land covers. The four most abundant species wereAedes taeniorhynchus,Culex quinquefasciatus,Aedes aegpytiandDeinocerites magnus, and their relative abundance varied with season and land cover.Aedes aegyptiwas the most commonly occurring mosquito on the island, with a 90% probability of occurring at between 24 and 30 (median = 26) sites. Mangroves yielded the most mosquitoes, withAe. taeniorhynchus, Cx. quinquefasciatusandDe. magnuspredominating.Psorophora pygmaeaandToxorhynchites guadeloupensiswere only captured in scrub habitat. Capture rates in rainforests were low. Our count models also suggested the extent to which monthly average precipitation influenced counts varied according to species.

Conclusions

There is high seasonality in mosquito abundances, and land cover influences the diversity, distribution, and relative abundance of species on St. Kitts. Further, human-adapted mosquito species (e.g.Ae. aegyptiandCx. quinquefasciatus) that are known vectors for many human relevant pathogens (e.g. chikungunya, dengue and Zika viruses in the case ofAe. aegypti; West Nile, Spondweni, Oropouche virus, and equine encephalitic viruses in the case ofCx. quinqefasciatus) are the most wide-spread (across land covers) and the least responsive to seasonal variation in precipitation.
Rapid on-site diagnosis of canine giardiosis: time versus performance
Authors: Symeonidou Isaia , Gelasakis Athanasios Ι. , Miliotou Androulla N. , Angelou Athanasios , Arsenopoulos Konstantinos V. , Loukeri Sofia , Papadopoulos Elias
Published: November 2020

Background

Infections by protozoans of the genus Giardia are a common cause of diarrhea in dogs. Canine giardiosis constitutes a disease with a zoonotic potential; however, it is often underestimated due to its challenging diagnosis. The objective of the study was to assess the diagnostic performance of an immunochromatographic strip test (SpeedTMGiardia, Virbac, France) comparing it with microscopy (zinc sulfate flotation) by utilizing the combination of an enzyme immunoassay (ProSpecTTMGiardia EZ Microplate Assay, Oxoid Ltd., UK) and the PCR as the gold standard. A positive result in both ELISA and PCR was set as the gold standard.

Methods

Initially, fecal samples from dogs with clinical signs compatible with giardiosis were tested with the SpeedTMGiardia test and separated into two groups of 50 samples each: group A (positive) and group B (negative). Thereafter, all samples were examined by zinc sulfate centrifugal flotation technique and assayed by the ProSpecTTMGiardia Microplate Assay and PCR. The performance of the SpeedTMGiardia and zinc sulfate centrifugal flotation tests were calculated estimating sensitivity, specificity, and positive and negative likelihood ratio; the chi-square and McNemar tests were used for the comparison of the two methods.

Results

Giardia cysts were not detected by microscopy in 16 out of the 50 samples (32%) of group A and in none of group B samples. Eight out of 50 samples in group B (16%) were tested positive both with the ProSpecTTMGiardia Microplate Assay and PCR. Fecal examination with the SpeedTMGiardia test was more sensitive (86.2%) than the parasitological method (58.6%, P < 0.001) while the specificity of both methods was 100%.

Conclusions

The SpeedTMGiardia test is an easy-to-perform diagnostic method for the detection of Giardia spp., which can increase laboratory efficiency by reducing time and cost and decrease underdiagnosis of Giardia spp. infections. This immunochromatographic strip test may be routinely exploited when a rapid and reliable diagnosis is required, other diagnostic techniques are unavailable and microscopy expertise is inefficient. In negative dogs with compatible clinical signs of giardiosis, it is recommended either to repeat the exam or proceed with further ELISA and PCR testing.
A single centre retrospective study of systemic reactions to subcutaneous immunotherapy
Authors: Robertson Kara , Montazeri Nazanin , Shelke Urvashi , Jeimy Samira , Kim Harold
Published: November 2020

Background

Subcutaneous immunotherapy (SCIT) is the standard approach for treating patients with sensitizations to aeroallergens. However, immunotherapy can trigger severe systemic reactions if delivered inappropriately or to high risk patients. We sought to characterize and quantify SCIT systemic reactions requiring epinephrine administration during a 6-year period in a Canadian setting following the recommendations for components and dosages published in the 2010 Canadian Society of Allergy and Clinical Immunology (CSACI) Immunotherapy Manual.

Methods

A single centre retrospective chart review was performed for all patients with systemic reactions to subcutaneous immunotherapy requiring intramuscular epinephrine injection between January 2011 and October 2017. Each systemic reaction requiring epinephrine was reviewed for baseline patient characteristics, details of the reaction, and reaction severity. Research ethics approval was obtained through McMaster University.

Results

28 of 380 patients experienced a systemic reaction requiring epinephrine administration, with an incidence rate of 1 per 1,047 injection visits (0.095%). 26 of the 28 reactions occurred within the mandatory 30-minute observation period post allergen immunotherapy. Of the 28 patients that experienced a systemic reaction to SCIT, 11 patients had asthma and 5 patients had a history of possible food allergy. All of the systemic reactions occurred during injections from vial number 4, and five patients reacted to their first shot of a re-ordered extract. 10 of the 28 patients required more than one intramuscular injection of epinephrine, and 20 of 28 patients were transferred to the hospital by ambulance.

Conclusions

This is the first Canadian study to review patients with systemic reactions to subcutaneous immunotherapy. Several best practice methods were employed throughout the study to optimize subcutaneous delivery of immunotherapy extract, and our recorded per injection incidence rate for systemic reactions was comparable or below the rate published in similar studies. The recommendations in the CSACI Immunotherapy Manual provide an approach to standardizing prescriptions for SCIT to maximize immunotherapy efficacy and reduce the risk of systemic reactions, though similar studies in larger multicenter settings are needed to confirm these observations. These observations provide important objective information to clinicians about the potential risks for systemic reactions in patients considering SCIT.
Congenital muscular dystrophy-associated inflammatory chemokines provide axes for effective recruitment of therapeutic adult stem cell into muscles
Authors: Alexeev Vitali , Olavarria Jacquelyn , Bonaldo Paolo , Merlini Luciano , Igoucheva Olga
Published: November 2020

Background

Congenital muscular dystrophies (CMD) are a clinically and genetically heterogeneous group of neuromuscular disorders characterized by muscle weakness. The two most prevalent forms of CMD, collagen VI-related myopathies (COL6RM) and laminin α2 deficient CMD type 1A (MDC1A), are both caused by deficiency or dysfunction of extracellular matrix proteins. Previously, we showed that an intramuscular transplantation of human adipose-derived stem cells (ADSC) into the muscle of the Col6a1−/− mice results in efficient stem cell engraftment, migration, long-term survival, and continuous production of the collagen VI protein, suggesting the feasibility of the systemic cellular therapy for COL6RM. In order for this therapeutic approach to work however, stem cells must be efficiently targeted to the entire body musculature. Thus, the main goal of this study is to test whether muscle homing of systemically transplanted ADSC can be enhanced by employing muscle-specific chemotactic signals originating from CMD-affected muscle tissue.

Methods

Proteomic screens of chemotactic molecules were conducted in the skeletal muscles of COL6RM- and MDC1A-affected patients and CMD mouse models to define the inflammatory and immune activities, thus, providing potential markers of disease activity or treatment effect. Also using a pre-clinical animal model, recapitulating mild Ullrich congenital muscular dystrophy (UCMD), the therapeutic relevance of identified chemotactic pathways was investigated in vivo, providing a basis for future clinical investigations.

Results

Comprehensive proteomic screens evaluating relevant human and mouse skeletal muscle biopsies offered chemotactic axes to enhance directional migration of systemically transplanted cells into CMD-affected muscles, including CCL5-CCR1/3/5, CCL2-CCR2, CXCL1/2-CXCR1,2, and CXCL7-CXCR2. Also, the specific populations of ADSC selected with an affinity for the chemokines being released by damaged muscle showed efficient migration to injured site and presented their therapeutic effect.

Conclusions

Collectively, identified molecules provided insight into the mechanisms governing directional migration and intramuscular trafficking of systemically infused stem cells, thus, permitting broad and effective application of the therapeutic adult stem cells for CMD treatment.