bluuebunny/crossref_metadata_2025 huggingface dataset:
A four-stage process for intervention description and guide development of a practice-based intervention: refining the Namaste Care intervention implementation specification for people with advanced dementia prior to a feasibility cluster randomised trial
Authors: Walshe Catherine , Kinley Julie , Patel Shakil , Goodman Claire , Bunn Frances , Lynch Jennifer , Scott David , Lund Anne Davidson , Stacpoole Min , Preston Nancy , Froggatt Katherine
Published: October 2019

Background

Some interventions are developed from practice, and implemented before evidence of effect is determined, or the intervention is fully specified. An example is Namaste Care, a multi-component intervention for people with advanced dementia, delivered in care home, community, hospital and hospice settings. This paper describes the development of an intervention description, guide and training package to support implementation of Namaste Care within the context of a feasibility trial. This allows fidelity to be determined within the trial, and for intervention users to understand how similar their implementation is to that which was studied.

Methods

A four-stage approach: a) Collating existing intervention materials and drawing from programme theory developed from a realist review to draft an intervention description. b) Exploring readability, comprehensibility and utility with staff who had not experienced Namaste Care. c) Using modified nominal group techniques with those with Namaste Care experience to refine and prioritise the intervention implementation materials. d) Final refinement with a patient and public involvement panel.

Results

Eighteen nursing care home staff, one carer, one volunteer and five members of our public involvement panel were involved across the study steps. A 16-page A4 booklet was designed, with flow charts, graphics and colour coded information to ease navigation through the document. This was supplemented by infographics, and a training package. The guide describes the boundaries of the intervention and how to implement it, whilst retaining the flexible spirit of the Namaste Care intervention.

Conclusions

There is little attention paid to how best to specify complex interventions that have already been organically implemented in practice. This four-stage process may have utility for context specific adaptation or description of existing, but untested, interventions. A robust, agreed, intervention and implementation description should enable a high-quality future trial. If an effect is determined, flexible practice implementation should be enabled through having a clear, evidence-based guide.
Characteristics of residual lymph nodes after six months of antituberculous therapy in HIV-negative individuals with cervical tuberculous lymphadenitis
Authors: Seok Hyeri , Jeon Ji Hoon , Oh Kyung Ho , Choi Hee Kyoung , Choi Won Suk , Lee Young Hen , Seo Hyung Suk , Kwon Soon Young , Park Dae Won
Published: October 2019

Background

The therapeutic response of cervical tuberculous lymphadenitis (CTBL) may be delayed or paradoxical, with the frequent development of residual lymph nodes (LNs) during and after antituberculous treatment. We investigated the incidence of residual LNs and the clinical, radiological, microbiological, and pathologic responses of patients with CTBL after 6 months of antituberculous therapy.

Methods

The medical records of HIV-negative adult patients with CTBL diagnosed between July 2009 and December 2017 were analyzed. After 6 months of first-line antituberculous treatment, computed tomography (CT) scans were conducted to evaluate for residual LNs. Fine-needle aspiration biopsy (FNAB) was carried out if a patient presented with residual LNs > 10 mm in diameter with central necrosis, peripheral rim enhancement, or perinodal inflammation on CT scan.

Results

Residual LNs were detected in 35 of 157 patients who underwent follow-up CT scans and were more commonly observed in younger patients who completed the treatment (mean years ± standard deviation [SD]: 33 ± 13 vs. 44 ± 16, p < 0.001). The recurrence rate was approximately 5%, which was not significantly different in both groups. Among the 15 patients who underwent FNAB, 3 (30%) presented with granuloma, and 2 of 15 and 10 of 14 patients had positive AFB and TB PCR results, respectively. The TB culture results of 15 patients were negative.

Conclusions

Residual LNs may still be observed after 6 months of antituberculous treatment. Although the radiologic and pathologic findings after treatment are still indicative of TB, not all residual LNs indicate recurrence or treatment failure. A six-month therapy may be sufficient for cervical tuberculous lymphadenitis.
MMP-8 C-799 T, Lys460Thr, and Lys87Glu variants are not related to risk of cancer
Authors: Zhang Li-Feng , Zhu Li-Jie , Zhang Wei , Yuan Wei , Song Ning-Hong , Zuo Li , Mi Yuan-Yuan , Wang Zeng-Jun , Zhang Wei
Published: October 2019

Background

Several studies have focused on the relationship between MMP-8 variants and cancer risk, but they have been unsuccessful in drawing reliable conclusions.

Methods

We employed odds ratio (OR) together with 95% confidence interval (CI) to assess the correlation between MMP-8 C-799 T, Lys460Thr, and Lys87Glu polymorphisms and cancer risk. We further employed in silico tools to evaluate the effect of MMP-8 expression on cancer susceptibility and overall survival time.

Results

A total of 8140 patients with malignant carcinoma and 10,529 healthy individuals (control) were enrolled. Overall, the analysis showed that the relationship between three MMP-8 variants and cancer susceptibility was not significant (allelic contrast, C-799 T: OR = 0.98, 95% CI = 0.92–1.04, Pheterogeneity = 0.068; Lys460Thr: OR = 0.94, 95% CI = 0.67–1.32, Pheterogeneity = 0.905; Lys87Glu: OR = 1.05, 95% CI = 0.93–1.18, Pheterogeneity = 0.968). Similar results were observed in subgroup analysis by ethnicity, cancer type, and source of control. In silico analysis indicated that MMP-8 expression was elevated in bladder cancer tissue compared to that in the control. However, both the higher and lower MMP-8 expression groups did not show an impact on the overall survival time of the patients.

Conclusions

MMP-8 C-799 T, Lys460Thr, and Lys87Glu variants are not participant with the susceptibility of cancer.
Experiences regarding nutrition and exercise among women during early postpartum: a qualitative grounded theory study
Authors: Murray-Davis Beth , Grenier Lindsay , Atkinson Stephanie A. , Mottola Michelle F. , Wahoush Olive , Thabane Lehana , Xie Feng , Vickers-Manzin Jennifer , Moore Caroline , Hutton Eileen K.
Published: October 2019

Background

Excess gestational weight gain has long- and short-term implications for women and children, and postpartum weight retention is associated with an increased risk of long-term obesity. Despite the existence of dietary and exercise guidelines, many women struggle to return to pre-pregnancy weight. Experiences of women in tackling postpartum weight loss are poorly understood. We undertook this study to explore experiences related to nutrition, exercise and weight in the postpartum in women in Ontario, Canada.

Methods

This was a nested qualitative study within The Be Healthy in Pregnancy Study, a randomized controlled trial. Women randomized to the control group were invited to participate. Semi-structured focus groups were conducted at 4–6 months postpartum. Focus groups were audio recorded, transcribed verbatim, coded and analyzed thematically using a constructivist grounded theory approach.

Results

Women experienced a complex relationship with their body image, due to unrealistic expectations related to their postpartum body. Participants identified barriers and enablers to healthy habits during pregnancy and postpartum. Gestational weight gain guidelines were regarded as unhelpful and unrealistic. A lack of guidance and information about weight management, healthy eating, and exercise in the postpartum period was highlighted.

Conclusion

Strategies for weight management that target the unique characteristics of the postpartum period have been neglected in research and in patient counselling. Postpartum women may begin preparing for their next pregnancy and support during this period could improve their health for subsequent pregnancies.

Trial registration

NCT01689961 registered September 21, 2012.
Mutations in both SAMD9 and SLC19A2 genes caused complex phenotypes characterized by recurrent infection, dysphagia and profound deafness – a case report for dual diagnosis
Authors: Zhang Yan , Zhang Yi , Zhang Victor Wei , Zhang Chunyi , Ding Hongke , Yin Aihua
Published: October 2019

Background

Phenotypic difference is general in Mendelian disease. Due to the extremely low incidence for a single disease, phenotype spectrum needs to be expanded. Meanwhile, earlier knowledge says patients who suffered from two kinds of different Mendelian disease are very rare.

Case presentation

We describe a case of neonatal male with genital anomalies, growth delay, skin hyperpigmentation, chronic lung disease with recurrent infection, anemia, and severe deafness. Without any clear etiology after routine workflow, whole exome sequencing was carried on. A pathogenic de novo SAMD9 mutation and compound heterozygous likely-pathogenic variants in SLC19A2 were identified. Some symptoms were improved after the patient was treated with vitamin B1. Unfortunately, the boy died from sepsis and multiple organ failure before 1 year old.

Conclusion

Combining the phenotype and clinical progress of treatment, we report that it is the first case of a patient with both MIRAGE syndrome and TRMA syndrome.
Community based integrated vector management for malaria control: lessons from three years’ experience (2016–2018) in Botor-Tolay district, southwestern Ethiopia
Authors: Asale Abebe , Kussa Dereje , Girma Melaku , Mbogo Charles , Mutero Clifford Maina
Published: October 2019

Background

Integrated vector management (IVM) remains a key strategy in the fight against vector-borne diseases including malaria. However, impacts of the strategy should be regularly monitored based on feedback obtained through research. The objective of this study was to assess the impact of IVM for malaria control in Botor-Tolay district, southwestern Ethiopia after three years (2016–2018) of IVM implementation.

Method

Prior to the implementation of IVM, a survey of socio-demographic, malaria burden, and communities’ perception towards malaria control was conducted in 200 households selected at random from 12 villages using standard questionnaire. Households were revisited after three years of project implementation for impact assessment. Compiled malaria case data was obtained from district health bureau for the three years period of the study while adult mosquito collection was conducted during each year using CDC light traps. Monthly larval mosquito collections were made each year using standard dipping method. Community education and mobilization (CEM) was made through different community-based structures.

Results

The proportion of respondents who sought treatment in health facilities showed a significant increase from 76% in 2015 to 90% in 2018(P < 0.001). An average of 6.3 working and 2.3 school days were lost per year in a household due to parents and children falling sick with malaria. Malaria costs in a household in Botor-Tolay averaged 13.3 and 4.5 USD per episode for medical treatment and transportation respectively. Significantly fewer adult mosquitoes were collected in 2018 (0.37/house/trap-night) as compared to 2015 (0.73/house/trap-night) (P < .001). Malaria cases significantly declined in 2018 (262) when compared to the record in 2015 (1162) (P < 0.001). Despite improved human behavioral changes towards mosquito and malaria control, there were many setbacks too. These include reluctance to seek treatment in a timely manner, low user compliance of LLINs and low net repairing habit.

Conclusion

The coordinated implementation of community-based education, environmental management, larviciding together with main core vector control interventions in Botor-Tolay district in Southwestern Ethiopia have contributed to significant decline in malaria cases reported from health facilities. However, commitment to seeking treatment by people with clinical symptoms of malaria and to repair of damaged mosquito nets remained low.
Socioeconomic gradient in physical activity: findings from the PERSIAN cohort study
Authors: Kazemi Karyani Ali , Karmi Matin Behzad , Soltani Shahin , Rezaei Satar , Soofi Moslem , Salimi Yahya , Moradinazar Mehdi , Hajizadeh Mohammad , Pasdar Yahya , Hamzeh Behrooz , Barzegar Loghman , Haghdoost Ali Akbar , Malekzadeh Reza , Poustchi Hossein , Mohammadi Zahra , Faramarzi Elnaz , Safarpour Ali Reza , Pourfarzi Farhad , Moosazadeh Mahmood , Nejatizadeh Azim , Farjam Mojtaba , Vahabzadeh Davoud , Ahmadi Ali , Ghorat Fereshteh , Ahmadi Jafar , Mansour-Ghanaei Fariborz , Mirjalili Mohammad Reza , Eslami Saeid , Maharlouei Najmeh , Tabatabaei Seyed Mehdi , Sarvandian Sara , Najafi Farid
Published: October 2019

Background

The level of socioeconomic-related inequality in physical activity in Iran is largely unknown. This study investigates socioeconomic-related inequality in poor-physical activity (PPA) among Iranian adults.

Methods

A total of 129,257 adult participants enrolled in the PERSIAN (Prospective Epidemiological Research Studies in IrAN) Cohort were included in this study. Physical activity of adults was measured using metabolic equivalent rates (METs). Physical activity less than 41 METs/hour/day was considered PPA. The Concentration index (C) was used to quantify socioeconomic-related inequality in PPA. Moreover, the C was decomposed to identify the relative contribution of explanatory variables to inequality in PPA.

Results

There were significant regional variations in physical activity level among Iranian adults (29.8–76.5%). The positive value of C (0.098, 95% CI = 0.092 to 0.104) suggested that the higher concentration of PPA among higher socioeconomic status (SES) adults in Iran which was consistently observed in all cohort sites.

Conclusions

The higher prevalence of PPA among Iranian adults, especially, women and older adults, warrant further public health attention. Since PPA is concentrated more among the high-SES population in Iran, strategies for the promotion of physical activity should focus more on economically well-off population.
Robotic stereotactic ablative radiotherapy for renal cell carcinoma in patients with impaired renal function
Authors: Senger C. , Conti A. , Kluge A. , Pasemann D. , Kufeld M. , Acker G. , Lukas M. , Grün A. , Kalinauskaite G. , Budach V. , Waiser J. , Stromberger C.
Published: October 2019

Background

Robotic stereotactic ablative radiotherapy (SABR) is currently under investigation as a noninvasive treatment option for patients with renal cell carcinoma (RCC). For radiation therapy of RCC, tumor motion and the need for high ablative doses while preserving the remaining renal parenchyma is a challenge. We aimed to analyze the safety and efficacy of robotic radiosurgery in RCC in a specific difficult subgroup of patients with impaired renal function.

Methods

We retrospectively identified all patients with RCC, treated with robotic SABR and motion compensation in our institution between 2012 and 2017. Either single fraction SABR of 24 or 25 Gy or 3 fractions of 12 Gy prescribed to the 70% isodose line was applied. Local control, overall survival, radiation side effects were evaluated together with renal function and tumor motion.

Results

We analyzed data of 13 lesions treated in 10 patients with clear cell RCC and a mean age of 70.5 ± 13.6 years (range: 48–87). Prior to SABR, 8 patients underwent previous complete and/or partial nephrectomy, 7 patients presented with chronic kidney disease ≥ stage 3. The median of minimum, mean and maximum planning target volume doses were 23.2, 29.5 and 35.0 Gy for single fraction and 24.4, 42.5 and 51.4 Gy for the three fractions regime. Persistent local control by robotic SABR was achieved in 9 out of 10 patients (92.3% of all lesions) within a median follow-up period of 27 month (range: 15–54). One patient underwent nephrectomy due to progressive disease and sufficient renal function of the contralateral kidney. Renal function remained stable with a mean estimated glomerular filtration rate (eGFR) of 51.3 ± 19.7 ml/min at baseline and 51.6 ± 25.8 ml/min at follow-up. The largest respiratory-induced tumor motion was seen in superior-inferior direction, compensated by the CyberKnife with mean targeting errors of maximal 2.2 mm.

Conclusions

Robotic SABR is technically feasible for the treatment of RCC in preexisting kidney disease with good local tumor control at about 2 years follow-up. Robotic SABR with motion tracking offers a valid treatment option for patients, who are at increased risk for progression to end-stage renal disease due to partial nephrectomy or ablative techniques.
How do community health actors explain their roles? Exploring the roles of community health actors in promoting maternal health services in rural Ethiopia
Authors: Mamo Abebe , Morankar Sudhakar , Asfaw Shifera , Bergen Nicole , Kulkarni Manisha A. , Abebe Lakew , Labonté Ronald , Birhanu Zewdie , Abera Muluemebet
Published: October 2019

Background

Maternal and child morbidity and mortality remains one of the most important public health challenges in developing countries. In rural settings, the promotion of household and community health practices through health extension workers in collaboration with other community members is among the key strategies to improve maternal and child health. Little has been studied on the actual roles and contributions of various individuals and groups to date, especially in the rural areas of Ethiopia. In this study, we explored the role played by different actors in promoting ANC, childbirth and early PNC services, and mainly designed to inform a community based Information, Education & Communication intervention in rural Ethiopia.

Methods

An exploratory qualitative study was conducted on 24 in-depth interviews with health extension workers, religious leaders, women developmental army leaders, and selected community members; and 12 focus group discussions, six with female and six with male community members. Data was captured using voice recorders and field notes and transcribed verbatim in English, and analyzed using Atlas.ti software. Ethical approval for the fieldwork was obtained from Jimma University and the University of Ottawa.

Results

Participants described different roles and responsibilities that individuals and groups have in promoting maternal/child health, as well as the perceived roles of family members/husband. Commonly identified roles included promotion of health care services; provision of continuous support during pregnancy, labour and postnatal care; and serving as a link between the community and the health system. Participants also felt unable to fully engage in their identified roles, describing several challenges existing within both the health system and the community.

Conclusions

Involvement of different actors based on their areas of focus could contribute to community members receiving health information from people they trust more, which in turn is likely to increase use of services. Therefore, if our IEC interventions focus on overcoming challenges that limit actors’ abilities to engage effectively in promoting use of MCH services, it will be feasible and effective in rural settings, and these actors can become an epicenter in providing community based intervention in using ANC, childbirth and early PNC services.
Understanding corporate governance of healthcare quality: a comparative case study of eight Australian public hospitals
Authors: Brown Alison
Published: October 2019

Background

Patients are sometimes harmed in the course of receiving hospital care. Existing research has highlighted a positive association between board engagement in healthcare quality activities and healthcare outcomes. However, most research has been undertaken through surveys examining board engagement in a limited number of governance processes. This paper presents evidence of a comprehensive range of processes related to governing healthcare quality undertaken at the corporate governance level. This provides a more detailed picture than previously described of how corporate governance of healthcare quality is enacted by boards and management.

Methods

A comparative case study of eight Australian public hospitals was undertaken. Case studies varying is size and location were selected from two Australian states. Data collection included a review of key governance documentation, semi structured interviews with board members and senior management and an observation of a board quality committee meeting. Thematic analysis was undertaken to identify processes related to key tasks in governing healthcare quality.

Results

Two key tasks in the corporate governance of healthcare quality, evaluating healthcare quality and overseeing quality priorities, were examined. Numerous processes related to these two tasks were found. Case studies, while found to be similar in engagement on previously identified processes, were found to differ in engagement in these additional processes. While generally low levels of engagement in processes of overseeing quality priorities were found, cases differed markedly in their engagement in evaluating healthcare quality processes. Additional processes undertaken at some case studies represent innovative and mature responses to the need for effective corporate governance of healthcare quality. In addition, a group of processes, related to broader governance taskwork, were found to be important in enabling effective corporate governance of healthcare quality.

Conclusion

The work of governing healthcare quality, undertaken at the corporate governance level, is redefined in terms of these more detailed processes. This paper highlights that it is how well these key tasks are undertaken that is important in effective governance. When processes related to key tasks are omitted, the rituals of governance may appear to be satisfied but the responsibility may not be met. Boards and managers need to differentiate between common approaches to governance and practices that enable the fulfilment of governance responsibilities. This study provides practical guidance in outlining processes for effective corporate governance of healthcare quality and highlights areas for further examination.
Cry for health: a quantitative evaluation of a hospital-based advocacy intervention for domestic violence and abuse
Authors: Halliwell Gemma , Dheensa Sandi , Fenu Elisabetta , Jones Sue K. , Asato Jessica , Jacob Suzanne , Feder Gene
Published: October 2019

Background

Domestic violence and abuse (DVA) damages the health of survivors and increases use of healthcare services. We report findings from a multi-site evaluation of hospital-based advocacy services, designed to support survivors attending emergency departments and maternity services.

Methods

Independent Domestic Violence Advisors (IDVA) were co-located in five UK hospitals. Case-level data were collected at T1 (initial referral) and T2 (case closure) from survivors accessing hospital (T1 N = 692; T2 N = 476) and community IDVA services (T1 N = 3544; T2 N = 2780), used as a comparator. Measures included indicators of sociodemographic characteristics, experience of abuse, health service use, health and safety outcomes. Multivariate analyses tested for differences in changes in abuse, health and factors influencing safety outcomes. Health service use data in the 6 months pre-and post- intervention were compared to generate potential cost savings by hospital IDVA services.

Results

Hospital IDVAs worked with survivors less visible to community IDVA services and facilitated intervention at an earlier point. Hospital IDVAs received higher referrals from health services and enabled access to a greater number of health resources. Hospital survivors were more likely to report greater reductions in and cessation of abuse. No differences were observed in health outcomes for hospital survivors. The odds of safety increased two-fold if hospital survivors received over five contacts with an IDVA or accessed six or more resources / programmes over a longer period of time. Six months preceding IDVA intervention, hospital survivors cost on average £2463 each in use of health services; community survivors cost £533 each. The cost savings observed among hospital survivors amounted to a total of £2050 per patient per year. This offset the average cost of providing hospital IDVA services.

Conclusions

Hospital IDVAs can identify survivors not visible to other services and promote safety through intensive support and access to resources. The co-location of IDVAs within the hospital encouraged referrals to other health services and wider community agencies. Further research is required to establish the cost-effectiveness of hospital IDVA services, however our findings suggest these services could be an efficient use of health service resources.
Age-treatment subgroup analyses in Cochrane intervention reviews: a meta-epidemiological study
Authors: Liu Patrick , Ioannidis John P. A. , Ross Joseph S. , Dhruva Sanket S. , Luxkaranayagam Anita T. , Vasiliou Vasilis , Wallach Joshua D.
Published: October 2019

Background

There is growing interest in evaluating differences in healthcare interventions across routinely collected demographic characteristics. However, individual subgroup analyses in randomized controlled trials are often not prespecified, adjusted for multiple testing, or conducted using the appropriate statistical test for interaction, and therefore frequently lack credibility. Meta-analyses can be used to examine the validity of potential subgroup differences by collating evidence across trials. Here, we characterize the conduct and clinical translation of age-treatment subgroup analyses in Cochrane reviews.

Methods

For a random sample of 928 Cochrane intervention reviews of randomized trials, we determined how often subgroup analyses of age are reported, how often these analyses have a P < 0.05 from formal interaction testing, how frequently subgroup differences first observed in an individual trial are later corroborated by other trials in the same meta-analysis, and how often statistically significant results are included in commonly used clinical management resources (BMJ Best Practice, UpToDate, Cochrane Clinical Answers, Google Scholar, and Google search).

Results

Among 928 Cochrane intervention reviews, 189 (20.4%) included plans to conduct age-treatment subgroup analyses. The vast majority (162 of 189, 85.7%) of the planned analyses were not conducted, commonly because of insufficient trial data. There were 22 reviews that conducted their planned age-treatment subgroup analyses, and another 3 reviews appeared to perform unplanned age-treatment subgroup analyses. These 25 (25 of 928, 2.7%) reviews conducted a total of 97 age-treatment subgroup analyses, of which 65 analyses (in 20 reviews) had non-overlapping subgroup levels. Among the 65 age-treatment subgroup analyses, 14 (21.5%) did not report any formal interaction testing. Seven (10.8%) reported P < 0.05 from formal age-treatment interaction testing; however, none of these seven analyses were in reviews that discussed the potential biological rationale or clinical significance of the subgroup findings or had results that were included in common clinical practice resources.

Conclusion

Age-treatment subgroup analyses in Cochrane intervention reviews were frequently planned but rarely conducted, and implications of detected interactions were not discussed in the reviews or mentioned in common clinical resources. When subgroup analyses are performed, authors should report the findings, compare the results to previous studies, and outline any potential impact on clinical care.
Dietary supplementation of menthol-rich bioactive lipid compounds alters circadian eating behaviour of sheep
Authors: Patra Amlan K. , Geiger Sebastian , Braun Hannah-Sophie , Aschenbach Jörg R.
Published: October 2019

Background

Plant bioactive lipid compounds (PBLC), commonly known as essential oils, are increasingly evaluated as feed additives in ruminants due to beneficial effects on animal performance and health; however, there is no study evaluating circadian eating behaviour in ruminants. Altered eating behaviour may be implicated in changes of feed intake in ruminants. Therefore, the present study investigated the influence of menthol-rich PBLC on circadian eating behaviour in 24 growing sheep that were equally divided into three treatments, control (without PBLC), a lower dose (80 mg/d) or a higher dose (160 mg/d) of PBLC. Daily doses of PBLC were supplied with 600 g/d of concentrates fed in three equal portions at 07:00, 11:00 and 15:00 h for 4 weeks, whereas, meadow hay was fed ad libitum.

Results

The eating behaviour recorded by an automatic transponder-operated feeding system revealed that daily eating time and feeder visits increased with increasing doses of PBLC. The circadian distribution of eating time and feeder visits (with 1-h resolution) was influenced by the treatment. Eating time during concentrate-offering hours and between concentrate-offering hours increased or tended to increase linearly with greater concentrations of PBLC. Feeder visits did not change significantly during concentrate-offering hours, but were greater in the PBLC groups compared with the control between concentrate-feeding hours. Average length of the longest meals (5th percentile) decreased due to PBLC feeding. Daily feed intake was greater in the PBLC groups than the control.

Conclusions

Menthol-rich PBLC in the applied dose range stimulate circadian eating behaviour, which cannot only be attributed to their presence during concentrate feeding hours, but persist during post-concentrate feeding hours.
miR-335-5p inhibits TGF-β1-induced epithelial–mesenchymal transition in non-small cell lung cancer via ROCK1
Authors: Du Wenwen , Tang Haicheng , Lei Zhe , Zhu Jianjie , Zeng Yuanyuan , Liu Zeyi , Huang Jian-an
Published: October 2019

Background

Significant evidence has shown that the miRNA pathway is an important component in the downstream signaling cascades of TGF-β1 pathway. Our previous study has indicated that miR-335-5p expression was significantly down-regulated and acted as a vital player in the metastasis of non-small cell lung cancer (NSCLC), however the underlying mechanism remained unclear.

Methods

The differential expression level of miR-335-5p and ROCK1 were determined by qRT-PCR and IHC analysis in human tissue samples with or without lymph node metastasis. Transwell assay was conducted to determine cell ability of migration and invasion. SiRNA interference, microRNA transfection and western blot analysis were utilized to clarify the underlying regulatory mechanism.

Results

We showed that down-regulated expression of miR-335-5p and up-regulated expression of ROCK1 in NSCLC tissues were associated with lymph node metastasis. Over-expresion of miR-335-5p significantly inhibited TGF-β1-mediated NSCLC migration and invasion. Furthermore, luciferase reporter assays proved that miR-335-5p can bind to 3′-UTR of ROCK1 directly. Moreover, we confirmed that siRNA-mediated silencing of ROCK1 significantly diminished TGF-β1-mediated EMT and migratory and invasive capabilities of A549 and SPC-A1 cells.

Conclusion

This is the first time to report that miR-335-5p regulates ROCK1 and impairs its functions, thereby playing a key role in TGF-β1-induced EMT and cell migration and invasion in NSCLC.
Insufficient serum L-ficolin is associated with disease presence and extent of pulmonary Mycobacterium avium complex disease
Authors: Kobayashi Tomofumi , Kuronuma Koji , Saito Atsushi , Ikeda Kimiyuki , Ariki Shigeru , Saitou Atsushi , Otsuka Mitsuo , Chiba Hirofumi , Takahashi Satoshi , Takahashi Motoko , Takahashi Hiroki
Published: October 2019

Background

The incidence of infectious disease caused by nontuberculous mycobacteria is increasing worldwide. Pulmonary Mycobacterium avium complex (MAC) disease is difficult to treat with chemotherapy, and its mechanism of infection, infection route, disease onset, and severity remain unknown. Ficolins are oligomeric defense lectins. L-ficolin plays an important role in innate immunity. This study’s aim was to identify L-ficolin’s role in patients with pulmonary MAC disease.

Methods

Between April 2011 and September 2017, 61 Japanese patients with pulmonary MAC disease were seen at our hospital. A control group, comprising 30 healthy individuals, without respiratory disease were enrolled in our study. The relationship between serum L-ficolin levels and disease severity was assessed, and L-ficolin’s antibacterial role was examined.

Results

Serum L-ficolin levels were significantly lower in patients with pulmonary MAC disease than in healthy subjects (1.69 ± 1.27 μg/ml vs. 3.96 ± 1.42 μg/ml; p < 0.001). The cut-off value, based on receiver operating characteristic (ROC) analysis results, was 2.48 μg/ml (area under the curve (AUC) 0.90, sensitivity and specificity 83.6 and 86.7%, respectively). Serum L-ficolin levels were significantly lower in the patients with nodular bronchiectatic type disease compared with the patients with fibrocavitary type disease and were lower in the high-resolution computed tomography high-scoring group compared with low-scoring group. An in vitro analysis showed that purified recombinant L-ficolin bound to M. avium and its major cell wall component, lipoarabinomannan, in a concentration-dependent manner. In addition, recombinant L-ficolin suppressed M. avium growth in a concentration-dependent manner.

Conclusions

Insufficient serum L-ficolin is associated with disease progression in pulmonary MAC disease, and the level of serum L-ficolin is a possible biomarker.

Trial registration

This study is registered with UMIN (UMIN000022392).
Computed tomography-derived area and density of pectoralis muscle associated disease severity and longitudinal changes in chronic obstructive pulmonary disease: a case control study
Authors: Bak So Hyeon , Kwon Sung Ok , Han Seon-Sook , Kim Woo Jin
Published: October 2019

Background

Muscle wasting is associated with prognosis in patients with chronic obstructive pulmonary disease (COPD). The cross-sectional area of skeletal muscles on computed tomography (CT) could serve as a method to evaluate body composition. The present study aimed to determine the ability of CT-derived pectoralis muscle area (PMA) and pectoralis muscle density (PMD) to determine the severity of COPD and change in longitudinal pulmonary function in patients with COPD.

Methods

A total of 293 participants were enrolled in this study, a whom 222 had undergone at least two spirometry measurements within 3 years after baseline data acquisition. PMA and PMD were measured from a single axial slice of chest CT above the aortic arch at baseline. The emphysema index and bronchial wall thickness were quantitatively assessed in all scans. The generalized linear model was used to determine the correlation between PMA and PMD measurements and pulmonary function.

Results

PMA and PMD were significantly associated with baseline lung function and the severity of emphysema (P < 0.05). Patients with the lowest PMA and PMD exhibited significantly more severe airflow obstruction (β = − 0.06; 95% confidence interval: − 0.09 to − 0.03]. PMA was statistically associated with COPD assessment test (CAT) score (P = 0.033). However, PMD did not exhibit statistically significant correlation with either CAT scores or modified Medical Research Council scores (P > 0.05). Furthermore, neither PMA nor PMD were associated with changes in forced expiratory volume in 1 s over a 3-year periods.

Conclusions

CT-derived features of the pectoralis muscle may be helpful in predicting disease severity in patients with COPD, but are not necessarily associated with longitudinal changes in lung function.
There should be a World Health Assembly resolution for malaria eradication
Authors: Gaye Oumar
Published: October 2019

Several efforts are being made now for malaria elimination with a goal for eradication. New tools and strategies are being developed and there is currently renewed political engagement and interest. Several technical groups have produced a guide on elimination for policymakers and indicated different research questions to be addressed. The World Health Assembly resolution and the United Nations General Assembly convened a high-level roundtable “From High Burden to High Impact: Getting back on track to end Malaria”. In Africa, the Head of states pronounced a vision for an Africa free of malaria and launched the slogan “Zero malaria starts with me”. Massive efforts to sustain research capacity in the endemic countries will be critical. It will be important to both increase domestic financing, and advocate to sustain and increase funding from major donor countries. It is unethical to continue to observe deaths of so many children in malaria endemic countries, the most vulnerable populations. Considering malaria eradication as a vision and working with all the opportunities we now have could accelerate the process. Eliminating malaria with a country regional approach and progressing step by step will give us consistent information on our way towards eradication.
Is microsatellite instability-high really a favorable prognostic factor for advanced colorectal cancer? A meta-analysis
Authors: Wang Bingyan , Li Fei , Zhou Xin , Ma Yanpeng , Fu Wei
Published: October 2019

Background

Stage II colorectal cancer with microsatellite instability-high (MSI-H) has been proven to have a better prognosis. However, in advanced stage, this trend remains controversial. This study aimed to explore the prognostic role of MSI-H in stage III and IV colorectal cancer (CRC) through meta-analysis.

Methods

A comprehensive search was performed in PubMed, Cochrane Central Library, and Embase databases. All randomized clinical trials and non-randomized studies were included based on inclusion and exclusion criteria and on survival after a radical operation with or without chemotherapy. The adjusted log hazard ratios (HRs) were used to estimate the prognostic value between MSI-H and microsatellite-stable CRCs. The random-effects model was used to estimate the pooled effect size.

Results

Thirty-six studies were included. Randomized controlled trials (RCT) and non-RCT were analyzed separately. For stage III CRCs, pooled HR for overall survival (OS) was 0.96 (95% confidence interval [CI] 0.75–.123) in the RCT subgroup and 0.89 (95% CI 0.62–1.28) in the non-RCT subgroup. For disease-free survival (DFS), the HR for the RCT group was 0.83 (95% CI 0.65–1.07), similar to the non-RCT subgroup (0.83, 95% CI 0.65–1.07). Disease-specific survival (DSS) was also calculated, which had an HR of 1.07 (95% CI 0.68–1.69) in the non-RCT subgroup. All these results showed that MSI-H has no beneficial effects in stage III CRC. For stage IV CRC, the HR for OS in the RCT subgroup was 1.23 (95% CI 0.92–1.64) but only two RCTs were included. For non-RCT study, the combined HR for OS and DFS was 1.10 (95% CI 0.77–1.51) and 0.72 (95% CI 0.53–0.98), respectively, suggesting the beneficial effect for DFS and non-beneficial effect for OS.

Conclusion

For stage III CRC, MSI-H had no prognostic effect for OS, DFS, and DSS. For stage IV CRC, DFS showed a beneficial result, whereas OS did not; however, the included studies were limited and needed further exploration.
Counselling interventions to enable women to initiate and continue breastfeeding: a systematic review and meta-analysis
Authors: McFadden Alison , Siebelt Lindsay , Marshall Joyce L. , Gavine Anna , Girard Lisa-Christine , Symon Andrew , MacGillivray Stephen
Published: October 2019

Background

Many infants worldwide are not breastfeeding according to WHO recommendations and this impacts on the health of women and children. Increasing breastfeeding is identified as a priority area supported by current policy targets. However, interventions are complex and multi-component and it is unclear which elements of interventions are most effective to increase breastfeeding in which settings. Breastfeeding counselling is often part of complex interventions but evidence is lacking on the specific effect of counselling interventions on breastfeeding practices. The aim of this systematic review is to examine evidence on effectiveness of breastfeeding counselling to inform global guidelines.

Methods

A systematic search was conducted of six electronic databases in January 2018. Randomised controlled trials comparing breastfeeding counselling with no breastfeeding counselling or different formulations of counselling were included if they measured breastfeeding practices between birth and 24 months after birth.

Results

From the 5180 records identified in searches and a further 11 records found by hand searching, 63 studies were included. Of these, 48 were individually-randomised trials and 15 were cluster-randomised trials. A total of 69 relevant comparisons were reported involving 33,073 women. There was a significant effect of counselling interventions on any breastfeeding at 4 to 6 weeks (Relative risk [RR] 0.85, 95% CI 0.77, 0.94) and 6 months (RR 0.92, 95% CI 0.87, 0.94). Greater effects were found on exclusive breastfeeding at 4 to 6 weeks (RR 0.79, 95% CI 0.72, 0.87) and 6 months (RR 0.84, 95% CI 0.78, 0.91). Counselling delivered at least four times postnatally is more effective than counselling delivered antenatally only and/or fewer than four times. Evidence was mostly of low quality due to high or unclear risk of bias of the included trials and high heterogeneity.

Conclusions

Breastfeeding counselling is an effective public health intervention to increase rates of any and exclusive breastfeeding. Breastfeeding counselling should be provided face-to-face, and in addition, may be provided by telephone, both antenatally and postnatally, to all pregnant women and mothers with young children. To inform scale-up globally there is a need to further understand the elements of breastfeeding interventions such as counselling and their effectiveness in different contexts and circumstances.

Study registration

This systematic review was registered in Prospero (CRD42018086494).
Adjuvant intensity modulated whole-abdominal radiation therapy for high-risk patients with ovarian cancer FIGO stage III: final results of a prospective phase 2 study
Authors: Arians Nathalie , Kieser Meinhard , Benner Laura , Rochet Nathalie , Schröder Lars , Katayama Sonja , Herfarth Klaus , Schubert Kai , Schneeweiss Andreas , Sohn Christof , Lindel Katja , Debus Jürgen
Published: October 2019

Background

To assess late toxicity, quality of life and oncological outcome after consolidative whole abdominal radiotherapy (WART) following cytoreductive surgery and carboplatin/paclitaxel chemotherapy in high risk patients with advanced ovarian cancer FIGO stage III using IMRT (Intensity modulated radiation therapy).

Methods

The OVAR-IMRT-02 study is a multi-center single-arm phase-II-trial. Twenty patients with optimally debulked ovarian cancer stage FIGO III with complete remission after chemotherapy were treated with intensity modulated WART. A total dose of 30 Gy in 20 fractions was applied to the entire peritoneal cavity. Primary endpoint was treatment tolerability; secondary objectives were acute and chronic toxicities, quality of life, rates of therapy disruption/abortion, progression-free survival (PFS) and overall survival (OS).

Results

All patients completed treatment and 10/20 patients (50%) reached the final study follow-up of 36 months. Late side effects consisted of °1-°2 lower limb edema (44.5%), with one patient (5.6%) showing °3 edema. Three patients (16.7%) showed elevated gamma-Glutamyltransferase. There were no severe late side effects regarding renal or hepatic function or any gastrointestinal toxicity greater than °2. During WART, mean global health status decreased by 18.1 points (95%-CI: 7.1–29.0), but completely normalized after 6 months. The same trend was observed for the function scale scores. Kaplan-Meier-estimated 1-, 2- and 3-year PFS was 74, 51 and 40%, respectively. 1-, 2- and 3-year OS was 89, 83 and 83%, respectively.

Conclusions

Intensity modulated WART after aggressive surgery and carboplatin/paclitaxel chemotherapy is associated with an acceptable risk of acute and late toxicity and minor impact on long-term quality of life. Together with the promising results for PFS and OS, intensity modulated WART could offer a new therapeutic option for consolidation treatment of patients with advanced ovarian cancer.

Trial registration

The study is registered with ClinicalTrials.gov (NCT01180504). Registered 12 August 2010 – retrospectively registered.
Expanded access with intravenous hydroxypropyl-β-cyclodextrin to treat children and young adults with Niemann-Pick disease type C1: a case report analysis
Authors: Hastings Caroline , Vieira Camilo , Liu Benny , Bascon Cyrus , Gao Claire , Wang Raymond Y. , Casey Alicia , Hrynkow Sharon
Published: October 2019

Background

Niemann-Pick Disease Type C (NPC) is an inherited, often fatal neurovisceral lysosomal storage disease characterized by cholesterol accumulation in every cell with few known treatments. Defects in cholesterol transport cause sequestration of unesterified cholesterol within the endolysosomal system. The discovery that systemic administration of hydroxypropyl-beta cyclodextrin (HPβPD) to NPC mice could release trapped cholesterol from lysosomes, normalize cholesterol levels in the liver, and prolong life, led to expanded access use in NPC patients. HPβCD has been administered to NPC patients with approved INDs globally since 2009.

Results

Here we present safety, tolerability and efficacy data from 12 patients treated intravenously (IV) for over 7 years with HPβCD in the US and Brazil. Some patients subsequently received intrathecal (IT) treatment with HPβCD following on average 13 months of IV HPβCD. Several patients transitioned to an alternate HPβCD. Moderately affected NPC patients treated with HPβCD showed slowing of disease progression. Severely affected patients demonstrated periods of stability but eventually showed progression of disease. Neurologic and neurocognitive benefits were seen in most patients with IV alone, independent of the addition of IT administration. Physicians and caregivers reported improvements in quality of life for the patients on IV therapy. There were no safety issues, and the drug was well tolerated and easy to administer.

Conclusions

These expanded access data support the safety and potential benefit of systemic IV administration of HPβCD and provide a platform for two clinical trials to study the effect of intravenous administration of HPβCD in NPC patients.