bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of the Affordable Care Act's Medicaid Expansion With 1-Year Survival Among Patients With Ovarian Cancer
Authors: Bodurtha Smith Anna Jo , Applebaum Jeremy , Fader Amanda Nickles
Published: June 2022

OBJECTIVE:

The Affordable Care Act's (ACA) 2014 Medicaid expansion is associated with gains in insurance and early-stage diagnosis among patients with gynecologic cancer, but its association with mortality remains unknown. This study aims to assess whether the ACA's Medicaid expansion was associated with improved survival among patients with ovarian cancer.

METHODS:

In this retrospective cohort study of patients with newly diagnosed ovarian cancer, we compared 1-year survival before and after 2014 Medicaid expansion in patients aged 40–64 years in Medicaid expansion states (intervention group) to patients aged 40–64 years in non–Medicaid expansion states using a difference-in-difference analysis. Results were adjusted for age, comorbidities, treatment at an academic center, and variables associated with Medicaid insurance status (race, income, high-school education, distance traveled for care, and living in a rural area).

RESULTS:

Our sample included 19,558 patients with ovarian cancer: 9,013 in Medicaid expansion states and 10,545 in nonexpansion states. The ACA's Medicaid expansion was associated with increased 1-year survival among patients in expansion states compared with nonexpansion states (adjusted difference-in-difference 2.2%, 95% CI 0.4–4.1). After adding stage at diagnosis, the mortality difference between expansion and nonexpansion states was no longer evident. Medicaid expansion was associated with a significant improvement in 1-year survival for White patients (2.4%, 95% CI 0.4–4.4), but the difference was not significant for Black patients (1.3%, 95% CI −5.7 to 8.2) or rural patients (9.5%, 95% CI −8.0 to 26.9).

CONCLUSION:

The ACA's Medicaid expansion was associated with improvements in 1-year survival among patients with ovarian cancer, which was mediated by an earlier stage at diagnosis. Continued insurance expansion to nonexpansion states may improve survival and reduce disparities for patients with ovarian cancer.
Relugolix Combination Therapy for Uterine Leiomyoma–Associated Pain in the LIBERTY Randomized Trials
Authors: Stewart Elizabeth A. , Lukes Andrea S. , Venturella Roberta , Arjona Ferreira Juan-Camilo , Li Yulan , Hunsche Elke , Wagman Rachel B. , Al-Hendy Ayman
Published: June 2022

OBJECTIVE:

To assess the effect of once-daily relugolix combination therapy (relugolix-CT: relugolix 40 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg) compared with placebo on moderate-to-severe pain in women with uterine leiomyomas and heavy menstrual bleeding.

METHODS:

Two replicate, multinational, double-blind, 24-week, randomized, phase 3 studies (LIBERTY 1 and 2) were conducted in premenopausal women with uterine leiomyoma–associated heavy menstrual bleeding (80 mL or greater per cycle for two cycles or 160 mL or greater during one cycle). A predefined secondary objective was to determine the effect of relugolix-CT on moderate-to-severe uterine leiomyoma–associated pain in the pain subpopulation (women with maximum pain scores of 4 or higher on the 0–10 numerical rating scale at baseline, with pain score reporting compliance of 80% (ie, 28 days or more over the last 35 days of treatment). This key secondary endpoint was defined as the proportion of women achieving minimal-to-no uterine leiomyoma–associated pain (maximum numerical rating scale score 1 or lower) at week 24; menstrual and nonmenstrual pain were evaluated in prespecified secondary analyses. Treatment comparisons were performed in the pooled LIBERTY 1 and 2 pain subpopulation using the Cochran-Mantel-Haenszel test stratified by baseline menstrual blood loss volume.

RESULTS:

Across both trials, 509 women were randomized to relugolix-CT or placebo (April 2017–December 2018). Of these, 277 (54.4%) met pain subpopulation requirements. With relugolix-CT, 45.2% (95% CI 36.4–54.3) of women achieved minimal-to-no pain compared with 13.9% (95% CI 8.8–20.5) with placebo (nominal P<.001). The proportions of women with minimal-to-no pain during menstrual days and during nonmenstrual days were significantly higher with relugolix-CT (65.0% [95% CI 55.6–73.5] and 44.6% [95% CI 32.3–57.5], respectively) compared with placebo (19.3% [95% CI 13.2–26.7], nominal P<.001, and 21.6% [95% CI 12.9–32.7], nominal P=.004, respectively).

CONCLUSION:

Over 24 weeks, relugolix-CT significantly reduced moderate-to-severe uterine leiomyoma–associated pain with a more pronounced effect on menstrual pain. These data support that relugolix-CT had clinically meaningful effects on women's experience of uterine leiomyoma–associated pain.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov: LIBERTY 1, NCT03049735; LIBERTY 2, NCT03103087.

FUNDING SOURCE:

Myovant Sciences GmbH.
Same-Day Compared With Overnight Cervical Preparation Before Dilation and Evacuation Between 16 and 19 6/7 Weeks of Gestation
Authors: Kim Chi-Son , Dragoman Monica , Porsch Lauren , Markowitz Jess , Lunde Britt , Stoffels Guillaume , Dayananda Ila
Published: June 2022

We performed a double-blind, placebo-controlled, randomized noninferiority trial to compare same-day osmotic dilators plus misoprostol with overnight osmotic dilators alone for cervical preparation before dilation and evacuation (D&E) between 16 0/7 and 19 6/7 weeks of gestation. The primary outcome was procedure time. The study was halted early owing to poor accrual. However, the median procedure time was 5.7 minutes in the same-day group compared with 4.2 minutes in the overnight group. The median absolute difference in procedure time was 1.5 minutes, which corresponded to a 35% increase in procedure time (relative difference 35%, one-sided 95% CI −Inf to 52%). Same-day cervical preparation with osmotic dilators plus buccal misoprostol before D&E may be a timely option.

Clinical Trial Registration: ClinicalTrials.gov, NCT03002441.
Folliculosebaceous Cystic Hamartoma With Prominent Adipose Tissue Resembling Spindle Cell Lipoma
Authors: Oulee Aislyn , Cassarino David
Published: June 2022

Folliculosebaceous cystic hamartomas (FSCH) are a rare form of cutaneous hamartoma composed of follicular, sebaceous, and mesenchymal elements. These lesions are most often seen in the central face and scalp and rarely exceed 2 cm in size. Here, we report a case of a folliculosebaceous cystic hamartoma with a prominent adipose tissue component resembling a spindle cell lipoma. The patient is a 36-year-old man with a slowly enlarging, flesh-colored, lobulated lesion on his right ala that had been previously biopsied. The clinical differential included a hypertrophic scar or recurrent hamartoma. A full-thickness excisional biopsy was performed, which revealed prominent, large, irregularly shaped, folliculosebaceous structures, including multiple dilated follicles associated with prominent hyperplastic-appearing sebaceous glands, findings consistent with FSCH. The mesenchymal component contained a proliferation of spindle-shaped cells associated with mucin and thickened, ropey-appearing bundles of collagen, features mimicking a spindle cell lipoma. This combination of a folliculosebaceous cystic hamartoma with prominent adipose tissue resembling spindle cell lipoma is unusual and has only been previously reported once in the literature, and therefore, our case contributes to the expanding knowledge of this rare variant of FSCH.
The Association Between Regional Macula Vessel Density and Central Visual Field Damage in Advanced Glaucoma Eyes
Authors: Ghahari Elham , Bowd Christopher , Zangwill Linda M. , Proudfoot James A. , Penteado Rafaella C. , Kyung Haksu , Hou Huiyuan , Moghimi Sasan , Weinreb Robert N.
Published: June 2022

Précis:

Both macular superficial vessel density and ganglion cell complex (GCC) thickness measurement are significantly associated with regional and global 10-degree central visual field (VF) sensitivity in advanced glaucoma.

Purpose:

The purpose of this study was to evaluate the regional and global structure-function relationships between macular vessel density (MVD) assessed by optical coherence tomography angiography (OCTA) and 10-2 VF sensitivity in advanced open angle glaucoma eyes.

Methods:

Macular OCTA and 10-2 VF sensitivity of 44 patients [mean deviation (MD) <−10 dB] were evaluated. Regional and global VF mean sensitivity (MS) was calculated from total deviation plots. Superficial and deep MVD were obtained from 3×3 and 6×6 mm2 OCTA scans using 2 sectoral definitions. Spectral-domain optical coherence tomography macular GCC thickness was obtained simultaneously from the same scan as the MVD measurements. Linear regression models were used to assess the associations (R
2).

Results:

Lower MS was significantly associated with a reduction in superficial MVD and GCC in each region of both scan sizes for both maps. Associations were weaker in the individual sectors of the whole image grid than the Early Treatment Diabetic Retinopathy Study map. Deep-layer MVD was not associated with central MS. Although 6×6 mm2 and perifoveal vessel density had better associations with central 10-degree MS compared with GCC thickness (eg, R
2 from 25.7 to 48.1 µm and 7.8% to 32.5%, respectively), GCC associations were stronger than MVD associations in the central 5-degree MS.

Conclusions:

Given a stronger MVD-central 10-degree VF association compared with GCC, as well as stronger GCC-central 5-degree VF association compared with MVD, MVD and GCC are complementary measurements in eyes with advanced glaucoma. A longitudinal analysis is needed to determine the relative utility of the GCC and MVD measurements.
Low Risk of Cardiac Complications in Collegiate Athletes After Asymptomatic or Mild COVID-19 Infection
Authors: Klawitter Paul , Cowen Leslie , Carhart Robert
Published: June 2022

Objective:

The objective of this study was to determine the utility of “standard” cardiac screening with EKG, echocardiography, and serum troponin T (hs-Tn T) testing after COVID infection in competitive college athletes.

Design:

Prospective cohort study.

Setting:

Tertiary cardiology clinic, university training room.

Participants:

Sixty-five Division 1 athletes recovered from COVID-19 and 465 controls.

Assessment:

All COVID-recovered athletes underwent cardiac screening on return to campus in fall 2020. Controls were screened if indicated by preparticipation examination. Students cleared for sports participation were followed for the development of cardiac complications.

Main Outcome Measure:

Incidence of cardiac complications after COVID infection.

Results:

Infected athletes experienced mild (26/65), moderate (8/65), or no (31/65) COVID symptoms. No athletes had severe symptoms. Men were more likely to have been asymptomatic (20/31), and women were more likely to have had moderate (7/8) symptoms (P = 0.015). All athletes, except 2 with anosmia, were asymptomatic at the time of cardiac testing. One athlete had persistently elevated hs-Tn T but no evidence of myocarditis on cardiac MRI. All other cardiac testing was negative. No athletes were diagnosed with myocarditis (95% CI: 0%-5.5%). All athletes were cleared for athletic participation. None suffered complications over the next 9 months.

Conclusions:

After COVID-19 infection, no college athletes with mild, moderate, or no symptoms had signs of myocarditis, and all returned to play without cardiac complication. These findings support consensus opinion recommendations that college-age athletes who recovered from COVID-19 and who experienced mild or no symptoms may return to play without cardiac testing.
Healing Predictors of Conservative Treatment for Juvenile Osteochondritis Dissecans of the Talus
Authors: Kim Hyun Woo , Park Kun-Bo , Kim Chan Woo , Lee Koo Yeon , Park Hoon
Published: June 2022

Objective:

To investigate the healing response of juvenile osteochondritis dissecans (JOCD) of the talus after conservative treatment, identify healing predictors, and develop a predictive model for healing.

Design:

Retrospective study.

Setting:

Clinics at a tertiary-level pediatric medical center.

Patients:

Fifty-five patients (55 ankles) who presented with JOCD.

Interventions:

Patients were managed with cast immobilization followed by activity restriction.

Main Outcome Measures:

The primary outcome measure of progressive lesion reossification was determined from the latest radiograph, after at least 6 months of nonoperative treatment. Final clinical evaluation was performed by a questionnaire and complementary telephone interview. Multivariate logistic regression was used to determine the influence of age, sex, lesion size, classification, location, duration of symptoms, containment lesion, and the occurrence of cyst-like lesions on healing potential.

Results:

After nonoperative treatment, 18 (33%) of 55 lesions had failed to progress toward healing. An older age (P = 0.034) and a completely detached but undisplaced (grade III) lesion (P < 0.001) at the time of diagnosis were predictive for the failure of conservative treatment. A multivariate logistic regression best predictor model that included age and grade resulted in the best predicted healing and yielded an area under the curve of 0.920 (P < 0.001).

Conclusion:

In two-thirds of skeletally immature patients, conservative treatment resulted in the progressive healing of JOCD of the talus. For older patients with grade III lesions showing a lower healing probability, surgical treatment should be considered.
Surviving cardiac arrest - what do we know about recovery & survivorship?
Authors: Sawyer Kelly N.
Published: June 2022

Purpose of review

There has been increasing interest in examining how cardiac arrest survivors and their families experience life after sudden cardiac arrest (SCA). Understanding their experiences provides a basis to study tools and interventions to improve short- and long-term recovery and rehabilitation.

Recent findings

Qualitative interview and survey-style studies explored the lived experience of SCA survivors and revealed common themes (e.g., need for recovery expectations and long-term follow-up resources). A heightened awareness for the unique needs of family and loved ones of survivors led to qualitative studies focusing on these members as well. Methodology papers published portend prospective assessment and follow-up cohort studies. However, no investigations evaluating discharge processes or specific interventions directed at domain impairments common after SCA were identified in the review period. International work continues to identify patient and family-centered priorities for outcome measurement and research.

In line with increased recognition of the importance for recovery and rehabilitation after SCA, there has been a commensurate increase in investigations documenting the needs of survivors and families surviving SCA. Pediatric and underserved populations continue to be understudied with regards to recovery after SCA.
Extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest - who, when, and where?
Authors: Gottula Adam L. , Neumar Robert W. , Hsu Cindy H.
Published: June 2022

Purpose of review

Extracorporeal cardiopulmonary resuscitation (ECPR) is an invasive and resource-intensive therapy used to care for patients with refractory cardiac arrest. In this review, we highlight considerations for the establishment of an ECPR system of care for patients suffering refractory out-of-hospital cardiac arrest (OHCA).

Recent findings

ECPR has been shown to improve neurologically favorable outcomes in patients with refractory cardiac arrest in numerous studies, including a single randomized control trial. Successful ECPR programs are typically part of a comprehensive system of care that optimizes all phases of OHCA management. Given the resource-intensive and time-sensitive nature of ECPR, patient selection criteria, timing of ECPR, and location must be well defined. Many knowledge gaps remain within ECPR systems of care, postcardiac arrest management, and neuroprognostication strategies for ECPR patients.

To be consistently successful, ECPR must be a part of a comprehensive OHCA system of care that optimizes all phases of cardiac arrest management. Future investigation is needed for the knowledge gaps that remain.
Artificial intelligence and clinical deterioration
Authors: Malycha James , Bacchi Stephen , Redfern Oliver
Published: June 2022

Purpose of review

To provide an overview of the systems being used to identify and predict clinical deterioration in hospitalised patients, with focus on the current and future role of artificial intelligence (AI).

Recent findings

There are five leading AI driven systems in this field: the Advanced Alert Monitor (AAM), the electronic Cardiac Arrest Risk Triage (eCART) score, Hospital wide Alert Via Electronic Noticeboard, the Mayo Clinic Early Warning Score, and the Rothman Index (RI). Each uses Electronic Patient Record (EPR) data and machine learning to predict adverse events. Less mature but relevant evolutions are occurring in the fields of Natural Language Processing, Time and Motion Studies, AI Sepsis and COVID-19 algorithms.

Research-based AI-driven systems to predict clinical deterioration are increasingly being developed, but few are being implemented into clinical workflows. Escobar et al. (AAM) provide the current gold standard for robust model development and implementation methodology. Multiple technologies show promise, however, the pathway to meaningfully affect patient outcomes remains challenging.
Management of Magnet Ingestions at a Large Tertiary Care Children’s Hospital
Authors: Shaul Eliana , Agawu Atu , Wood Phoebe , Umhoefer Katherine , Mamula Petar
Published: June 2022

Objectives:

To review the clinical management and outcomes of magnet ingestions at a large tertiary children’s hospital. To determine the association of frequency of high-powered magnet ingestion with the regulation of these magnets.

Methods:

Children <18 years who presented to the emergency room and were admitted to the Children’s Hospital of Philadelphia for ingestion of single or multiple magnets from January 2008 to December 2020 were included. Demographics, symptoms, management, and outcomes were analyzed. The frequency of magnet ingestion was compared over 3 eras: (1) pre-ban (2008–2012), (2) intra-ban (2013–2016), and (3) post-ban (2017–2020).

Results:

There were 167 magnet ingestions, including 99 with multiple magnets. Most patients (59%) were male and median age was 6 (interquartile range, 3–9) years. Most single magnet ingestions (86%) were discharged with outpatient monitoring, and none experienced severe outcomes. Multiple magnet ingestions led to significant morbidity including hospitalizations (68%), endoscopic procedures (48%), surgical procedures (14%), and severe outcomes (12%). Most patients (75%) were asymptomatic, however, there was a higher risk of surgery and severe complications based on the presence of symptoms (P = 0.003). The rate of surgical intervention was higher with ≥3 magnets (31.7%) compared to 2 magnets (2.4%) (P < 0.003). Additionally, we found an 160% increase in children with magnet ingestions in the post-ban period (P = 0.021).

Conclusions:

Multiple magnet ingestion is associated with high morbidity and rate of severe outcomes. There is a relationship between public policy of magnet sale and frequency of magnet ingestion.
Peroral Endoscopic Myotomy (POEM) in Children: A State of the Art Review
Authors: Mencin Ali A. , Sethi Amrita , Barakat Monique T. , Lerner Diana G.
Published: June 2022

Esophageal achalasia is a relatively rare disease in children that has been treated with balloon dilatation, botulinum toxin injection, and Heller myotomy. Peroral endoscopic myotomy (POEM) is another treatment that has been successfully employed to treat adults with achalasia for over a decade and has been increasingly used in children. This State of the Art Review from the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Endoscopy Committee reviews the current literature in pediatric POEM including the technique, success rate, complications as well as training guidelines. Though there is limited data, POEM in children has shown encouraging success rates and with further study may become the mainstay of pediatric achalasia treatment.
Tissue IgG2/IgG4 Ratio as an Additional Tool to Distinguish IgG4-Related Disease From Other Fibroinflammatory Disorders
Authors: Detiger Sanne E. , Paridaens Dion , van Hagen Martin , Karim Faiz , van Laar Jan A.M. , Verdijk Robert M.
Published: June 2022

Interpretation of biopsies taken on suspicion of immunoglobulin (Ig)G4-related disease (IgG4-RD) may be hampered by uninterpretable immunohistochemical stains for IgG because of strong background signals. This study aims to determine the significance of tissue IgG2 positive plasma cell counts in IgG4-RD in comparison with non-IgG4-related inflammatory disorders. Descriptive, retrospective case-control study of 16 patients with IgG4-related orbital disease (IgG4-ROD) and 24 with extraorbital IgG4-RD. Histopathology and serology of this group was compared with 16 patients with orbital non-IgG4-related disorders and 22 patients with extraorbital non-IgG4-related disorders. The mean tissue IgG2/IgG4 ratio was 0.16 in IgG4-ROD and 0.27 in extraorbital IgG4-RD and far below 1 in 98% of patients. This was significantly lower compared with the non-IgG4-related disorders that showed a mean tissue IgG2/IgG4 ratio of 1.98 in the orbital and 2.20 in the extraorbital group (range: 0.20 to 10, P<0.05). In 74% of tissue samples an IgG2/IgG4 ratio >1 was seen. The tissue IgG2/IgG ratio was significantly lower in IgG4-RD compared with non-IgG4-related inflammatory disorders. Serum IgG2 concentration was not abnormal in patients with IgG4-RD. A significantly lower tissue IgG2/IgG4 and IgG2/IgG ratio was observed in IgG4-RD, compared with non-IgG4-related inflammatory disorders. Additional immunohistochemical staining for IgG2 positive plasma cells can be helpful in the diagnosis of IgG4-RD. Especially in cases with uninterpretable IgG staining, a well-recognized problem that may give rise to a failed interpretation of the biopsy.
On How, and Why, and When, We Grow Old
Authors: Citti Luca , Su Jessica , Michaelson James S
Published: June 2022

Growth and aging are fundamental features of animal life. The march from fertilization to oblivion comes in enormous variety: days and hundreds of cells for nematodes, decades and trillions of cells for humans.1-4 Since Verhulst (18385) proposed the Logistic Equation - exponential growth with countervailing linear decline in rate – biologists have searched for ever better density dependent growth equations,6-12 none which accurately capture the relationship between size and time for real animals.13-15 Furthermore, while growth and aging run in parallel, whether the relationship is causal has been unknown. Here we show, by examining growth and lifespan in units of numbers of cells, N, (Cellular Phylodynamics6), that both processes are linked to the same reduction in the fraction of cells dividing, occurring by a simple expression, the Universal Mitotic Fraction Equation. Lifespan is correlated with an age when fewer than one-in-a-thousand cells are dividing, quantifying the long-appreciated mechanism of aging, the failure of cells to be rejuvenated by dilution with new materials made, and DNA repaired, at mitosis.24-26 These observations provide practical mathematical expressions for comprehending, and managing, the challenges of growth and aging, for such tasks as improving the effectiveness of COVID-19 vaccination in the elderly.
Immunity response against mild-to-moderate breakthrough COVID-19
Authors: Mongkolsucharitkul Pichanun , Surawit Apinya , Sookrung Nitat , Tungtrongchitr Anchalee , Phisalprapa Pochamana , Sayabovorn Naruemit , Srivanichakorn Weerachai , Washirasaksiri Chaiwat , Auesomwang Chonticha , Sitasuwan Tullaya , Chaisathaphol Thanet , Tinmanee Rungsima , Chayakulkeeree Methee , Phoompoung Pakpoom , Tangjittipokin Watip , Senawong Sansanee , Sanpawitayakul Gornmigar , Muangman Saipin , Mayurasakorn Korapat ,   the SPHERE Investigators
Published: June 2022

BACKGROUND

The Omicron variant prevails the Delta variant after December 2021 in Thailand. Both variants of concern embody diverse epidemiological trends and immunogenicity, raising enormous public health concerns. We determined whether biological and clinical characteristics and immunogenicity of patients differ between Delta and Omicron during post-coronavirus disease 2019 (COVID-19) stage.

METHODS

A retrospective cohort study involved patients with mild-to-moderate COVID-19 who were under a home isolation (HI) strategy. Clinical outcomes and laboratory data of 2704 and 2477 patients during the Delta and Omicron pandemics were analyzed, respectively. We evaluated anti-receptor binding domain immunoglobulin G (anti-RBD IgG) and surrogate viral neutralizing (sVNT) activity in a subset of 495 individuals post-COVID-19 infection during the Delta pandemic.

RESULTS

Eighty-four percent of all patients received antiviral treatment. The peak cycle threshold (Ct) values, which inversely related to viral load, were lower in the Omicron (19 [IQR=17-22]) compared with the Delta (21 [IQR=18-26]; p<0.001), regardless of vaccination status. Upper respiratory tract symptoms were common signs during the Omicron compared with the Delta pandemic. At least two-dose vaccination reduced the chance of hospital readmissions by 10–30% and death by less than 1%. Furthermore, anti-RBD IgG and sVNT against the Delta variants tended to be higher among the older individuals after post-COVID 19 infections and expressed in the long interval after two-dose vaccination than in other groups.

CONCLUSIONS

Mild-to-moderate Delta and Omicron breakthrough infection with prior full vaccination is limitedly immunogenic; thereby exerting reduced protection against reinfection and infection from novel variants. However, this may be only sufficient to prevent hospitalization and death, particularly in countries where vaccines are limited. (ClinicalTrials.gov number, NCT05328479.)
Evaluating the yaws diagnostic gap: a survey to determine the capacity of and barriers to improving diagnostics in all yaws-endemic countries
Authors: Handley Becca L. , Tchatchouang Serges , Grout Lise , Johnson Roch Christian , Tabah Earnest Njih , Boua Bernard , Boock Alphonse Um , Koffi Aboa Paul , Phanzu Delphin Mavinga , Kotey Nana Konama , Rogers Emerson , Dofitas Belen , Jung Younghee , Maweke Tchalim , Beiras Camila G. , Maman Issaka , Basing Laud Anthony , Ngazoa Solange , Houezo Jean Gabin , Togbey Kwamy , Telan Elizabeth Freda , Sarmento Nevio , Marion Estelle , Addo Kwasi Kennedy , Mitjà Oriol , Asideu Kinsley , Harding-Esch Emma , Marks Michael
Published: June 2022

Background

Yaws, caused by Treponema pallidum subsp. pertenue, is a skin neglected tropical disease. It is targeted for eradication by 2030, primarily using mass drug administration (MDA) with azithromycin. Traditionally, diagnosis of yaws has relied on clinical examination and serological testing. However, these approaches have poor diagnostic performance. To achieve eradication, more accurate diagnostics are required to determine whether MDA should be initiated or continued as well as for post-elimination surveillance. Molecular tools will be crucial for detecting antimicrobial resistant cases, which have the potential to derail eradication efforts. In order to determine the feasibility of introducing novel, more accurate, diagnostics for yaws surveillance purposes, it is necessary to understand current in-country diagnostic capacity. This study therefore aimed to understand the current capacity of, and challenges to, improving diagnostics for yaws in all yaws-endemic countries worldwide.

Methodology/ principal findings

An online survey was sent to all 15 yaws-endemic countries in July 2021. The survey asked about past prevalence estimates, the availability of different diagnostic tools, and perceived barriers to enhancing capacity. Fourteen countries responded to the survey, four of which did not have a current National Policy for yaws eradication in place. Over 95% of reported that yaws cases from the past five years had not been confirmed with serological or molecular tools, largely due to the limited supply of rapid serological tests. Only four countries reported having operational laboratories for molecular yaws diagnosis, with only one of these having a validated assay to detect azithromycin resistance.

Conclusions and Significance

This study highlights the diagnostic capacity constraints across all respondent countries. Countries are in need of access to a sustainable supply of serological tests, and development of molecular testing facilities. Sufficient sustainable funding should be made available to ensure that appropriate diagnostic tools are available and utilised.
A prospective study of adherence to lenalidomide for multiple myeloma using Medication Event Monitoring System (MEMS) caps
Authors: Silberstein Alice E. , Fiala Mark A. , Loh Kah Poh , Cordner Theresa , Mian Hira , Wildes Tanya M
Published: June 2022

Purpose

In patients with multiple myeloma, characterizing adherence to orally administered therapies, such as lenalidomide, is critical given their frequent use and potential for poorer outcomes associated with nonadherence. However, little data exist using prospective measures of adherence in this population. Our study piloted use of Medication Event Monitoring System (MEMS) caps and the patient-reported Brief Adherence Rating Scale (BARS) for 3 months in older adults with multiple myeloma.

Methods

We enrolled 13 patients with multiple myeloma receiving lenalidomide. Baseline characteristics were summarized; mean adherence to lenalidomide was reported with 95% confidence intervals.

Results

The median follow-up was 84 days. Of the 12 participants evaluable, median adherence, as assessed by the MEMS cap data, was 98%. Only 5 had 100% adherence. Deviations from intended use included missed prescribed doses made up during scheduled off week, additional days off between cycles, or taking fewer than anticipated days off. None of these events evident in MEMS data were self-disclosed. The mean difference in adherence estimated between the BARS and MEMS caps was 2%.

Conclusion

In this small sample, the observed adherence was higher than reported in retrospective studies using Medication Possession Ratio as a proxy for adherence. The BARS can be easily integrated into clinical encounters but has potential for reporting bias. MEMS caps can help characterize patterns of nonadherence, though there are limitations to their utility and the data can require thorough manual review to reconcile suspected occurrences of nonadherence. Studies should use more than 1 complementary measure of adherence.

Clinicaltrials.gov ID: NCT03779555, Registered 12/19/2018
Severe acute respiratory syndrome coronavirus 2 breakthrough infections in healthcare workers vaccinees with BNT162b2 (Pfizer-BioNtech) in Bogotá, Colombia
Authors: Tavera-Rodríguez Pilar , Barbosa-Ramírez Juliana , Bermúdez-Forero Andrea , Prada-Cardozo Diego , Reales-González Jhonnatan , Peláez-Carvajal Dioselina , Malo-Sanchez Diana , Meneses-Gil Maria-Ximena , Mercado-Reyes Marcela
Published: June 2022

The healthcare workers are considered as a high-risk group for infection with SARS-CoV-2, so they were included in the first stage of the National Plan for Vaccination against COVID-19 in Colombia.

An ongoing prospective cohort study to evaluate immune response to vaccination included 490 workers from health institutions in Bogotá, Colombia, vaccinated between March and June 2021 with BNT162b2 (Pfizer-BioNtech). Multiple samples were collected during a follow-up period of 6 months after immunization. We report cases of asymptomatic and symptomatic SARS-CoV-2 infections detected in this cohort. For each participant demographic data, vaccination dates, results for SARS-CoV-2 RT-PCR, and detection of antibody (IgG) tests during the follow-up period were collected.

SARS-CoV-2 infection was detected in 38 (7.7 %) volunteers. Of these, 81.6% had a positive RT-PCR for SARS-CoV-2, and 18.4% were confirmed by detection of IgG anti-SARS-CoV-2 nucleoprotein; 76.3% of infections occurred after 7 days of second dose. A total of 57.9% of the cases were asymptomatic. No hospitalizations or deaths were registered. When infection occurred, 81.6% of infected participants had presence of IgG anti-S antibodies. In 12 samples in which genomic characterization was achieved, 83.4% corresponded to the variant Mu, 8.3% Gamma, and 8.3% Delta.

All findings agree with other reports in different studies that show the benefit of COVID-19 vaccines, protecting specially against severe disease but not against infection or re-infection.
Cilostazol and isosorbide mononitrate for the prevention of progression of cerebral small vessel disease: Baseline data and statistical analysis plan for the Lacunar Intervention Trial-2 (LACI-2) (ISRCTN14911850)
Authors: Bath Philip M , Mhlanga Iris , Woodhouse Lisa J , Doubal Fergus , Oatey Katherine , Montgomery Alan A , Wardlaw Joanna M ,   the LACI-2 Investigators
Published: June 2022

Background

Cerebral small vessel disease (SVD) causes lacunar strokes (25% of all ischaemic strokes), physical frailty and cognitive impairment and vascular and mixed dementia. There is no specific treatment to prevent progression of SVD.

Methods

The LACunar Intervention Trial-2 (LACI-2) is an investigator-initiated prospective randomised open-label blinded-endpoint (PROBE) phase II feasibility study assessing cilostazol and isosorbide mononitrate for preventing SVD progression. We aimed to recruit 400 patients with clinically-evident lacunar ischaemic stroke and randomised to cilostazol, isosorbide mononitrate, both or neither, in addition to guideline secondary ischaemic stroke prevention, in a partial factorial design. The primary outcome is feasibility of recruitment and adherence to medication; key secondary outcomes include: drug tolerability; recurrent vascular events, cognition and function at one year after randomisation; and safety (bleeding, falls, death). Data are number (%), and median [interquartile range].

Results

The trial commenced on 5th of February 2018 and ceased recruitment on 31st of May 2021 with 363 patients randomised, with the following baseline characteristics: average age 64 [56.0, 72.0] years, female 112 (30.9%), stroke onset to randomisation 79.0 [27.0, 244.0] days, hypertension 267 (73.6%), median blood pressures 143.0 [130.0, 157.0]/83.0 [75.0, 90.0] mmHg, current smokers 67 (18.5%), educationally achieved end of school examinations (A-level) or higher 118 (32.5%), modified Rankin scale 1.0 [0.0, 1.0], National Institutes Health stroke scale (NIHSS) 1.0 (1.4), Montreal Cognitive Assessment 26.0 [23.0, 28.0] and total SVD score on brain imaging 1.0 [0.0, 2.0]. This publication summarises the baseline data and presents the statistical analysis plan.

The trial is currently in follow-up which will complete on 31 May 2022 with results expected in October 2022.
Symptom variation, correlations, and relationship to physical activity in Long Covid: intensive longitudinal study
Authors: Burton Christopher , Dawes Helen , Goodwill Simon , Thelwell Michael , Dalton Caroline
Published: June 2022

Background

People with Long Covid (Post-Acute Sequelae of Covid-19) describe multiple symptoms which vary between and within individuals over relatively short time intervals. We aimed to describe the real-time associations between different symptoms and between symptoms and physical activity at the individual patient level.

Methods and Findings

Intensive longitudinal study of 82 adults with self-reported Long Covid (median duration 12-18 months). Data collection involved a smartphone app with 5 daily entries over 14 days and continuous wearing of a wrist accelerometer. Data items included 7 symptoms (Visual Analog Scales) and perceived demands in the preceding period (Likert scales). Activity was measured using mean acceleration in the 3-hour periods preceding and following app data entry. Analysis used within-person correlations of symptoms pairs and both pooled and individual symptom networks derived from graphical vector autoregression.

App data was suitable for analysis from 74 participants (90%) comprising 4022 entries representing 77.6% of possible entries. Symptoms varied substantially within individuals and were only weakly auto-correlated. The strongest between-subject symptom correlations were of fatigue with pain (partial coefficient 0.5) and cognitive difficulty with light-headedness (0.41). Pooled within-subject correlations showed fatigue correlated with cognitive difficulty (partial coefficient 0.2) pain (0.19) breathlessness (0.15) and light-headedness (0.12) but not anxiety. Cognitive difficulty was correlated with anxiety and light-headedness (partial coefficients 0.16 and 0.17). Individual participant correlation heatmaps and symptom networks showed no clear patterns indicative of distinct phenotypes.

Symptoms, including fatigue, were inconsistently correlated with prior or subsequent physical activity: this may reflect adjustment of activity in response to symptoms. Delayed worsening of symptoms after the highest activity peak was observed in 7 participants.

Conclusion

Symptoms of Long Covid vary within individuals over short time scales, with heterogenous patterns of symptom correlation. The findings are compatible with altered central symptom processing as an additional factor in Long Covid.
A systematic review and meta analysis of the valve of SHOX2 and RASSF1A gene methylation in bronchial elveslar lavage fluid in the diagnosis of lung cancer
Authors: Su Shanyang , Huang Yanling , Lu Xiang , Li Wenjia , Li Yongshun , Zhou Jihong
Published: June 2022

Introduction

The incidence of lung cancer worldwide has been increasing in recent years, and the latest cancer data published by the WHO International Agency for Research on Cancer in 2021 shows that lung cancer remains the cancer with the highest mortality rate. The sensitivity of early screening methods for lung cancer is not ideal. Because early lung cancer is mostly located in nodules with a diameter of 1 cm, it is difficult to obtain a definite pathological diagnosis from living tissue specimens. Therefore, it is necessary to find less invasive and effective tests to help detect lung cancer early. Therefore, the purpose of this systematic review (SR) and meta-analysis will be to analyze and explore the correlation between promoter methylation of SHOX2 and RASSF1A genes and lung cancer, and to provide a reference for early clinical diagnosis.

Methods and Analysis

The relevant literature will be comprehensively searched in 4 international electronic databases (PubMed, Cochrane Library, EMBASE and Web of Science) and 4 Chinese electronic databases (CNKI, VIP, Wanfang, Chinese Biomedicine). We only included studies from inception until publication in May 2022. The primary outcome measure was the methylation rate of the SHOX2 and RASSF1A gene promoters in lung cancer tissue and normal lung tissue in the control group in lung cancer patients. Secondary outcome measures included methylation rates of promoters of SHOX2 and RASSF1A genes in different tissue samples. Two reviewers will conduct independent research selection, data extraction, data synthesis and quality assessment. The assessment of bias risk and data synthesis will be conducted using Review Manager 5.3 software. The Cochrane Collaboration’s Bias Risk Assessment Tool (QUADAS) will be used to assess the quality of the individual studies included.

Discussion

This systematic review will help to clarify the correlation between PROMOTER methylation of the SHOX2 and RASSF1A genes with lung cancer, providing clinical evidence for early clinical diagnosis.

Trial registration number

CRD42022330609 (PROSPERO)
Correlation of IL-6, Coping, &Depression in Adolescent and Adult Patients Receiving Hemodialysis: A Comparative Study
Authors: Kamal Sanaa A. , Khoweiled Aref A. , Gomaa Maged E. , Al-Dawy Sameh A. , Kamel Reham M. , Ayoub Doaa R.
Published: June 2022

Background

The research has long reported that depression and stress are highly prevalent among patients with end-stage kidney disease requiring dialysis. Growing studies suggest that the inflammatory gene IL-6, in particular, contributes to the etiology of depression & stress by affecting the function of serotonin; one of the other explanations is by causing hypercortisolemia with overstimulation of the HPA axis. This study aimed to assess the inflammatory gene IL-6 in adolescent & adult patients with end-stage kidney disease receiving hemodialysis. Furthermore, to assess the coping skills of those patients upon the emergence of depressive symptoms & stress levels.

Method

One hundred and twenty-one patients receiving hemodialysis were recruited in a cross-sectional study from King Fahd Unit at Kasr Al-Ainy Hospital, Cairo University, Egypt. They were assessed for depression using Beck’s II depression inventory, stress by the stress perceived scale, coping by the short COPE questionnaire & they had inflammatory gene IL-6 level measured.

Results

Seventy-six patients showed depressive symptoms; adults were more depressed than adolescent patients, yet adolescents were subjected to more stress. The mean level of Interleukin-6 was 148.0±50.5pg/ml, which is higher than average. Perceived Stress Scale mean scores showed a statistically significant difference between depressed adults and adolescents (p=0.050).

Conclusions

Inflammatory gene IL-6 shows a higher level in depressed adolescent and adult patients receiving hemodialysis. Adult patients are more depressed than adolescent patients with end-stage kidney disease yet coping strategies are far better in depressed adolescents than adults.
A genetic strategy to measure insulin signaling regulation and physiology in Drosophila
Authors: Tsao Deborah D. , Chang Kathleen R. , Kockel Lutz , Park Sangbin , Kim Seung K.
Published: June 2022

Insulin regulation is a hallmark of health, and impaired insulin signaling promotes metabolic diseases like diabetes mellitus. However, current assays for measuring insulin signaling in all animals remain semi-quantitative and lack the sensitivity, tissue-specificity or temporal resolution needed to quantify in vivo physiological signaling dynamics. Insulin signal transduction is remarkably conserved across metazoans, including insulin-dependent phosphorylation and regulation of Akt/Protein kinase B. Here, we generated transgenic fruit flies permitting tissue-specific expression of an immunoepitope-labelled Akt (AktHF). We developed enzyme-linked immunosorption assays (ELISA) to quantify picomolar levels of phosphorylated (pAktHF) and total AktHF in single flies, revealing dynamic tissue-specific physiological regulation of pAktHF in response to fasting and re-feeding, exogenous insulin, or targeted genetic suppression of established insulin signaling regulators. Genetic screening revealed Pp1-87B as an unrecognized regulator of Akt and insulin signaling. Tools and concepts here provide opportunities to discover tissue-specific regulators of in vivo insulin signaling responses.

Author Summary

Insulin is an essential hormone that controls metabolism in all animals, by regulating energy use and growth of target tissues. Impaired insulin signaling (“resistance”) in humans underlies development of type 2 diabetes, a pandemic disease causing significant morbidity and mortality. The genetic risk for insulin resistance is complex, and studies of diabetes are limited by a lack of tools to measure insulin resistance in a sensitive, quantitative, and tissue-specific way. Here, we describe a new technique to measure the strength of insulin signaling in fruit flies. By combining fruit fly genetics with antibody-based assays, we can quantify phosphorylated Akt, an evolutionarily conserved target of insulin signaling, in specific tissues of the adult fly. We show this technique can detect changes in insulin signaling after fasting and refeeding, addition of exogenous insulin, or genetic disruption of the insulin signaling pathway. We used this method to discover a new regulator of insulin signaling, a phosphatase enzyme encoded by Pp1-87B. This exciting new tool should advance our ability to study and discover additional regulators of insulin signaling and resistance.
Symptoms and signs of lung cancer prior to diagnosis: Comparative study using electronic health records
Authors: Prado Maria G. , Kessler Larry G. , Au Margaret A. , Burkhardt Hannah A. , Suchsland Monica Zigman , Kowalski Lesleigh , Stephens Kari A. , Yetisgen Meliha , Walter Fiona M. , Neal Richard D. , Lybarger Kevin , Thompson Caroline A. , Achkar Morhaf Al , Sarma Elizabeth A. , Turner Grace , Farjah Farhood , Thompson Matthew
Published: June 2022

Background

Lung cancer is the most common cause of cancer-related death in the United States (US), with most patients diagnosed at later stages (3 or 4). While most patients are diagnosed following symptomatic presentation, no studies have compared symptoms and physical examination signs at or prior to diagnosis from electronic health records (EHR) in the United States (US).

Objective

To identify symptoms and signs in patients prior to lung cancer diagnosis in EHR data.

Study Design

Case-control study.

Methods

We studied 698 primary lung cancer cases in adults diagnosed between January 1, 2012 and December 31, 2019, and 6,841 controls matched by age, sex, smoking status, and type of clinic. Coded and free-text data from the EHR were extracted from 2 years prior to diagnosis date for cases and index date for controls. Univariate and multivariate conditional logistic regression were used to identify symptoms and signs associated with lung cancer. Analyses were repeated excluding symptom data from 1, 3, 6, and 12 months before the diagnosis/index dates.

Results

Eleven symptoms and signs recorded during the study period were associated with a significantly higher chance of being a lung cancer case in multivariate analyses. Of these, seven were significantly associated with lung cancer six months prior to diagnosis: hemoptysis (OR 3.2, 95%CI 1.9-5.3), cough (OR 3.1, 95%CI 2.4-4.0), chest crackles or wheeze (OR 3.1, 95%CI 2.3-4.1), bone pain (OR 2.7, 95%CI 2.1-3.6), back pain (OR 2.5, 95%CI 1.9-3.2), weight loss (OR 2.1, 95%CI 1.5-2.8) and fatigue (OR 1.6, 95%CI 1.3-2.1).

Conclusions

Patients diagnosed with lung cancer appear to have symptoms and signs recorded in the EHR that distinguish them from similar matched patients in ambulatory care, often six months or more before their diagnosis. These findings suggest opportunities to improve the diagnostic process for lung cancer in the US.
Artificial intelligence tool for the study of COVID-19 microdroplet spread across the human diameter and airborne space
Authors: Alsaadi Hesham H. , Aldwairi Monther , Yasin Faten , Cachinho Sandra C. P. , Hussein Abdullah
Published: June 2022

The 2019 novel coronavirus (SARS-COV2 / COVID-19), with a point of origin in Wuhan, China, has spread rapidly all over the world. It turned into a raging pandemic wrecking havoc on health care facilities, world economy and affecting everyone’s life to date. With every new variant, rate of transmission, spread of infections and the number of cases continues to rise at an international level and scale. There are limited reliable researches that study microdroplets spread and transmissions from human sneeze or cough in the airborne space. In this paper, we propose an intelligent technique to visualize, detect, measure the distance of the spread in a real-world settings of microdroplet transmissions in airborne space, called ”COVNET45”. In this paper, we investigate the microdroplet transmission and validate the measurements accuracy compared to published researches, by examining several microscopic and visual images taken to investigate the novel coronavirus (SARS-COV2 / COVID-19). The ultimate contribution is to calculate the spread of the microdroplets measurements precisely with graphical presentation.