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BACKGROUND: We assessed human papillomavirus (HPV) vaccine effectiveness (VE) against anal HPV among men who have sex with men (MSM) in 2018-2023. METHODS: Residual anal specimens from MSM without HIV ages 18-45 years were tested for HPV. We calculated adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) for associations between vaccination (≥1 dose) and quadrivalent vaccine (4vHPV)-type prevalence adjusting for city, race/ethnicity, and non-vaccine-type HPV prevalence, stratified by age group (18-26, 27-45). VE was calculated as (1-aPR)x100. RESULTS: Among 2802 persons aged 18-26, 4vHPV-type prevalence was lower in those vaccinated at age <18 (aPR=0.13, CI: 0.08-0.22, VE=87%) and those vaccinated ≥2 years before specimen collection (aPR=0.52, CI: 0.42-0.64, VE=48%), compared with unvaccinated persons. Among 3548 persons aged 27-45, 4vHPV-type prevalence was lower in those vaccinated at ages 18-26 (aPR=0.68, CI: 0.57-0.82, VE=32%) and those vaccinated ≥2 years before specimen collection (aPR=0.66, CI: 0.57-0.77, VE=33%), compared with unvaccinated persons. While we observed no VE in persons vaccinated at age >26 overall, 4vHPV-type prevalence was lower in the subgroup vaccinated ≥2 years before specimen collection (aPR=0.71, CI: 0.56-0.89, VE=29%). CONCLUSIONS: We found high VE against anal 4vHPV-type prevalence among MSM aged 18-26 who were vaccinated at age <18. Lower VE was observed among MSM ages 27-45 who were vaccinated at age 18-26 or ≥2 years before specimen collection. While ideally vaccination should be given at younger ages, vaccination can prevent some future infections in this population.
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BACKGROUND: The extent to which infections may have been undetected in an epicenter of the 2022 mpox outbreak is unknown. METHODS: A serosurvey (July and August 2022) assessed the seroprevalence and correlates of mpox infection among a diverse sample of asymptomatic patients with no prior mpox diagnoses and no known histories of smallpox or mpox vaccination. We present seropositivity stratified by participant characteristics collected via survey. RESULTS: Two-thirds of 419 participants were cismen (281 of 419), of whom 59.1% (166 of 281) reported sex with men (MSM). The sample also included 109 ciswomen and 28 transgender/gender nonconforming/nonbinary individuals. Overall seroprevalence was 6.4% (95% confidence interval [CI], 4.1%-8.8%); 3.7% among ciswomen (95% CI, 1.0%-9.1%), 7.0% among cismen with only ciswomen partners (95% CI, 2.0%-11.9%), and 7.8% among MSM (95% CI, 3.7%-11.9%). There was little variation in seroprevalence by race/ethnicity, age group, HIV status, or number of recent sex partners. No participants who reported close contact with mpox cases were seropositive. Among participants without recent mpox-like symptoms, 6.3% were seropositive (95% CI, 3.6%-9.0%). CONCLUSIONS: Approximately 1 in 15 vaccine-naive people in our study had antibodies to mpox during the height of the NYC outbreak, indicating the presence of asymptomatic infections that could contribute to ongoing transmission.
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In sub-Saharan Africa, adolescent girls and young women aged 15-24 (AGYW) experience high risk of early and unintended pregnancy. We assessed the impact of youth-friendly health services (YFHS) on pregnancy risk among AGYW who participated in the Girl Power study. In 2016, Girl Power randomly assigned four government-run health centers in Lilongwe, Malawi, to provide a standard (n=1) or youth-friendly (n=3) model of service delivery. At six and 12 months, study participants (n=250 at each health center) self-reported their current pregnancy status and received a urine pregnancy test. Because of missing pregnancy test results, we used multiple imputation to correct for outcome misclassification in self-reported pregnancy status, and applied the parametric g-formula on the corrected data to estimate the effect of YFHS on the 12-month risk of pregnancy. After correcting for outcome misclassification, the risk of pregnancy under the scenario where all health centers offered YFHS was 15.8% compared to 23.2% under the scenario where all health centers offered standard of care (risk difference: -7.3%, 95% CI: -15.5%, 0.8%). Access to a model of YFHS that integrates provider training with youth-friendly clinic modifications and community outreach activities may decrease risk of pregnancy among AGYW relative to standard of care.
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Capsid assembly mediated by hepatitis B virus (HBV) core protein (HBc) is an essential part of the HBV replication cycle, which is the target for different classes of capsid assembly modulators (CAMs). While both CAM-A ("aberrant") and CAM-E ("empty") disrupt nucleocapsid assembly and reduce extracellular HBV DNA, CAM-As can also reduce extracellular HBV surface antigen (HBsAg) by triggering apoptosis of HBV-infected cells in preclinical mouse models. However, there have not been substantial HBsAg declines in chronic hepatitis B (CHB) patients treated with CAM-As to date. To investigate this disconnect, we characterized the antiviral activity of tool CAM compounds in HBV-infected primary human hepatocytes (PHHs), as well as in HBV-infected human liver chimeric mice and mice transduced with adeno-associated virus-HBV. Mechanistic studies in HBV-infected PHH revealed that CAM-A, but not CAM-E, induced a dose-dependent aggregation of HBc in the nucleus which is negatively regulated by the ubiquitin-binding protein p62. We confirmed that CAM-A, but not CAM-E, induced HBc-positive cell death in both mouse models via induction of apoptotic and inflammatory pathways and demonstrated that the degree of HBV-positive cell loss was positively correlated with intrahepatic HBc levels. Importantly, we determined that there is a significantly lower level of HBc per hepatocyte in CHB patient liver biopsies than in either of the HBV mouse models. Taken together, these data confirm that CAM-As have a unique secondary mechanism with the potential to kill HBc-positive hepatocytes. However, this secondary mechanism appears to require higher intrahepatic HBc levels than is typically observed in CHB patients, thereby limiting the therapeutic potential.
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Vírus da Hepatite B , Hepatite B Crônica , Hepatócitos , Humanos , Hepatócitos/virologia , Hepatócitos/efeitos dos fármacos , Animais , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/fisiologia , Camundongos , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Proteínas do Core Viral/metabolismo , Antivirais/farmacologia , Antivirais/uso terapêutico , Antígenos do Núcleo do Vírus da Hepatite B/metabolismo , Capsídeo/metabolismo , Capsídeo/efeitos dos fármacos , Fígado/virologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Antígenos de Superfície da Hepatite B/metabolismo , Montagem de Vírus/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Replicação Viral/efeitos dos fármacosRESUMO
BACKGROUND: Public health emergencies can lead to reduced or suspended services in sexual health clinics (SHCs), raising questions about optimal ways to maintain access to care. We examined changes in sexual behaviors, HIV pre-exposure prophylaxis (PrEP) use, telehealth preference, and correlates of delayed sexual health care among patients attending New York City (NYC) publicly funded SHCs during the COVID-19 pandemic. METHODS: 470 patients from four SHCs (July-September 2021) completed a self-administered survey that collected data on access to sexual health care, overall and over three distinct time periods [Spring 2020 (COVID-19 wave 1), Summer 2020, Fall 2020/Winter 2021 (COVID-19 wave 2)]. We used log-binomial models to examine factors associated with delayed sexual health care. RESULTS: Participants reporting multiple in-person sexual contacts increased from 28% to 57% (P < 0.0001) between the first and second wave. Almost half of participants (35/72) taking HIV PrEP cited decreased use. Over 90% (423/460) of participants preferred in-person clinic visits over telehealth. Overall, delays in routine and urgent sexual health care were reported by 34% (129/375) and 12% (46/373) of participants, respectively. More men who have sex with men (MSM) and transgender/gender non-conforming/nonbinary (TGNCNB) individuals experienced delayed care compared with women [MSM: aPR 1.43 (95% CI, 1.00-2.03); TGNCNB: 1.67 (1.04-2.69)]. Compared with participants who primarily sought sexual health care from private providers, those who primarily used SHCs experienced significantly more delayed care [1.72 (1.14-2.59)]. CONCLUSIONS: Delays in sexual health care access can have serious implications for certain patient populations. Additional resources are needed to maintain access to sexual health clinic services.
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OBJECTIVE: The purpose of this paper is to systematically and critically appraise the available scientific evidence concerning the prevalence of edentulism among diabetic patients compared to non-diabetic people. METHODS: MEDLINE-PubMed and Cochrane-CENTRAL databases were comprehensively searched up to April 2023 to identify appropriate studies. The inclusion criteria were observational studies conducted in human subjects ≥18 years of age with the primary aim of investigating the prevalence of edentulism among diabetic patients. Based on the extracted data, a meta-analysis was performed. Recommendations based on the body of evidence were formulated using the GRADE approach. RESULTS: Independent screening of 2085 unique titles and abstracts revealed seven publications that met the eligibility criteria. Study size ranged from 293 to 15,943 participants. Data from all seven studies were suitable for meta-analysis. Overall, 8.3% of the studied population was edentulous. The weighted mean prevalence of edentulism among diabetic and non-diabetics was 14.0% and 7.1%, respectively. The overall odds ratio for diabetic patients to be edentulous as compared to non-diabetics was 2.39 (95% CI [1.73, 3.28], p < 0.00001). CONCLUSION: There appears to be moderate certainty that the risk of being edentulous for diabetic patients compared to non-diabetic people is significant, but the odds ratio is estimated to be small.
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Diabetes Mellitus , Arcada Edêntula , Humanos , Diabetes Mellitus/epidemiologia , Arcada Edêntula/complicaçõesRESUMO
The standard of care for the treatment of chronic hepatitis B (CHB) is typically lifelong treatment with nucleos(t)ide analogs (NAs), which suppress viral replication and provide long-term clinical benefits. However, infectious virus can still be detected in patients who are virally suppressed on NA therapy, which may contribute to the failure of these agents to cure most CHB patients. Accordingly, new antiviral treatment options are being developed to enhance the suppression of hepatitis B virus (HBV) replication in combination with NAs ("antiviral intensification"). Here, we describe GS-SBA-1, a capsid assembly modulator (CAM) belonging to class CAM-E, that demonstrates potent inhibition of extracellular HBV DNA in vitro (EC50 [50% effective concentration] = 19 nM) in HBV-infected primary human hepatocytes (PHHs) as well as in vivo in an HBV-infected immunodeficient mouse model. GS-SBA-1 has comparable activities across HBV genotypes and nucleos(t)ide-resistant mutants in HBV-infected PHHs. In addition, GS-SBA-1 demonstrated in vitro additivity in combination with tenofovir alafenamide (TAF). The administration of GS-SBA-1 to PHHs at the time of infection prevents covalently closed circular DNA (cccDNA) formation and, hence, decreases HBV RNA and antigen levels (EC50 = 80 to 200 nM). Furthermore, GS-SBA-1 prevents the production of extracellular HBV RNA-containing viral particles in vitro. Collectively, these data demonstrate that GS-SBA-1 is a potent CAM that has the potential to enhance viral suppression in combination with an NA.
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Hepatite B Crônica , Hepatite B , Animais , Camundongos , Humanos , Hepatite B Crônica/tratamento farmacológico , Capsídeo , Vírus da Hepatite B , Antivirais/farmacologia , Antivirais/uso terapêutico , Proteínas do Capsídeo/genética , RNA , DNA Viral/genética , DNA Circular , Hepatite B/tratamento farmacológicoRESUMO
Lenacapavir (LEN) is a picomolar first-in-class capsid inhibitor of human immunodeficiency virus type 1 (HIV-1) with a multistage mechanism of action and no known cross resistance to other existing antiretroviral (ARV) drug classes. LEN exhibits a low aqueous solubility and exceptionally low systemic clearance following intravenous (IV) administration in nonclinical species and humans. LEN formulated in an aqueous suspension or a PEG/water solution formulation showed sustained plasma exposure levels with no unintended rapid drug release following subcutaneous (SC) administration to rats and dogs. A high total fraction dose release was observed with both formulations. The long-acting pharmacokinetics (PK) were recapitulated in humans following SC administration of both formulations. The SC PK profiles displayed two-phase absorption kinetics in both animals and humans with an initial fast-release absorption phase, followed by a slow-release absorption phase. Noncompartmental and compartmental analyses informed the LEN systemic input rate from the SC depot and exit rate from the body. Modeling-enabled deconvolution of the input rates from two processes: absorption of the soluble fraction (minor) from a direct fast-release process leading to the early PK phase and absorption of the precipitated fraction (major) from an indirect slow-release process leading to the later PK phase. LEN SC PK showed flip-flop kinetics due to the input rate being substantially slower than the systemic exit rate. LEN input rates via the slow-release process in humans were slower than those in both rats and dogs. Overall, the combination of high potency, exceptional stability, and optimal release rate from the injection depot make LEN well suited for a parenteral long-acting formulation that can be administered once up to every 6 months in humans for the prevention and treatment of HIV-1.
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Fármacos Anti-HIV , HIV-1 , Humanos , Ratos , Animais , Cães , Antirretrovirais , Capsídeo , Fármacos Anti-HIV/farmacologia , Proteínas do CapsídeoRESUMO
Few longitudinal studies have measured contraceptive continuation past one year in sub-Saharan Africa. We surveyed 674 women who had been randomized to receive the three-month intramuscular contraceptive injectable (DMPA-IM), levonorgestrel (LNG) implant, or copper intrauterine device (IUD) during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial in South Africa and Zambia and were subsequently followed for two additional years to explore method continuation, reasons for discontinuation, and access to implant and IUD removal services. We also conducted in-depth qualitative interviews with 39 participants. We estimated cumulative discontinuation probabilities using Kaplan-Meier estimates and assessed factors associated with discontinuation using Cox-proportional hazards models. The LNG implant continuation rate over the maximum 44-month study period was 60 percent, while rates for the copper IUD and DMPA-IM were 52 percent and 44 percent, respectively. Reasons for method discontinuation included side effects, particularly menstrual changes, and method stock-outs. Most implant and IUD users who sought removal were able to access services; however, room for improvement exists. In this cohort originally randomized to receive a contraceptive method and attend regular study visits, implants and IUDs continued to be highly acceptable over an additional two years, but facilities should continue to ensure that insertions and removals are available as requested.
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Anticoncepcionais Femininos , Dispositivos Intrauterinos de Cobre , Feminino , Humanos , Levanogestrel/efeitos adversos , Dispositivos Intrauterinos de Cobre/efeitos adversos , África do Sul , Zâmbia , Anticoncepção/métodos , Anticoncepcionais Femininos/efeitos adversosRESUMO
INTRODUCTION: In 2018, the Malawi Ministry of Health adopted the recommendation to switch first-line antiretroviral therapy (ART) from an efavirenz (EFV)-based to a dolutegravir (DTG)-based regimen. Little is known about patients' experience during this transition. We conducted a qualitative study to explore DTG-related counselling challenges among providers of HIV care and factors influencing regimen switching or non-switching among women living with HIV in Lilongwe, Malawi. METHODS: Between February-July 2020, we recruited participants who took part in DTG counselling on reasons to switch, side effects, and benefits from two government health facilities providing HIV care: Area 18 health centre and Bwaila district hospital in Lilongwe, Malawi. We purposively sampled and interviewed 8 women living with HIV who remained on an EFV-based regimen after counselling, 10 women who switched to a DTG-based regimen, and 10 HIV care providers who provided counselling about ART switching. In-depth interviews were used to explore patient's perceptions of DTG, factors affecting the decision to switch, and both patient and provider experience with counselling. Interview data was coded for themes using inductive and deductive codes. Interviews were conducted until thematic saturation was achieved. Data matrices were used for analysis and thematic extraction. RESULTS: Most women in both groups were well versed on DTG's potential side effects and felt well counselled on the benefits of switching, such as quicker viral load suppression. Many women associated DTG with birth defects and expressed concern. However, the primary reason for not switching was concern with how the new medication would be tolerated, especially when they were satisfied with their current regimen. Almost all providers expressed difficulty providing DTG counselling. Primary reasons included feeling inadequately trained and/or not having resources to use during counselling, such as diagrams or brochures. CONCLUSION: DTG counselling was well accepted by women; however, some felt that their concerns were not fully addressed. Providers reflected this sentiment in that they did not feel adequately trained or well-equipped to provide adequate counselling. Training on counselling for new ART regimens should be intensified and utilize patient-centered educational materials to address the concerns raised by both patients and health care providers.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Infecções por HIV , Humanos , Feminino , Benzoxazinas , Aconselhamento , Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológicoRESUMO
BACKGROUND: "Self-care" for sexual and reproductive health (SRH) includes contraceptive methods and other supplies that people can use with or without the support of a healthcare provider. Self-administered tests, self-injection of injectable contraception, or self-removal of intrauterine devices (IUDs) can increase people's access to and autonomy over their own SRH. Objectives of this study were to assess women's current interest in and use of SRH self-care and explore key informants' (KI) opinions of self-care, especially during the COVID-19 pandemic. METHODS: Data for this study came from female participants in the longitudinal Contraceptive Use Beyond ECHO (CUBE) study, and KIs, including healthcare providers, in South Africa and Zambia between September 2020 and June 2021. For this analysis, we used data from a participant phone survey (n = 537), and from in-depth interviews (IDIs) completed with a sub-sample of women (n = 39) and KIs (n = 36). Survey data were analyzed with descriptive statistics, and IDI data were analyzed using applied thematic analysis. RESULTS: Female survey participants in South Africa were more interested in learning about emergency contraceptive pills, subcutaneous injectable contraception, and CycleBeads, while Zambian participants wanted more information and access to condoms. However, in IDIs in both countries, women described minimal experience with self-care beyond condom use. In the Zambian KI IDIs, COVID-19 led to increased self-care counseling on subcutaneous injectable contraception and HIV self-testing. KIs who do not counsel on self-care were concerned that women may harm themselves or blame the provider for difficulties. Two KIs thought that women could possibly self-remove IUDs, but most expressed concerns. Reported barriers to self-care included COVID movement restrictions, transport costs, lack of accessible pharmacies, women's low awareness, and possible stigma. CONCLUSIONS: Women surveyed reported interest in learning more about SRH self-care methods and resources, but in IDIs did not report extensive previous use besides condoms. KIs described some concerns about women's ability to use self-care methods. Counseling on and provision of self-care methods and supplies may have increased during the COVID-19 pandemic, but ensuring that self-care is more than just a temporary measure in health systems has the potential to increase access to SRH care and support women's autonomy and healthcare needs.
BACKGROUND: "Self-care" refers to healthcare that does not have to be given by a provider, but that people can use themselves. In sexual and reproductive health (SRH), this includes medicines or supplies like pills and injections that people can use to prevent or test for pregnancy or sexually transmitted infections. This study wanted to better understand women's interest in and use of SRH self-care and explore key informants' opinions of self-care, especially during the COVID-19 pandemic. METHODS: We surveyed 537 women in KwaZulu-Natal province, South Africa and Lusaka, Zambia in 20202021. We also conducted interviews with 39 women and 36 key informants, including healthcare providers, government officials, and community advocates. RESULTS: Women surveyed in South Africa were more interested than those in Zambia in learning more about self-care contraception, especially daily pills, emergency pills, and injections they could give themselves. In interviews, some key informants said that they do not tell women about self-care because they worried that women could hurt themselves or blame the provider if they experienced problems. COVID movement restrictions, transport costs, and inaccessible pharmacies were all barriers that key informants mentioned to accessing tests, tools, or contraceptive methods that women could give or use themselves. CONCLUSIONS: Women surveyed were interested in learning more about self-care and those interviewed reported minimal previous use of self-care methods besides condoms. Providers also have some concerns about women's ability to use self-care methods. Counseling on and providing self-care methods and supplies may have increased during COVID-19, but increasing access to self-care could help more women take care of their own sexual and reproductive healthcare.
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COVID-19 , Saúde Reprodutiva , Feminino , Humanos , Zâmbia/epidemiologia , África do Sul , Pandemias , Anticoncepção , Pessoal de SaúdeRESUMO
BACKGROUND: Low-income and uninsured people with a cervix (PWC) are at the highest risk of being underscreened for cervical cancer. We evaluated the prevalence of high-risk human papillomavirus (hrHPV) on home self-collected samples, as well as rates of in-clinic follow-up and risk factors associated with hrHPV positivity in this at-risk population. METHODS: My Body My Test 3 was conducted between 2016 and 2019 in North Carolina among individuals aged 25 to 64 years, overdue for cervical cancer screening, and with incomes of <250% of the US Federal Poverty Level. Our analytic sample included participants randomized to the self-collection arm who returned self-collected cervicovaginal brush samples for HPV testing (n = 329). Samples were tested for 14 hrHPV types by an HPV RNA assay and further genotyped for HPV-16 and HPV-18/45. We examined behavioral risk factors for hrHPV positivity using logistic regression and between-subject t tests. RESULTS: High-risk HPV RNA prevalence was 16% (n = 52/329) in self-collected samples. Of the hrHPV-positive participants, 24 (46%) presented for in-clinic cervical cancer screening, compared with 56 (20%) of hrHPV-negative participants. Those with ≥2 sexual partners in the past year were twice as likely to be hrHPV positive in adjusted analyses (adjusted odds ratio, 2.00 [95% confidence interval, 1.03-3.88]). High-risk HPV-positive and HPV-negative participants had similar attitudes toward screening, with the exception of hrHPV-positive participants who reported a lower perceived risk of cervical cancer than those who were hrHPV negative (P < 0.05). CONCLUSION: The hrHPV RNA prevalence was similar to findings in other underscreened PWC in the United States. Efforts to reach underscreened PWC are critical for cervical cancer prevention. Future studies aimed at home self-collection should address methods of increasing clinic attendance and completion of treatment among those with HPV-positive results.
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Alphapapillomavirus , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Adulto , Alphapapillomavirus/genética , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Pessoa de Meia-Idade , North Carolina/epidemiologia , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Aceitação pelo Paciente de Cuidados de Saúde , Prevalência , RNA , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controleRESUMO
Acyl glucuronides (AGs) are common metabolites of carboxylic acid-containing compounds. In some circumstances, AGs are suspected to be involved in drug toxicity due to formation of acyl migration products that bind covalently to cellular components. The risk of this adverse effect has been found to be correlated with the chemical stability of the AG, and assays have been described that monitor acyl migration by liquid chromatography coupled with mass spectrometry (LC-MS). This analysis can be challenging as it requires baseline chromatographic separation of the unmigrated 1-ß-acyl glucuronide from the migrated isomers and thus needs to be individually optimized for each aglycone. Therefore, a high-throughput assay that eliminates LC method development is desirable. Herein, we report an improved acyl glucuronide stability assay based on the rate of 18O-incorporation from [18O] water, which is compatible with high-throughput bioanalytical LC-MS workflows. Synthetic AGs with shorter migration half-lives showed faster incorporation of 18O. The level of differential incorporation of 18O following a 24 h incubation correlates well with the migration tendency of AGs. This assay was developed further, exploring in situ generation of AGs by human hepatic microsomal fraction. The results from 18 in situ-formed acyl glucuronides were similar to those obtained using authentic reference standards. In this format, this new 18O-labeling method offers a simplified workflow, requires no LC method development or AG reference standard, and thus facilitates AG liability assessment in early drug discovery.
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Ácidos Carboxílicos , Glucuronídeos , Cromatografia Líquida/métodos , Glucuronídeos/metabolismo , Humanos , Isomerismo , Espectrometria de MassasRESUMO
This editorial comment refers to the article: "Diagnosing autism spectrum disorder in children using conventional MRI and apparent diffusion coefficient based deep learning algorithms" by Guo et al. (Eur Radiol, 2021). KEY POINTS: â¢Deep learning may help to uncover imaging features of autism spectrum disorder on MRI.
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Transtorno do Espectro Autista , Aprendizado Profundo , Algoritmos , Transtorno do Espectro Autista/diagnóstico por imagem , Criança , Imagem de Difusão por Ressonância Magnética , Humanos , Imageamento por Ressonância MagnéticaRESUMO
OBJECTIVES: Whether and how symptom clusters are associated with care utilization remains understudied. This study aims to investigate the economic impact of symptom clusters. METHODS: We conducted cross-sectional analyses of data collected from 3255 older adults aged 60 years and over in Hong Kong using the Patient Health Questionnaire-9 and the Client Service Receipt Inventory to measure depressive symptoms and service utilization to calculate 1-year care expenditure. Based on Research Domain Criteria framework, we categorized depressive symptoms into four clusters: Negative Valance Systems and Externalizing (NVSE; anhedonia and depression), Negative Valance Systems and Internalizing (guilt and self-harm), Arousal and Regulatory Systems (sleep, fatigue, and appetite), and Cognitive and Sensorimotor Systems (CSS; concentration and psychomotor). Two-part models were used with four symptom clusters to estimate economic impacts on care utilization. RESULTS: Core affective symptoms had the largest economic impact on non-psychiatric care expenditure; a one-point increase in NVSE was associated with USD$ 571 additional non-psychiatric care expenditure. The economic impacts of CSS on non-psychiatric care expenditure was attenuated when the severity level of NVSE was higher. CONCLUSIONS: Our findings highlight the importance of understanding economic impacts on care utilization based on symptom profiles with a particular emphasis on symptom combinations. Policymakers should optimize care allocation based on older adults' depressive symptom profiles rather than simply considering their depression sum-score or the severity defined by cut-off points.
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Depressão , Vida Independente , Idoso , Estudos Transversais , Fadiga , Humanos , Pessoa de Meia-Idade , Questionário de Saúde do PacienteRESUMO
Bictegravir (BIC) is a potent small-molecule integrase strand-transfer inhibitor (INSTI) and a component of Biktarvy®, a single-tablet combination regimen that is currently approved for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. The in vitro properties, pharmacokinetics (PK), and drug-drug interaction (DDI) profile of BIC were characterised in vitro and in vivo.BIC is a weakly acidic, ionisable, lipophilic, highly plasma protein-bound BCS class 2 molecule, which makes it difficult to predict human PK using standard methods. Its systemic plasma clearance is low, and the volume of distribution is approximately the volume of extracellular water in nonclinical species. BIC metabolism is predominantly mediated by cytochrome P450 enzyme (CYP) 3A and UDP-glucuronosyltransferase 1A1. BIC shows a low potential to perpetrate clinically meaningful DDIs via known drug metabolising enzymes or transporters.The human PK of BIC was predicted using a combination of bioavailability and volume of distribution scaled from nonclinical species and a modified in vitro-in vivo correlation (IVIVC) correction for clearance. Phase 1 studies in healthy subjects largely bore out the prediction and supported the methods used. The approach presented herein could be useful for other drug molecules where standard projections are not sufficiently accurate. .
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Infecções por HIV , Inibidores de Integrase de HIV , HIV-1 , Humanos , Amidas , Interações Medicamentosas , Compostos Heterocíclicos com 3 Anéis/farmacocinética , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/farmacocinética , PiridonasRESUMO
The popularity of minimally invasive injectable aesthetic treatments has grown exponentially with over thirteen million neurotoxin and dermal filler injections being performed in 2014. While aesthetic results can be dramatic and convalescence minimal, significant complications including vascular compromise, neuropraxia, and blindness have been reported. Thorough knowledge of the complex anatomy in this area and the use of anatomic landmarks can help the physician obtain improved aesthetic results by deploying fillers in the appropriate anatomic plane and avoiding inadvertent injury to important neurovascular structures in this area. J Drugs Dermatol. 2022;21(4):354-362. doi:10.36849/JDD.6642.
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Técnicas Cosméticas , Preenchedores Dérmicos , Técnicas Cosméticas/efeitos adversos , Preenchedores Dérmicos/efeitos adversos , Estética , Face , Humanos , Ácido Hialurônico/efeitos adversos , InjeçõesRESUMO
BACKGROUND: Community health workers (CHWs) are essential field-based personnel and increasingly used to deliver priority interventions to achieve universal health coverage. Existing literature allude to the potential for detrimental effects of multi-tasking CHWs. This study objective was to assess the impact of integrating cervical cancer screening and prevention therapy (CCSPT) with family planning (FP) on time utilization among CHWs. METHODS: A time and motion study was conducted in 7 health facilities in Malawi. Data was collected at baseline between October-July 2019, and 12 months after CCSPT implementation between July and August 2021. CHWs trained to deliver CCSPT were continuously observed in real time while their activities were timed by independent observers. We used paired sample t-test to assess pre-post differences in average hours CHWs spent on the following key activities, before and after CCSPT implementation: clinical and preventive care; administration; FP; and non-work-related tasks. Regression models were used to ascertain impact of CCSPT on average durations CHWs spent on key activities. RESULTS: Thirty-seven (n = 37) CHWs were observed. Their mean age and years of experience were 42 and 17, respectively. Overall, CHWs were observed for 323 hours (inter quartile range: 2.8-5.5). Compared with the period before CCSPT, the proportion of hours CHWs spent on clinical and preventive care, administration and non-work-related activities were reduced by 13.7, 8.7 and 34.6%, respectively. CHWs spent 75% more time on FP services after CCSPT integration relative to the period before CCSPT. The provision of CCSPT resulted in less time that CHWs devoted towards clinical and preventive care but this reduction was not significant. Following CCPST, CHWs spent significantly few hours on non-work-related activities. CONCLUSION: Introduction of CCSPT was not very detrimental to pre-existing community services. CHWs managed their time ensuring additional efforts required for CCSPT were not at the expense of essential activities. The programming and policy implications are that multi-tasking CHWs with CCSPT will not have substantial opportunity costs.
Assuntos
Agentes Comunitários de Saúde , Neoplasias do Colo do Útero , Detecção Precoce de Câncer , Feminino , Humanos , Malaui , Estudos de Tempo e Movimento , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controleRESUMO
BACKGROUND: Many patients with keloids experience symptoms, such as pain and pruritus, and may present with significant psychosocial burdens. However, no single therapeutic regimen has been firmly established for treatment of keloids. OBJECTIVES: The aim of this study was to assess patients' perspectives on their keloids after treatment by comparing preoperative and postoperative surveys. METHODS: All patients seen at the keloid clinic, both preoperatively and postoperatively, were contacted by telephone call. Information about demographics, keloid characteristics, and levels of pain and pruritus were recorded. Participants also completed all 3 parts (appearance, symptoms, and psychosocial impact) of the SCAR-Q, a validated patient-reported outcome measure questionnaire. Statistical analysis was performed with SPSS version 23 (IBM Corp., Armonk, NY). RESULTS: Of the 60 patients who participated in the study, 35 preoperative and 34 postoperative surveys were completed. Patients experienced significant reductions in mean [standard deviation] pain levels (from 5.6 [4.0] to 0.1 [0.4], Pâ <â 0.001) and pruritus (from 6.5 [3.0] to 0.8 [1.5], Pâ <â 0.001) postintervention. Significant improvements in all 3 parts of the SCAR-Q were noted. Appearance improved from 26.5 [22.3] to 73.4 [23.0] (Pâ <â 0.001); symptoms from 44.0 [15.7] to 81.4 [16.7] (Pâ <â 0.001); and psychosocial impact from 27.7 [30.7] to 82.6 [26.3] (Pâ <â 0.001). CONCLUSIONS: Patients with keloids experience significant improvement in their symptomatic and psychosocial burden after treatment. Although management modalities are not well established, it is essential that plastic surgeons do not overlook the therapeutic benefits for their patients' well-being.
Assuntos
Queloide , Humanos , Injeções Intralesionais , Queloide/tratamento farmacológico , Queloide/cirurgia , Dor/tratamento farmacológico , Prurido/tratamento farmacológico , Prurido/etiologia , Resultado do TratamentoRESUMO
Malawi has the highest invasive cervical cancer (ICC) mortality rate worldwide, and ICC is the leading cause of cancer death among women. In 2004, Malawi adopted visual inspection with acetic acid (VIA) and ablative treatment with cryotherapy. However, screening coverage has remained low (<30%) and few women (<50%) who require ablative treatment receive it. Additional barriers include long distances to health facilities and challenges with maintaining gas supplies. Thermal ablation is a safe and effective alternative to cryotherapy. We assessed the safety and uptake of community-based ICC screening with VIA and same-day treatment using a handheld thermocoagulator (HTU) in rural Malawi. We held educational talks alongside community leaders and conducted VIA screening in nonclinic community settings to nonpregnant women aged 25 to 49 years without history of hysterectomy or genital cancer/precancer. Eligible women received same-day thermal ablation and HIV testing/counseling. We collected cervical biopsies before treatment and followed up women at Weeks 6 and 12, with repeat biopsy at Week 12. Between July and August 2017, 408 (88%) of 463 eligible women underwent VIA. Overall, 7% (n = 30) of women had a positive VIA, of whom 93% (n = 28) underwent same-day thermal ablation. Among the 30 VIA-positive women, 5 had cervical intraepithelial neoplasia (CIN) 1, 4 had CIN 2/3 and 21 had benign histologic findings. Abnormal vaginal discharge (60%) and light vaginal bleeding (52%) were the most reported adverse events. There was high uptake of the community-based ICC screening in the study population and treatment was safe in this setting. Similar strategies that minimize false-positive results are urgently needed in Malawi.