bluuebunny/crossref_metadata_2025 huggingface dataset:
Missed opportunities for HIV testing in patients newly diagnosed with HIV in Morocco
Authors: Marih Latifa , Sawras Victoire , Pavie Juliette , Sodqi Mustapha , Malmoussi Mourad , Tassi Noura , Bensghir Rajaa , Nani Samira , Lahsen Ahd Oulad , Laureillard Didier , El Filali Kamal Marhoum , Champenois Karen , Weiss Laurence
Published: January 2021

Background

In Morocco, of the estimated 29,000 people living with HIV in 2011, only 20% were aware of their HIV status. More than half of diagnoses were at the AIDS stage. We assumed that people who were unaware of their infection had contacts with the healthcare system for HIV indicators that might prompt the healthcare provider to offer a test. The aim was to assess missed opportunities for HIV testing in patients newly diagnosed with HIV who accessed care in Morocco.

Methods

A cross-sectional study was conducted in 2012–2013 in six Moroccan HIV centers. Participants were aged ≥18, and had sought care within 6 months after their HIV diagnosis. A standardized questionnaire administered during a face-to-face interview collected the patient’s characteristics at HIV diagnosis, HIV testing and medical history. Contacts with care and the occurrence of clinical conditions were assessed during the 3 years prior to HIV diagnosis. Over this period, we assessed whether healthcare providers had offered HIV testing to patients with HIV-related clinical or behavioral conditions.

Results

We enrolled 650 newly HIV-diagnosed patients (median age: 35, women: 55%, heterosexuals: 81%, diagnosed with AIDS or CD4 < 200 cells/mm3: 63%). During the 3 years prior to the HIV diagnosis, 71% (n = 463) of participants had ≥1 contact with the healthcare system. Of 323 people with HIV-related clinical conditions, 22% did not seek care for them and 9% sought care and were offered an HIV test by a healthcare provider. The remaining 69% were not offered a test and were considered as missed opportunities for HIV testing. Of men who have sex with men, 83% did not address their sexual behavior with their healthcare provider, 11% were not offered HIV testing, while 6% were offered HIV testing after reporting their sexual behavior to their provider.

Conclusions

Among people who actually sought care during the period of probable infection, many opportunities for HIV testing, based on at-risk behaviors or clinical signs, were missed. This highlights the need to improve the recognition of HIV clinical indicators by physicians, further expand community-based HIV testing by lay providers, and implement self-testing to increase accessibility and privacy.
The transition to Xpert MTB/RIF ultra: diagnostic accuracy for pulmonary tuberculosis in Kampala, Uganda
Authors: Andama A. , Jaganath D. , Crowder R. , Asege L. , Nakaye M. , Katumba D. , Mukwatamundu J. , Mwebe S. , Semitala C. F. , Worodria W. , Joloba M. , Mohanty S. , Somoskovi A. , Cattamanchi A.
Published: January 2021

Background

The World Health Organization (WHO) has endorsed the next-generation Xpert MTB/RIF Ultra (Ultra) cartridge, and Uganda is currently transitioning from the older generation Xpert MTB/RIF (Xpert) cartridge to Ultra as the initial diagnostic test for pulmonary tuberculosis (TB). We assessed the diagnostic accuracy of Ultra for pulmonary TB among adults in Kampala, Uganda.

Methods

We sampled adults referred for Xpert testing at two hospitals and a health center over a 12-month period. We enrolled adults with positive Xpert and a random 1:1 sample with negative Xpert results. Expectorated sputum was collected for Ultra, and for solid and liquid culture testing for Xpert-negative patients. We measured sensitivity and specificity of Ultra overall and by HIV status, prior history of TB, and hospitalization, in reference to Xpert and culture results. We also assessed how classification of results in the new “trace” category affects Ultra accuracy.

Results

Among 698 participants included, 211 (30%) were HIV-positive and 336 (48%) had TB. The sensitivity of Ultra was 90.5% (95% CI 86.8–93.4) and specificity was 98.1% (95% CI 96.1–99.2). There were no significant differences in sensitivity and specificity by HIV status, prior history of TB or hospitalization. Xpert and Ultra results were concordant in 670 (96%) participants, with Ultra having a small reduction in specificity (difference 1.9, 95% CI 0.2 to 3.6,p=0.01). When “trace” results were considered positive for all patients, sensitivity increased by 2.1% (95% CI 0.3 to 3.9,p=0.01) without a significant reduction in specificity (− 0.8, 95% CI − 0.3 to 2.0,p=0.08).

Conclusions

After 1 year of implementation, Ultra had similar performance to Xpert. Considering “trace” results to be positive in all patients increased case detection without significant loss of specificity. Longitudinal studies are needed to compare the benefit of greater diagnoses to the cost of overtreatment.
A deep learning model for diagnosing dystrophinopathies on thigh muscle MRI images
Authors: Yang Mei , Zheng Yiming , Xie Zhiying , Wang Zhaoxia , Xiao Jiangxi , Zhang Jue , Yuan Yun
Published: January 2021

Background

Dystrophinopathies are the most common type of inherited muscular diseases. Muscle biopsy and genetic tests are effective to diagnose the disease but cost much more than primary hospitals can reach. The more available muscle MRI is promising but its diagnostic results highly depends on doctors’ experiences. This study intends to explore a way of deploying a deep learning model for muscle MRI images to diagnose dystrophinopathies.

Methods

This study collected 2536 T1WI images from 432 cases who had been diagnosed by genetic analysis and/or muscle biopsy, including 148 cases with dystrophinopathies and 284 cases with other diseases. The data was randomly divided into three sets: the data from 233 cases were used to train the CNN model, the data from 97 cases for the validation experiments, and the data from 102 cases for the test experiments. We also validated our models expertise at diagnosing by comparing the model’s results on the 102 cases with those of three skilled radiologists.

Results

The proposed model achieved 91% (95% CI: 0.88, 0.93) accuracy on the test set, higher than the best accuracy of 84% in radiologists. It also performed better than the skilled radiologists in sensitivity : sensitivities of the models and the doctors were 0.89 (95% CI: 0.85 0.93) versus 0.79 (95% CI:0.73, 0.84; p = 0.190).

Conclusions

The deep model achieved excellent accuracy and sensitivity in identifying cases with dystrophinopathies. The comparable performance of the model and skilled radiologists demonstrates the potential application of the model in diagnosing dystrophinopathies through MRI images.
Mild cognitive impairment in novel SPG11 mutation-related sporadic hereditary spastic paraplegia with thin corpus callosum: case series
Authors: Li Chuan , Yan Qi , Duan Feng-ju , Zhao Chao , Zhang Zhuo , Du Ying , Zhang Wei
Published: January 2021

Background

SPG11 mutation-related autosomal recessive hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is the most common cause in complicated forms of HSP, usually presenting comprehensive mental retardation on early-onset stage preceding spastic paraplegias in childhood. However, there are many instances of sporadic late-onset HSP-TCC cases with a negative family history, and potential mild cognitive deficits in multiple domains may be easily neglected and inaccurately described.

Methods

In this study, we performed next generation sequencing in four sporadic late-onset patients with HSP-TCC, and combined Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) to evaluate cognition of the patients.

Results

By evolutionary conservation and structural modeling analysis, we have revealed 4 novel pathogenic SPG11 mutations, and firstly confirmed mild cognitive impairment (MCI) with normal MMSE scores (≥27) and decreased MoCA scores (< 26) in these SPG11 mutation-related HSP-TCC patients, predominantly presenting impairment of executive function, delayed recall, abstraction and language.

Conclusions

The results expand the mutational spectrum of SPG11-associated HSP-TCC from sporadic cases, and confirm MCI with combination of decreased MoCA and normal MMSE assessment, suggesting that clinicians should consider doing a MoCA to detect MCI in patients with HSP, particularly those with HSP-TCC.
Associations between first-trimester intrauterine hematoma and twin pregnancy outcomes: a retrospective cohort study
Authors: Ji Wanqing , Hou Bo , Li Weidong , Guo Fang , He Ping , Zheng Jie
Published: January 2021

Background

In recent years, first-trimester intrauterine hematoma (IUH) has become increasingly common in twin pregnancy. The majority of studies on IUH have excluded twin pregnancies, and others did not differentiate between singleton and twin pregnancies. The impact of IUH on twin pregnancy is unclear. Therefore, the primary objective of our study was to examine associations between first-trimester IUH and pregnancy outcomes in twin pregnancies.

Methods

The data of 1020 twin pregnancies in women who received a routine examination from January 2014 to December 2018 were reviewed. We compared baseline data and pregnancy outcomes between those with and without IUH. Multivariable logistic regression analysis was used to adjust for possible confounding factors.

Results

A total of 209 patients (21.3%) developed IUH in the first trimester. First-trimester IUH was significantly associated with increased odds of miscarriage (adjusted odds ratio 14.27, 95% CI 8.25–24.70) and vanishing twin syndrome (adjusted odds ratio 3.26, 95% CI 1.11–4.61). However, there were no differences in the rates of stillbirth, preeclampsia, preterm labor (< 34 weeks), low birth weight, postpartum hemorrhage or fetal distress between the two groups. Maternal age, previous preterm birth, chorionicity in twins and the gestational week at first ultrasound did not differ between the two groups. The women with IUH had high rates of previous miscarriage (46.73% vs 38.37%, p = 0.01), assisted conception (48.56% vs 32.60%, p < 0.001) and accompanied vaginal bleeding (67.46% vs 13.43%, p < 0.001). According to the logistic regression analyses, these characteristics were not associated with pregnancy loss or vanishing twin syndrome. No IUH characteristics, including volume, largest diameter, or the presence of vaginal bleeding, were associated with pregnancy loss or vanishing twin syndrome before 20 weeks of gestation (P > 0.05).

Conclusion

In women with twin pregnancy, the presence of IUH in the first trimester was associated with the loss of one or both fetuses before 20 weeks of gestation. However, previous miscarriage, the conception method, the IUH size and the presence of vaginal bleeding were not independently associated with miscarriage or vanishing twin syndrome.
Current lung cancer screening guidelines may miss high-risk population: a real-world study
Authors: Ji Guiyi , Bao Ting , Li Zhenzhen , Tang Huairong , Liu Dan , Yang Ping , Li Weimin , Huang Yan
Published: January 2021

Background

Despite much research published on lung cancer screening, China has had no large-scale study on the missed diagnosis of lung cancer in a health examination population. We therefore did a real-world study using the current lung cancer screening guidelines to a health examination population in China to determine the proportion of lung cancer cases that have been missed.

Methods

A real-world cohort study of screening, with the use of low-dose computed tomography, was conducted among people who took yearly health checkup in health management center of West China Hospital between 2006 and 2017. We respectively used current guidelines including lung cancer screening guidelines of the U.S. Preventive Services Task Force (USPSTF) and expert consensus on low dose spiral CT lung cancer screening in China.

Results

In a total of 15,996 participants with health examination who completed the baseline screening, 6779 (42.4%) subjects had at least one positive finding, and 142 (2.1%) cases of lung cancer were screened positive. The false positive rate was 97.9%. Of 142 lung cancer cases detected in our study, only 9.2% met the lung cancer screening guidelines proposed by the USPSTF, and 24.4% met that of China. The rates of missed diagnosis were as high as 90.8 and 75.6% respectively. In addition, we did an in-depth analysis by gender. We found that among male patients with lung cancer, the proportion of smokers was 75%, and the proportion of young people under 50 was 23.2%. Among female patients with lung cancer, the proportion of smokers was only 5.8%, and the proportion of young people under 50 was up to 33.3%.

Conclusions

The rate of missed diagnosis was as high as 90.8% applying the current lung cancer screening guidelines to the health examination population in China. Further study to determine screening guidelines for targeted populations, is warranted.
Comparison of epidermal growth factor receptor tyrosine kinase inhibitors for patients with lung adenocarcinoma harboring different epidermal growth factor receptor mutation types
Authors: Park Sojung , Lee Sung Yong , Kim Dojin , Sim Yun Su , Ryu Jeong-Seon , Choi Juwhan , Lee Su Hwan , Ryu Yon Ju , Lee Jin Hwa , Chang Jung Hyun
Published: January 2021

Background

Epidermal growth factor receptor (EGFR) mutations in non–small-cell lung cancer predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs). EGFR mutation types are associated with efficacy of EGFR TKIs. We investigated the clinical outcomes of afatinib, erlotinib, and gefitinib according to EGFR mutation type in patients with lung adenocarcinoma.

Methods

Between May 2010 and December 2018, we investigated 363 patients with advanced lung adenocarcinoma harboring EGFR mutations who received EGFR TKIs. Efficacies of EGFR TKIs such as response rate, progression-free survival (PFS), and overall survival (OS) were retrospectively evaluated according to exon 19 deletion (E19del), L858R point mutation (L858R) and uncommon mutations.

Results

The frequency of E19del was 48.2%, that of L858R was 42.4%, and that of uncommon mutations was 9.4%. E19del and L858R were associated with superior PFS and OS compared with uncommon mutations. Erlotinib showed significantly inferior OS than other TKIs (30.8 ± 3.3 in erlotinib vs. 39.1 ± 4.3 in afatinib vs. 48.4 ± 6.3 in gefitinib; p = 0.031) in patients with L858R. Gefitinib showed significantly inferior PFS (4.6 ± 1.1 in gefitinib vs. 11.6 ± 2.7 in afatinib vs. 10.6 ± 2.7 in erlotinib; p = 0.049) in patients with uncommon mutations.

Conclusion

Afatinib was significantly associated with a longer PFS, presenting constant effectiveness in all EGFR mutation types. Caution may be needed on the use of erlotinib for L858R and the use of gefitinib for uncommon EGFR mutations.
Adverse childhood experiences and maternal anxiety and depression: a meta-analysis
Authors: Racine Nicole , Devereaux Chloe , Cooke Jessica E. , Eirich Rachel , Zhu Jenney , Madigan Sheri
Published: January 2021

Background

It has been proposed that adverse childhood experiences (ACEs) can put women at risk for mental illness in the pregnancy and postpartum periods. While some studies have found strong support for this proposition, others have found weak or no support. This study is a meta-analysis of the association between ACEs and maternal mental health to resolve between-study discrepancies, and to examine potential moderators of associations.

Methods

Three electronic databases (i.e., MEDLINE, Embase, and PsycINFO) were searched up to November 2018 by a health sciences librarian. A hand search was conducted in January 2020 and relevant studies were added. Included studies reported on associations between ACEs and maternal depression and/or anxiety in the perinatal period (pregnancy to 1-year postpartum). Pregnancy and postpartum outcomes were examined separately for both depression and anxiety. Random-effect meta-analyses were conducted. Moderator analyses were conducted using meta-regression. Study quality was evaluated using a 15-point scale.

Results

The initial search yielded 4646 non-duplicate records and full text review occurred for 196 articles. A total of 15 studies (N = 7788) were included in the meta-analyses, of which 2 were also described narratively. Publication year ranged from 1998 to 2019. Mothers were approximately 28.93 years of age when they retrospectively reported on their ACEs. All studies had maternal self-report questionnaires for the mental health outcomes. Study quality ranged from 7 to 12. The pooled effect sizes between ACEs and prenatal (N = 12; r = .19; 95% CI= .13, .24) and postpartum (N = 7; r = .23; 95% CI = .06 to .39) depressive symptoms were significant. The pooled effect size between ACEs and prenatal anxiety was also significant (N = 5; r = .14; 95% CI= .07, .21). Moderator analyses indicated that timing of depressive and anxiety symptoms may be important for understanding associations.

Conclusions

ACEs confer risk to maternal mental health, albeit effect sizes are small to moderate in magnitude. Trauma-informed approaches, as well as increased mental health support during and after pregnancy, may help to offset the relative risk of ACEs on maternal mental health.
Effects of the Active Kids voucher program on children and adolescents’ physical activity: a natural experiment evaluating a state-wide intervention
Authors: Foley Bridget C. , Owen Katherine B. , Bauman Adrian E. , Bellew William , Reece Lindsey J.
Published: January 2021

Background

There is an urgent need for scaled-up effective interventions which overcome barriers to health-enhancing physical activity for children and adolescents. In New South Wales (NSW), Australia, the state government implemented a universal voucher program, ‘Active Kids’ to support the cost of structured physical activity registration for school-enrolled children aged 4.5–18 years old. The objective of this study was to understand the effects a financial incentive intervention delivered in a real-world setting has on children and adolescent’s physical activity participation.

Method

In 2018, all children and adolescents registered for an Active Kids voucher provided sociodemographic characteristics, physical activity and research consent. This prospective cohort study used an online survey with validated items to measure physical activity and other personal and social factors in children and adolescents who used an Active Kids voucher. Generalized linear mixed models were used to examine changes from registration to after voucher use at ≤8 weeks, 9–26 weeks and ≥ 6 months.

Results

Study participants reported increasing their days achieving physical activity guidelines from 4.0 days per week (95%CI 3.8, 4.2) at registration (n = 37,626 children) to 4.9 days per week (95%CI 4.7, 5.1) after 6 months (n = 14,118 children). Increased physical activity was observed for all sociodemographic population groups. The voucher-specific activity contributed 42.4% (95%CI 39.3, 45.5) to the total time children participated in structured physical activities outside of school. Children and adolescents who increased to, or maintained, high levels of activity were socially supported to be active, had active parent/caregivers, had better concentration and were overall happier than their low-active counterparts.

Conclusion

The Active Kids program significantly increased children’s physical activity levels and these increases continued over a six-month period. The Active Kids voucher program shows promise as a scaled-up intervention to increase children and adolescents’ physical activity participation.

Trial registration

Australian New Zealand Clinical Trial RegistryACTRN12618000897268, approved May 29th, 2018 - Retrospectively registered.
Can a multi-level intervention approach, combining behavioural disciplines, novel technology and incentives increase physical activity at population-level?
Authors: Chew Ling , Tavitian-Exley Isabel , Lim Nicole , Ong Alice
Published: January 2021

Background

Despite a global call for action and growing burden of non-communicable diseases (NCD) associated with physical inactivity, effective interventions to increase community-wide physical activity (PA) remain few. NCDs accounted for 80% of Singapore’s disease burden (2015) and yet 40% of Singaporeans did not meet minimum recommended weekly PA despite evidence of the benefits to cardiorespiratory health, diabetes and cancer prevention.

Methods

A large-scale public health intervention was initiated in 2015 to increase population-level PA through incidental daily walking. Intervention components included fitness trackers, redeemable rewards and gamification, implemented in a mutually-reinforcing manner within an eco-system supportive of PA and informed by real-time data analytics. Mean daily step count at baseline and post-intervention were compared across periods, and the influence of participant sub-groups characteristics on overall results, using significance tests. Standards for Reporting on Implementation Studies (StaRI) were adhered to.

Results

Intervention reach increased fourfold from 129,677 participants in wave 1 (2015–16) to 690,233 in wave 3 (2017–18) amounting to a total of 1,184,410 Step Challenge participations. Mean days of fitness tracker use increased from 2.4 to 5.0 days/week among participants completing the Challenge in wave 1 and from 5.3 to 6.0 days/week in wave 3. The mean number of daily steps between pre-Challenge and Challenge periods increased by 4163 (sd=1360; p< 0.001) in wave 1, by 2242 (sd=334; p< 0.001) in wave 2 and by 1645 steps/day (sd=54; p< 0.001) in wave 3. Mean daily step increases between wave 1 and 3 also suggest that incidental PA was maintained, a finding supported by a 2017 national population survey showing that incidental PA among adults increased from 5% in 2010 to 14% in 2017 while moderate-intensity PA increased from 5 to 10% over the same period.

Conclusion

Population-level PA was effectively increased through multi-level interventions integrating technology, behavioural economics, gamification, marketing, communications and community linkages within a supportive context- and climate-appropriate environment. Responsive data analytics were instrumental to strengthen implementation by tailoring modalities that maximise effectiveness at population-level. Further analyses are needed to explore potential barriers, challenges or unmet needs in sub-groups with lower uptake to tailor future interventions for greater reach and impact.
Toward patient-centered tuberculosis preventive treatment: preferences for regimens and formulations in Lima, Peru
Authors: Yuen Courtney M. , Millones Ana K. , Galea Jerome T. , Puma Daniela , Jimenez Judith , Lecca Leonid , Becerra Mercedes C. , Keshavjee Salmaan
Published: January 2021

Background

To ensure patient-centered tuberculosis preventive treatment, it is important to consider factors that make it easier for patients to complete treatment. However, there is little published literature about patient preferences for different preventive treatment regimen options, particularly from countries with high tuberculosis burdens.

Methods

We conducted a qualitative research study using a framework analysis approach to understand tuberculosis preventive treatment preferences among household contacts. We conducted three focus group discussions with 16 members of families affected by tuberculosis in Lima, Peru. Participants were asked to vote for preferred preventive treatment regimens and discuss the reasons behind their choices. Coding followed a deductive approach based on prior research, with data-driven codes added.

Results

In total, 7 (44%) participants voted for 3 months isoniazid and rifapentine, 4 (25%) chose 3 months isoniazid and rifampicin, 3 (19%) chose 4 months rifampicin, and 2 (13%) chose 6 months isoniazid. Preferences for shorter regimens over 6 months of isoniazid were driven by concerns over “getting tired” or “getting bored” of taking medications, the difficulty of remembering to take medications, side effects, and interference with daily life. For some, weekly dosing was perceived as being easier to remember and less disruptive, leading to a preference for 3 months isoniazid and rifapentine, which is dosed weekly. However, among caregivers, having a child-friendly formulation was more important than regimen duration. Caregivers reported difficulty in administering pills to children, and preferred treatments available as syrup or dispersible formulations.

Conclusions

There is demand for shorter regimens and child-friendly formulations for tuberculosis preventive treatment in high-burden settings. Individual preferences differ, suggesting that patient-centered care would best be supported by having multiple shorter regimens available.
Developing a framework for cash transfer programs that foster sustained economic empowerment to reduce sexual risk among adolescent girls and young women: a qualitative study
Authors: Gangaramany Alok , Balvanz Peter , Gichane Margaret Waruguru , Goetschius Stephan , Sharma Saransh , Sharma Krittika , Mulhausen Jeff , Noble-Campbell Paul , Wamoyi Joyce , Maman Suzanne , Prasad Ram
Published: January 2021

Background

Transactional sexual relationships contribute to a high incidence of HIV infection among adolescent girls and young women (AGYW) living in low-resource settings. Cash transfers (CT) are a structural approach to reduce sexual risk behaviors, but their positive economic effects frequently fade after the program ends. We aimed to understand AGYW’s decision-making processes related to sexual, relationship, and financial decisions, in order to design a framework for a CT program that could lead to long-term financial independence and reduced transactional sex among AGYW.

Methods

We conducted qualitative research with AGYW participating in a CT program in Tanzania. Phase one was formative research to understand the context and experiences of AGYW regarding sexual behavior, relationships, and finances. Participants included 36 AGYW (15–23 years old), 15 influencers of AGYW (mothers and male partners) and 10 financially empowered women (FEW – women aged 20–30 with a sustained, reliable source of income independent of their partner). Decisions and decision-making contexts of AGYW that we identified in phase one informed the content of phase two. In phase two we simulated scenarios for decision-making and economic goals with 80 AGYW and 40 FEW, in order to identify key principles or intervention opportunities to guide development of a CT program framework.

Results

Through phases one and two of our research we identified three key themes in AGYW’s vision of their desired future economic state: 1) positive social image, 2) power balance and respect, and 3) emotional and economic security. An important theme distinguishing AGYW from FEW was that AGYW lacked a vision to build self-agency.

Conclusions

Our findings suggest that providing economic resources to AGYW through CT without ensuring self-agency is unlikely to be an effective long-term intervention for economic empowerment. Using these findings we developed a framework for CT programs with three key pillars for developing self-agency: 1) emotional efficacy, to increase AGYW’s perception of rewards associated with developing self-agency; 2) social efficacy, to build constructive relationships and exit negative relationships that inhibit self-agency, and 3) economic efficacy, to help AGYW build a resilient stream of financial resources.
Anxiety amongst physicians during COVID-19: cross-sectional study in Pakistan
Authors: Mahmood Qaisar Khalid , Jafree Sara Rizvi , Jalil Aisha , Nadir Syed Mujtaba Hasnain , Fischer Florian
Published: January 2021

Background

Ensuring safety and wellbeing of healthcare providers is crucial, particularly during times of a pandemic. In this study, we aim to identify the determinants of anxiety in physicians on duty in coronavirus wards or quarantine centers.

Methods

We conducted a cross-sectional quantitative survey with an additional qualitative item. Five constructs of workload, exhaustion, family strain, feeling of protection, and anxiety were measured using items from two validated tools. Modifications were made for regional relevance. Factor analysis was performed showing satisfactory Cronbach alpha results. Overall, 103 physicians completed the questionnaire.

Results

T-test results revealed significant associations between gender and anxiety. Structural equation modeling identified that high workload contributed to greater exhaustion (β = 0.41, R2 = 0.17,p < 0.001) and greater family strain (β = 0.47, R2 = 0.22,p < 0.001). Exhaustion (β = 0.17,p < 0.005), family strain (β = 0.34,p < 0.001), and feelings of protection (β = − 0.30,p < 0.001) significantly explained anxiety (R2 = 0.28). Qualitative findings further identified specific needs of physicians with regard to protective equipment, compensation, quarantine management, resource allocation, security and public support, governance improvement, and health sector development.

Conclusions

It is imperative to improve governmental and social support for physicians and other healthcare providers during the corona pandemic. Immediate attention is needed to reduce anxiety, workload, and family strain in frontline practitioners treating coronavirus patients, and to improve their (perceptions of) protection. This is a precondition for patient safety.
Correction to: Impact of reducing the duration of antibiotic treatment on the long-term prognosis of community acquired pneumonia
Authors: Uranga Ane , Artaraz Amaia , Bilbao Amaia , Quintana Jose María , Arriaga Ignacio , Intxausti Maider , Lobo Jose Luis , García Julia Amaranta , Camino Jesus , España Pedro Pablo
Published: January 2021

An amendment to this paper has been published and can be accessed via the original article.
The IlluminOss® photodynamic bone stabilization system for pathological osteolyses and fractures of the humerus: indications, advantages and limits in a series of 12 patients at 24 months of minimum follow‐up
Authors: Zoccali Carmine , Attala Dario , Pugliese Mattia , di Uccio Alessandra Scotto , Baldi Jacopo
Published: January 2021

Background

Locked titanium nails are considered the reference treatment for metastatic bone lesions of the humerus in patients with aggressive histotypes, high risk of fracture or when estimated survival is lower than 6 months.Nevertheless, they are responsible for CT and MRI artifacts which interfere with postoperative radiotherapy and follow-up.The IlluminOss® is an intramedullary stabilization system which is introduced inside the humeral canal in a deflated state, and is then distended with a monomer which hardens after exposure to blue light,stabilizing the segment; it does not cause artifacts, allowing easier and more effective radiotherapy and follow-up.

The aim of this study is to report our experience, indications, possible advantages and limitations of this stabilization system at 24 months of minimum follow-up in a series of 12 patients affected by pathological fractures or impending fractures of the humerus.

Methods

This is a retrospective case-series that included all patients who underwent surgery with the IlluminOss® Photodynamic Bone Stabilization System for pathological osteolyses and fractures of the humerus. Intraoperative and postoperative complications were valued.

Results

12 patients and 13 procedures were included in the study. All surgeries were performed without intraoperative complications. No early postoperative complications were noted. The wounds healed in all cases and stitches were removed at two weeks from surgery, so the patients were able to perform chemotherapy after three weeks. All patients except one had a painless active range of motion which reached 90°.The VAS score was 7 preoperatively and 2.6 at one month from surgery. Pain relief was also associated to radiotherapy and chemotherapy.

Unfortunately, two nail ruptures were reported at 4 and 12 months of follow-up.

No artifacts were noted in the postoperative CT scans so the radiotherapy plans were easily performed without the need of dose compensation.

Conclusions

The IlluminOss® intramedullary stabilization system can provide primary stability in humeral fractures and impending fractures;the surgical technique is easy and minimally invasive.Moreover,it does not present artifacts at postoperative imaging,probably giving a better chance to perform prompt radiotherapy and chemotherapy.However, randomized clinical studies are necessary to verify its potential strength and if precocious adjuvant radio- and chemotherapy are associated to a reduction of the local progression rate.
Positive airway pressure therapy for obstructive sleep apnea in patients with Osteogenesis imperfecta: a prospective pilot study
Authors: Arponen Heidi , Bachour Adel , Bäck Leif , Valta Helena , Mäkitie Antti , Mäkitie Outi , Waltimo-Sirén Janna
Published: January 2021

Background

Obstructive sleep apnea (OSA) is prevalent in individuals with Osteogenesis imperfecta (OI). To date, no study has investigated treatment of OSA in adult individuals with OI using positive airway pressure (PAP). This observational pilot study examined the adherence of adults with OI to treatment of OSA with PAP therapy, and the evolution of self-experienced sleepiness and depression symptoms before and after treatment.

Methods

We included 20 patients, with a mean age of 51 years, who represented varying severity of OI and displayed an apnea and hypopnea index ≥ 5 /sleeping hour as recorded by an overnight polysomnography. PAP therapy was proposed to all patients. Epworth Sleepiness Scale (ESS) questionnaire to evaluate daytime sleepiness, and a validated self-rating depression questionnaire to identify possible depression, were completed prior to PAP therapy and repeated after a minimum of one year. The datasets supporting the conclusions of this article are included within the article.

Results

From the 20 patients, 15 initiated PAP therapy, and two patients later interrupted it. The mean PAP follow-up period was 1230 days. At baseline, an abnormally high ESS score was reported by 29% of the respondents, and an abnormally high number of symptoms suggesting depression by 29%. Follow-up questionnaires were completed by 60% of the patients, of whom 83% were adherent to PAP treatment. ESS score and depression symptoms did not decrease significantly with PAP therapy.

Conclusions

Patients with OI accepted well PAP therapy and remained compliant. Sleepiness and depression persisted unaltered despite good PAP adherence. These unexpectedly poor improvements in symptoms by PAP therapy may be due to subjective depression symptoms and the complexity of factors underlying persisting sleepiness in OI. Further research is needed to confirm this novel finding.
A retrospective cohort study on prevalence of postoperative complications in comminuted patellar fractures: comparisons among stabilized with Cannulated-Screw, Kirschner-Wire, or Ring-Pin Tension Bands
Authors: Zhu Xiao-zhong , Huang Teng-li , Zhu Hong-yi , Bao Bing-bo , Gao Tao , Li Xing-wei , Lin Jun-qing , Zheng Xian-You
Published: January 2021

Background

Displaced patellar fractures are commonly treated with open reduction and fixation with several different types of tension-band (TB) constructs. The main objective of this study was to compare the prevalence of postoperative complications after surgical stabilization of comminuted patellar fractures with either a modified Kirschner-wire tension band (MKTB), a cannulated-screw tension band (CSTB), or a ring-pin tension band (RPTB).

Methods

We conducted a retrospective and consecutive cohort study of comminuted patellar fractures (n = 334) stabilized using a TB construct. Postoperative premature loss of reduction, infection, and skin breakdown were compared according to the type of TB constructs received (MKTB, CSTB, or RPTB). The rate of implant removal due to symptomatic hardware was also evaluated.

Results

Fixation failure rate was significantly different among the groups (P = 0.013), with failure rates of 4.7% observed in the MKTB group,14.5% in the CSTB group, and 4.9% in the RPTB group. Skin breakdown and infection were not significantly different among the groups (Ps > 0.05). Due to symptomatic hardware, 40.5% of the patients in the MKTB group, 22.9% in the CSTB group, and 24.3% in the RPTB group underwent implant removal (P = 0.004). After adjusting for age, gender, comorbidities, number of supplementary screws/K-wires, and use of cerclage cables, multivariate regression analysis revealed that CSTB contributed to a 2.08-times greater risk of fixation failure compared to RPTB, while MKTB and RPTB were similar in risk of failure. In addition, it was found that patients who underwent MKTB fixation were more than twice as likely to undergo implant removal for symptomatic hardware compared with RPTB (odds ratio = 2.11, 95% CI = 1.20 to 3.72;P = 0.010).

Conclusions

RPTB have advantage over MKTB and CSTB fixation in terms of symptomatic hardware and premature failure, respectively.

Level of evidence

Therapeutic Level III
The osteogenic differentiation of human dental pulp stem cells in alginate-gelatin/Nano-hydroxyapatite microcapsules
Authors: Alipour Mahdieh , Firouzi Nima , Aghazadeh Zahra , Samiei Mohammad , Montazersaheb Soheila , Khoshfetrat Ali Baradar , Aghazadeh Marziyeh
Published: January 2021

Background

Microcapsule is considered as a promising 3D microenvironment for Bone Tissue Engineering (BTE) applications. Microencapsulation of cells in an appropriate scaffold not only protected the cells against excess stress but also promoted cell proliferation and differentiation. Through the current study, we aimed to microcapsulate the human Dental Pulp Stem Cells (hDPSCs) and evaluated the proliferation and osteogenic differentiation of those cells by using MTT assay, qRT-PCR, Alkaline phosphatase, and Alizarine Red S.

Results

The SEM results revealed that Alg/Gel microcapsules containing nHA showed a rough and more compact surface morphology in comparison with the Alg/Gel microcapsules. Moreover, the microencapsulation by Alg/Gel/nHA could improve cell proliferation and induce osteogenic differentiation. The cells cultured in the Alg/Gel and Alg/Gel/nHA microcapsules showed 1.4-fold and 1.7-fold activity of BMP-2 gene expression more in comparison with the control group after 21 days. The mentioned amounts for the BMP-2 gene were 2.5-fold and 4-fold more expression for the Alg/Gel and Alg/Gel/nHA microcapsules after 28 days. The nHA, addition to hDPSCs-laden Alg/Gel microcapsule, could up-regulate the bone-related gene expressions of osteocalcin, osteonectin, and RUNX-2 during the 21 and 28 days through the culturing period, too. Calcium deposition and ALP activities of the cells were observed in accordance with the proliferation results as well as the gene expression analysis.

Conclusion

The present study demonstrated that microencapsulation of the hDPSCs inside the Alg/Gel/nHA hydrogel could be a potential approach for regenerative dentistry in the near future.

Graphical abstract
Associations of six adiposity-related markers with incidence and mortality from 24 cancers—findings from the UK Biobank prospective cohort study
Authors: Parra-Soto Solange , Cowley Emma S. , Rezende Leandro F. M. , Ferreccio Catterina , Mathers John C. , Pell Jill P. , Ho Frederick K. , Celis-Morales Carlos
Published: January 2021

Background

Adiposity is a strong risk factor for cancer incidence and mortality. However, most of the evidence available has focused on body mass index (BMI) as a marker of adiposity. There is limited evidence on relationships of cancer with other adiposity markers, and if these associations are linear or not. The aim of this study was to investigate the associations of six adiposity markers with incidence and mortality from 24 cancers by accounting for potential non-linear associations.

Methods

A total of 437,393 participants (53.8% women; mean age 56.3 years) from the UK Biobank prospective cohort study were included in this study. The median follow-up was 8.8 years (interquartile range 7.9 to 9.6) for mortality and 9.3 years (IQR 8.6 to 9.9) for cancer incidence. Adiposity-related exposures were BMI, body fat percentage, waist-hip ratio, waist-height ratio, and waist and hip circumference. Incidence and mortality of 24 cancers sites were the outcomes. Cox proportional hazard models were used with each of the exposure variables fitted separately on penalised cubic splines.

Results

During follow-up, 47,882 individuals developed cancer and 11,265 died due to cancer during the follow-up period. All adiposity markers had similar associations with overall cancer incidence. BMI was associated with a higher incidence of 10 cancers (stomach cardia (hazard ratio per 1 SD increment 1.35, (95% CI 1.23; 1.47)), gallbladder (1.33 (1.12; 1.58)), liver (1.27 (1.19; 1.36)), kidney (1.26 (1.20; 1.33)), pancreas (1.12 (1.06; 1.19)), bladder (1.09 (1.04; 1.14)), colorectal (1.10 (1.06; 1.13)), endometrial (1.73 (1.65; 1.82)), uterine (1.68 (1.60; 1.75)), and breast cancer (1.08 (1.05; 1.11))) and overall cancer (1.03 (1.02; 1.04)). All these associations were linear except for breast cancer in postmenopausal women. Similar results were observed when other markers of central and overall adiposity were used. For mortality, nine cancer sites were linearly associated with BMI and eight with waist circumference and body fat percentage.

Conclusion

Adiposity, regardless of the marker used, was associated with an increased risk in 10 cancer sites.
Yulink, predicted from evolutionary analysis, is involved in cardiac function
Authors: Kuo Ming-Wei , Tsai Hsiu-Hui , Wang Sheng-Hung , Chen Yi-Yin , Yu Alice L. , Yu John
Published: January 2021

Background

The comparative evolutionary genomics analysis was used to study the functions of novel Ka/Ks-predicted human exons in a zebrafish model. The Yulink (MIOS, Entrez Gene: 54,468), a conserved gene from zebrafish to human with WD40 repeats at N-terminus, was identified and found to encode an 875 amino acid in human. The biological function of this Yulink gene in cardiomyocytes remains unexplored. The purpose of this study is to determine the involvement of Yulink in the functions of cardiomyocytes and to investigate its molecular regulatory mechanism.

Methods

Knockdown of Yulink was performed using morpholino or shRNA in zebrafish, mouse HL-1 cardiomyocytes, and human iPSC-derived cardiomyocytes. The expression levels of mRNA and protein were quantified by qPCR and western blots. Other methods including DNA binding, ligand uptake, agonists treatment and Ca2+ imaging assays were used to study the molecular regulatory mechanism by Yulink. Statistical data were shown as mean ± SD or mean ± standard error.

Results

The knockdown of yulink with three specific morpholinos in zebrafish resulted in cardiac dysfunctions with pericardial edema, decreased heart beats and cardiac output. The Yulink knockdown in mouse HL-1 cardiomyocytes disrupted Ca2+ cycling, reduced DNA binding activity of PPARγ (peroxisome proliferator-activated receptor gamma) and resulted in a reduction of Serca2 (sarcoplasmic reticulum Ca2+ ATPase 2) expression. Expression of Serca2 was up-regulated by PPARγ agonists and down-regulated by PPARγ-shRNA knockdown, suggesting that Yulink regulates SERCA2 expression through PPARγ in mouse HL-1 cardiomyocytes. On the other hand, YULINK, PPARγ or SERCA2 over-expression rescued the phenotypes of Yulink KD cells. In addition, knockdown of YULINK in human iPSC-derived cardiomyocytes also disrupted Ca2+ cycling via decreased SERCA2 expression.

Conclusions

Overall, our data showed that Yulink is an evolutionarily conserved gene from zebrafish to human. Mechanistically Yulink regulated Serca2 expression in cardiomyocytes, presumably mediated through PPARγ nuclear entry. Deficiency of Yulink in mouse and human cardiomyocytes resulted in irregular Ca2+ cycling, which may contribute to arrhythmogenesis.
Real-world outcomes of different treatment strategies in patients with diabetes and three-vessel coronary disease: a mean follow-up 6.3 years study from China
Authors: Zhao Xueyan , Xu Lianjun , Jiang Lin , Tian Jian , Zhang Yin , Wang Dong , Sun Kai , Xu Bo , Zhao Wei , Hui Rutai , Gao Runlin , Song Lei , Yuan Jinqing
Published: January 2021

Background

Patients with diabetes and triple-vessel disease (TVD) are associated with a high risk of events. The choice of treatment strategies remains a subject of discussion. In the real-world, we aim to compare the outcomes of medical therapy (MT), coronary artery bypass grafting (CABG), and percutaneous coronary intervention (PCI) treatment strategies in patients with diabetes and TVD.

Methods

A total of 3117 consecutive patients with diabetes and TVD were enrolled. The primary endpoint was all-cause death and the secondary endpoint was major adverse cardiac and cerebrovascular events (MACCE, composite of all-cause death, myocardial infarction, or stroke).

Results

During the mean follow-up of 6.3 ± 2.6 years, 573 (18.4%) deaths and 1094 (35.1%) MACCE occurred. Multivariate analysis showed that PCI (hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.32–0.51) and CABG (HR 0.33, 95% CI 0.26–0.44) were associated with a lower risk of death compared with MT, with no difference between the PCI and CABG groups. When MACCE was the endpoint, PCI (HR 0.71, 95% CI 0.60–0.84) and CABG (HR 0.48, 95% CI 0.39–0.57) had a lower risk than MT. CABG was associated with a significantly lower risk of MACCE compared with PCI (HR 0.67, 95% CI 0.55–0.81), which was mainly attributed a lower risk in myocardial infarction, but a higher risk of stroke.

Conclusions

In this big real-world data and intermediate-term follow-up study, for patients with diabetes and TVD, PCI and CABG were associated with a lower risk of death and MACCE more than MT. The results suggest the importance of appropriate revascularization for diabetic patients with TVD. However, CABG was not associated with a lower risk of death, but with a lower risk of MACCE, compared with PCI. In the future, we perhaps should strengthen comprehensive treatment in addition to PCI or CABG.
Sodium–glucose transporter-2 inhibitors for prevention and treatment of cardiorenal complications of type 2 diabetes
Authors: Giugliano Dario , Longo Miriam , Scappaticcio Lorenzo , Caruso Paola , Esposito Katherine
Published: January 2021

Hospitalization for major diabetes complications, including myocardial infarction, stroke, lower-extremity amputation, and end-stage kidney disease, is on the rise and represents a great health burden for patients with type 2 diabetes (T2D), in particular for older people. Newer glucose-lowering medications have generated some optimism on the possibility to influence the natural history of cardiorenal complications of T2D. This review summarizes work in the area of sodium–glucose cotransporter 2 inhibitors (SGLT-2i) treatment and prevention of cardiorenal complications in patients with T2D (major adverse cardiovascular events, hospitalization for heart failure, kidney outcomes), with a particular emphasis on the effect of age, the role of primary versus secondary prevention and the possible extension of their cardiorenal benefits to the entire class of SGLT-2i.