bluuebunny/crossref_metadata_2025 huggingface dataset:
Population segmentation of type 2 diabetes mellitus patients and its clinical applications - a scoping review
Authors: Seng Jun Jie Benjamin , Monteiro Amelia Yuting , Kwan Yu Heng , Zainudin Sueziani Binte , Tan Chuen Seng , Thumboo Julian , Low Lian Leng
Published: March 2021

Background

Population segmentation permits the division of a heterogeneous population into relatively homogenous subgroups. This scoping review aims to summarize the clinical applications of data driven and expert driven population segmentation among Type 2 diabetes mellitus (T2DM) patients.

Methods

The literature search was conducted in Medline®, Embase®, Scopus® and PsycInfo®. Articles which utilized expert-based or data-driven population segmentation methodologies for evaluation of outcomes among T2DM patients were included. Population segmentation variables were grouped into five domains (socio-demographic, diabetes related, non-diabetes medical related, psychiatric / psychological and health system related variables). A framework for PopulAtion Segmentation Study design for T2DM patients (PASS-T2DM) was proposed.

Results

Of 155,124 articles screened, 148 articles were included. Expert driven population segmentation approach was most commonly used, of which judgemental splitting was the main strategy employed (n = 111, 75.0%). Cluster based analyses (n = 37, 25.0%) was the main data driven population segmentation strategies utilized. Socio-demographic (n = 66, 44.6%), diabetes related (n = 54, 36.5%) and non-diabetes medical related (n = 18, 12.2%) were the most used domains. Specifically, patients’ race, age, Hba1c related parameters and depression / anxiety related variables were most frequently used. Health grouping/profiling (n = 71, 48%), assessment of diabetes related complications (n = 57, 38.5%) and non-diabetes metabolic derangements (n = 42, 28.4%) were the most frequent population segmentation objectives of the studies.

Conclusions

Population segmentation has a wide range of clinical applications for evaluating clinical outcomes among T2DM patients. More studies are required to identify the optimal set of population segmentation framework for T2DM patients.
Identifying target behaviors for weight management interventions for women who are overweight during pregnancy and the postpartum period: a qualitative study informed by the Behaviour Change Wheel
Authors: Saarikko Johanna , Niela-Vilén Hannakaisa , Rahmani Amir M. , Axelin Anna
Published: March 2021

Background

Maternal overweight is increasing, and it is associated with several risk factors for both the mother and child. Healthy lifestyle behaviors adopted during pregnancy are likely to impact women’s health positively after pregnancy. The study’s aim was to identify and describe weight management behaviors in terms of the Capability, Opportunity and Motivation Behaviour (COM-B) -model to target weight management interventions from both the perspectives of women who are overweight and maternity care professionals.

Methods

This qualitative, descriptive study was conducted between 2019 and 2020. Individual interviews with pregnant and postpartum women who were overweight (n = 11) and focus group interviews with public health nurses (n = 5) were undertaken in two public maternity clinics in Southwest Finland. The data were analyzed using deductive content analysis consistent with the COM-B model.

Results

In the capability category, the women and the public health nurses thought that there was a need to find consistent ways to approach overweight, as it had often become a feature of the women’s identities. The use of health technology was considered to be an element of antenatal care that could be used to approach the subject of weight and weight management. Smart wearables could also support an evaluation of the women’s lifestyles. The opportunity category highlighted the lack of resources for support during perinatal care, especially after birth. Both groups felt that support from the family was the most important facilitating factor besides motivation. The women also expressed a conflict between pregnancy as an excuse to engage in unhealthy habits and pregnancy as a motivational period for a change of lifestyle. Furthermore, the women wanted to be offered a more robust stance on weight management and discreet counseling.

Conclusions

Our findings offer a theoretical basis on which future research can define intervention and implementation strategies. Such interventions may offer clear advice and non-judgmental support during pregnancy and after delivery by targeting women’s capabilities, opportunities, and motivation. Health technology could be a valuable component of intervention, as well as an implementation strategy, as they provide ways during maternity care to approach this topic and support women.
Inter-rater reliability and test-retest reliability of the Performance and Fitness (PERF-FIT) test battery for children: a test for motor skill related fitness
Authors: Smits-Engelsman Bouwien C. M. , Smit Eline , Doe-Asinyo Rosemary Xorlanyo , Lawerteh Stella Elikplim , Aertssen Wendy , Ferguson Gillian , Jelsma Dorothee L.
Published: March 2021

Background

The Performance and Fitness (PERF-FIT) test battery for children is a recently developed, valid assessment tool for measuring motor skill-related physical fitness in 5 to 12-year-old children living in low-income settings. The aim of this study was to determine: (1) inter-rater reliability and (2) test-retest reliability of the PERF-FIT in children from 3 different countries (Ghana, South Africa and the Netherlands).

Method

For inter-rater reliability 29 children, (16 boys and 13 girls, 6–10 years) were scored by 2 raters simultaneously. For test–retest reliability 72 children, (33 boys and 39 girls, 5–12 years) performed the test twice, minimally 1 week and maximally 2 weeks apart. Relative and absolute reliability indices were calculated. ANOVA was used to examine differences between the three assessor teams in the three countries.

Results

The PERF-FIT demonstrated excellent inter-rater reliability (ICC, 0.99) and good test-retest reliability (ICC, ≥ 0.80) for 11 of the 12 tasks, with a poor ICC for the Jumping item, due to low spread in values. A significant difference between first and second test occasion was present on half of the items, but the differences were small (Cohen’s d 0.01–0.17), except for Stepping, Side jump and Bouncing and Catching (Cohen’s d 0.34, 0.41 and 0.33, respectively). Overall, measurement error, Limits of Agreement and Coefficient of Variation had acceptable levels to support clinical use. No systematic dissimilarities in error were found between first and second measurement between the three countries but for one item (Overhead throw).

Conclusions

The PERF-FIT can reliably measure motor skill related fitness in 5 to 12-year-old children in different settings and help clinicians monitor levels of fundamental motor skills (throwing, bouncing, catching, jumping, hopping and balance), power and agility.
Sagittal abdominal diameter and its socioeconomic correlates: perspective of sex differences
Authors: Li Chang , Harris Marcelline , Tsilimingras Dennis , Liu Sophia Z. , Sheng Ying , Liu Xuefeng
Published: March 2021

Background

Sagittal abdominal diameter (SAD) is an anthropometric index associated with visceral adiposity. It remains unclear whether SAD and its socio-economic correlates differ in women and men, which limits the epidemiological and clinical applications of the SAD measurement. The aims of this study are to examine the sex differences in SAD and its socio-economic correlates.

Methods

A complex stratified multistage clustered sampling design was used to select 6975 men and 7079 women aged 18 years or more from the National Health Nutrition and Examination Survey 2011–2016, representative of the US civilian non-institutionalized population. SAD was measured in accordance to the standard protocols using a two-arm abdominal caliper. The sex differences in SAD and its socio-economic correlates were evaluated by performing weighted independent t tests and weighted multiple regression.

Results

SAD was lower in women than in men in the entire sample, as well as in all the subgroups characterized by age, race, birth place, household income, and body mass index except for non-Hispanic blacks and those with household income < $20,000. Adjusted for other characteristics, age, birth place, household income, and body mass index were associated with SAD in both women and men. Black women were associated with higher SAD then white women (p < .0001), and Hispanic and Asian men were associated with lower SAD than white men (bothp < .01). Women born in other countries were more likely to have lower SAD than women born in the US (p < .0001), and so were men (p = .0118). Both women and men with a household income of <$75,000 had higher SAD than those with an income of over $75,000. The associations of age, race, and household income with SAD differed in women and men.

Conclusion

SAD is lower in women than in men, in the general population as well as in the most socio-economic subgroups. While socio-economic correlates of SAD are similar in women and men, the associations of age, race, and household income with SAD vary across sex.
Socio-economic drivers of drug-resistant tuberculosis in Africa: a scoping review
Authors: Cannon Lesley-Ann Lynnath , Oladimeji Kelechi Elizabeth , Goon Daniel Ter
Published: March 2021

Background

Drug-resistant TB (DR-TB) remains a public health concern due to the high morbidity and mortality rates from the disease. The DR-TB is a multifaceted illness with expensive treatment regimens, toxic medications and most often the long duration of treatment constitutes a substantial financial burden on both infected patients and the health system. Despite significant research advances in the diagnosis and treatment, there is a paucity of synthesized evidence on how socio-economic factors are associated with DR-TB. This review aims to address this gap by synthesizing available evidence and data on the common socio-economic drivers of DR-TB infection in Africa.

Methods

A systematic search was conducted on PUBMED and Google Scholar databases from January 2011 to January 2020 using Joanna Briggs Institute’s scoping review approach. An updated search was conducted on 21 September 2020. The eligibility criteria only included systematic reviews and studies with quantitative research methods (cross-sectional, case-control, cohort, and randomized-control trials). Studies conducted in Africa and focusing on socio-economic factors influencing DR-TB burden in African countries were also considered. Data was extracted from all the studies that met the eligibility criteria based on the study’s objectives.

Results

Out of the 154 articles that were retrieved for review, 20 abstracts of these articles met all the eligibility criteria. Of the 20 articles, 17 quantitative and 3 reviews. Two additional articles were found eligible, following the updated search. The following themes were identified as major findings: Social and economic drivers associated with DR-TB. Substance abuse of which, stigma and discrimination were the prominent social drivers. Economic drivers included poverty, financial constraints because of job loss, loss of productive time during hospital admission and treatment costs.

Conclusion

This review has highlighted which socio-economic factors contribute to DR- TB This is relevant to assist DR-TB management program and TB stakeholders in different settings to address identified socio-economic gaps and to reduce its negative impact on the programmatic management of DR TB. Therefore, redirecting strategies with more focus on socio-economic empowerment of DR-TB patients could be one of the innovative solutions to reduce the spread and eliminate DR-TB in Africa.
Determinants of self-rated health among an older Tibetan population in a Chinese plateau area: analysis based on the conceptual framework for determinants of health
Authors: Li Yajie , Nima Qucuo , Yu Bin , Xiao Xiong , Zeng Peibin , Suolang Deji , He Ruifeng , Ciren Zhuoga , Wangqing Pingcuo , Laba Ciren , Silang Yangzong , Song Ling , Kangzhu Yixi , Li Jingzhong
Published: March 2021

Background

Self-rated health (SRH) has been frequently used in population health surveys. However, most of these studies only focus on specific factors that might directly affect SRH, so only partial or confounding information about the determinants of SRH is potentially obtained. Conducted in an older Tibetan population in a Chinese plateau area, the aim of our study is to assess interrelationships between various factors affecting SRH based on the conceptual framework for determinants of health.

Methods

Between May 2018 and September 2019, 2707 Tibetans aged 50 years or older were recruited as part of the China Multi-Ethnic Cohort Study (CMEC) from the Chengguan District of Lhasa city in Tibet. The information included SRH and variables based on the conceptual framework for determinants of health (i.e., socioeconomic status, health behaviors, physical health, mental health, and chronic diseases). Structural equation modeling (SEM) was used to estimate the direct and indirect effects of multiple factors in the conceptual framework.

Results

Among all participants, 5.54% rated their health excellent, 51.16% very good, 33.58% good, 9.12% fairly poor and 0.59% poor. Physical health (β = − 0.23, P <  0.001), health behaviors (β = − 0.44, P <  0.001), socioeconomic status (β = − 0.29, P <  0.001), chronic diseases (β = − 0.32, P <  0.001) and gender (β = 0.19, P <  0.001) were directly associated with SRH. Socioeconomic status, physical health and gender affected SRH both directly and indirectly. In addition, there are potential complete mediator effects in which age and mental health affect SRH through mediators, such as physical health, health behaviors and chronic diseases.

Conclusions

The findings suggested that interventions targeting behavioral changes, health and chronic disease management should be attached to improve SRH among older populations in plateau areas without ignoring gender and socioeconomic disparities.
Experiences of persons in COVID-19 institutional quarantine in Uganda: a qualitative study
Authors: Ndejjo Rawlance , Naggayi Gloria , Tibiita Ronald , Mugahi Richard , Kibira Simon P. S.
Published: March 2021

Background

Quarantine has been adopted as a key public health measure to support the control of the Coronavirus disease (COVID-19) pandemic in many countries Uganda adopted institutional quarantine for individuals suspected of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to be placed in institutions like hotels and/or hostels of institutions for at least 14 days. This study explored experiences of individuals who underwent institutional quarantine in Uganda to inform measures to increase its effectiveness and reduce its associated negative impact.

Methods

We conducted a qualitative description study using in-depth interviews with 20 purposively selected individuals who had spent time in institutional quarantine facilities. These were mainly phone-based interviews that were audio recorded and transcribed verbatim. Electronic data coding was conducted using Atlas.ti 7 software. Thematic content analysis was used to synthesize the findings with similar codes grouped to form sub-themes and ultimately study themes. The findings are presented thematically with typical participant quotes.

Results

Study participants spent between 14 to 25 days in institutional quarantine. Four themes emerged describing the experiences of study participants during institutional quarantine, which determined whether participants’ experiences were positive or negative. These themes were: quarantine environment including facility related factors and compliance with COVID-19 measures; quarantine management factors of entity paying the costs, communication and days spent in quarantine; individual factors comprising attitude towards quarantine, fears during and post-quarantine and coping mechanisms; and linkage to other services such as health care and post-quarantine follow-up.

Conclusion

The planning, management and implementation of the quarantine process is a key determinant of the experiences of individuals who undergo the measure. To improve the experience of quarantined individuals and reduce its associated negative impact, the pre-quarantine process should be managed to comply with standards, quarantined persons should be provided as much information as possible, their quarantine duration should kept short and costs of the process ought to be minimised. Furthermore, quarantine facilities should be assessed for suitability and monitored to comply with guidelines while avenues for access to healthcare for the quarantined need to be arranged and any potential stigma associated with quarantine thoroughly addressed.
Effects of physical activity on cognitive function among patients with diabetes in China: a nationally longitudinal study
Authors: Bai Anying , Tao Liyuan , Huang Jia , Tao Jing , Liu Jue
Published: March 2021

Background

We aimed to examine the effect of physical activity on different cognitive domains among patients with diabetes.

Methods

We used two waves of data from the Chinese Health and Retirement Longitudinal Study (CHARLS, 2013–2015), a nationally representative dataset of Chinese population aged over 45. Total physical activity scores were calculated based on the International Physical Activity Questionnaire (IPAQ). Executive function and episodic memory were used as measures of cognitive function. We conducted lagged dependent variable models to explore the association between physical activity and cognitive function in full sample as well as two different age groups (45–65, ≥65). Results: 862 diabetic patients were included. We found that diabetic participants who had greater level of physical activity at baseline were associated with better episodic memory function in 2 years (p < 0.05). Moreover, physical activity was significantly associated with less decline in episodic memory in fully adjusted models, and the associations were stronger among patients aged 45–65 years (p < 0.05). No statistically significant association was found between physical activity and executive function in all age groups.

Conclusions

Physical activity may prevent some of the potential decline in episodic memory in diabetic patients. Clinicians and public health departments should strengthen the promotion of physical activity and develop early screening tools among diabetic participants to prevent the progression of cognitive impairment.
Keeping children healthy during and after COVID-19 pandemic: meeting youth physical activity needs
Authors: Pavlovic Andjelka , DeFina Laura F. , Natale Breanna L. , Thiele Shelby E. , Walker Timothy J. , Craig Derek W. , Vint Georgina R. , Leonard David , Haskell William L. , Kohl Harold W.
Published: March 2021

Background

The purpose of this study was to: 1) examine the maintenance of Physical Education and physical activity during the distance learning time, 2) determine the resources educators are utilizing to deliver PE curricula, and 3) understand the challenges experienced by educators during distance learning.

Methods

A survey was sent to a cohort of school-based fitness assessment software users. Respondents were largely school-based individuals including PE teachers (n = 1789), school (n = 62) and district administrators (n = 64), nurses (n = 3), and “other” (n = 522).

Results

Of 2440 respondents, most were from a city or suburb (69.7%), elementary or middle school (72.3%), and had Title 1 status (60.4%), an indicator of low socioeconomic status. Most campuses were closed during the COVID-19 pandemic (97.8%). Of the schools closed during the pandemic, only 2.8% had no prior PE requirements and that increased to 21% during the pandemic. In schools that remained open during the pandemic, 7.7% had no prior PE requirements and this increased to 60.5%. Importantly, 79% of respondents reported that students were either “significantly less” or “somewhat less” physically active during the closure. For closed schools, the most frequently cited challenges included “student access to online learning“, “teacher/student communication” and “teacher remote work arrangements”. For open schools, the most commonly reported challenges included “social distancing”, “access to gymnasium/equipment”, and “concern for personal health and wellbeing”.

Conclusion

The COVID-19 pandemic has caused important reductions in PE requirements and time engaged in physical activity. Challenges experienced by teachers were identified for closed and open schools.
Management of acute Achilles tendon ruptures: a survey of Army orthopaedic surgeons
Authors: Nadig Nischal , Dowd Thomas , Huh Jeannie
Published: March 2021

Background

Despite the literature on acute Achilles tendon ruptures, there remains a lack of consensus regarding the optimal treatment. The purpose of this survey study was to investigate treatment preferences among Army orthopaedic surgeons when presented with a standardized case of an acute Achilles rupture and determine if surgeon factors correlated with treatment preference.

Methods

A hypothetical case of a 37-year-old male with history, physical exam, and imaging consistent with an Achilles rupture was sent to board-certified Army orthopaedic surgeons to determine their preferred management. Demographic data was collected to include: practice setting, years from residency graduation, and completion of fellowship. Correlations analyzed between demographics and treatment preferences.

Results

Sixty-two surgeons responded. 62% of respondents selected surgical intervention. Of these, 59% chose a traditional open technique. 50% of respondents were general orthopaedic. There was a correlation between fellowship training and operative management (P = 0.042). Within the operative management group there was no statistical difference (P > 0.05) in need for further imaging, technique used, post-operative immobilization, length of immobilization, weight-bearing protocol, and time to release to running. The majority of non-operative responders would splint/cast in plantarflexion or CAM boot with heel lift for < 3 weeks (50%) and keep non-weight bearing for < 4 weeks (63%). Only 38% of respondents would use DVT chemoprophylaxis.

Conclusion

When provided with a hypothetic case of an acute Achilles tendon rupture, queried Army orthopaedic surgeons would more often treat with a surgical procedure. This difference in treatment is secondary to training, fellowship or other. This propensity of surgical management, likely stems from the highly active population and the desire to return to duty.
Association of lymph vessel density with occult lymph node metastasis and prognosis in oral squamous cell carcinoma
Authors: Faustino Simone E. S. , Tjioe Kellen C. , Assao Agnes , Pereira Michele C. , Carvalho André L. , Kowalski Luiz P. , Oliveira Denise T.
Published: March 2021

Background

The aims of this study were to determine intra (ILVD) and peritumoral (PLVD) lymphatic vessel density (LVD), and to investigate the relationship of LVD with occult metastasis and prognosis.

Methods

Eighty-seven oral squamous cell carcinomas, in clinical stages I or II, arising in the tongue or floor of the mouth were stained with podoplanin. Lymphatic vessels were quantified in intra and peritumoral areas by sequential analysis and hot spot evaluation. Associations of the ILVD and PLVD with clinicopathologic parameters were determined by Chi-square or Fisher’s exact test. The 5 and 10-year survival rates were calculated by the Kaplan–Meier and compared using the log-rank test.

Results

No significant association was observed between ILVD or PLDV and clinicopathologic variables including occult lymph node metastasis, or clinical follow-up. However, ILVD showed a significant association with regional recurrence (p = 0.040). The perineural invasion was associated with PLVD (p = 0.041). Disease-specific (p = 0.044) and disease-free survivals (p = 0.016) had significant association with PLVD.

Conclusions

The intra or peritumoral lymphatic vessel density had no predictive value for occult lymph node metastasis in the early stages of oral cancer arising in the tongue or floor of mouth.
Reduction of extrinsic tooth stain by a toothpaste containing 10% high cleaning silica, 0.5% sodium phytate and 0.5% sodium pyrophosphate: an 8-week randomised clinical trial
Authors: Liu Hongchun , Tu Jiazhen
Published: March 2021

Objective

To assess the effects for controlling extrinsic tooth stain of a whitening toothpaste containing 10% high cleaning silica, 0.5% sodium phytate and 0.5% sodium pyrophosphate, in comparison with a negative control toothpaste.

Methods

A total of 86 adults who met with the inclusion and exclusion criteria were invited to take part in the study. They were distributed into test and control groups randomly. At baseline, 4 weeks and 8 weeks, the same examiner provided the clinical examinations, including evaluations of oral soft and hard tissues and measurements of tooth stain of the anterior teeth using the Lobene Stain Index. Adverse events and any changes in general health conditions of the patients were monitored.

Results

When the study was completed, comparisons between patients in test and control groups yielded statistically significant differences in Lobene stain adjusted mean area score [0.83 (0.05) vs. 1.13 (0.05)], Lobene stain adjusted mean intensity score [0.99 (0.06) vs. 1.32 (0.06)] and Lobene stain adjusted mean composite score [1.45 (0.13) vs. 2.50 (0.13)] (All, P < 0.001). Patients in the test group exhibited reductions of 26.55%, 25% and 42%, respectively in Lobene stain area, intensity and composite scores, relative to patients in the control group. Comparisons within groups showed that all three Lobene scores at 8 weeks in both groups were lower than those at baseline (All, P < 0.001).

Conclusion

This study demonstrates that 8-week use of a toothpaste containing 10% high cleaning silica, 0.5% sodium phytate and 0.5% sodium pyrophosphate can effectively reduce extrinsic tooth stain.

Trial registration NCT04238429 (before enrollment of the first participant). Data register: March 4, 2018.
Mental health nurses experience of the introduction and practice of the Safewards model: a qualitative descriptive study
Authors: Lee Heather , Doody Owen , Hennessy Therese
Published: March 2021

Background

A lack of safety experienced by patients and staff in acute psychiatric units is a major concern and containment methods used to manage conflict have the potential to cause harm and upset to both staff and patients. To ensure safety for all, it is highly desirable to reduce levels of conflict and containment and the Safewards model is an evidence-based model aimed at reducing conflict and containment rates by improving nurse-patient relationships and safety.

Methods

The aim of this study was to explore mental health nurses’ experience of the introduction and practice of three Safewards interventions; reassurance, soft words and discharge messages. A qualitative descriptive research design utilising a purposive sample (n = 21) of registered psychiatric nurses (n = 16) and managers (n = 5) in an acute psychiatric unit in Ireland. Following a 12-week implementation of Safewards, three focus groups were conducted, two with nursing staff and one with nurse managers. Data were analysed using Braun and Clarke thematic analysis framework which supported the identification of four themes: introducing Safewards, challenges of Safewards, impact of Safewards and working towards success.

Results

The findings indicate that the process of implementation was inadequate in the training and education of staff, and that poor support from management led to poor staff adherence and acceptance of the Safewards interventions. The reported impact of Safewards on nursing practice and patient experience were mixed. Overall, engagement and implementation under the right conditions are essential for success and while some participants perceived that the interventions already existed in practice, participants agreed Safewards enhanced their communication skills and relationships with patients.

Conclusion

The implementation of Safewards requires effective leadership and support from management, mandatory training for all staff, and the involvement of staff and patients during implementation. Future research should focus on the training and education required for successful implementation of Safewards and explore the impact of Safewards on nursing practice and patient experience.
Cost-effectiveness of a stepwise cardiometabolic disease prevention program: results of a randomized controlled trial in primary care
Authors: Stol Daphne M. , Over Eelco A. B. , Badenbroek Ilse F. , Hollander Monika , Nielen Mark M. J. , Kraaijenhagen Roderik A. , Schellevis François G. , de Wit Niek J. , de Wit G. Ardine
Published: March 2021

Background

Cardiometabolic diseases (CMD) are the major cause of death worldwide and are associated with a lower quality of life and high healthcare costs. To prevent a further rise in CMD and related healthcare costs, early detection and adequate management of individuals at risk could be an effective preventive strategy. The objective of this study was to determine long-term cost-effectiveness of stepwise CMD risk assessment followed by individualized treatment if indicated compared to care as usual. A computer-based simulation model was used to project long-term health benefits and cost-effectiveness, assuming the prevention program was implemented in Dutch primary care.

Methods

A randomized controlled trial in a primary care setting in which 1934 participants aged 45–70 years without recorded CMD or CMD risk factors participated. The intervention group was invited for stepwise CMD risk assessment through a risk score (step 1), additional risk assessment at the practice in case of increased risk (step 2) and individualized follow-up treatment if indicated (step 3). The control group was not invited for risk assessment, but completed a health questionnaire. Results of the effectiveness analysis on systolic blood pressure (− 2.26 mmHg; 95% CI − 4.01: − 0.51) and total cholesterol (− 0.15 mmol/l; 95% CI − 0.23: − 0.07) were used in this analysis. Outcome measures were the costs and benefits after 1-year follow-up and long-term (60 years) cost-effectiveness of stepwise CMD risk assessment compared to no assessment. A computer-based simulation model was used that included data on disability weights associated with age and disease outcomes related to CMD. Analyses were performed taking a healthcare perspective.

Results

After 1 year, the average costs in the intervention group were 260 Euro higher than in the control group and differences were mainly driven by healthcare costs. No meaningful change was found in EQ 5D-based quality of life between the intervention and control groups after 1-year follow-up (− 0.0154; 95% CI − 0.029: 0.004). After 60 years, cumulative costs of the intervention were 41.4 million Euro and 135 quality-adjusted life years (QALY) were gained. Despite improvements in blood pressure and cholesterol, the intervention was not cost-effective (ICER of 306,000 Euro/QALY after 60 years). Scenario analyses did not allow for a change in conclusions with regard to cost-effectiveness of the intervention.

Conclusions

Implementation of this primary care-based CMD prevention program is not cost-effective in the long term. Implementation of this program in primary care cannot be recommended.

Trial registration

Dutch Trial Register NTR4277, registered on 26 November 2013
Assessment of Plasmodium falciparum anti-malarial drug resistance markers in pfk13-propeller, pfcrt and pfmdr1 genes in isolates from treatment failure patients in Democratic Republic of Congo, 2018–2019
Authors: Yobi Doudou M. , Kayiba Nadine K. , Mvumbi Dieudonné M. , Boreux Raphael , Kabututu Pius Z. , Situakibanza Hippolyte N. T. , Umesumbu Solange E. , De Mol Patrick , Speybroeck Niko , Mvumbi Georges L. , Hayette Marie-Pierre
Published: March 2021

Background

The national policy for malaria treatment of the Democratic Republic of Congo recommends two first-line artemisinin-based combinations for the treatment of uncomplicated malaria: artesunate-amodiaquine and artemether-lumefantrine. This study investigated the presence of markers associated with resistance to the current first-line artemisinin-based combination therapy (ACT) in isolates of Plasmodium falciparum from treatment failure patients in the Democratic Republic of Congo.

Methods

From November 2018 to November 2019, dried blood spots were taken from patients returning to health centres for fever within 28 days after an initial malaria treatment in six sentinel sites of the National Malaria Control Programme across Democratic Republic of Congo. The new episode of malaria was first detected by a rapid diagnostic test and then confirmed by a real-time PCR assay to define treatment failure. Fragments of interest in pfk13 and pfcrt genes were amplified by conventional PCR before sequencing and the Pfmdr1 gene copy number was determined by a TaqMan real-time PCR assay.

Results

Out of 474 enrolled patients, 364 (76.8%) were confirmed positive by PCR for a new episode of P. falciparum malaria, thus considered as treatment failure. Of the 325 P. falciparum isolates obtained from 364 P. falciparum-positive patients and successfully sequenced in the pfk13-propeller gene, 7 (2.2%) isolates carried non-synonymous mutations, among which 3 have been previously reported (N498I, N554K and A557S) and 4 had not yet been reported (F506L, E507V, D516E and G538S). Of the 335 isolates successfully sequenced in the pfcrt gene, 139 (41.5%) harboured the K76T mutation known to be associated with chloroquine resistance. The SVMNT haplotype associated with resistance to amodiaquine was not found. None of the isolates carried an increased copy number of the pfmdr1 gene among the 322 P. falciparum isolates successfully analysed.

Conclusion

No molecular markers currently known to be associated with resistance to the first-line ACT in use were detected in isolates of P. falciparum from treatment failure patients. Regular monitoring through in vivo drug efficacy and molecular studies must continue to ensure the effectiveness of malaria treatment in Democratic Republic of Congo.
Upregulation of ACE2 and TMPRSS2 by particulate matter and idiopathic pulmonary fibrosis: a potential role in severe COVID-19
Authors: Li Hsin-Hsien , Liu Chen-Chi , Hsu Tien-Wei , Lin Jiun-Han , Hsu Jyuan-Wei , Li Anna Fen-Yau , Yeh Yi-Chen , Hung Shih-Chieh , Hsu Han-Shui
Published: March 2021

Background

Air pollution exposure and idiopathic pulmonary fibrosis (IPF) cause a poor prognosis after SARS-CoV-2 infection, but the underlying mechanisms are not well explored. Angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) are the keys to the entry of SARS-CoV-2. We therefore hypothesized that air pollution exposure and IPF may increase the expression of ACE2 and TMPRSS2 in the lung alveolar region. We measured their expression levels in lung tissues of control non-IPF and IPF patients, and used murine animal models to study the deterioration of IPF caused by particulate matter (PM) and the molecular pathways involved in the expression of ACE2 and TMPRSS2.

Results

In non-IPF patients, cells expressing ACE2 and TMPRSS2 were limited to human alveolar cells. ACE2 and TMPRSS2 were largely upregulated in IPF patients, and were co-expressed by fibroblast specific protein 1 (FSP-1) + lung fibroblasts in human pulmonary fibrotic tissue. In animal models, PM exposure increased the severity of bleomycin-induced pulmonary fibrosis. ACE2 and TMPRSS2 were also expressed in FSP-1+ lung fibroblasts in bleomycin-induced pulmonary fibrosis, and when combined with PM exposure, they were further upregulated. The severity of pulmonary fibrosis and the expression of ACE2 and TMPRSS2 caused by PM exposure were blocked by deletion of KC, a murine homologue of IL-8, or treatment with reparixin, an inhibitor of IL-8 receptors CXCR1/2.

Conclusions

These data suggested that risk of SARS-CoV-2 infection and COVID-19 disease severity increased by air pollution exposure and underlying IPF. It can be mediated through upregulating ACE2 and TMPRSS2 in pulmonary fibroblasts, and prevented by blocking the IL-8/CXCR1/2 pathway.
Next-generation sequencing facilitates differentiating between multiple primary lung cancer and intrapulmonary metastasis: a case series
Authors: Liu Changjiang , Liu Chengang , Zou Xiao , Shao Lin , Sun Ying , Guo Yang
Published: March 2021

Background

In lung cancer management, differential diagnosis between multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IMP) is a critical point that is of direct therapeutic and clinical importance. However, this process often suffers from absence of a gold standard, resulting in equivocal cases. Herein, we present a series of three cases, in which genomic alteration patterns revealed by next-generation sequencing (NGS) facilitated the differential diagnosis between MPLC and IMP.

Case presentation

Case 1 was a 57-year-old female with two separate lesions in the upper lobe and the lower lobe of left lung, which were both histopathologically determined as T2aN0M0 adenocarcinomas. NGS identified an EGFR L858R in one lesion and an EGFR 20 exon insertion in the other one, suggestive of double primary malignancies. The patient underwent wedge resections and received an adjuvant treatment of icotinib and chemotherapy. She had a disease-free survival (DFS) of 19 months and counting. Case 2 was a 55-year-old female with multiple small lesions in both lungs. Histopathological examinations of resected lesions from right upper lobe revealed three subtypes: atypical adenomatous hyperplasia of alveolar epithelium, adenocarcinomas in situ and minimally invasive adenocarcinoma. NGS identified two different BRAF driver mutations G466E and V600_K601delinsE in two lesions of adenocarcinoma in situ, and a BRAF K601E in a lesion of minimally invasive adenocarcinoma. Case 3, a 68-year-old male, had the right upper lobe lesion histophathologically classified as a stage T3NxM0 mixed adenoneuroendocrine carcinoma and the left upper lobe lesion as a stage T1aN0M0 adenocarcinoma. NGS performed with different loci of surgical tissues revealed a rare sensitizing EGFR mutation G719A shared by the right upper lobe lesion and lymph node, and two EGFR mutations L861Q and G719S in left upper lobe lesion. The patient received icotinib treatment postoperatively and achieved a stable disease with a progression-free survival of 5 months.

Conclusion

Our cases provide evidence for utility of NGS in facilitating diagnosis and treatment decisions.
Guided growth in the correction of knee deformity in patients with congenital insensitivity to pain
Authors: Baghdadi Soroush , Saberi Sadegh , Baghdadi Taghi
Published: March 2021

Background

Orthopedic manifestations of congenital insensitivity to pain (CIP) can be devastating if left untreated. Knee deformities are common in patients with CIP and might lead to joint destruction and loss of walking ability. The purpose of the present study was to report the results and complications of guided growth procedures around the knee in patients with CIP.

Methods

In a retrospective review, all patients with CIP who underwent guided growth procedures around the knee from 2009 to 2017 at a tertiary referral hospital were evaluated. Patients with secondary insensitivity to pain (e.g., syringomyelia), as well as patients with incomplete records, were excluded. Demographic data, clinical findings, correction rate, and complications were recorded.

Results

Ten knees in six patients fulfilled the inclusion criteria. The median age was 10 (range, 5–12), with a mean follow-up of 31 months (range, 16–56). Distal femoral tension-band hemiepiphysiodesis was the most common procedure, followed by proximal tibial hemiepiphysiodesis. The mean correction rate was 0.28°/month for femoral deformity. Staples were removed prematurely in one patient due to extrusion. No cases of infection or skin dehiscence were observed. None of the patients needed a reconstructive knee procedure during the study period.

Conclusions

The findings of this study suggest that guided growth procedures might have a role in the correction of knee deformities in patients with CIP. However, the correction rate is lower than that of typically developing children, patients should be closely followed to prevent complications, and stringent patient selection criteria should be followed to ensure success.
Correction to: The lncRNA LAMP5-AS1 drives leukemia cell stemness by directly modulating DOT1L methyltransferase activity in MLL leukemia
Authors: Wang Wen-Tao , Chen Tian-Qi , Zeng Zhan-Cheng , Pan Qi , Huang Wei , Han Cai , Fang Ke , Sun Lin-Yu , Yang Qian-Qian , Wang Dan , Luo Xue-Qun , Sun Yu-Meng , Chen Yue-Qin
Published: March 2021

The original article [1] contains an error in Fig. 6b for the image of western blot panels.
ROS-dependent HIF1α activation under forced lipid catabolism entails glycolysis and mitophagy as mediators of higher proliferation rate in cervical cancer cells
Authors: Castelli Serena , Ciccarone Fabio , Tavian Daniela , Ciriolo Maria Rosa
Published: March 2021

Background

In the last decades, the concept of metabolic rewiring as a cancer hallmark has been expanded beyond the “Warburg effect” and the importance of other metabolic routes, including lipid metabolism, has emerged. In cancer, lipids are not only a source of energy but are also required for the formation of membranes building blocks, signaling and post-translational modification of proteins. Since lipid metabolism contributes to the malignancy of cancer cells, it is an attractive target for therapeutic strategies.

Methods

Over-expression of the adipose triglyceride lipase (ATGL) was used to boost lipid catabolism in cervical cancer cells. The cervical cancer cell line HeLa was employed as the primary experimental model for all subsequent studies. The lipolytic activity of ATGL was mimicked by caproate, a short-chain fatty acid that is efficiently oxidized in mitochondria.

Results

Here, we provide evidence of the association between boosted lipid catabolism and the increased proliferation and migration capability of cervical cancer cells. These pro-tumoral effects were ascribed to the reactive oxygen species (ROS)-mediated induction of hypoxia-inducible factor-1α (HIF1α) triggered by the increased mitochondrial fatty acids (FAs) oxidation. HIF1α activation increases glycolytic flux and lactate production, promoting cell proliferation. At the same time, HIF1α increases protein and mRNA levels of its known target BCL2 and adenovirus E1B 19-kDa-interacting protein 3 (BNIP3), which in turn activates mitophagy as a pro-survival process, as demonstrated by the induction of apoptosis upon inhibition of mitophagy. These effects were mimicked by the short-chain fatty acid caproate, confirming that forcing lipid catabolism results in HIF1α induction.

Conclusions

Boosting lipid catabolism by ATGL over-expression has a pro-tumor role in cervical cancer cells, dependent on ROS production and HIF1α induction. Together with the bioinformatics evidence of the correlation of ATGL activity with the aggressiveness of cervical cancer cells, our data suggest that ATGL could be a promising prognostic marker for cervical cancer and highlight the need of further investigations on the role of this lipase in cancer cells. This evidence could be exploited to develop new personalized therapy, based on the functionality of the antioxidant equipment of cancer cells, considering that ROS content could affect ATGL role.
Evaluation of whole-body modalities for diagnosis of multifocal osteonecrosis—a pilot study
Authors: Yokota Shunichi , Sakamoto Keita , Shimizu Yukie , Asano Tsuyoshi , Takahashi Daisuke , Kudo Kohsuke , Iwasaki Norimasa , Shimizu Tomohiro
Published: March 2021

Background

This study aimed to investigate the ability of whole-body bone scintigraphy (WB-BS) in the detection of multifocal osteonecrosis (ON) compared to whole-body magnetic resonance imaging (WB-MRI) and to clarify the characteristics of patients with multifocal ON among those with ON of the femoral head (ONFH) using WB-MRI.

Methods

Forty-six patients who had symptomatic ONFH and underwent surgery in our hospital from April 2019 to October 2020 were included in the study. Data on patient demographics, including age, sex, body mass index (BMI), history of corticosteroid intake, alcohol abuse, smoking, and symptomatic joints, were collected from their medical records. All patients underwent WB-MRI and WB-BS before surgery.

Results

The agreement in the detection of ON by WB-MRI vs the uptake lesions by WB-BS in the hip joints was moderate (κ = 0.584), while that in other joints was low (κ < 0.40). Among the 152 joints with ON detected by WB-MRI, 92 joints (60.5%) were symptomatic, and 60 joints (39.5%) were asymptomatic. Twelve out of the 46 (26.0%) patients had multifocal (three or more distinct anatomical sites) ON. Nonetheless, while WB-BS detected symptomatic ON detected by WB-MRI as uptake lesions in 82.6% (76/92) of the joints, asymptomatic ON detected by WB-MRI was detected as uptake lesions in 21.7% (13/60) of the joints. All patients with multifocal ON had a history of steroid therapy, which was significantly higher than that in patients with oligofocal ON (P = 0.035). The patients with a hematologic disease had multifocal ON at a higher rate (P = 0.015).

Conclusions

It might be difficult for WB-BS to detect the asymptomatic ON detected by WB-MRI compared to symptomatic ON. Considering the cost, examination time, and radiation exposure, WB-MRI might be useful for evaluating multifocal ON. Larger longitudinal studies evaluating the benefits of WB-MRI for detecting the risk factors for multifocal ON are required.
Emerging role of 18F-FDG PET/CT in Castleman disease: a review
Authors: Koa Benjamin , Borja Austin J. , Aly Mahmoud , Padmanabhan Sayuri , Tran Joseph , Zhang Vincent , Rojulpote Chaitanya , Pierson Sheila K. , Tamakloe Mark-Avery , Khor Johnson S. , Werner Thomas J. , Fajgenbaum David C. , Alavi Abass , Revheim Mona-Elisabeth
Published: March 2021

Castleman disease (CD) describes a group of rare hematologic conditions involving lymphadenopathy with characteristic histopathology and a spectrum of clinical abnormalities. CD is divided into localized or unicentric CD (UCD) and multicentric CD (MCD) by imaging. MCD is further divided based on etiological driver into human herpesvirus-8-associated MCD, POEMS-associated MCD, and idiopathic MCD. There is notable heterogeneity across MCD, but increased level of pro-inflammatory cytokines, particularly interleukin-6, is an established disease driver in a portion of patients. FDG-PET/CT can help determine UCD versus MCD, evaluate for neoplastic conditions that can mimic MCD clinico-pathologically, and monitor therapy responses. CD requires more robust characterization, earlier diagnosis, and an accurate tool for both monitoring and treatment response evaluation; FDG-PET/CT is particularly suited for this. Moving forward, future prospective studies should further characterize the use of FDG-PET/CT in CD and specifically explore the utility of global disease assessment and dual time point imaging.

Trial registrationClinicalTrials.gov, NCT02817997, Registered 29 June 2016,https://clinicaltrials.gov/ct2/show/NCT02817997