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PloS One 2024This cross-sectional study aims to describe doubts regarding the diagnosis and treatment of syphilis in pregnancy among primary care professionals in a telehealth...
This cross-sectional study aims to describe doubts regarding the diagnosis and treatment of syphilis in pregnancy among primary care professionals in a telehealth service. All teleconsultations (TCs) offered through TelessaúdeRS-UFRGS to primary health care (PHC) services in the state of Rio Grande do Sul between 2018 and 2021 involving syphilis in pregnancy were included. A total of 356 (TCs) were analyzed. The main doubts about syphilis during pregnancy raised by primary care professionals were related to the need for retreatment (35%), diagnostic definition (23%) and initial treatment (16%). In addition, 95% of TCs were suitable for diagnosing and treating syphilis based on the 2020 Brazilian Ministry of Health guideline. This study suggests that TCs can identify failures in the diagnosis and treatment of public health problems and support decision making in PHC involving syphilis in pregnancy.
Topics: Humans; Female; Pregnancy; Syphilis; Telemedicine; Primary Health Care; Cross-Sectional Studies; Adult; Pregnancy Complications, Infectious; Brazil; Health Personnel
PubMed: 38941327
DOI: 10.1371/journal.pone.0306192 -
PloS One 2024Frequent use of pain relief medications among patients with migraine can result in disease worsening and medication-overuse headache (MOH), a painful and debilitating...
Frequent use of pain relief medications among patients with migraine can result in disease worsening and medication-overuse headache (MOH), a painful and debilitating condition. We sought to conduct a cross-sectional survey among adult patients diagnosed with migraine to determine: 1) their awareness of MOH, and 2) their knowledge of the condition and its prevention, and 3) the association of these factors with actual use of pain relief medications. We recruited and interviewed 200 English-speaking adults with migraine who had a clinic visit with a neurologist or primary care provider within the past month. Patients were identified via an electronic health record query. Almost 40% of participants had never heard of the term 'medication-overuse headache.' In bivariate analyses, participants who were Black or Hispanic and those with limited health literacy were less likely to have heard of MOH. Participants scored an average of 2.1 (range: 0-3) on a MOH knowledge measure; older participants, those with limited health literacy, lower education, and little or no migraine-related disability demonstrated less knowledge. Almost a third (31.5%) of patients reported overusing pain relief medication and were at risk for MOH. Overuse was not significantly associated with MOH awareness, knowledge, or sociodemographic factors, but was related to greater migraine-related disability. Our findings suggest that patient awareness and knowledge of MOH is suboptimal, particularly among older adults, racial and ethnic minority groups, and those with limited health literacy. Interventions are needed to prevent MOH and better inform patients about risks associated with frequent use of pain relief medications.
Topics: Humans; Male; Female; Adult; Migraine Disorders; Middle Aged; Health Knowledge, Attitudes, Practice; Headache Disorders, Secondary; Cross-Sectional Studies; Health Literacy; Analgesics; Aged; Young Adult; Awareness
PubMed: 38941310
DOI: 10.1371/journal.pone.0306264 -
The Journal of Clinical Investigation Jun 2024STING agonists can reprogram the tumor microenvironment to induce immunological clearance within the central nervous system. Using multiplexed sequential...
STING agonists can reprogram the tumor microenvironment to induce immunological clearance within the central nervous system. Using multiplexed sequential immunofluorescence (SeqIF) and the Ivy Glioblastoma Atlas, STING expression was found in myeloid populations and in the perivascular space. The STING agonist 8803 increased median survival in multiple preclinical models of glioblastoma, including QPP8, an immune checkpoint blockade-resistant model, where 100% of mice were cured. Ex vivo flow cytometry profiling during the therapeutic window demonstrated increases in myeloid tumor trafficking and activation, alongside enhancement of CD8+ T cell and NK effector responses. Treatment with 8803 reprogrammed microglia to express costimulatory CD80/CD86 and iNOS, while decreasing immunosuppressive CD206 and arginase. In humanized mice, where tumor cell STING is epigenetically silenced, 8803 therapeutic activity was maintained, further attesting to myeloid dependency and reprogramming. Although the combination with a STAT3 inhibitor did not further enhance STING agonist activity, the addition of anti-PD-1 antibodies to 8803 treatment enhanced survival in an immune checkpoint blockade-responsive glioma model. In summary, 8803 as a monotherapy demonstrates marked in vivo therapeutic activity, meriting consideration for clinical translation.
Topics: Animals; Glioblastoma; Tumor Microenvironment; Mice; Membrane Proteins; Humans; Cell Line, Tumor; Brain Neoplasms
PubMed: 38941297
DOI: 10.1172/JCI175033 -
PloS One 2024Art v4.01 is a well-known profilin protein belonging to the pan-allergens group and is commonly involved in triggering allergic asthma, polyallergy, and...
Art v4.01 is a well-known profilin protein belonging to the pan-allergens group and is commonly involved in triggering allergic asthma, polyallergy, and cross-sensitization. It is also referred to as Wormwood due to its origin. Crude wormwood extracts are applied for allergen-specific immunotherapy (AIT). Whether the recombinant Art v4.01 (rArt v4.01) can produce in vivo immunological tolerance by subcutaneous immunotherapy (SCIT) remains elusive. In this study, to investigate the in vivo immunological response of rArt v4.01, Th2, Th1, Treg, Th17 type-related cytokines and phenotypes of immune cells were tested, facilitating the exploration of the underlying mechanisms. The expression and purification of Art v4.01 were carried out using recombinant techniques. Allergic asthma female BALB/c mice were induced by subcutaneous sensitization of wormwood pollen extract and intranasal challenges. SCIT without adjuvant was performed using the rArt v4.01 and wormwood pollen extract for 2 weeks. Following exposure to challenges, the levels of immunoglobulin E (IgE), cytokines, and inflammatory cells were assessed through enzyme-linked immunosorbent assay (ELISA) and histological examination of sera, bronchoalveolar lavage fluid (BALF), and lung tissue. These parameters were subsequently compared between treatment groups receiving rArt v4.01 and wormwood pollen extract. The rArt v4.01 protein was expressed, which had a high purity (>90%) and an allergenic potency. Compared with the pollen extract, rArt v4.01 was superior in terms of reducing the number of white blood cells (WBCs), total nucleated cells (TNCs), and monocytes (MNs) in BALF and the degree of lung inflammation (1.77±0.99 vs. 2.31±0.80, P > 0.05). Compared with the model group, only rArt v4.01 reduced serum IgE level (1.19±0.25 vs. 1.61±0.17 μg/ml, P = 0.062), as well as the levels of Th2 type-related cytokines (interleukin-4 (IL-4) (107.18±16.17 vs. 132.47±20.85 pg/ml, P < 0.05) and IL-2 (19.52±1.19 vs. 24.02±2.14 pg/ml, P < 0.05)). The study suggested that rArt v4.01 was superior to pollen extract in reducing the number of inflammatory cells in BALF, pneumonitis, levels of pro-inflammatory cytokines, and serum IgE level. These findings confirmed that Art v4.01 could be a potential candidate protein for allergen-specific immunotherapy.
Topics: Animals; Female; Asthma; Mice; Mice, Inbred BALB C; Disease Models, Animal; Immune Tolerance; Recombinant Proteins; Cytokines; Immunoglobulin E; Pollen; Desensitization, Immunologic; Allergens; Profilins; Bronchoalveolar Lavage Fluid; Injections, Subcutaneous
PubMed: 38941291
DOI: 10.1371/journal.pone.0280418 -
JAMA Network Open Jun 2024
Topics: Humans; Opioid-Related Disorders; Primary Health Care; Health Knowledge, Attitudes, Practice; Female; Male; Adult; Middle Aged; Analgesics, Opioid; Cross-Sectional Studies; Surveys and Questionnaires
PubMed: 38941101
DOI: 10.1001/jamanetworkopen.2024.19094 -
JAMA Network Open Jun 2024Significant evidence gaps exist regarding the safety of smoking cessation pharmacotherapies during pregnancy, especially for the risk of congenital malformations....
IMPORTANCE
Significant evidence gaps exist regarding the safety of smoking cessation pharmacotherapies during pregnancy, especially for the risk of congenital malformations. Consequently, professional bodies advise against the use of varenicline and bupropion and recommend caution with nicotine replacement therapy (NRT). Contemporary estimates of the use of smoking cessation pharmacotherapies during pregnancy are lacking.
OBJECTIVE
To quantify the proportion of individuals using prescribed smoking cessation pharmacotherapies during pregnancy and during the first trimester specifically, in 4 countries.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective, population-based cohort study used linked birth records, hospital admission records, and dispensing records of prescribed medications from all pregnancies resulting in birth between 2015 and 2020 in New South Wales, Australia; New Zealand; Norway; and Sweden. Data analyses were conducted in October and November 2023.
EXPOSURE
Prescribed smoking cessation pharmacotherapy use (varenicline, NRT, and bupropion) during pregnancy was defined as days' supply overlapping the period from date of conception to childbirth.
MAIN OUTCOMES AND MEASURES
Prevalence of use among all pregnancies and pregnancies with maternal smoking were calculated. Among women who used a pharmacotherapy, the proportion of women with use during the first trimester of pregnancy was also calculated.
RESULTS
Among 1 700 638 pregnancies in 4 countries, 138 033 (8.1%) had maternal smoking and 729 498 (42.9%) were younger than 30 years. The prevalences ranged from 0.02% to 0.14% for varenicline, less than 0.01% to 1.86% for prescribed NRT, and less than 0.01% to 0.07% for bupropion. Among pregnant individuals who smoked, use of pharmacotherapies was up to 10 times higher, with maximum prevalences of 1.25% for varenicline in New South Wales, 11.39% for NRT in New Zealand, and 0.39% for bupropion in New Zealand. Use in the first trimester occurred among more than 90% of individuals using varenicline, approximately 60% among those using NRT, and 80% to 90% among those using bupropion.
CONCLUSIONS AND RELEVANCE
In this cohort study of pregnant individuals in 4 high-income countries, the low prevalence of varenicline and bupropion use during pregnancy and higher prevalence of NRT use aligned with current clinical guidelines. As most use occurred in the first trimester, there is a need for evidence on the risk of congenital malformations for these medications.
Topics: Humans; Female; Pregnancy; Smoking Cessation; Adult; Retrospective Studies; Smoking Cessation Agents; Varenicline; Bupropion; New Zealand; Tobacco Use Cessation Devices; Pregnancy Complications; Sweden; New South Wales; Norway; Young Adult; Smoking; Pregnancy Trimester, First
PubMed: 38941092
DOI: 10.1001/jamanetworkopen.2024.19245 -
JAMA Health Forum Jun 2024Despite growing interest in psychedelics, there is a lack of routine population-based surveillance of psychedelic microdosing (taking "subperceptual" doses of...
IMPORTANCE
Despite growing interest in psychedelics, there is a lack of routine population-based surveillance of psychedelic microdosing (taking "subperceptual" doses of psychedelics, approximately one-twentieth to one-fifth of a full dose, over prolonged periods). Analyzing Google search queries can provide insights into public interest and help address this gap.
OBJECTIVE
To analyze trends in public interest in microdosing in the US through Google search queries and assess their association with cannabis and psychedelic legislative reforms.
DESIGN, SETTING, AND PARTICIPANTS
In this cross-sectional study, a dynamic event-time difference-in-difference time series analysis was used to assess the impact of cannabis and psychedelic legislation on microdosing search rates from January 1, 2010, to December 31, 2023. Google search rates mentioning "microdosing," "micro dosing," "microdose," or "micro dose" within the US and across US states were measured in aggregate.
EXPOSURE
Enactment of (1) local psychedelic decriminalization laws; (2) legalization of psychedelic-assisted therapy and statewide psychedelic decriminalization; (3) statewide medical cannabis use laws; (4) statewide recreational cannabis use laws; and (5) all cannabis and psychedelic use restricted.
MAIN OUTCOME AND MEASURES
Microdosing searches per 10 million Google queries were measured, examining annual and monthly changes in search rates across the US, including frequency and nature of related searches.
RESULTS
Searches for microdosing in the US remained stable until 2014, then increased annually thereafter, with a cumulative increase by a factor of 13.4 from 2015 to 2023 (7.9 per 10 million to 105.6 per 10 million searches, respectively). In 2023, there were 3.0 million microdosing searches in the US. Analysis at the state level revealed that local psychedelic decriminalization laws were associated with an increase in search rates by 22.4 per 10 million (95% CI, 7.5-37.2), statewide psychedelic therapeutic legalization and decriminalization were associated with an increase in search rates by 28.9 per 10 million (95% CI, 16.5-41.2), statewide recreational cannabis laws were associated with an increase in search rates by 40.9 per 10 million (95% CI, 28.6-53.3), and statewide medical cannabis laws were associated with an increase in search rates by 11.5 per 10 million (95% CI, 6.0-16.9). From August through December 2023, 27.0% of the variation in monthly microdosing search rates between states was explained by differences in cannabis and psychedelics legal status.
CONCLUSION AND RELEVANCE
This cross-sectional study found that state-led legislative reforms on cannabis and psychedelics were associated with increased public interest in microdosing psychedelics.
Topics: Hallucinogens; Humans; United States; Cross-Sectional Studies; Cannabis; Legislation, Drug
PubMed: 38941086
DOI: 10.1001/jamahealthforum.2024.1653 -
Oncology and Therapy Jun 2024Breast cancer presents diverse molecular subtypes affecting treatment strategies. Human epidermal growth factor receptor 2 (HER2)-low, hormone receptor-positive (HR+)...
BACKGROUND
Breast cancer presents diverse molecular subtypes affecting treatment strategies. Human epidermal growth factor receptor 2 (HER2)-low, hormone receptor-positive (HR+) breast cancer poses a challenge due to limited targeted therapies. Current neoadjuvant treatment primarily utilizes chemotherapy, with conflicting results regarding efficacy in patients with HER2-low breast cancer. Trastuzumab deruxtecan (T-DXd) shows promise in HER2-low metastatic disease, and preliminary evidence suggests synergy with endocrine therapy.
OBJECTIVE
This editorial explores the hypothesis that neoadjuvant T-DXd with or without endocrine therapy offers efficacy in the clinical management of HR+/HER2-low breast cancer.
METHODS
We propose a phase II study with two treatment arms: T-DXd + letrozole and T-DXd alone. The primary endpoint is the radiological complete response rate. Secondary endpoints include pathological complete response rate, safety, event-free survival, and overall survival. Exploratory analyses will compare the arms to identify potential for optimizing treatment efficacy and minimizing side effects.
CONCLUSIONS
This study design allows for initial assessment of T-DXd with or without endocrine therapy in the treatment of HER2-low breast cancer. The findings may pave the way for personalized treatment strategies and inform future research, potentially leading to a chemotherapy-sparing approach.
PubMed: 38941050
DOI: 10.1007/s40487-024-00286-3 -
Alternative Therapies in Health and... Jun 2024Non-suicidal self-injury (NSSI) refers to direct and deliberate suicidal actions that damage the body but are not recognized by society and culture. Adolescence is the...
BACKGROUND
Non-suicidal self-injury (NSSI) refers to direct and deliberate suicidal actions that damage the body but are not recognized by society and culture. Adolescence is the transition period when children change into adult roles. At this time, teenagers are in the critical development period of physical and mental intelligence, and all aspects of their development have not yet been fully developed, so there are fierce inner conflicts. If the psychological problems of teenagers do not get timely counseling, it is very likely to choose self-injury suicide behavior, in such an extreme way to vent their bad emotions. The prevalence rate of NSSI among adolescents is much higher than that of other age groups. Studies have shown that psychological nursing is safe and effective, which can alleviate patients' negative emotions and avoid NSSI.
OBJECTIVE
To explore the impact of group psychological nursing with guardian participation on reducing NSSI behaviors and improving psychological well-being among adolescents.
DESIGN
This was a retrospective study.
SETTING
This study was performed in the Departments of the Third Psychiatry, Hangzhou Seventh People's Hospital.
PARTICIPANTS
132 adolescent patients with NSSI admitted to our center from August 2020 to July 2022 were selected as subjects and divided into 2 groups according to the time of admission, with 66 patients in each group.
INTERVENTIONS
Patients in the control group (CG) received drug therapy and commonly used cognitive behavioral therapy. Patients in the observation group (OG) received group psychological nursing with guardian participation. The participation of the guardian strengthens the level of understanding, tolerance and support of both parties, and helps to enhance the strength of family support, which in turn relives negative emotions.
PRIMARY OUTCOME MEASURES
(1) Ottawa self-injury inventory (OSI) scores were used to assess NSSI behavior severity; (2) Self-rating Anxiety Scale (SAS) and self-rating Depression Scale (SDS) scores were used to assess anxiety and depression; (3) General Self-efficacy Scale (GSES) scores were used to assess self-efficacy; (4) Trait Coping Style Questionnaire (TCSQ) scores were used to assess the quality of life; (5) social function Assessment Scale (SSPI) scores were used to assess social function; (6) Adolescent Life Events Scale (ASLEC) scores were used to evaluate the stress intensity of coping with life events; (7) multidimensional sub-health questionnaire assessment (MSQA) scores were used to assess adolescents' physical and psychological sub-health.
RESULTS
Before intervention, there were no significant differences in OSI, SAS, SDS, GSES, TCSO, SSPI ASLEC, and MSQA scores in both groups (P > .05). Compared to before intervention, the scores of OSI, SAS, SDS, GSES, TCSO, SSPI ASLEC and MSQA in both groups were improved after intervention (P < .05). The observation group showed significant improvements across all measures compared to the control group, indicating a reduction in NSSI behaviors and improvements in mental health.
CONCLUSION
Application of group psychological nursing with guardian participation in adolescent patients with NSSI behavior can better reduce NSSI behavior and improve physical and mental health, underline the importance of family support in treating NSSI, which also highlights the importance of family support in the treatment of NSSI.
PubMed: 38940803
DOI: No ID Found -
Translational Vision Science &... Jun 2024To compare changes in superficial retinal vascular density (SRVD), deep retinal vascular density (DRVD), and retinal thickness (RT) of the macular zone after repeated... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
PURPOSE
To compare changes in superficial retinal vascular density (SRVD), deep retinal vascular density (DRVD), and retinal thickness (RT) of the macular zone after repeated low-level red light (RLRL) and 0.01% atropine exposure in premyopic schoolchildren.
METHODS
Prospective randomized trial. Sixty-nine schoolchildren with cycloplegic refraction >-0.75 D and ≤0.50 D were randomly assigned to RLRL and 0.01% atropine groups. SRVD, DRVD, and RT were measured using swept-source optical coherence tomography at baseline and six months. The macular zone was divided into three concentric rings (fovea, parafovea, and perifovea) using the Early Treatment Diabetic Retinopathy Study.
RESULTS
After six months, the whole, parafoveal, and perifoveal SRVD significantly increased in the two groups (all P < 0.05). Multivariate regression analyses showed that none of these changes varied significantly between the two groups (all P > 0.05), whereas foveal SRVD remained stable in both groups (all P > 0.05). In the RLRL group, the whole and perifoveal DRVD increased significantly (all P < 0.05), whereas no statistical difference was observed in the foveal and parafoveal DRVD. DRVD remained stable in the 0.01% atropine group (all P > 0.05). No significant differences were observed in RT changes between the two groups (all P > 0.05). In comparison, there were no significant changes in SRVD, DRVD, or RT after six months in the placebo group in our previous study.
CONCLUSIONS
SRVD increased similarly in the RLRL and 0.01% atropine groups, whereas DRVD increased only in the former group. There were no significant RT changes in either group after six months of treatment in premyopic schoolchildren.
TRANSLATIONAL RELEVANCE
This research observed the effects of low-level red light and 0.01% atropine on retinal vasculature, offering valuable insights into myopia progression prevention.
Topics: Humans; Atropine; Male; Female; Child; Prospective Studies; Retinal Vessels; Mydriatics; Tomography, Optical Coherence; Myopia; Ophthalmic Solutions; Phototherapy; Microvascular Density; Red Light
PubMed: 38940757
DOI: 10.1167/tvst.13.6.23