bluuebunny/crossref_metadata_2025 huggingface dataset:
Nursing and Health Care Preferences Among Opioid and Stimulant Using Black Sexual Minority Men: An Exploratory Study
Authors: Dangerfield Derek T. , Cooper Jessica , Heidari Omeid , Allen Sophia , Winder Terrell J.A. , Lucas Gregory M.
Published: December 2020

Black sexual minority men (BSMM) experience the worst HIV treatment outcomes in the United States. Drug use increases HIV transmission risks and reduces health care engagement. Perceived health care provider stigma and medical mistrust minimizes treatment efforts. This study identified nursing and health care preferences among drug-using BSMM. In-depth qualitative interviews were conducted among 30 BSMM who reported drug use in Baltimore City, MD, from December 2018 to March 2019. Analysis identified themes as client preferences for nursing practices and gaps in clinical services. Participants' ages ranged from 23 to 63 years (M = 41.1). Most (91%) reported living with HIV. The following themes were identified as nursing and health care preferences: (a) being genuine, (b) knowing drug treatment and social services, (c) understanding drug use effects, (d) providing mental health services, and (e) clarifying treatment recommendations. Nurses and health care facilities can improve cultural competency for drug-using BSMM. Future research should identify the impact of these preferences on HIV care outcomes among BSMM.
Employment and Occupational Productivity Among Women Living With HIV: A Conceptual Framework
Authors: Wise Jenni M. , Vance David E. , Heaton Karen , Raper James L. , Konkle-Parker Deborah , Azuero Andres , Kempf Mirjam-Colette
Published: December 2020

Women living with HIV (WLWH) have lower employment rates and more difficulty finding and keeping employment compared with their counterparts without HIV. These disparities affect physical, psychological, and socioeconomic outcomes, and they may compound the disadvantages associated with living with HIV. Although historical literature has emphasized the impact of clinical factors on employment, current evidence suggests that socioeconomic and psychosocial factors associated with HIV should be included for a more comprehensive view. Based on this broader inclusion, a conceptual framework is presented describing how socioeconomic and psychosocial characteristics influence employment acquisition and maintenance among WLWH. The framework posits that there is a reciprocal relationship between employment acquisition and occupational productivity, and psychological health, physical health, social support, and empowerment. Implications for future research and interventions include (a) an extended conceptualization of vocational rehabilitation and (b) the use of peer support groups to increase social capital, empowerment, knowledge, and resources among WLWH.
Syphilis Testing Among Female Prisoners in Brazil: Results of a National Cross-sectional Survey
Authors: Santana Rosane da Silva , Kerr Ligia , Mota Rosa Maria Salani , Kendall Carl , Justa Neto Roberto da , Macena Hermelinda Maia , Seal David , Sousa Alvaro Francisco Lopes , McFarland Willi
Published: December 2020

Brazil has the third largest prison population in the world and is also experiencing a high and rising rate of syphilis infection. To establish the gaps in syphilis testing, we examined data from a nationally representative sample of incarcerated women in Brazil. Data originated from a cross-sectional survey designed to represent all regions of Brazil (N = 1,327). Data were collected by Audio Computer-Assisted Self-Interview, including variables in several blocks or domains. 49.2% had a lifetime history of being tested for syphilis. Increased likelihood of syphilis testing was significantly associated with completed elementary education (odds ratio ajustado [AOR] 1.75, 95% confidence interval [CI] 1.28–2.40), completed high school or more (AOR 2.04, 95% CI 1.36–3.06), income below minimum wage (AOR 1.46, 95% CI 1.10–1.94), homelessness (AOR 1.83, 95% CI 1.21–2.76), having heard of the female condom (AOR 1.92, 95% CI 1.25–2.95), received a condom in prison (AOR 1.56, 95% CI 1.11–2.21) or in public health services (AOR 1.50, 95% CI 1.13–1.98), lifetime history of pregnancy (AOR 2.55, 95% CI 1.67–3.89), had a gynecological examination (AOR 1.73, 95% CI 1.05–2.83), and perceived they had some chance (AOR 1.61, 95% CI 1.17–2.20) or a big chance (AOR 1.89, 95% CI 1.31–2.73) that they were likely to have been infected with HIV before entering prison.
Has Diarrhea Ceased to be a Concern in Persons Living With HIV? Results From a Cross-sectional Study
Authors: Hardwicke Robin L. , Guthrie Estefania , Chen Han-Yang , Grimes Richard M.
Published: December 2020

Diarrhea has been associated with HIV throughout the epidemic. Few recent studies have addressed diarrhea in persons living with HIV (PLWH) despite evolving knowledge and ever-changing practice standards. The fact that patient care has become more complex, with comorbid conditions requiring additional attention without additional time allotment, potentiates the risk of common symptoms being overlooked. Patients (n = 190) 18 years and older, living with HIV, completed a questionnaire collecting information specific to attitudes, definitions, and beliefs regarding diarrhea. Of the 190 participants, only 5.3% said that they had diarrhea, but 11.1% described their bowel movements as being in the group associated with diarrhea. Approximately, 93.7% of the participants defined diarrhea as either soft or watery; 34.2% defined frequency as more than three times per day, but 64.2% said that it would have to be more than three times per day to mention it to a provider. PLWH continue to experience diarrhea warranting assessment and discussions between the PLWH and the provider.
Internalized Sexual Minority Stigma is Associated With HIV Testing Behavior Among Chinese Men Who Have Sex With Men: A Cross-Sectional Study
Authors: Chi Yuanyuan , Huang Daoping , Pachankis John , Valimaki Maritta , Shen Yan , Li Xianhong
Published: December 2020

Although studies have examined the relationship between HIV-related stigma and HIV testing among men who have sex with men (MSM) in China, there is still a lack of knowledge regarding whether sexual minority stigma and HIV testing are associated. The purpose of this study was to identify the association between sexual minority- and HIV-related stigmas with HIV-testing behavior. A cross-sectional study was conducted in the Hunan Province of China. After controlling for covariates, the multivariate analyses showed that high internalized sexual minority stigma was negatively associated with HIV testing behavior in the previous year. However, anticipated sexual minority- and HIV-related stigmas were not associated with HIV-testing behavior. Findings suggest that internalized sexual minority stigma should be addressed in health care settings to encourage MSM to seek HIV testing services, especially considering the continuing HIV epidemic among MSM in China.
A Quality Improvement Project Using Microlearning to Increase Provider Adherence to Extragenital Sexually Transmitted Infection Screening Guidelines in Men Who Have Sex With Men
Authors: Shihabuddin Courtney DuBois , Leasure Angela Renee , Agudelo Higuita Nelson Iván , Overcash Janine
Published: December 2020

The Centers for Disease Control and Prevention (CDC) recommend screening men who have sex with men who are living with HIV for sexually transmitted infections at appropriate extragenital contact sites for bacterial sexually transmitted infections. In an effort to increase provider adherence to CDC recommended guidelines at a Ryan White Clinic, microlearning educational sessions were used. A quality improvement project was designed to determine the rate of provider adherence to CDC guidelines pre/post microlearning sessions. Student t-test was used to compare the number of patients who received urine and extragenital screening to those who received urine-only screening, to before and after the microlearning sessions. The rate of extragenital screening significantly increased after the microlearning sessions (4/460 vs. 70/507, p < .0001). The rate of urine screening remained unchanged (p = 1). Although extragenital screening significantly increased, it remained low. A decision tree in the electronic medical record to prompt providers to screen was developed.
A Nurse-Led Initiative to Improve Implementation of HIV Preconception Care Services
Authors: Simone Joanne Phillips , Hoyt Mary Jo , Bogert Laura , Storm Deborah S.
Published: December 2020

United States guidelines recommend preconception care (PCC) as an integral part of primary care to improve maternal and fetal/newborn outcomes and promote planned pregnancies. Persons living with HIV have additional, specialized needs for PCC. However, PCC is not reliably integrated in HIV care, and few studies have examined strategies to improve the provision of PCC services. We describe a successful, nurse-led initiative that incorporated collaborative strategic planning in conjunction with staff education and continuous quality improvement to strengthen implementation of PCC in a small urban HIV care clinic. Key features of this project included consensus building, training, and action planning with clinic staff; addressing clinic-specific barriers; and providing ongoing support/technical assistance. Continuous quality improvement reviews at 12, 18, and 36 months demonstrated improved and sustained implementation of PCC services for women and men. Our experiences serve as a model for HIV primary care clinics working to advance implementation of PCC services.
Community-Level Factors and HIV Health Among Older People Living With HIV (PLWH) in Alabama, United States: A Qualitative Analysis
Authors: Lee Yookyong , Walton Rick , Jackson Lindsey , Batey D. Scott
Published: December 2020

As the number of older people living with HIV (PLWH) is increasing, there is an urgent need for research on community-level factors to better understand the health care needs of this population. In-depth interview transcripts of 20 older PLWH who participated in a community-based participatory research study conducted in Alabama, in the United States, were analyzed through a phenomenological research approach. Results suggest that crime, lack of resources, and social isolation experienced at the community levels were found to be associated with the wellbeing of older PLWH. Moreover, community characteristics may confound older PLWH's comorbid conditions and resultant polypharmacy. An increased understanding of the impact of contextual factors on HIV health can inform more holistic individual- and community-level interventions aimed at addressing barriers to retention or re-engagement in HIV medical care and viral suppression among older PLWH.
The effectiveness of far-infrared irradiation on foot skin surface temperature and heart rate variability in healthy adults over 50 years of age
Authors: Peng Tai-Chu , Chang Su-Ping , Chi Lee-Mei , Lin Li-Mei
Published: December 2020

Background:

Far-infrared irradiation (FIR) is used in the medical field to improve wound healing, hemodialysis with peripheral artery occlusive disease, and osteoarthritis but seldom used in ameliorating poor lower extremity circulation. The purpose of this study was to evaluate the effect of FIR on changes in foot skin surface temperature (FSST) and autonomic nerve system (ANS) activity to evaluate its effectiveness in improving lower limb circulation.

Methods:

A randomized controlled study was conducted. Subjects (n = 44), all over the age of 50 years and satisfying the inclusion criteria, were randomly allocated into 2 groups. The intervention group received FIR on a lower limb for 40 minutes and the control group received no intervention. Left big toe (LBT), right big toe (RBT), left foot dorsal (LFD), right foot dorsal (RFD) surface skin temperature, autonomic nervous activity, and blood pressure were assessed.

Results:

The main results were skin surface temperature at the LBT increased from 30.8 ± 0.4°C to 34.8 ± 0.4°C, at RBT increased from 29.6 ± 0.4°C to 35.3 ± 0.4°C and LFD increased from 31.9 ± 0.3°C to 36.4 ± 0.4°C, RFD increased from 30.7 ± 0.3°C to 37.7 ± 0.2°C. FIR caused a significant increase of the FSST ranging in a 4°C to 7°C increase after 40 minutes irradiation (P < .001). The ANS low-frequency (LF) and high-frequency (HF) activity showed a statistically significant increase in the FIR group (P < .05) but not the LF/HF ratio.

Conclusion:

FIR significantly increased the FSST from between 4°C and 7°C after 40 minutes irradiation, which might improve lower extremity circulation and regulation of ANS activity.
Adversarial attack on deep learning-based dermatoscopic image recognition systems
Authors: Allyn Jérôme , Allou Nicolas , Vidal Charles , Renou Amélie , Ferdynus Cyril
Published: December 2020

Deep learning algorithms have shown excellent performances in the field of medical image recognition, and practical applications have been made in several medical domains. Little is known about the feasibility and impact of an undetectable adversarial attacks, which can disrupt an algorithm by modifying a single pixel of the image to be interpreted. The aim of the study was to test the feasibility and impact of an adversarial attack on the accuracy of a deep learning-based dermatoscopic image recognition system.

First, the pre-trained convolutional neural network DenseNet-201 was trained to classify images from the training set into 7 categories. Second, an adversarial neural network was trained to generate undetectable perturbations on images from the test set, to classifying all perturbed images as melanocytic nevi. The perturbed images were classified using the model generated in the first step. This study used the HAM-10000 dataset, an open source image database containing 10,015 dermatoscopic images, which was split into a training set and a test set. The accuracy of the generated classification model was evaluated using images from the test set. The accuracy of the model with and without perturbed images was compared. The ability of 2 observers to detect image perturbations was evaluated, and the inter observer agreement was calculated.

The overall accuracy of the classification model dropped from 84% (confidence interval (CI) 95%: 82–86) for unperturbed images to 67% (CI 95%: 65–69) for perturbed images (Mc Nemar test, P < .0001). The fooling ratio reached 100% for all categories of skin lesions. Sensitivity and specificity of the combined observers calculated on a random sample of 50 images were 58.3% (CI 95%: 45.9–70.8) and 42.5% (CI 95%: 27.2–57.8), respectively. The kappa agreement coefficient between the 2 observers was negative at -0.22 (CI 95%: −0.49–−0.04).

Adversarial attacks on medical image databases can distort interpretation by image recognition algorithms, are easy to make and undetectable by humans. It seems essential to improve our understanding of deep learning-based image recognition systems and to upgrade their security before putting them to practical and daily use.
Clinical usefulness of single photon emission tomography/computed tomography with stress analysis in early diagnoses of stem instability of noncemented hip arthroplasty
Authors: Zhang Li-Zhi , Li Shuang , Jiang Yao , Qiu Zhong-Ling , Wang Yang , Lu Han-Kui , Zhu Rui-Sen , Tuladhar Rujan , Chang Shi-Min
Published: December 2020

Objective

Hip pain arising from implant instability is generally caused by repetitive stress injury, which subsequently leads to induction or exacerbation of abnormal metabolism of bone around the implant. single photon emission tomography/computed tomography (SPECT–CT) has advantages in localizing areas of increased tracer uptake that reflects such abnormal bone metabolism. Therefore, we investigated whether the application of SPECT/CT with stress analysis can be an effective practice in evaluating the instability of stem in noncemented hip arthroplasty or not.

Method

In total 16 patients were collected for unexplained painful hip arthroplasties. When physical examination and blood tests were unremarkable, radiographs were inconclusive and bone scan indicated increased scintigraphic uptake at the proximal part and at the tip of the stem; SPECT/CT was performed. Stem stability was assessed by measuring whether there was consistency between the increased scintigraphic uptake and the direction of the stress around the implant along with the location of the prosthesis.

Result

Among the 16 symptomatic hips, 9 hips showed the stability of the stem, 3 hips showed the stem instability and 4 hips showed the acetabular loosening with the stem stability. With the application of SPECT/CT with stress analysis, 15 out of 16 (93.7%) cases were found to have the change in the diagnoses, and managements were implemented in 11 out of 16 (68.7%) cases. When comparing before and after SPECT/CT, there was no significant association in clinical diagnosis and management (Pearson chi- square test = 4.61 and 1.33, P = 0.33 and 0.25).

Conclusion

SPECT/CT combined with stress analysis can be a useful tool in early diagnosis of stem instability and can assist surgeons in subsequent management and decision implementation when other radiographic imagings are inconclusive.
Baseline metabolic tumor volume calculation using different SUV thresholding methods in Hodgkin lymphoma patients: interobserver agreement and reproducibility across software platforms
Authors: Tutino Francesca , Puccini Giulia , Linguanti Flavia , Puccini Benedetta , Rigacci Luigi , Kovalchuk Sofya , Sciagrà Roberto , Berti Valentina
Published: December 2020

Aim:

Although it is not yet used in clinical practice, metabolic tumor volume (MTV) assessed on the baseline FDG-PET has shown consistent prognostic value in various lymphoma types. The aim of our study was to compare interobserver agreement and reproducibility across platforms of MTV calculation using different SUV thresholding methods in a large series of patients with newly diagnosed Hodgkin lymphoma.

Materials and methods:

We retrospectively studied 121 patients. MTV at baseline FDG-PET was independently computed by three readers with three programs of semi-automatic segmentation, Fiji, LifeX, and Accurate. MTV measurement was performed with different thresholds: SUV >2.5, SUV >4, and SUV >41% of SUV max.

Results:

At inter-observer agreement analysis all Intraclass Correlation Coefficients (ICCs) were excellent (ICC >0.9), except for Accurate SUV >41% of SUV max (ICC = 0.8). The highest correlations were obtained at the SUV >4 threshold. The second best was SUV >2.5 threshold. Regarding reproducibility across software, we found statistically significant differences between Fiji versus LifeX and Accurate at fixed thresholds and between LifeX and Accurate at SUV >41% of SUV max, while no significant differences emerged between LifeX and Accurate using fixed thresholds.

Conclusion:

The three SUV thresholds studied are all suitable for MTV calculation in terms of reproducibility. The best reproducibility is achieved using fixed thresholds, both SUV >4 and SUV >2.5. If more than one software has to be used in a study, we suggest the use of fixed thresholds and the platforms LifeX and Accurate.
Is F-18 FDG PET/computed tomography a useful tool to restage the patients with tongue carcinoma?
Authors: Jain Tarun Kumar , Singh Guman , Goyal Sumit , Malhotra Hemant , Yadav Ajay , Kumbhaj Prashant , Yadav Dinesh , Khunteta Nitin
Published: December 2020

Objective

The aim of this study was to evaluate the diagnostic performance of contrast-enhanced F-18 fluoro-2-deoxyglucose (F-18 FDG) PET/computed tomography (CT) in restaging of tongue carcinoma.

Material and methods

Retrospectively analysis of carcinoma tongue patients (n = 110) who were treated and referred for FDG PET/CT. Histopathological examination and clinical or imaging follow-up were taken as gold standard.

Results

Of 110 patients, FDG PET/CT detected FDG avid lesions in 69 (62.7%) patients. Sensitivity, specificity and diagnostic accuracy of FDG PET/CT were 92.9%, 90.0% and 91.8%, respectively, for residual/recurrence disease detection (P < 0.05). Additionally, in six patients, metachronous primaries were also detected [lung (4), esophagus and lymphoma (1) each]. The mean maximum standardized uptake value (SUVmax) with 95% confidence interval for primary site recurrence, regional lymph nodes and metastatic lesions was 11.51 (9.53–13.48), 69 (62.7%) (7.88–11.48) and 8.94 (3.11–14.76), respectively.

Conclusion

FDG PET/CT demonstrates high diagnostic accuracy for detection of residual/recurrent disease in treated tongue cancer patients and PET/CT should be considered as first-line diagnostic investigation in these patients.
What to Expect From the New ASCO/CAP Guideline Recommendations for Hormone Receptor Testing in Breast Cancer: A National Reference Laboratory Experience
Authors: Mahlow Jonathon , Goold Eric A. , Jedrzkiewicz Jolanta , Gulbahce H. Evin
Published: December 2020

The new ASCO/CAP guidelines on hormone receptor testing in breast cancer recommends standard operating procedures (SOPs) established to confirm or adjudicate estrogen receptor (ER) results with weak or ≤10% staining, and the status of internal controls (ICs) reported for cases with 0% to 10% staining. The aim of this study is to determine the frequency of ER testing with weak or ≤10% staining that may require additional steps following SOPs and to identify any correlation between hormone receptor status of the tumor and the likelihood of finding IC. Breast cancer cases between January 2014 and April 2019 were included to identify negative, low-positive and weak-positive cases. The presence/absence of IC was correlated to tumor type. Following ASCO/CAP guidelines, 29.8% of cases (374/1261) will need additional steps to confirm/adjudicate results due to negative, low, or weak positive ER status. The probability of finding IC is ~50% lower in cases of ER and progesterone receptor (PgR) negative tumors. Repeat testing may be warranted in 13.1% (92/700) of all cases due to lack of IC. In conclusion, the new ASCO/CAP guidelines recommend laboratories to establish and follow SOP to confirm or adjudicate ER results for about 30% of the cases before reporting hormone receptors status. Over 40% of cases with <10% tumor ER positivity lacked IC that may need a comment per the guidelines indicating a repeat testing may be warranted. However, the presence/absence of IC may be related to the subtype of breast cancer and should not necessarily bring into question the validity of the test.
Circulating extracellular vesicles as new inflammation marker in HIV infection
Authors: Falasca Katia , Lanuti Paola , Ucciferri Claudio , Pieragostino Damiana , Cufaro Maria Concetta , Bologna Giuseppina , Federici Luca , Miscia Sebastiano , Pontolillo Michela , Auricchio Antonio , Del Boccio Piero , Marchisio Marco , Vecchiet Jacopo
Published: December 2020

Background:

Extracellular vesicles, released by cell pullulation, are surrounded by a phospholipid bilayer and carry proteins as well and genetic material. It has been shown that extracellular vesicles mediate intercellular communication in several conditions, such as inflammation, immunodeficiency, tumor growth, and viral infections. Here, we analyzed circulating levels of extracellular vesicles in order to clarify their role in chronic inflammation mechanisms characterizing HIV patients.

Methods:

We analyzed and subtyped circulating levels of extracellular vesicles, through a recently developed flow cytometry method. In detail, endothelial-derived extracellular vesicles (CD31+/CD41a−/CD45−, EMVs), extracellular vesicles stemming from leukocytes (CD45+, LMVs) and platelets (CD41a+/CD31+) were identified and enumerated. Moreover, we analyzed the extracellular vesicle protein cargo with proteomic analysis.

Results:

Circulating levels of total extracellular vesicles, EMVs and LMVs were significantly lower in the HIV+ patients than in healthy subjects, whereas platelet-derived extracellular vesicles resulted higher in patients than in the healthy population. Proteomic analysis showed the upregulation of gammaIFN and IL1α, and down-regulation of OSM, NF-kB, LIF, and RXRA signaling resulted activated in this patients.

Conclusion:

These data demonstrate, for the first time that HIV infection induces the production of extracellular vesicles containing mediators that possibly feed the chronic inflammation and the viral replication. These two effects are connected as the inflammation itself induces the viral replication. We, therefore, hypothesize that HIV infection inhibits the production of extracellular vesicles that carry anti-inflammatory molecules.
High-risk human papillomavirus test in anal smears: can it optimize the screening for anal cancer?
Authors: Kimura Cintia M.S. , Nahas Caio S.R. , Silva-Filho Edésio V. , Ribeiro Vinícius L. , Segurado Aluisio C. , Alcântara Flávio F.P. , Cecconello Ivan , Nahas Sergio C.
Published: December 2020

Objective:

The current method for screening anal cancer is anal cytology, which has low sensitivity. Since high-risk human papillomavirus (HR-HPV) is associated with almost 90% of cases of anal cancer, the objective of this study is to evaluate whether testing for HR-HPV can optimize the screening.

Design:

Prospective study with patients enrolled in a screening program for anal dysplasia. Considering high-resolution anoscopy (HRA)-guided biopsy as the gold standard for diagnosis of high-grade squamous intraepithelial lesions, the diagnostic performance of anal cytology, HR-HPV testing, and the combination of both was calculated.

Settings:

A single center for anal dysplasia.

Participants:

A total of 364 patients (72% males, 82% HIV-positive).

Intervention:

Patients underwent anal cytology, HR-HPV test, and HRA-guided biopsy of the anal canal.

Main outcome measures:

Ability of cytology and HR-HPV test (individually and combined) to detect high-grade squamous intraepithelial lesions, and analysis of the cost of each diagnostic algorithm.

Results:

Cytology alone was the cheapest approach, but had the lowest sensitivity [59%, 95% confidence interval (CI) 46–71%], despite of highest specificity (73%, 95% CI 68–78%). Cotesting had the highest sensitivity (85%, 95% CI 74–93%) and lowest specificity (43%, 95% CI 38–49%), and did not seem to be cost-effective. However, HR-HPV testing can be used to triage patients with normal and atypical squamous cells of undetermined significance cytology for HRA, resulting in an algorithm with high sensitivity (80%, 95% CI 68–89%), and specificity (71%, 95% CI 65–76%), allied to a good cost-effectiveness.

Conclusion:

HR-HPV testing is helpful to optimize the screening in cases of normal and atypical squamous cells of undetermined significance cytology.
Enhanced and Timely Investigation of ARVs for Use in Pregnant Women
Authors: Abrams Elaine J. , Mofenson Lynne M. , Pozniak Anton , Lockman Shahin , Colbers Angela , Belew Yodit , Clayden Polly , Mirochnick Mark , Siberry George K. , Ford Nathan , Khoo Saye , Renaud Francoise , Vitoria Marco , Venter Willem D. F. , Doherty Meg , Penazzato Martina ,   on Behalf of the PADO and CADO Experts Groups
Published: December 2020

Background:

Concerns have been voiced that the exclusion of pregnant women from clinical trials results in a lack of safety and pharmacokinetic data for antiretroviral drugs (ARVs) in pregnancy, creating clear risks to pregnant women living with HIV (PWLHIV), and their infants.

Setting:

The World Health Organization convened a Paediatric Antiretroviral Drug Optimization group meeting, December 10–12, 2018, in Geneva, Switzerland.

Methods:

The group, comprised of clinicians, scientists, HIV program managers, regulators, and community representatives, were tasked to consider how ARVs are studied in PWLHIV, define alternative approaches to studying ARVs in PWLHIV, identify ways to shorten the timeline to determine safe use of new agents during pregnancy, and define strategies to collaborate with regulators and industry to change longstanding practices.

Results:

Most new ARVs are not studied in pregnant populations until after drug licensure, primarily opportunistically among women who become pregnant while taking the ARV of interest. Acceleration of the timeline will require earlier completion of preclinical studies and a new paradigm, namely—under certain conditions—allow women who become pregnant while participating in phase III ARV studies the option of remaining on study and enroll pregnant women into phase III trials of new agents to obtain preliminary safety and dosing and efficacy data.

Conclusion:

A revision of the current approach to the study of antiretrovirals in pregnant women is urgently needed to improve timely access and safe use of new agents during pregnancy.
Compliance of Familial Mediterranean Fever Patients With Regular Follow-up Visits and Associated Factors
Authors: Bilici Salman Reyhan , Babaoglu Hakan , Satiş Hasan , Yapar Dilek , Avanoglu Güler Aslihan , Karadeniz Hazan , Ataş Nuh , Haznedaroğlu Şeminur , Öztürk Mehmet Akif , Göker Berna , Tufan Abdurrahman
Published: December 2020

Background

Follow-up is crucial to detect asymptomatic complications of familial Mediterranean fever (FMF). The current European League Against Rheumatism recommendations state that patients with FMF should be evaluated at least every 6 months to monitor attacks, acute phase response, and proteinuria.

Objectives

This study aimed to assess compliance of FMF patients with regular follow-up visits and the associated factors.

Methods

Adult patients with a diagnosis of FMF who had their initial visit at least over 1 year ago were included. Demographic and socioeconomic data, family history, and comorbid diseases were obtained from medical records. The International Severity Score for FMF and the Autoinflammatory Disease Damage Index scores were calculated. We defined patients as “compliant with follow-up visits” both if they had at least 2 visits during the previous year and a compatible physician's assessment. The characteristics of the compliant and noncompliant patients were compared, and multivariable logistic regression analysis was used to determine the factors influencing visit compliance.

Results

Four hundred seventy-four patients with FMF were included. Two hundred thirty (48.5%) were compliant, and 244 (51.5%) were noncompliant with follow-up visits. A family history of FMF in parents, the absence of a family history of FMF in siblings, treatment with biologic agents, concomitant medication use, multisite involvement during FMF attacks, and treatment satisfaction were independent predictors of visit compliance.

Conclusions

Only half of the patients with FMF were compliant with follow-up visits. Better strategies should be implemented to increase the compliance of FMF patients. Identifying independent predictors would help to build one.
bootComb - An R Package to Derive Confidence Intervals for Combinations of Independent Parameter Estimates
Authors: Henrion Marc Y. R.
Published: December 2020

Motivation

The epidemiologist sometimes needs to combine several independent parameter estimates: e.g. (i) adjust an incidence rate for healthcare utilisation, (ii) derive a disease prevalence from the conditional prevalence on another condition and the prevalence of that condition, (iii) adjust a seroprevalence for test sensitivity and specificity. While obtaining the combined parameter estimate is usually straightforward, deriving a corresponding confidence interval often is not.bootCombis an R package using parametric bootstrap sampling to derive such confidence intervals.

Implementation

bootCombis a package for the statistical computation environment R.

General features

As well as a function that returns confidence intervals for parameters combined from several independent estimates,bootCombprovides auxiliary functions for 6 common distributions (beta, normal, exponential, gamma, Poisson and negative binomial) to derive best-fit distributions (and their sampling functions) for parameters given their reported confidence intervals.

Availability

bootCombis available from the Comprehensive R Archive Network (https://CRAN.R-project.org/package=bootComb).

Key Features

bootCombderives confidence intervals with the required coverage for parameters that are computed from independent parameter estimates for which confidence intervals are reported.

Includes auxilliary functions for 6 common distributions (beta, normal, exponential, gamma, Poisson and negative binomial) to derive best-fit distributions (and their sampling functions) for parameters given their reported confidence intervals.

R package: open-source, easy-to-use, platform independent.

Stable version hosted on CRAN:https://CRAN.R-project.org/package=bootComb

Latest development version available from GitHub:https://github.com/gitMarcH/bootComb
Effect of lysergic acid diethylamide (LSD) on reinforcement learning in humans
Authors: Kanen Jonathan W. , Luo Qiang , Kandroodi Mojtaba R. , Cardinal Rudolf N. , Robbins Trevor W. , Carhart-Harris Robin L. , den Ouden Hanneke E.M.
Published: December 2020

The non-selective serotonin 2A (5-HT2A) receptor agonist lysergic acid diethylamide (LSD) holds promise as a treatment for some psychiatric disorders. Psychedelic drugs such as LSD have been suggested to have therapeutic actions through their effects on learning. The behavioural effects of LSD in humans, however, remain largely unexplored. Here we examined how LSD affects probabilistic reversal learning in healthy humans. Healthy volunteers received intravenous LSD (75μg in 10 mL saline) or placebo (10mL saline) in a within-subjects design and completed a probabilistic reversal learning task. Participants had to learn through trial and error which of three stimuli was rewarded most of the time, and these contingencies switched in a reversal phase. Computational models of reinforcement learning were fitted to the behavioural data to assess how LSD affected the updating (“learning rates”) and deployment (“reinforcement sensitivity”) of value representations during choice, as well as “stimulus stickiness”, which assays choice repetition irrespective of reinforcement history. Conventional measures assessing sensitivity to immediate feedback (“win-stay” and “lose-shift” probabilities) were unaffected, whereas LSD increased the impact of the strength of initial learning on perseveration. Computational modelling revealed that the most pronounced effect of LSD was enhancement of the reward learning rate. The punishment learning rate was also elevated. Stimulus stickiness was decreased by LSD, reflecting heightened exploratory behaviour, while reinforcement sensitivity was unaffected. Increased reinforcement learning rates suggest LSD induced a state of heightened plasticity. These results indicate a potential mechanism through which revision of maladaptive associations could occur in the clinical application of LSD.

Significance statement

The psychedelic (“mind-manifesting”) drug LSD holds promise for the treatment of some psychiatric disorders. Theories have postulated its therapeutic potential centres on enhancing learning and flexible thinking. Here we provide substantiating empirical evidence by examining the computations underlying behaviour as healthy volunteers learned through trial and error under LSD. Viewing choice as based on representations of an action’s value, LSD increased the speed at which value was updated following feedback, which was more pronounced following reward than punishment. Behaviour was also more exploratory under LSD, irrespective of the outcome of actions. These results indicate that LSD impacted a fundamental belief-updating process inherent in the brain which can be leveraged to revise maladaptive associations characteristic of a range of mental disorders.
Amphibian Collapses Exacerbated Malaria Outbreaks in Central America
Authors: Springborn Michael R. , Weill Joakim A. , Lips Karen R. , Ibáñez Roberto , Ghosh Aniruddha
Published: December 2020

Ecosystems play an important role in supporting human welfare, including regulating the transmission of infectious diseases. Many of these services are not fully-appreciated due to complex environmental dynamics and lack of baseline data. Multicontinental amphibian decline due to the fungal pathogen Batrachochytrium dendrobatidis (Bd) provides a stark example. Even though amphibians are known to affect natural food webs—including mosquitoes that transmit human diseases—the human health impacts connected to their massive decline have received little attention. Here we show a causal link between a wave of Bd-driven collapse of amphibians in Central America and increased human malaria incidence. At the canton-level in Costa Rica and district-level in Panama, expected malaria incidence increased for eight years subsequent to amphibian losses, peaking at an additional 1.0 cases per 1,000 population (CPK). The increase is substantial in comparison to annual incidence levels from outbreaks in these countries, which peaked at 1.1-1.5 CPK during our period of study from 1976-2016. This pattern holds across multiple alternative approaches to the estimation model. This previously unidentified impact of biodiversity loss illustrates the often hidden human welfare costs of conservation failures. These findings also show the importance of mitigating international trade-driven spread of similar emergent pathogens like Batrachochytrium salamandrivorans.

Significance Statement

Despite substantial multicontinental collapses in amphibian populations from spread of the fungal pathogen Batrachochytrium dendrobatidis (Bd), the implications for humans have not been systematically studied. Amphibians are known to affect food webs, including mosquitoes that serve as a vector for the spread of disease. However, little is known about how their loss erodes ecosystem services, including the regulation of the transmission of infectious diseases. Using Central America as a case study, this study shows that Bd-driven amphibian loss led to a substantial increase in malaria incidence. The results highlight the often underappreciated social costs of biodiversity loss, including the potential stakes of ecosystem disruption from failing to stop spread of future novel pathogens.
CDK5 Inhibitor Seliciclib Promotes Osteoblastic Differentiation of MSCs and Suppresses the Migration of MG-63 Osteosarcoma Cells
Authors: Fu Hong , Zhao Haoyu , Yang Yali , Duan Ke , Guo Tailin
Published: December 2020

CDK5 belongs to the cycling dependent kinase family, which is multifunctional and plays an important role in neural differentiation. However, the role of CDK5 in osteoblastic differentiation remains unclear. The present study investigated functions and molecular mechanism of CDK5 in osteoblastic differentiation. It was found that, the addition of CDK5 inhibitor Seliciclib promoted the expression ofRunx2,ALP,OCNandOPNof MSCs and the mineralization of MC-3T3E1 cells. Seliciclib enhanced the development of F-actin, nuclear localization of β-catenin and YAP, as well as the expression of RMRP RNA. When F-actin was suppressed by Blebbistatin, the nuclear localization of YAP and β-catenin, and expression ofRMRP RNAas well asRunx2andALPwere decreased. These indicate Seliciclib promotes osteoblastic differentiation mainly by F-actin. Moreover, Seliciclib also suppressed the migration of MG-63, suggesting a potential application for Seliciclib in bone defect repair and inhibition of the migratiion of osteosarcoma cells.
Risk Model for Intraoperative Complication during Cataract Surgery Based on Data from 900,000 Eyes – Previous Intravitreal Injection is a Risk Factor
Authors: af Segerstad Poya Hård
Published: December 2020

Background/Aims

The aim of this study was to develop a risk model for intraoperative complication during cataract surgery and to include previous intravitreal therapy in the model.

Methods

This retrospective register-based study covered patients reported to the Swedish National Cataract Register (SNCR) between Jan. 1, 2010 and Jun. 30, 2018. Odds ratios (OR) were used to quantify association strength of each variable with intraoperative complication. Data from the SNCR were cross referenced with the Swedish Macula Register (SMR) to include data on previous intravitreal therapy. Variables statistically significant in the univariate analyses (P<0.05) were included in a multivariate logistic regression model.

Results

The inclusion criteria were met by 907,499 eyes. The overall rate of intraoperative complication was 0.86%. After cross referencing, 3,451 eyes were identified in the SMR as having undergone intravitreal therapy prior to cataract surgery. Variables significantly associated with intraoperative complication (P<0.05) were best corrected visual acuity ≥1.0 LogMAR (adjusted OR): 1.75), age ≥90 years (OR: 1.25), male sex (OR: 1.09), pseudoexfoliation (OR: 1.33), glaucoma (OR: 1.11), diabetic retinopathy (OR: 1.35), previous intravitreal therapy (OR: 1.45), surgeon’s experience <600 surgeries (OR: 2.77), use of rhexis hooks (OR: 6.14), blue staining (OR: 1.87), and mechanical pupil dilation (OR: 1.52).

Conclusion

The risk model can be used in the preoperative setting to predict the probability of intraoperative complication, to facilitate planning of surgery, and improving patient communication. Patients who have undergone intravitreal therapy prior to cataract surgery have an increased risk of intraoperative complication during cataract surgery.
The physiological demands of Singing for Lung Health compared to treadmill walking
Authors: Philip Keir EJ , Lewis Adam , Buttery Sara C , McCabe Colm , Manivannan Bishman , Fancourt Daisy , Orton Christopher , Polkey Michael I , Hopkinson Nicholas S
Published: December 2020

Participating in singing is considered to have a range of social and psychological benefits. However, the physiological demands of singing, whether it can be considered exercise, and its intensity as a physical activity are not well understood. We therefore compared cardiorespiratory parameters while completing components of Singing for Lung Health (SLH) sessions, with treadmill walking at differing speeds (2, 4, and 6km/hr). Eight healthy adults were included, none of whom reported regular participation in formal singing activities. Singing induced physiological responses that were consistent with moderate intensity activity (METS: median 4.12, IQR 2.72 - 4.78), with oxygen consumption, heart rate, and volume per breath above those seen walking at 4km/hr. Minute ventilation was higher during singing (median 22.42L/min, IQR 16.83 - 30.54) than at rest (11L/min, 9 - 13), lower than 6km/hr walking (30.35L/min, 26.94 - 41.11), but not statistically different from 2km/hr (18.77L/min, 16.89 - 21.35) or 4km/hr (23.27L/min, 20.09 - 26.37) walking. Our findings suggest the metabolic demands of singing may contribute to the health and wellbeing benefits attributed to participation. However, if physical training benefits result remains uncertain. Further research including different singing styles, singers, and physical performance impacts when used as a training modality is encouraged.
SARS-CoV-2 infections in kindergartens and associated households at the start of the second wave in Berlin, Germany – a cross sectional study
Authors: Thielecke Marlene , Theuring Stefanie , van Loon Welmoed , Hommes Franziska , Mall Marcus A. , Rosen Alexander , Böhringer Falko , von Kalle Christof , Kirchberger Valerie , Kurth Tobias , Seybold Joachim , Mockenhaupt Frank P.
Published: December 2020

Objectives

The comparatively large proportion of asymptomatic SARS-CoV-2 infections in the youngest children opens up the possibility that kindergartens represent reservoirs of infection. However, actual surveys in kindergartens beyond individual outbreaks are rare. At the beginning of the second pandemic wave in Berlin, Germany, i.e., end of September 2020, we screened SARS-CoV-2 infections among kindergarten children, staff and connected household members.

Methods

Twelve kindergartens were randomly selected in the Berlin metropolitan area, and a total of 720 participants were recruited (155 pre-school children, 78 staff, 487 household members). Participants were briefly examined and interviewed, and SARS-CoV-2 infections and anti-SARS-Cov-2 IgG antibodies were assessed.

Results

Signs and symptoms, largely resembling common cold, were present in 24.2% of children and 28.9% of staff. However, no SARS-CoV-2 infection was detected among 701 PCR-tested individuals, and only one childcare worker showed IgG seroreactivity (0.15%; 1/672).

Conclusions

Against a backdrop of increased pandemic activity in the community, this cross-sectional study does not suggest that kindergartens are silent transmission reservoirs. Nevertheless, at increasing pandemic activity, reinforced precautionary measures and repeated routine testing appears advisable.
Efficacy of pulmonary rehabilitation in severe and critical-ill COVID-19 patients: a controlled study
Authors: Büsching Gilbert , Zhang Zhongxing , Schmid Jean Paul , Sigrist Thomas , Khatami Ramin
Published: December 2020

Severe and critical ill COVID-19 patients frequently need acute care hospitalization including mechanical ventilation at ICU due to acute respiratory distress. A high proportion of these patients will develop ICU-acquired weakness and a need for rehabilitation. However data on rehabilitation outcomes in these patients are scarce and the efficacy of rehabilitation remains essentially unclear. We therefore compared the rehabilitation outcomes between COVID-19 patients with pneumonia and other patients with common pneumonia to assess their rehabilitation efficacies.

We retrospectively compared the performances of six-min walk test (6MWT), chronic respiratory questionnaire (CRQ), and functional independence measure (FIM) at the discharge from pulmonary rehabilitation between 51 Covid-19 patients and 51 patients with common pneumonia using linear regression controlled for baseline values at entrance, age, sex and cumulative Illness rating scale. Fisher exact test was applied to test whether the odd ratios (ORs) of non-improvement/improvement in 6MWT (>30-m) and CRQ (>10-point) at discharge were different between the two groups.

Covid-19 patients had similar performances at discharge in 6MWT (P-value=0.14), CRQ (P-value=0.55), and 4.2-point higher (P-value=0.004) in FIM compared to the control group. No differences in the outcomes were found between severe and critical COVID-19 patients. The OR of non-improvement/improvement in 6MWT was 0.30 (P-value=0.13) between COVID-19 and control groups; but the odd of non-improvement in CRQ tended to be 3.02 times higher (P-value =0.075) in COVID-19 group.

In-house rehabilitation is effective and suitable for COVID-19 patients irrespective from disease severity. The discrepancy of high physical improvement and relatively low gains of disease related quality of life compared to control patients with common pneumonia is however remarkable. Further studies need to evaluate whether this discrepancy is an indicator of chronic disease development.