bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of dietary compositions and patterns on the prevalence of nonalcoholic fatty liver disease in Japanese men: a cross-sectional study
Authors: Nakashita Chihiro , Xi Lu , Inoue Yasushi , Kabura Ryota , Masuda Shota , Yamano Yuko , Katoh Takahiko
Published: September 2021

Background

This study aimed to examine the impact of dietary compositions and patterns on nonalcoholic fatty liver disease (NAFLD) morbidity in Japanese men.

Methods

We conducted a cross-sectional study of 281 individuals who underwent comprehensive medical examinations during health screening. Dietary intake was assessed using a semi-quantitative food frequency questionnaire, and factor analysis was performed to detect dietary patterns. NAFLD was diagnosed by the presence of fatty liver on abdominal ultrasonography in nondrinkers (< 30 g/day), and patients were categorized into control (n = 192) and NAFLD groups (n = 89).

Results

Compared with the control group, the NAFLD group consumed fewer mushrooms. Three dietary patterns were identified, namely, a healthy pattern, a western pattern, and a snack pattern. The score of healthy pattern was negatively correlated with the risk of NAFLD. Compared with the lowest tertile of the healthy pattern, the middle tertile was associated with a lower risk of NAFLD after adjusting for age, physical activity, and smoking (odds ratio: 0.47, 95% confidence interval: 0.25–0.91). After further adjustments for body mass index, the middle tertile was associated with a lower risk of NAFLD (odds ratio: 0.46, 95% confidence interval: 0.23–0.92).

Conclusions

A healthy dietary pattern comprising frequent intake of seaweeds, vegetables, mushrooms, pulses, and potatoes and starches was associated with a lower risk of NAFLD in Japanese men. In our opinion, this healthy pattern closely resembles the Japanese Washoku diet, indicating that adherence to Washoku may help prevent NAFLD.
Longitudinal impact of oral health on geriatric syndromes and clinical outcomes in community-dwelling older adults
Authors: Lim Jihye , Park Hyungchul , Lee Heayon , Lee Eunju , Lee Danbi , Jung Hee-Won , Jang Il-Young
Published: September 2021

Background

Oral health is essential for daily living and plays a pivotal role in overall health conditions and well-being. This study evaluated the impact of self-reported oral health on geriatric conditions, institutionalization, and mortality.

Methods

This study analyzed the population of the Aging Study of Pyeongchang Rural Area that had undergone geriatric assessments between 2016 and 2017. The oral health status of the participants was determined using three items from the General Oral Health Assessment Index, and the participants were classified into three groups according to the total sum of the scores as good (3), fair (4–7), or poor (8–15). The outcomes were the incidence of geriatric syndromes at 2 years and the composite outcome of mortality and institutionalization.

Results

Among the 1189 participants, 44.1 % were women, and the mean age of the study population was 75.0 years. Good, fair, and poor oral health were observed in 597 (50.2 %), 406 (34.1 %), and 186 (15.6 %) individuals, respectively. Worsening oral health status was associated with the incidences of various geriatric syndromes at follow-up, and these associations were attenuated after adjusting for baseline demographic and geriatric parameters. Similarly, the significant association between baseline oral health status and the incidence of the composite outcome was attenuated after adjusting for demographic and geriatric parameters.

Conclusions

Oral health affected the geriatric health conditions in this prospective, longitudinal cohort of community-dwelling older adults. The correlations and interactions of oral health status with other functional parameters may deserve consideration as a geriatric domain.
The longitudinal associations between change in physical activity and cognitive functioning in older adults with chronic illness (es)
Authors: Volders Esmee , de Groot Renate H. M. , Bolman Catherine A. W. , Lechner Lilian
Published: September 2021

Background

Regular physical activity (PA) is potentially beneficial for age-related cognitive decline. Although moderate-to-vigorous physical activity (MVPA) is mostly advised, older adults with chronic illnesses might benefit more from light physical activity (LPA), as they suffer from mobility problems, pain, and fatigue, limiting high-intensity PA. Therefore, the longitudinal association between change in LPA and MVPA and the change in cognitive functioning (CF) is investigated in older adults with chronic illnesses.

Methods

In total 432 older adults (mean age 73.7 [±6.1] years; 46.8% female) with at least one chronic illness participated in this longitudinal observational study. Longitudinal associations between accelerometer-assessed change in PA (LPA and MVPA) and change in CF, measured with an objective validated neuropsychological test battery, were tested with multivariate linear regressions.

Results

An increase in LPA between baseline and 6 months follow-up was significantly associated with improved short-term verbal memory and inhibition over the first 6 months. In addition, the change score in LPA over the first 6 months was predictive for the change score in short-term verbal memory over 12 months. Furthermore, an increase in MVPA between baseline and 6 months follow-up was significantly associated with a decrease in longer-term verbal memory scores over the same six-month period.

Conclusions

For older adults with chronic illnesses who may experience difficulties in being sufficiently active, an increase in LPA is probably more achievable than an increase in MVPA. In addition, an increase in LPA enhances CF more than an increase in MVPA does.

Trial registration

Netherlands Trial Register NL6005; Date of Registration 21-03-2017.
Prevalence of undetectable and suppressed viral load in HIV-infected pregnant women initiating Option B+ in Uganda: an observational study nested within a randomized controlled trial
Authors: Gabagaya Grace , Rukundo Gordon , Amone Alexander , Wavamunno Priscilla , Namale-Matovu Joyce , Lubega Irene , Nakabiito Clemensia , Namukwaya Zikulah , Nolan Monica , Malamba Samuel S. , King Rachel , Homsy Jaco , Fowler Mary Glenn , Musoke Philippa
Published: September 2021

Background

Viral load (VL) testing is key in monitoring adherence to antiretroviral therapy (ART) and documenting HIV treatment response. As per HIV treatment guidelines in Uganda, the first VL test is recommended 6 months after initiation of ART. Undetectable VL (uVL) at ART initiation may be helpful in detecting elite controllers in the absence of previous ART use. We investigated viral suppression at ART initiation among a cohort of HIV-positive pregnant women enrolled in the Friends for Life Circles (FLC) for Option B+ randomized controlled trial (RCT).

Methods

Pregnant women ≥ 18 years of age testing positive for HIV at their first antenatal care visit and starting on ART Option B+ as per the National PMTCT Program guidelines were enrolled into the FLC for Option B+ RCT in urban Kampala and rural Mityana districts of Uganda. Each participant had whole blood samples collected at enrolment to assess baseline VL. Plasma HIV-1 RNA was quantified using COBAS Ampliprep /COBAS Taqman. Baseline VL below 400 RNA copies/ml was considered as viral suppression while baseline VL below 20 RNA copies/ml was considered uVL.

Results

The mean duration from the date of ART initiation to time of sample collection for baseline VL assessment was 4.4 days (SD 3.6). Of the 532 HIV-positive pregnant women enrolled in the FLC for Option B+ study and newly starting Option B+ without a self-reported history of prior ART use, 29 (5.5%) had uVL and 113 (21.4%) had suppressed VL at baseline. There was no association between participants’ age, gravidity, marital status, mean monthly income, educational level, disclosure of HIV status to partner, and uVL or viral suppression at baseline. However, non-disclosure of HIV status to any other person was associated with decreased odds of viral suppression at baseline (OR 0.640; 0.416–0.982).

Conclusion

Twenty-one percent of HIV-positive Ugandan pregnant women initiating ART (Option B+) showed virological suppression at baseline and were presumed to be “elite controllers” or to have misreported being ART-naive. Further studies are needed to better understand the biologic mechanisms of elite controllers among pregnant women as well as to differentiate elite controllers from concealed ART use.

Trial Registration The trial was registered as NCT02515370 (04/08/2015) on Clinicaltrials.gov.
Automatic identification of suspicious bone metastatic lesions in bone scintigraphy using convolutional neural network
Authors: Liu Yemei , Yang Pei , Pi Yong , Jiang Lisha , Zhong Xiao , Cheng Junjun , Xiang Yongzhao , Wei Jianan , Li Lin , Yi Zhang , Cai Huawei , Zhao Zhen
Published: September 2021

Background

We aimed to construct an artificial intelligence (AI) guided identification of suspicious bone metastatic lesions from the whole-body bone scintigraphy (WBS) images by convolutional neural networks (CNNs).

Methods

We retrospectively collected the 99mTc-MDP WBS images with confirmed bone lesions from 3352 patients with malignancy. 14,972 bone lesions were delineated manually by physicians and annotated as benign and malignant. The lesion-based differentiating performance of the proposed network was evaluated by fivefold cross validation, and compared with the other three popular CNN architectures for medical imaging. The average sensitivity, specificity, accuracy and the area under receiver operating characteristic curve (AUC) were calculated. To delve the outcomes of this study, we conducted subgroup analyses, including lesion burden number and tumor type for the classifying ability of the CNN.

Results

In the fivefold cross validation, our proposed network reached the best average accuracy (81.23%) in identifying suspicious bone lesions compared with InceptionV3 (80.61%), VGG16 (81.13%) and DenseNet169 (76.71%). Additionally, the CNN model's lesion-based average sensitivity and specificity were 81.30% and 81.14%, respectively. Based on the lesion burden numbers of each image, the area under the receiver operating characteristic curve (AUC) was 0.847 in the few group (lesion number n ≤ 3), 0.838 in the medium group (n = 4–6), and 0.862 in the extensive group (n > 6). For the three major primary tumor types, the CNN-based lesion identifying AUC value was 0.870 for lung cancer, 0.900 for prostate cancer, and 0.899 for breast cancer.

Conclusion

The CNN model suggests potential in identifying suspicious benign and malignant bone lesions from whole-body bone scintigraphic images.
Wearable inertial sensors are highly sensitive in the detection of gait disturbances and fatigue at early stages of multiple sclerosis
Authors: Müller Roy , Hamacher Daniel , Hansen Sascha , Oschmann Patrick , Keune Philipp M.
Published: September 2021

Background

The aim of the current study was to examine multiple gait parameters obtained by wearable inertial sensors and their sensitivity to clinical status in early multiple sclerosis (MS). Further, a potential correlation between gait parameters and subjective fatigue was explored.

Methods

Automated gait analyses were carried out on 88 MS patients and 31 healthy participants. To measure gait parameters (i.e. walking speed, stride length, stride duration, duration of stance and swing phase, minimal toe-to-floor distance), wearable inertial sensors were utilized throughout a 6-min 25-ft walk. Additionally, self-reported subjective fatigue was assessed.

Results

Mean gait parameters consistently revealed significant differences between healthy participants and MS patients from as early as an Expanded Disability Status Scale (EDSS) value of 1.5 onwards. Further, MS patients showed a significant linear trend in all parameters, reflecting continuously deteriorating gait performance throughout the test. This linear deterioration trend showed significant correlations with fatigue.

Conclusions

Wearable inertial sensors are highly sensitive in the detection of gait disturbances, even in early MS, where global scales such as the EDSS do not provide any clinical information about deviations in gait behavior. Moreover, these measures provide a linear trend parameter of gait deterioration that may serve as a surrogate marker of fatigue. In sum, these results suggest that classic timed walking tests in routine clinical practice should be replaced by readily and automatically applicable gait assessments, as provided by inertial sensors.
Socio-demographic determinants of pregnancy termination among adolescent girls and young women in selected high fertility countries in sub-Saharan Africa
Authors: Ahinkorah Bright Opoku
Published: September 2021

Background

Most of the unintended pregnancies that occur among adolescent girls and young women (AGYW) in sub-Saharan Africa (SSA) end up in pregnancy termination. In this study, the socio-demographic determinants of pregnancy termination among AGYW (aged 15–24) in selected countries with high fertility rates in SSA were examined.

Methods

This was a cross-sectional analysis of data from the most recent Demographic and Health Surveys of nine countries in SSA. The countries included are Angola, Burkina Faso, Burundi, Chad, Gambia, Mali, Niger, Nigeria, and Uganda. A total of 62,747 AGYW constituted the sample size for the study. Fixed and random effects models were used to examine the determinants of pregnancy termination with statistical significance at p < 0.05.

Results

Higher odds of pregnancy termination were found among AGYW aged 20–24, those who were cohabiting and married, those who listened to radio and watched television at least once a week and those who lived in communities with high literacy level. Conversely, the odds of pregnancy termination were lower among AGYW with three or more births and those with secondary/higher education.

Conclusion

The socio-demographic determinants of pregnancy termination among AGYW in this study were age, level of education, marital status, exposure to radio and television, parity, and community literacy level. The findings provide the needed information for designing health interventions to reduce unwanted pregnancies and unsafe abortions in countries with high fertility rates in SSA. It is recommended that governments and non-governmental organisations in these countries should enhance sexuality education and regular sensitization of adolescent sexual and reproductive health programmes targeted at AGYW who are at risk of pregnancy termination.
Coverage and factors associated with mother and newborn skin-to-skin contact in Nigeria: a multilevel analysis
Authors: Ekholuenetale Michael , Barrow Amadou , Benebo Faith Owunari , Idebolo Ashibudike Francis
Published: September 2021

Background

Mother and newborn skin-to-skin contact (SSC) is an immediate postpartum intervention known to improve the health of newborn and mothers alike. Albeit, there is paucity of data that explored the coverage or factors associated with SSC in Nigeria. Therefore, we aimed to explore the coverage and hierarchical nature of the factors associated with SSC among women of reproductive age in Nigeria.

Methods

The 2018 Nigeria Demographic and Health Survey (NDHS) data was used for this study. Data on 29,992 women who had ever given birth were extracted for analysis. SSC was the outcome variable as determined by women’s report. A multivariable multilevel logistic regression model was used to estimate the fixed and random effects of the factors associated with SSC. Statistical significance was determined at p< 0.05.

Results

The coverage of SSC was approximately 12.0%. Educated women had higher odds of SSC, when compared with women with no formal education. Those who delivered through caesarean section (CS) had 88% reduction in SSC, when compared with women who had vaginal delivery (OR= 0.12; 95%CI: 0.07, 0.22). Women who delivered at health facility were 15.58 times as likely to practice SSC, when compared with those who delivered at home (OR= 15.58; 95%CI: 10.64, 22.82). Adequate ANC visits and low birth weight significantly increased the odds of SSC. Women from richest household were 1.70 times as likely to practice SSC, when compared with women from poorest household (OR= 1.70; 95%CI: 1.04, 2.79). There was 65% reduction in SSC among women with high rate of community non-use of media, when compared with women from low rate of community non-use of media (OR= 0.35; 95%CI: 0.20, 0.61).

Conclusion

SSC coverage was low in Nigeria. Moreover, individual, household and community level factors were associated with SSC. More enlightenment should be created among women to bring to limelight the importance of SSC specifically to newborn’s health.
A case of bilateral pachychoroid disease: polypoidal choroidal vasculopathy in one eye and peripheral exudative hemorrhagic chorioretinopathy in contralateral eye
Authors: Kitagawa Yorihisa , Shimada Hiroyuki , Kawamura Akiyuki , Tanaka Koji , Mori Ryusaburo , Onoe Hajime , Nakashizuka Hiroyuki
Published: September 2021

Background

We report a case of bilateral pachychoroid disease manifesting polypoidal choroidal vasculopathy (PCV) with punctate hyperfluorescent spot (PHS) in one eye, and peripheral exudative hemorrhagic choroidal retinopathy (PEHCR) with central serous chorioretinopathy (CSC) and PHS in the contralateral eye.

Case presentation

: A 51-year-old healthy woman presented with complaint of blurred vision in her right eye. Corrected visual acuity was 20/20 in the right and 24/20 in the left eye. Fundus examination was normal in the left eye. In the right eye, fundus finding of an orange-red nodular lesion and optical coherence tomography (OCT) finding of polypoidal lesions led to a diagnosis of PCV. Four aflibercept intravitreal injections were performed in her right eye. After treatment, indocyanine green angiography (ICGA) confirmed residual polypoidal lesions with branching vascular networks and PHS with choroidal vascular hyperpermeability. OCT showed PHS associated with small sharp-peaked retinal pigment epithelium (RPE) elevation in peripheral fundus and small RPE elevation in posterior fundus. Based on the above findings, PCV with PHS was finally diagnosed in the right eye. Posttreatment corrected visual acuity in the right eye was 20/20. She presented again 32 months later, with complaint of vision loss in her left eye. Left corrected visual acuity was 20/20, and fundus examination showed mild vitreous hemorrhage. Vitrectomy was performed. In temporal midperipheral fundus, fluorescein angiography revealed CSC, and OCT showed pachychoroid. ICGA depicted abnormal choroidal networks and PHS in peripheral fundus. Furthermore, polypoidal lesions were confirmed by OCT. Based on the above findings, PEHCR and CSC with PHS was finally diagnosed in the left eye. Postoperative corrected visual acuity in the left eye was 20/20, and aflibercept intravitreal injection was performed for prevention of recurrence of vitreous hemorrhage.

Conclusions

This is the first case report of PCV with PHS in one eye, and PEHCR with CSC and PHS in the contralateral eye. This case suggests that PCV, PEHCR, and CSC may be linked pathologies of pachychoroid spectrum disease.
Vertebral fracture as a risk factor for self-harm: a retrospective cohort study
Authors: Prior James A. , Crawford-Manning Fay , Whittle Rebecca , Abdul-Sultan Alyshah , Chew-Graham Carolyn A. , Muller Sara , Shepherd Tom A. , Sumathipala Athula , Mallen Christian D. , Paskins Zoe
Published: September 2021

Background

The prevention of self-harm is an international public health priority. It is vital to identify at-risk populations, particularly as self-harm is a risk factor for suicide. This study aims to examine the risk of self-harm in people with vertebral fractures.

Methods

Retrospective cohort study. Patients with vertebral fracture were identified within the Clinical Practice Research Datalink and matched to patients without fracture by sex and age. Incident self-harm was defined by primary care record codes following vertebral fracture. Overall incidence rates (per 10,000 person-years (PY)) were reported. Cox regression analysis determined risk (hazard ratios (HR), 95 % confidence interval (CI)) of self-harm compared to the matched unexposed cohort. Initial crude analysis was subsequently adjusted and stratified by median age and sex.

Results

The number of cases of vertebral fracture was 16,293, with a matched unexposed cohort of the same size. Patients were predominantly female (70.1 %), median age was 76.3 years. Overall incidence of self-harm in the cohort with vertebral fracture was 12.2 (10.1, 14.8) /10,000 PY. There was an initial crude association between vertebral fracture and self-harm, which remained after adjustment (HR 2.4 (95 %CI 1.5, 3.6). Greatest risk of self-harm was found in those with vertebral fractures who were aged below 76.3 years (3.2(1.8, 5.7)) and male (3.9(1.8, 8.5)).

Conclusions

Primary care patients with vertebral fracture are at increased risk of self-harm compared to people without these fractures. Male patients aged below 76 years of age appear to be at greatest risk of self-harm. Clinicians need to be aware of the potential for self-harm in this patient group.
B cell activating factor regulates periodontitis development by suppressing inflammatory responses in macrophages
Authors: Wang Lixia , Zhang Tianyi , Zhang Zheng , Wang Zihan , Zhou Yu-Jie , Wang Zuomin
Published: September 2021

Background

B cell activating factor (BAFF) is a member of the tumor necrosis factor (TNF) superfamily with immunomodulatory effects on both innate and adaptive immune responses. Periodontitis is an inflammatory disease characterized by periodontal soft tissue inflammation and the progressive loss of periodontal ligament and alveolar bone. Macrophages are closely related to periodontitis progression. However, the role of BAFF in periodontitis development and macrophage polarization and the underlying mechanism remain unknown.

Methods

In vivo, a ligation-induced mouse model of periodontitis for BAFF blockade was established to investigate the expression of inducible nitric oxide synthase (iNOS) through real-time PCR (RT-PCR) and immunohistochemistry. In addition, the level of TNF-α in the periodontium, the number of osteoclasts, and alveolar bone resorption were observed. In vitro, RAW 264.7 macrophage cells were treated with 100 ng/mL Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS) in either the presence or absence of 50 nM small interfering RNA (siRNA) targeting BAFF, followed by further incubation for 24 h. These cells and supernatants were collected and stored for RT-PCR, enzyme-linked immunosorbent assay, western blotting and immunofluorescence microscopy.

Results

In vivo, BAFF blockade decreased the levels of TNF-α in the periodontium in a ligature-induced mouse periodontitis model. Reduced osteoclast formation and lower alveolar bone loss were also observed. In addition, BAFF blockade was related to the expression of polarization signature molecules in macrophages. In vitro, BAFF knockdown notably suppressed the production of TNF-α in RAW 264.7 cells stimulated by P. gingivalis LPS. Moreover, BAFF knockdown attenuated the polarization of RAW 264.7 cells into classically activated macrophages (M1), with reduced expression of iNOS.

Conclusions

Based on our limited evidence, we showed BAFF blockade exhibits potent anti-inflammatory properties in mice experimental periodontitis in vivo and in P. gingivalis LPS-treated RAW 264.7 cells in vitro, and macrophage polarization may be responsible for this effect.
Trends in specialized palliative care referrals at an oncology center from 2007 to 2019
Authors: Boltezar Lucka , Novakovic Barbara Jezersek , Moltara Maja Ebert
Published: September 2021

Background

Early referral to palliative care, at least 3 months before death, should be a standard of care in oncological practice. Real life data in this setting are invaluable since they provide a picture of everyday practice and serve as the basis for future improvements.

Methods

We conducted a retrospective cohort assessment of all patients referred to our specialized palliative care (SPC) services at the Institute of Oncology, Ljubljana, Slovenia. Our analysis includes patient referrals between 2007 and 2019.

Results

During the above-specified time period of 13 years, 3234 patients were referred for SPC services at our institution. The median age at SPC referral was 67 years. The majority of patients (63%) were assessed only once, while 31% of patients were seen on more than one occasion. Median time from SPC referral to death was 25 days for the whole group. 1693 patients (52.7%) were referred to SPC in the last 30 days before death, 785 (25.8%) patients between 31 and 90 days and 652 (21.4%) patients more than 3 months before death. Neither age nor sex correlated with the duration of referral time. However, there was a strong correlation between the year of referral to palliative care and the duration of palliative care service (ρ = 0.19, p < 0.001). The median referral to death interval for lymphoma patients and breast cancer patients were 15 and 18 days, respectively, and the median referral to death interval for colorectal cancer and lung tumor patients were 34 and 26 days before death, respectively.

Conclusion

Throughout the existence of our SPC services we have observed a positive trend in the number of referrals, a lengthening of time between referral and death, as well as an increase in the proportion of patients with an early referral to SPC (more than 3 months before death). Neither age nor sex correlated with the length of referral time.
Parental bereavement – impact of death of neonates and children under 12 years on personhood of parents: a systematic scoping review
Authors: Vig Prachi Simran , Lim Jia Yin , Lee Randal Wei Liang , Huang Huixin , Tan Xiu Hui , Lim Wei Qiang , Lim Marie Bernadette Xin Yi , Lee Alexia Sze Inn , Chiam Min , Lim Crystal , Baral Vijayendra Ranjan , Krishna Lalit Kumar Radha
Published: September 2021

Background

Losing a child tragically impacts the well-being and functioning of parents. With these effects extending beyond emotional, physical morbidity and compromising self-perceptions, appropriate, longitudinal, timely and personalised support is key to effective care of bereaved parents. However, in the absence of a comprehensive understanding of parental bereavement, effective support of bereaved parents remains suboptimal. To address this gap, we scrutinise prevailing data on the effects of a child’s death, aged 0–12 years, through the lens of the Ring Theory of Personhood (RToP).

Methods

To study prevailing accounts of bereaved parents following the death of a child, we adopt Krishna’s Systematic Evidence Based Approach (SEBA) to structure our Systematic Scoping Review (SSR in SEBA).

Results

Three thousand seventy-four abstracts were reviewed, 160 full text articles were evaluated, and 111 articles were included and analysed using thematic and content analysis. Four themes/categories were identified relating to the four rings of the RToP. Findings reveal that static concepts of protective and risk factors for grief are misplaced and that the support of healthcare professionals is key to assisting bereaved parents.

Conclusion

In the absence of consistent support of bereaved parents, this study highlights the need for effective training of healthcare professionals, beginning with an appreciation that every aspect of an individual parent’s personhood is impacted by the loss of their child. Acknowledging grief as a complex, evolving and personalised process subjected to parental characteristics, settings, context and available support, this SSR in SEBA calls attention to effective nurturing of the relationship between parents and healthcare professionals, and suggests use of the RToP to assess and direct personalised, timely, specific support of parents in evolving conditions. We believe the findings of this review also call for further studies to support healthcare professionals as they journey with bereaved parents.
Achieving inclusive research priority-setting: what do people with lived experience and the public think is essential?
Authors: Pratt Bridget
Published: September 2021

Background

Engagement of people with lived experience and members of the public is an ethically and scientifically essential component of health research. Authentic engagement means they are involved as full partners in research projects. Yet engagement as partnership is uncommon in practice, especially during priority-setting for research projects. What is needed for agenda-setting to be shared by researchers and people with lived experience and/or members of the public (or organisations representing them)? At present, little ethical guidance exists on this matter, particularly that which has been informed by the perspectives of people with lived experience and members of the public. This article provides initial evidence about what they think are essential foundations and barriers to shared decision-making in health research priority-setting and health research more broadly.

Methods

An exploratory, qualitative study was conducted in 2019. 22 semi-structured interviews were performed with key informants from the UK and Australia.

Results

Three main types of foundations were thought to be essential to have in place before shared decision-making can occur in health research priority-setting: relational, environmental, and personal. Collectively, the three types of foundations addressed many (but not all) of the barriers to power sharing identified by interviewees.

Conclusions

Based on study findings, suggestions are made for what researchers, engagement practitioners, research institutions, and funders should do in their policy and practice to support meaningful engagement. Finally, key international research ethics guidelines on community engagement are considered in light of study findings.
Journey mapping as a novel approach to healthcare: a qualitative mixed methods study in palliative care
Authors: Ly Stephanie , Runacres Fiona , Poon Peter
Published: September 2021

Background

Journey mapping involves the creation of visual narrative timelines depicting the multidimensional relationship between a consumer and a service. The use of journey maps in medical research is a novel and innovative approach to understanding patient healthcare encounters.

Objectives

To determine possible applications of journey mapping in medical research and the clinical setting. Specialist palliative care services were selected as the model to evaluate this paradigm, as there are numerous evidence gaps and inconsistencies in the delivery of care that may be addressed using this tool.

Methods

A purposive convenience sample of specialist palliative care providers from the Supportive and Palliative Care unit of a major Australian tertiary health service were invited to evaluate journey maps illustrating the final year of life of inpatient palliative care patients. Sixteen maps were purposively selected from a sample of 104 consecutive patients. This study utilised a qualitative mixed-methods approach, incorporating a modified Delphi technique and thematic analysis in an online questionnaire.

Results

Our thematic and Delphi analyses were congruent, with consensus findings consistent with emerging themes. Journey maps provided a holistic patient-centred perspective of care that characterised healthcare interactions within a longitudinal trajectory. Through these journey maps, participants were able to identify barriers to effective palliative care and opportunities to improve care delivery by observing patterns of patient function and healthcare encounters over multiple settings.

Conclusions

This unique qualitative study noted many promising applications of the journey mapping suitable for extrapolation outside of the palliative care setting as a review and audit tool, or a mechanism for providing proactive patient-centred care. This is particularly significant as machine learning and big data is increasingly applied to healthcare.
Renal hemodynamic effects differ between antidiabetic combination strategies: randomized controlled clinical trial comparing empagliflozin/linagliptin with metformin/insulin glargine
Authors: Ott Christian , Jung Susanne , Korn Manuel , Kannenkeril Dennis , Bosch Agnes , Kolwelter Julie , Striepe Kristina , Bramlage Peter , Schiffer Mario , Schmieder Roland E.
Published: September 2021

Background

Type 2 diabetes causes cardio-renal complications and is treated with different combination therapies. The renal hemodynamics profile of such combination therapies has not been evaluated in detail.

Methods

Patients (N = 97) with type 2 diabetes were randomized to receive either empagliflozin and linagliptin (E+L group) or metformin and insulin glargine (M+I group) for 3 months. Renal hemodynamics were assessed with para-aminohippuric acid and inulin for renal plasma flow (RPF) and glomerular filtration rate (GFR). Intraglomerular hemodynamics were calculated according the Gomez´ model.

Results

Treatment with E+L reduced GFR (p = 0.003), but RPF remained unchanged (p = 0.536). In contrast, M+I not only reduced GFR (p = 0.001), but also resulted in a significant reduction of RPF (p < 0.001). Renal vascular resistance (RVR) decreased with E+L treatment (p = 0.001) but increased with M+I treatment (p = 0.001). The changes in RPF and RVR were different between the two groups (both padjust < 0.001). Analysis of intraglomerular hemodynamics revealed that E+L did not change resistance of afferent arteriole (RA) (p = 0.116), but diminished resistance of efferent arterioles (RE) (p = 0.001). In M+I group RA was increased (p = 0.006) and RE remained unchanged (p = 0.538). The effects on RA (padjust < 0.05) and on RE (padjust < 0.05) differed between the groups.

Conclusions

In patients with type 2 diabetes and preserved renal function treatment with M+I resulted in reduction of renal perfusion and increase in vascular resistance, in contrast to treatment with E+I that preserved renal perfusion and reduced vascular resistance. Moreover, different underlying effects on the resistance vessels have been estimated according to the Gomez model, with M+I increasing RA and E+L predominantly decreasing RE, which is in contrast to the proposed sodium-glucose cotransporter 2 inhibitor effects.

Trial registration: The study was registered at www.clinicaltrials.gov (NCT02752113) on April 26, 2016
Molecular detection of blaCTX-M gene to predict phenotypic cephalosporin resistance and clinical outcome of Escherichia coli bloodstream infections in Vietnam
Authors: Son Trinh Van , Manh Nguyen Dang , Trung Ngo Tat , Quyen Dao Thanh , Meyer Christian G. , Phuong Nguyen Thi Kim , Hoan Phan Quoc , Sang Vu Viet , Nurjadi Dennis , Velavan Thirumalaisamy P. , Bang Mai Hong , Song Le Huu
Published: September 2021

Background

Blood stream infections (BSI) caused by Extended Spectrum Beta-Lactamases (ESBLs) producing Enterobacteriaceae is a clinical challenge leading to high mortality, especially in developing countries. In this study, we sought to describe the epidemiology of ESBL-producing Escherichia coli strains isolated from Vietnamese individuals with BSI, to investigate the concordance of genotypic-phenotypic resistance, and clinical outcome of ESBL E. coli BSI.

Methods

A total of 459 hospitalized patients with BSI were screened between October 2014 and May 2016. 115 E. coli strains from 115 BSI patients were isolated and tested for antibiotic resistance using the VITEK®2 system. The ESBL phenotype was determined by double disk diffusion method following the guideline of Clinical and Laboratory Standards Institute. Screening for beta-lactamase (ESBL and carbapenemase) genes was performed using a multiplex-PCR assay.

Results

58% (67/115) of the E. coli strains were ESBL-producers and all were susceptible to both imipenem and meropenem. Resistance to third-generation cephalosporin was common, 70% (81/115) were cefotaxime-resistant and 45% (52/115) were ceftazidime-resistant. blaCTX-M was the most common ESBL gene detected (70%; 80/115) The sensitivity and specificity of blaCTX-M-detection to predict the ESBL phenotype was 87% (76–93% 95% CI) and 54% (39–48% 95% CI), respectively. 28%% (22/80) of blaCTX-M were classified as non-ESBL producers by phenotypic testing for ESBL production. The detection of blaCTX-M in ESBL-negative E. coli BSI was associated with fatal clinical outcome (27%; 6/22 versus 8%; 2/26, p = 0.07).

Conclusion

A high prevalence of ESBL-producing E. coli isolates harbouring blaCTX-M was observed in BSI patients in Vietnam. The genotypic detection of blaCTX-M may have added benefit in optimizing and guiding empirical antibiotic therapy of E. coli BSI to improve clinical outcome.
Multiplex lateral flow immunochromatographic assay is an effective method to detect carbapenemases without risk of OXA-48-like cross reactivity
Authors: Kon Hadas , Abramov Shirin , Frenk Sammy , Schwartz David , Shalom Ohad , Adler Amos , Carmeli Yehuda , Lellouche Jonathan
Published: September 2021

Background

It is essential to detect carriers of carbapenemase-producing Enterobacterales in order to implement infection control measures. The objectives of this study was to evaluate the NG-Test® CARBA 5 (CARBA 5) assay for detection of five carbapenemases and to assess the cross reactivity of other OXA-type carbapenemases with the OXA-48-like specific antibodies.

Methods

A total of 197 Enterobacterales isolates were tested. To evaluate the cross reactivity, 73 carbapenem-resistant A. baumannii, harboring OXA-type variants, were tested. Polymerase chain reaction (PCR) served as gold standard for carbapenemase identification.

Results

Excellent agreement was found between PCR and CARBA 5, for all but one isolate. The single false positive result (a blaSME positive S. marcescens isolate) was incorrectly positive for blaOXA-48 by CARBA 5. No cross reactivity was observed. The sensitivity and specificity were 100.0% and 98.0%, respectively.

Conclusions

The CARBA 5 assay is highly sensitive and specific and is recommended as a tool for the detection of the main carbapenemases of interest in clinical microbiology laboratories.
A self-amplified nanocatalytic system for achieving “1 + 1 + 1 > 3” chemodynamic therapy on triple negative breast cancer
Authors: Zhou Lulu , Chen Jinjin , Sun Yunhao , Chai Keke , Zhu Zhounan , Wang Chunhui , Chen Mengyao , Han Wenmei , Hu Xiaochun , Li Ruihao , Yao Tianming , Li Hui , Dong Chunyan , Shi Shuo
Published: September 2021

Background

Chemodynamic therapy (CDT), employing Fenton or Fenton-like catalysts to convert hydrogen peroxide (H2O2) into toxic hydroxyl radicals (·OH) to kill cancer cells, holds great promise in tumor therapy due to its high selectivity. However, the therapeutic effect is significantly limited by insufficient intracellular H2O2 level in tumor cells. Fortunately, β-Lapachone (Lapa) that can exert H2O2-supplementing functionality under the catalysis of nicotinamide adenine dinucleotide (phosphate) NAD(P)H: quinone oxidoreductase-1 (NQO1) enzyme offers a new idea to solve this problem. However, extensive DNA damage caused by high levels of reactive oxygen species can trigger the “hyperactivation” of poly(ADP-ribose) polymerase (PARP), which results in the severe interruption of H2O2 supply and further the reduced efficacy of CDT. Herein, we report a self-amplified nanocatalytic system (ZIF67/Ola/Lapa) to co-deliver the PARP inhibitor Olaparib (Ola) and NQO1-bioactivatable drug Lapa for sustainable H2O2 production and augmented CDT (“1 + 1 + 1 > 3”).

Results

The effective inhibition of PARP by Ola can synergize Lapa to enhance H2O2 formation due to the continuous NQO1 redox cycling. In turn, the high levels of H2O2 further react with Co2+ to produce the highly toxic ·OH by Fenton-like reaction, dramatically improving CDT. Both in vitro and in vivo studies demonstrate the excellent antitumor activity of ZIF67/Ola/Lapa in NQO1 overexpressed MDA-MB-231 tumor cells. Importantly, the nanocomposite presents minimal systemic toxicity in normal tissues due to the low NQO1 expression.

Conclusions

This design of nanocatalytic system offers a new paradigm for combing PARP inhibitor, NQO1-bioactivatable drug and Fenton-reagents to obtain sustained H2O2 generation for tumor-specific self-amplified CDT.

Graphic Abstract
Lactic acidosis and hyperlactatemia associated with lamivudine accumulation and sepsis in a kidney transplant recipient—a case report and review of the literature
Authors: Hollinger Alexa , Cueni Nadine , Marzolini Catia , Dickenmann Michael , Landmann Emmanuelle , Battegay Manuel , Martinez Aurélien Emmanuel , Siegemund Martin , Leuppi-Taegtmeyer Anne
Published: September 2021

Background

We report a case of sudden, lethal metabolic acidosis in a 70-year-old man on long-term nucleoside reverse transcriptase inhibitor (NRTI) -based antiretroviral therapy (ART) who had developed atypical necrotizing fasciitis 1 month after kidney transplantation.

Case presentation

The HIV infection of the patient was treated for the last four months with an integrase strand inhibitor (dolutegravir 50 mg/d) plus a NRTI backbone including lamivudine (150 mg/d) and abacavir (600 mg/d). In this renal transplant patient we hypothesize that the co-existence of sepsis, renal failure and an accumulation of lamivudine led to the development of fatal metabolic acidosis and hyperlactatemia. Although lamivudine is only rarely associated with hyperlactatemia, there is evidence that overdose may be a risk factor for developing it. In our patient the lamivudine concentration two days after stopping and during hemodiafiltration was more than 50 times higher than therapeutic target trough concentrations. Likely reasons for this were renal impairment and concurrent treatment with trimethoprim, known to inhibit the renal elimination of lamivudine.

Conclusions

NRTIs could trigger the development of hyperlactatemia in septic patients. The use of NRTI sparing regimens might be considered in the presence of this critical condition.
The de novo FAIRification process of a registry for vascular anomalies
Authors: Groenen Karlijn H. J. , Jacobsen Annika , Kersloot Martijn G. , dos Santos Vieira Bruna , van Enckevort Esther , Kaliyaperumal Rajaram , Arts Derk L. , ‘t Hoen Peter A. C. , Cornet Ronald , Roos Marco , Kool Leo Schultze
Published: September 2021

Background

Patient data registries that are FAIR—Findable, Accessible, Interoperable, and Reusable for humans and computers—facilitate research across multiple resources. This is particularly relevant to rare diseases, where data often are scarce and scattered. Specific research questions can be asked across FAIR rare disease registries and other FAIR resources without physically combining the data. Further, FAIR implies well-defined, transparent access conditions, which supports making sensitive data as open as possible and as closed as necessary.

Results

We successfully developed and implemented a process of making a rare disease registry for vascular anomalies FAIR from its conception—de novo. Here, we describe the five phases of this process in detail: (i) pre-FAIRification, (ii) facilitating FAIRification, (iii) data collection, (iv) generating FAIR data in real-time, and (v) using FAIR data. This includes the creation of an electronic case report form and a semantic data model of the elements to be collected (in this case: the “Set of Common Data Elements for Rare Disease Registration” released by the European Commission), and the technical implementation of automatic, real-time data FAIRification in an Electronic Data Capture system. Further, we describe how we contribute to the four facets of FAIR, and how our FAIRification process can be reused by other registries.

Conclusions

In conclusion, a detailed de novo FAIRification process of a registry for vascular anomalies is described. To a large extent, the process may be reused by other rare disease registries, and we envision this work to be a substantial contribution to an ecosystem of FAIR rare disease resources.
Satisfaction with in-patient child and adolescent psychiatric treatment: development and psychometric properties of the BEST questionnaires for adolescents and for parents
Authors: Keller Ferdinand , Naumann Alexander , Fegert Jörg M.
Published: September 2021

Background

Interest in the assessment of patient satisfaction with in-patient psychiatric treatment has steadily increased and several measurement tools are available for the quantification of patients’ experience. However, they are often uni-dimensional or focus mainly on therapeutic relationship and environment, and neglect other important issues such as information about treatment and participation. The BEST questionnaires were developed as comprehensive instruments that include items on all of the mentioned topics. The present study evaluates the psychometric properties of the BEST in a version for adolescents and for parents. Furthermore, the dimensionality of the satisfaction ratings is analyzed.

Method

Descriptive statistics were applied to data of 1582 adolescents (mean age = 15.0 years, SD = 1.65; 62.4% female) and 1998 parents/guardians assessed in seven in-patient units across Germany. The factorial structure of the BEST questionnaires was determined by exploratory and confirmatory factor analyses, including a bifactor model.

Results

The psychometric quality of the scales was strong. Correlations with another assessment instrument of patient satisfaction were good to high, indicating good convergent validity. Exploratory factor analyses revealed three factors in adolescents that were labelled as: Therapeutic relationship, environment, and general satisfaction and treatment success. For parents, the same three factors could be distinguished. Confirmatory bifactor models suggested that the vast majority of variance was accounted for by the general factor; the three specific factors provided some additional information. Agreement between the subscales of adolescents and their parents was only moderate. Parents were usually more satisfied.

Conclusions

The BEST questionnaires can be considered as reliable and valid instruments to not only assess the “classical” aspects of patient satisfaction, but to also assess newer fundamental topics such as children’s rights and treatment participation. For scientific usage, the total score seems superior because of the high explained variance by the general factor, but the subscale scores provide further information. The use of single items seems advantageous for quality management purposes.