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PloS One 2024Danish women-who were HPV-vaccinated as girls-are now reaching an age where they are invited to cervical cancer screening. Because of their expected lower cervical... (Observational Study)
Observational Study
BACKGROUND
Danish women-who were HPV-vaccinated as girls-are now reaching an age where they are invited to cervical cancer screening. Because of their expected lower cervical cancer risk, we must reassess our screening strategies. We analyzed Danish HPV-vaccinated women's outcomes after the first screening test at age 23.
METHODS AND FINDINGS
Our study was embedded in Danish routine cytology-based screening. We conducted an observational study and included women born in 1994, offered the 4-valent HPV vaccine at age 14, and subsequently invited to screening at age 23. Cervical cytology was used for diagnostics and clinical management. Residual material was HPV tested with Cobas® 4800/6800. The most severe histology diagnosis within 795 days of screening was found through linkage with the Danish National Pathology Register. We calculated the number of women undergoing follow-up (repeated testing and/or colposcopy) per detected cervical intraepithelial neoplasia (CIN2+). A total of 6021 women were screened; 92% were HPV-vaccinated; 12% had abnormal cytology; 35% were high-risk HPV-positive, including 0.9% HPV16/18 positive, and 20% had follow-up. In women that were cytology-abnormal and HPV-positive (Cyt+/HPV+), 610 (98.5%) had been followed up, and 138 CIN2+ cases were diagnosed, resulting in 4.4 (95% CI 3.9-5.2) women undergoing follow-up per detected CIN2+. In contrast to recommendations, 182 (12.2%) cytology-normal and HPV-positive (Cyt-/HPV+) women were followed up within 795 days, and 8 CIN2+ cases were found, resulting in 22.8 (95% CI 13.3-59.3) women undergoing follow-up per detected CIN2+.
CONCLUSION
Overall, HPV prevalence was high in HPV-vaccinated women, but HPV16/18 had largely disappeared. In the large group of cytology-normal and HPV-positive women, 23 had been followed up per detected CIN2+ case. Our data indicated that primary HPV screening of young HPV-vaccinated women would require very effective triage methods to avoid an excessive follow-up burden.
TRIAL REGISTRATION
Trial registration number: NCT0304955.
Topics: Humans; Female; Denmark; Papillomavirus Vaccines; Uterine Cervical Neoplasms; Papillomavirus Infections; Early Detection of Cancer; Young Adult; Cohort Studies; Uterine Cervical Dysplasia; Adult; Adolescent; Vaccination; Human papillomavirus 18; Mass Screening
PubMed: 38917143
DOI: 10.1371/journal.pone.0306044 -
BMC Public Health Jun 2024Human trafficking is a human rights violation and urgent public health challenge. It involves the exploitation of a person by means of force, intimidation or deceit and...
BACKGROUND
Human trafficking is a human rights violation and urgent public health challenge. It involves the exploitation of a person by means of force, intimidation or deceit and causes severe health risks. Though it occurs all over the world, its true extent is still unknown. Refugees are especially vulnerable to human trafficking due to language barriers and difficult living conditions. Therefore, the purpose of this study was to estimate the prevalence and design a screening tool to identify survivors of all forms of human trafficking among refugees in a German state registration and reception centre.
METHODS
In cooperation with the local authorities and the Ministry of Justice and for Migration Baden-Württemberg, we interviewed newly arrived refugees at an initial reception centre in Southern Germany to assess the prevalence of human trafficking. We used both a combination of the Adult Human Trafficking Screening Tool and a publication by Mumma et al. to assess all forms of human trafficking.
RESULTS
In total, 13 of the 176 refugees had experienced trafficking, which corresponded to a prevalence of 7.3% (95%-CI = [3.5%, 11.3%]). Across all languages the questionnaire had a sensitivity of 76.9% and a specificity of 84.0% at a recommended cut-off of six positive responses. The recommended cut-off differed slightly for the Arabic, Farsi, Turkish, and English version. In an exploratory descriptive analysis on subregions, refugees from West Africa had a substantially higher prevalence (33.3%, 8 out of 24) for human trafficking within our sample, especially women. However, when we excluded this region from our analysis, we found no significant gender difference for the rest of the sample.
CONCLUSIONS
The high prevalence of trafficking in most regions, regardless of gender, suggests that more effort is needed to identify and protect all trafficked persons. The designed screening tool seems to be a promising tool to detect an especially vulnerable group of refugees and provides assistance in identifying survivors of human trafficking.
Topics: Humans; Refugees; Human Trafficking; Female; Male; Adult; Prevalence; Germany; Surveys and Questionnaires; Young Adult; Middle Aged; Mass Screening; Adolescent
PubMed: 38914998
DOI: 10.1186/s12889-024-18997-7 -
Scientific Reports Jun 2024COVID-19 has caused a worldwide pandemic, creating an urgent need for early detection methods. Breath analysis has shown great potential as a non-invasive and rapid...
COVID-19 has caused a worldwide pandemic, creating an urgent need for early detection methods. Breath analysis has shown great potential as a non-invasive and rapid means for COVID-19 detection. The objective of this study is to detect patients infected with SARS-CoV-2 and even the possibility to screen between different SARS-CoV-2 variants by analysis of carbonyl compounds in breath. Carbonyl compounds in exhaled breath are metabolites related to inflammation and oxidative stress induced by diseases. This study included a cohort of COVID-19 positive and negative subjects confirmed by reverse transcription polymerase chain reaction between March and December 2021. Carbonyl compounds in exhaled breath were captured using a microfabricated silicon microreactor and analyzed by ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). A total of 321 subjects were enrolled in this study. Of these, 141 (85 males, 60.3%) (mean ± SD age: 52 ± 15 years) were COVID-19 (55 during the alpha wave and 86 during the delta wave) positive and 180 (90 males, 50%) (mean ± SD age: 45 ± 15 years) were negative. Panels of a total of 34 ketones and aldehydes in all breath samples were identified for detection of COVID-19 positive patients. Logistic regression models indicated high accuracy/sensitivity/specificity for alpha wave (98.4%/96.4%/100%), for delta wave (88.3%/93.0%/84.6%) and for all COVID-19 positive patients (94.7%/90.1%/98.3%). The results indicate that COVID-19 positive patients can be detected by analysis of carbonyl compounds in exhaled breath. The technology for analysis of carbonyl compounds in exhaled breath has great potential for rapid screening and detection of COVID-19 and for other infectious respiratory diseases in future pandemics.
Topics: Humans; COVID-19; Breath Tests; Male; Middle Aged; Female; Adult; Aged; SARS-CoV-2; Exhalation; Aldehydes; Chromatography, High Pressure Liquid; Mass Spectrometry
PubMed: 38914586
DOI: 10.1038/s41598-024-61735-7 -
PloS One 2024Stroke stands as a significant macrovascular complication among individuals with Type 2 diabetes mellitus (T2DM), often resulting in the primary cause of mortality and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Stroke stands as a significant macrovascular complication among individuals with Type 2 diabetes mellitus (T2DM), often resulting in the primary cause of mortality and disability within this patient demographic. Presently, numerous studies have been conducted to investigate the underlying causes of stroke in individuals with T2DM, yet the findings exhibit inconsistencies.
OBJECTIVE
This paper aims to consolidate and summarize the available evidence concerning the influential factors contributing to stroke among patients diagnosed with T2DM.
METHODS
We conducted a comprehensive search across multiple databases, including Cochrane Library, PubMed, Web Of Science, Embase, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), Wanfang and Weipu up to August 2023. Google Scholar was also searched to retrieve gray literature. We calculated odds ratios (OR) and 95% confidence intervals (CI) using Stata software.
RESULTS
Our analysis encompassed 43 observational studies, exploring factors across sociodemographic, biochemical, complications, and hypoglycemic agent categories. The findings identified several risk factors for stroke in patients with T2DM: age, gender, T2DM duration, hypertension, body-mass index (BMI), smoking, Glycated hemoglobin (HbA1c), estimated Glomerular Filtration Rate (eGFR), albuminuria, Triglycerides (TG), Low density lipoprotein cholesterol (LDL-C), Coronary heart disease (CHD), Atrial fibrillation (AF), diabetic retinopathy (DR), Peripheral vascular disease (PVD), and carotid plaque. Conversely, exercise, High density lipoprotein cholesterol (HDL-C), metformin (MET), pioglitazone, and metformin combination therapy emerged as protective factors.
CONCLUSION
This study underscores the multitude of influencing factors contributing to stroke in people with T2DM patients, among which the microvascular complications of T2DM play an most important role. Therefore, we emphasize the importance of screening for microvascular complications in patients with T2DM. However, due to limitations arising from the number of articles reviewed, there remain areas where clarity is lacking. Further research efforts are warranted to expand upon and reinforce our current findings.
Topics: Diabetes Mellitus, Type 2; Humans; Stroke; Risk Factors; Hypoglycemic Agents; Glycated Hemoglobin
PubMed: 38913694
DOI: 10.1371/journal.pone.0305954 -
PloS One 2024HIV, opioid use disorder (OUD), and mental health challenges share multiple syndemic risk factors. Each can be effectively treated with routine outpatient appointments,...
BACKGROUND
HIV, opioid use disorder (OUD), and mental health challenges share multiple syndemic risk factors. Each can be effectively treated with routine outpatient appointments, medication management, and psychosocial support, leading implementers to consider integrated screening and treatment for OUD and mental health in HIV care. Provider perspectives are crucial to understanding barriers and strategies for treatment integration.
METHODS
We conducted in-depth qualitative interviews with 21 HIV treatment providers and social services providers (12 individual interviews and 1 group interview with 9 participants) to understand the current landscape, goals, and priorities for integrated OUD, mental health, and HIV care. Providers were purposively recruited from known clinics in Mecklenburg County, North Carolina, U.S.A. Data were analyzed using applied thematic analysis in the NVivo 12 software program and evaluated for inter-coder agreement.
RESULTS
Participants viewed substance use and mental health challenges as prominent barriers to engagement in HIV care. However, few organizations have integrated structured screening for substance use and mental health into their standard of care. Even fewer screen for opioid use. Although medication assisted treatment (MAT) is effective for mitigating OUD, providers struggle to connect patients with MAT due to limited referral options, social barriers such as housing and food insecurity, overburdened staff, stigma, and lack of provider training. Providers believed there would be clear benefit to integrating OUD and mental health treatment in HIV care but lacked resources for implementation.
CONCLUSIONS
Integration of screening and treatment for substance use and mental health in HIV care could mitigate many current barriers to treatment for all three conditions. Efforts are needed to train HIV providers to provide MAT, expand resources, and implement best practices.
Topics: Humans; HIV Infections; Opioid-Related Disorders; Male; Female; Qualitative Research; Mass Screening; Adult; Mental Health; Middle Aged; Health Personnel; North Carolina
PubMed: 38913659
DOI: 10.1371/journal.pone.0305174 -
JAMA Network Open Jun 2024Congenital heart disease (CHD) is the most common human organ malformation, affecting approximately 1 of 125 newborns globally.
IMPORTANCE
Congenital heart disease (CHD) is the most common human organ malformation, affecting approximately 1 of 125 newborns globally.
OBJECTIVES
Assessing the performance of 2 diagnostic tests using minimal amounts of dried blood spots (DBS) to identify high-risk CHD compared with controls in a Swedish cohort of neonates.
DESIGN, SETTING, AND PARTICIPANTS
This diagnostic study took place in Sweden between 2019 and 2023 and enrolled full-term babies born between 2005 and 2023. All cases were identified through centralized pediatric cardiothoracic surgical services in Lund and Gothenburg, Sweden. Controls were followed up for 1 year to ensure no late presentations of high-risk CHD occurred. Cases were verified through surgical records and echocardiography.
EXPOSURE
High-risk CHD, defined as cases requiring cardiac surgical management during infancy due to evolving signs of heart failure or types in which the postnatal circulation depends on patency of the arterial duct. Using 3-μL DBS samples, automated quantitative tests for NT-proBNP and interleukin 1 receptor-like 1 (IL-1 RL1; formerly known as soluble ST2) were compared against established CHD screening methods.
MAIN OUTCOMES AND MEASURES
Performance of DBS tests to detect high-risk CHD using receiver operating characteristic curves; Bland-Altman and Pearson correlation analyses to compare IL-1 RL1 DBS with plasma blood levels.
RESULTS
A total of 313 newborns were included (mean [SD] gestational age, 39.4 [1.3] weeks; 181 [57.8%] male). Mean (SD) birthweight was 3495 (483) grams. Analyzed DBS samples included 217 CHD cases and 96 controls. Among the CHD cases, 188 participants (89.3%) were high-risk types, of which 73 (38.8%) were suspected prenatally. Of the 188 high-risk cases, 94 (50.0%) passed pulse oximetry screening and 36 (19.1%) were initially discharged after birth without diagnoses. Combining NT-proBNP and IL-1 RL1 tests performed well in comparison with existing screening methods and enabled additional identification of asymptomatic babies with receiver operating characteristic area under the curve 0.95 (95% CI, 0.93-0.98).
CONCLUSIONS AND RELEVANCE
In this diagnostic study, NT-proBNP and IL-1 RL1 DBS assays identified high-risk CHD in a timely manner, including in asymptomatic newborns, and improved overall screening performance in this cohort from Sweden. Prospective evaluation of this novel approach is warranted.
Topics: Humans; Infant, Newborn; Heart Defects, Congenital; Neonatal Screening; Dried Blood Spot Testing; Biomarkers; Female; Male; Sweden; Natriuretic Peptide, Brain; Peptide Fragments; Case-Control Studies; Interleukin-1 Receptor-Like 1 Protein
PubMed: 38913376
DOI: 10.1001/jamanetworkopen.2024.18097 -
Microbiology Spectrum Jun 2024is a life-threatening fungal pathogen that is a causative agent for pulmonary infection and meningoencephalitis in both immunocompetent and immunodeficient individuals....
UNLABELLED
is a life-threatening fungal pathogen that is a causative agent for pulmonary infection and meningoencephalitis in both immunocompetent and immunodeficient individuals. Recent studies have elucidated the important function of the target of rapamycin (TOR) signaling pathway in the modulation of virulence factor production and pathogenicity in animal infection models. Herein, we discovered that Ypk1, a critical component of the TOR signaling pathway, acts as a critical modulator in fungal pathogenicity through post-translational modifications (PTMs). Mass spectrometry analysis revealed that Ypk1 is subject to protein acetylation at lysines 315 and 502, and both sites are located within kinase functional domains. Inhibition of the TOR pathway by rapamycin activates the deacetylation process for Ypk1. The strain, a hyper-acetylation of Ypk1, exhibited increased sensitivity to rapamycin, decreased capsule formation ability, reduced starvation tolerance, and diminished fungal pathogenicity, indicating that deacetylation of Ypk1 is crucial for responding to stress. Deacetylase inhibition assays have shown that sirtuin family proteins are critical to the Ypk1 deacetylation mechanism. After screening deacetylase mutants, we found that Dac1 and Dac7 directly interact with Ypk1 to facilitate the deacetylation modification process via a protein-protein interaction. These findings provide new insights into the molecular basis for regulating the TORC-Ypk1 axis and demonstrate an important function of protein acetylation in modulating fungal pathogenicity.
IMPORTANCE
is an important opportunistic fungal pathogen in humans. While there are currently few effective antifungal treatments, the absence of novel molecular targets in fungal pathogenicity hinders the development of new drugs. There is increasing evidence that protein post-translational modifications (PTMs) can modulate the pathogenicity of fungi. In this study, we discovered that the pathogenicity of was significantly impacted by the dynamic acetylation changes of Ypk1, the immediate downstream target of the TOR complex. We discovered that Ypk1 is acetylated at lysines 315 and 502, both of which are within kinase functional domains. Deacetylation of Ypk1 is necessary for formation of the capsule structure, the response to the TOR pathway inhibitor rapamycin, nutrient utilization, and host infection. We also demonstrate that the sirtuin protein family is involved in the Ypk1 deacetylation mechanism. We anticipate that the sirtuin-Ypk1 regulation axis could be used as a potential target for the development of antifungal medications.
PubMed: 38912819
DOI: 10.1128/spectrum.00038-24 -
Biomarker Insights 2024Colorectal cancer (CRC) prognosis is determined by the disease stage with low survival rates for advanced stages. Current CRC screening programs are mainly using...
BACKGROUND
Colorectal cancer (CRC) prognosis is determined by the disease stage with low survival rates for advanced stages. Current CRC screening programs are mainly using colonoscopy, limited by its invasiveness and high cost. Therefore, non-invasive, cost-effective, and accurate alternatives are urgently needed.
OBJECTIVE AND DESIGN
This retrospective multi-center plasma proteomics study was performed to identify potential blood-based biomarkers in 36 CRC patients and 26 healthy volunteers by high-resolution mass spectrometry proteomics followed by the validation in an independent CRC cohort (60 CRC patients and 44 healthy subjects) of identified selected biomarkers.
RESULTS
Among the 322 identified plasma proteins, 37 were changed between CRC patients and healthy volunteers and were associated with the complement cascade, cholesterol metabolism, and SERPIN family members. Increased levels in CRC patients of the complement proteins C1QB, C4B, and C5 as well as pro-inflammatory proteins, lipopolysaccharide-binding protein (LBP) and serum amyloid A4, constitutive (SAA4) were revealed for first time. Importantly, increased level of C5 was verified in an independent validation CRC cohort. Increased C4B and C8A levels were correlated with cancer-associated inflammation and CRC progression, while cancer-associated inflammation was linked to the acute-phase reactant leucine-rich alpha-2-glycoprotein 1 (LRG1) and ceruloplasmin. Moreover, a 4-protein signature including C4B, C8A, apolipoprotein C2 (APO) C2, and immunoglobulin heavy constant gamma 2 was changed between early and late CRC stages.
CONCLUSION
Our results suggest that C5 could be a potential biomarker for CRC diagnosis. Further validation studies will aid the application of these new potential biomarkers to improve CRC diagnosis and patient care.
PubMed: 38911905
DOI: 10.1177/11772719241257739 -
Plastic and Reconstructive Surgery.... Jun 2024Endometriosis is a common gynecological disorder described as the presence of functional endometrial tissue outside the uterus, which can also be found in extrapelvic...
BACKGROUND
Endometriosis is a common gynecological disorder described as the presence of functional endometrial tissue outside the uterus, which can also be found in extrapelvic locations. Although patients seeking treatment for endometriosis usually present to gynecologists, there are rare cases of endometriosis encountered by plastic surgeons in routine practice, either incidentally or as a concomitant finding.
METHODS
We present a rare case of a 36-year-old woman with symptoms of panniculitis desiring panniculectomy. During surgery, an abdominal mass was excised and confirmed by pathological analysis to be endometriosis. A comprehensive literature review was conducted using the PubMed search engine of the National Institutes of Health to identify cases of endometriosis in plastic surgery. Following screening of the results, 14 articles were included in this analysis that fit the criteria of our search.
RESULTS
Of the 14 articles reviewed, cutaneous endometriosis was the most common subtype found in plastic surgery. None of the studies described findings of endometriosis in routine panniculectomies. Several identified endometriosis discovered during cosmetic abdominoplasties.
CONCLUSIONS
Endometriosis encountered in plastic surgery is a rare but clinically important occurrence, with the cutaneous subtype representing the majority of cases. Endometriosis should always be on the differential diagnosis when an abdominal mass is found in a patient with a history of abdominal surgery. Abdominal masses found during routine aesthetic or reconstructive surgery should be submitted for tissue analysis to guide possible secondary treatments.
PubMed: 38911574
DOI: 10.1097/GOX.0000000000005904 -
Journal of the Medical Library... Jan 2024To evaluate the ability of DynaMedex, an evidence-based drug and disease Point of Care Information (POCI) resource, in answering clinical queries using keyword searches.
OBJECTIVE
To evaluate the ability of DynaMedex, an evidence-based drug and disease Point of Care Information (POCI) resource, in answering clinical queries using keyword searches.
METHODS
Real-world disease-related questions compiled from clinicians at an academic medical center, DynaMedex search query data, and medical board review resources were categorized into five clinical categories (complications & prognosis, diagnosis & clinical presentation, epidemiology, prevention & screening/monitoring, and treatment) and six specialties (cardiology, endocrinology, hematology-oncology, infectious disease, internal medicine, and neurology). A total of 265 disease-related questions were evaluated by pharmacist reviewers based on if an answer was found (yes, no), whether the answer was relevant (yes, no), difficulty in finding the answer (easy, not easy), cited best evidence available (yes, no), clinical practice guidelines included (yes, no), and level of detail provided (detailed, limited details).
RESULTS
An answer was found for 259/265 questions (98%). Both reviewers found an answer for 241 questions (91%), neither found the answer for 6 questions (2%), and only one reviewer found an answer for 18 questions (7%). Both reviewers found a relevant answer 97% of the time when an answer was found. Of all relevant answers found, 68% were easy to find, 97% cited best quality of evidence available, 72% included clinical guidelines, and 95% were detailed. Recommendations for areas of resource improvement were identified.
CONCLUSIONS
The resource enabled reviewers to answer most questions easily with the best quality of evidence available, providing detailed answers and clinical guidelines, with a high level of replication of results across users.
Topics: Humans; Point-of-Care Systems; Evidence-Based Medicine
PubMed: 38911524
DOI: 10.5195/jmla.2024.1770