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This study aims to understand the impact of early antiretroviral therapy (ART) on HIV-specific T-cell responses measured after treatment interruption may inform strategies to deliver ART-free immune-mediated viral suppression. HIV-specific T-cell immunity was analysed using gamma interferon enzyme-linked immunospot assays in two studies. SPARTAC included individuals with primary HIV infection randomised to 48 weeks of ART (n = 24) or no immediate therapy (n = 37). The PITCH (n = 7) cohort started antiretroviral therapy in primary infection for at least one year, followed by TI. In SPARTAC, participants treated in PHI for 48 weeks followed by TI for 12 weeks, and those who remained untreated for 60 weeks made similar HIV Gag-directed responses (both magnitude and breadth) at week 60. However, the treated group made a greater proportion of novel HIV Gag-directed responses by Week 60, suggestive of a greater reserve to produce new potentially protective responses. In the more intensively followed PITCH study, 6/7 participants showed dominant Gag and/or Pol-specific responses post-TI compared with pre-TI. Although early ART in PHI was not associated with major differences in HIV-specific immunity following TI compared with untreated participants, the potential to make more new Gag-directed responses warrants further investigation as this may inform strategies to achieve ART-free control.
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BACKGROUND: People with human immunodeficiency virus (HIV) on antiretroviral therapy (ART) with good CD4 T-cell counts make effective immune responses following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are few data on longer term responses and the impact of a booster dose. METHODS: Adults with HIV were enrolled into a single arm open label study. Two doses of ChAdOx1 nCoV-19 were followed 12 months later by a third heterologous vaccine dose. Participants had undetectable viraemia on ART and CD4 counts >350 cells/µL. Immune responses to the ancestral strain and variants of concern were measured by anti-spike immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA), MesoScale Discovery (MSD) anti-spike platform, ACE-2 inhibition, activation induced marker (AIM) assay, and T-cell proliferation. FINDINGS: In total, 54 participants received 2 doses of ChAdOx1 nCoV-19. 43 received a third dose (42 with BNT162b2; 1 with mRNA-1273) 1 year after the first dose. After the third dose, total anti-SARS-CoV-2 spike IgG titers (MSD), ACE-2 inhibition, and IgG ELISA results were significantly higher compared to Day 182 titers (P < .0001 for all 3). SARS-CoV-2 specific CD4+ T-cell responses measured by AIM against SARS-CoV-2 S1 and S2 peptide pools were significantly increased after a third vaccine compared to 6 months after a first dose, with significant increases in proliferative CD4+ and CD8+ T-cell responses to SARS-CoV-2 S1 and S2 after boosting. Responses to Alpha, Beta, Gamma, and Delta variants were boosted, although to a lesser extent for Omicron. CONCLUSIONS: In PWH receiving a third vaccine dose, there were significant increases in B- and T-cell immunity, including to known variants of concern (VOCs).
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COVID-19 , Infecciones por VIH , Adulto , Humanos , VIH , ChAdOx1 nCoV-19 , Vacuna BNT162 , SARS-CoV-2 , COVID-19/prevención & control , Activación de Linfocitos , Vacunación , Infecciones por VIH/tratamiento farmacológico , Inmunoglobulina G , Anticuerpos AntiviralesRESUMEN
BACKGROUND: There is paucity of information on obstructive sleep apnoea (OSA) and cardiac diseases among Aboriginal Australian patients. This study evaluates the association of various cardiac disease profiles among Aboriginal patients undergoing a diagnostic polysomnography (PSG). METHOD: In this 5-year retrospective study demographics, clinical characteristics, medical and cardiac -conditions were analysed. RESULTS: There were total of 340 eligible patients included in the study. The median age was 47 (38-57) years, 51% were males and obesity was noted in 78%. In the overall study participants, cardiac diseases were present in 46%: coronary artery disease (CAD) in 27%, pulmonary hypertension (PH) 19% and atrial fibrillation (AF) 14%. Diabetes and hypertension were noted in 42 and 41% of patients. Overall, 73/340 (21.5%) had two, 69/340 (20.3%) three, 55/340 (16.2%) four, 40/340 (11.8%) five and 10/340 (2.9%) had six comorbidities. In the overall study participants, 297/340 (87%) had OSA (Apnoea-Hypopnoea Index [AHI]>5/hour). Co-occurrence of OSA and cardiac diseases was found in 140/297 (47%), CAD being the commonest (27%). Patients with OSA had a higher number of comorbidities compared to patients without sleep apnoea. Hospital admissions frequency showed a median 2 (IQR: 0-4) times readmission rates since the diagnosis of OSA overall compliance with CPAP therapy was observed in 63 (43%). CONCLUSION: Our study demonstrated that a significant proportion of Aboriginal patients with OSA have co-existing cardiac diseases, with CAD being the commonest. Patients with OSA had a higher number of comorbidities compared to patients without sleep apnoea. Furthermore, hospital admission frequency increased among OSA patients with multiple comorbidities.
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Fibrilación Atrial , Enfermedad de la Arteria Coronaria , Apnea Obstructiva del Sueño , Presión de las Vías Aéreas Positiva Contínua , Humanos , Masculino , Persona de Mediana Edad , Northern Territory/epidemiología , Estudios Retrospectivos , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/epidemiologíaRESUMEN
Initiation of antiretroviral therapy (ART) in early compared with chronic human immunodeficiency virus (HIV) infection is associated with a smaller HIV reservoir. This longitudinal analysis of 60 individuals who began ART during primary HIV infection (PHI) investigates which pre- and posttherapy factors best predict HIV DNA levels (a correlate of reservoir size) after treatment initiation during PHI. The best predictor of HIV DNA at 1 year was pre-ART HIV DNA, which was in turn significantly associated with CD8 memory T-cell differentiation (effector memory, naive, and T-bet-Eomes- subsets), CD8 T-cell activation (CD38 expression) and T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) expression on memory T cells. No associations were found for any immunological variables after 1 year of ART. Levels of HIV DNA are determined around the time of ART initiation in individuals treated during PHI. CD8 T-cell activation and memory expansion are linked to HIV DNA levels, suggesting the importance of the initial host-viral interplay in eventual reservoir size.
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Linfocitos T CD8-positivos/inmunología , ADN Viral/sangre , Infecciones por VIH , Activación de Linfocitos/inmunología , Adulto , Antirretrovirales/uso terapéutico , Anticuerpos Antivirales/sangre , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Masculino , Carga ViralRESUMEN
The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n = 122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression. Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/µl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed. Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants. Expression of 'exhaustion' or 'immune checkpoint' markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches.
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Biomarcadores/análisis , Linfocitos T CD8-positivos/inmunología , Infecciones por VIH/inmunología , VIH-1 , Adulto , Antirretrovirales/uso terapéutico , Antígenos CD/análisis , Antígenos CD/biosíntesis , Antígenos CD/inmunología , Progresión de la Enfermedad , Femenino , Citometría de Flujo , Infecciones por VIH/tratamiento farmacológico , Receptor 2 Celular del Virus de la Hepatitis A/análisis , Receptor 2 Celular del Virus de la Hepatitis A/biosíntesis , Receptor 2 Celular del Virus de la Hepatitis A/inmunología , Humanos , Activación de Linfocitos/inmunología , Masculino , Receptor de Muerte Celular Programada 1/análisis , Receptor de Muerte Celular Programada 1/biosíntesis , Receptor de Muerte Celular Programada 1/inmunología , Proteína del Gen 3 de Activación de LinfocitosRESUMEN
INTRODUCTION: Few treatments are available for men with premature ejaculation (PE); oxytocin (OT) receptor antagonism in the central nervous system (CNS) is a potential new approach. AIM: To determine if cligosiban selectively inhibits human OT receptors, penetrates the CNS, shows pharmacology in the CNS, and effects ejaculatory physiology in pre-clinical systems. METHODS: Experiments complied with United Kingdom legislation and were subject to local ethical review. In vitro potency and selectivity of cligosiban was assessed using recombinant and native OT receptor systems including both neuronal and non-neuronal cell types. Selectivity was determined over neighboring V1A, V1B, and V2 vasopressin receptors using a combination of recombinant and native vasopressin receptor assay systems. To determine an effect on central OT receptors and on ejaculation, cligosiban was evaluated in 2 anesthetized rat models-the electromyography model of ejaculatory physiology and a model of OT-mediated CNS neuronal firing. The CNS penetration of cligosiban was also determined by measuring cerebrospinal fluid and plasma drug concentrations following an intravenous (IV) infusion in rats. MAIN OUTCOME MEASURE: These were functional measures of pharmacology in vitro, in cell lines and tissues, and in vivo in rats. RESULTS: Cligosiban is a potent OT receptor antagonist, with a base dissociation constant of 5.7 nmol/L against native human uterine smooth muscle cell OT receptors. Cligosiban displays similar antagonistic potency against human recombinant and rat native OT receptors, including neuronal OT receptors. Cligosiban demonstrates >100-fold selectivity over human V1A, V1B, and V2 vasopressin receptors. In the electromyography model, cligosiban (0.9 mg/kg, IV bolus) reduced the bulbospongiosum burst pattern and contraction amplitude associated with ejaculation. In the anesthetized CNS neuronal firing model, the same dosing regimen of cligosiban (0.9 mg/kg IV bolus) modulated the OT-mediated response in the nucleus tractus solitarius. After systemic dosing to rats, cligosiban showed good CNS penetration. CLINICAL IMPLICATIONS: As the first highly selective and centrally penetrant OT receptor antagonist, cligosiban represents a promising compound to test the clinical hypothesis that antagonism of central OT receptors may be of therapeutic benefit in the treatment of PE. STRENGTH & LIMITATIONS: The pharmacology and selectivity of cligosiban is determined using functional assays in recombinant cell lines, native cell lines, and tissue. Functional outcomes in in vivo systems are linked to CNS measures of pharmacology. The translation of the animal models of ejaculation to PE in man is unproven. CONCLUSION: Cligosiban, a potent, selective OT receptor antagonist, demonstrated CNS penetration and pharmacology and, using the same dosing regimen, inhibited apomorphine-induced ejaculation in rats. Cligosiban is a promising compound to test the clinical hypothesis that antagonism of central OT receptors may be of therapeutic benefit in the treatment of PE. Wayman C, Russell R, Tang K, et al. Cligosiban, A Novel Brain Penetrant Selective Oxytocin Receptor Antagonist, Inhibits Ejaculatory Physiology in Rodents. J Sex Med 2018;15:1698-1706.
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Eyaculación/efectos de los fármacos , Oxitocina/farmacología , Eyaculación Prematura/tratamiento farmacológico , Receptores de Oxitocina/antagonistas & inhibidores , Receptores de Vasopresinas/efectos de los fármacos , Animales , Encéfalo/metabolismo , Relación Dosis-Respuesta a Droga , Antagonistas de Hormonas/farmacología , Humanos , Masculino , Ratas , Roedores , Reino UnidoRESUMEN
The existence of viral variants that escape from the selection pressures imposed by cytotoxic T-lymphocytes (CTLs) in HIV-1 infection is well documented, but it is unclear when they arise, with reported measures of the time to escape in individuals ranging from days to years. A study of participants enrolled in the SPARTAC (Short Pulse Anti-Retroviral Therapy at HIV Seroconversion) clinical trial allowed direct observation of the evolution of CTL escape variants in 125 adults with primary HIV-1 infection observed for up to three years. Patient HLA-type, longitudinal CD8+ T-cell responses measured by IFN-γ ELISpot and longitudinal HIV-1 gag, pol, and nef sequence data were used to study the timing and prevalence of CTL escape in the participants whilst untreated. Results showed that sequence variation within CTL epitopes at the first time point (within six months of the estimated date of seroconversion) was consistent with most mutations being transmitted in the infecting viral strain rather than with escape arising within the first few weeks of infection. Escape arose throughout the first three years of infection, but slowly and steadily. Approximately one third of patients did not drive any new escape in an HLA-restricted epitope in just under two years. Patients driving several escape mutations during these two years were rare and the median and modal numbers of new escape events in each patient were one and zero respectively. Survival analysis of time to escape found that possession of a protective HLA type significantly reduced time to first escape in a patient (p = 0.01), and epitopes escaped faster in the face of a measurable CD8+ ELISpot response (p = 0.001). However, even in an HLA matched host who mounted a measurable, specific, CD8+ response the average time before the targeted epitope evolved an escape mutation was longer than two years.
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Epítopos de Linfocito T/genética , Productos del Gen gag/genética , Infecciones por VIH/genética , Productos del Gen nef del Virus de la Inmunodeficiencia Humana/inmunología , Productos del Gen pol del Virus de la Inmunodeficiencia Humana/inmunología , Adulto , Linfocitos T CD8-positivos/inmunología , Epítopos de Linfocito T/inmunología , Femenino , Productos del Gen gag/inmunología , Infecciones por VIH/inmunología , VIH-1/genética , VIH-1/inmunología , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Mutación , Linfocitos T Citotóxicos/inmunología , Productos del Gen nef del Virus de la Inmunodeficiencia Humana/genética , Productos del Gen pol del Virus de la Inmunodeficiencia Humana/genéticaRESUMEN
BACKGROUND: The public health impact of mass gatherings should not be underestimated, requiring careful planning. This evaluation identified the successes and failures of a programme targeted to mitigate against potential increases in sexual ill health during the London 2012 Olympics. METHODS: Programme planning was evaluated using documentary analysis. Stakeholders' experiences were explored using an online survey. Finally, selected stakeholders were interviewed in depth. RESULTS: Over 100 documents were analysed, 36 survey responses received and 12 interviews conducted. Most respondents felt aims were appropriate, potentially overambitious. 'Business as usual', with no disruption or increased demand, was reported in sexual health services. Some interviewees felt evidence for increased demand was limited, although contingency planning was needed. Signposting service users and providing 'residual risk responses' appeared successful. Planned service transformation was not fully achieved and perhaps inappropriate, although new service collaborations emerged. Over 2000 individuals participated; wider public engagement was seen as inappropriate. A 'Sex Factor 2012' competition was particularly successful. Legacy opportunities included planning work, groundwork for transformation, relationship building and continuing the resilience changes. CONCLUSIONS: The Games allowed sexual health services to explore new ways of working, engage with stakeholders and develop new relationships, although in reality demand for services did not increase.
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Planificación en Salud , Salud Reproductiva , Deportes , Atención a la Salud/métodos , Atención a la Salud/organización & administración , Planificación en Salud/métodos , Planificación en Salud/normas , Humanos , Entrevistas como Asunto , Londres , Evaluación de Programas y Proyectos de Salud , Encuestas y CuestionariosRESUMEN
OBJECTIVES: To explore barriers, challenges and best practice within patient and public engagement (PPE) in sexual and reproductive health and HIV (SRHH) services in London. METHODS: Consultation exercise using qualitative interviews with 27 stakeholders including commissioners, managers, voluntary/community organizations (VCOs) clinicians and patients, analysed using Framework Analysis and Atlas.ti software. RESULTS: Participants recognized PPE's importance, echoing recent political and NHS drives, and highlighted the need for meaningful, empowering PPE, including user-designed methods, peer research and participatory approaches. Although challenging in SRHH and requiring training and support, PPE may help tackle stigma, and promote self-management and patient-centred-care, including peer education and role modelling. Expertise may come from experienced VCOs. Themes in priority order were: organizational commitment (including lack of dedicated staff, time and money); motivating patients; changing NHS philosophy; informing patients/public; using public awareness/education campaigns; overcoming stigma; working with VCOs. 'Reaching out' to engage underrepresented groups in this sensitive area was emphasized through community outreach, incentivization and linking with existing organizations. Making engagement easy and addressing issues of public value were also important. Stigma was less hindering than anticipated, except for ethnic minorities. PPE was seen to improve patient satisfaction, increase service uptake and reduce inequalities, key priorities in SRHH, and identify innovative service delivery ideas. CONCLUSIONS: PPE is crucial in creating a patient-led NHS and responsible society. If organizations, including the NHS, commit to implementing meaningful PPE which actively targets those at risk of poor SRHH, services can be truly patient-led and patients and communities empowered to tackle the stigma of SRHH.
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Participación de la Comunidad/psicología , Infecciones por VIH/psicología , Servicios de Salud Reproductiva/organización & administración , Síndrome de Inmunodeficiencia Adquirida/psicología , Ganglios Parasimpáticos , Humanos , Entrevistas como Asunto , Londres , Participación del Paciente/psicología , Investigación Cualitativa , Servicios de Salud Reproductiva/normas , Características de la Residencia , Estigma Social , Medicina EstatalRESUMEN
OBJECTIVE: To explore consensus among Traditional Chinese Medicine (TCM)/integrative medicine (IM) journal executive editors in China regarding: (a) Their perceptions about the differences between papers published in Chinese/English journals; (b) the key elements required for publishing a good quality paper; (c) how editors manage and decide on the manuscripts submitted to their journals. METHODS: A three classic round Delphi was conducted with a purposive sample of TCM/M Chinese journal executive editors. The key themes and items generated from six open ended questions in the first round were redistributed to the editors in two subsequent questionnaire rounds and scored on a five-point Likert scale. Consensus, reliability and stability of responses were assessed between the editors in the same round and between rounds. RESULTS: All ten editors initially agreeing to participate completed the three rounds, provided 60 comments in the first round, relating to 6 themes on: elements of publishing good quality article; differences between Chinese and English published articles; reasons for low quality of Chinese studies; maintaining the journal's good reputation; initiatives and strategies; and differences between Chinese and English versions of the same journal. High levels of consensus were reached for 97% items. Intra-class correlation (ICC) coefficient for agreement among editors was high in both second and third round and there was a good stability between the two rounds. CONCLUSION: High inter/intra-editor agreement was identified in the differences between TCM/IM research papers published in English and Chinese. Publishing standards and probity are keys in elevating the reputation of research. Editors' perspectives in maintaining and improving quality journal can be viewed as fundamental for editors and researchers in publishing any articles.
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Consenso , Edición/normas , Publicaciones Seriadas/normas , Adulto , China , Técnica Delphi , Políticas Editoriales , Femenino , Humanos , Medicina Integrativa , Masculino , Medicina Tradicional China , Persona de Mediana Edad , Recursos HumanosRESUMEN
Acidification of the airway surface liquid in the respiratory system could play a role in the pathology of Cystic Fibrosis, but its low volume and proximity to the airway epithelium make it a challenging biological environment in which to noninvasively collect pH measurements. To address this challenge, we explored surface enhanced Raman scattering microsensors (SERS-MS), with a 4-mercaptobenzoic acid (MBA) pH reporter molecule, as pH sensors for the airway surface liquid of patient-derived in vitro models of the human airway. Using air-liquid interface (ALI) cultures to model the respiratory epithelium, we show that SERS-MS facilitates the optical measurement of trans-epithelial pH gradients between the airway surface liquid and the basolateral culture medium. SERS-MS also enabled the successful quantification of pH changes in the airway surface liquid following stimulation of the Cystic Fibrosis transmembrane conductance regulator (CFTR, the apical ion channel that is dysfunctional in Cystic Fibrosis airways). Finally, the influence of CFTR mutations on baseline airway surface liquid pH was explored by using SERS-MS to measure the pH in ALIs grown from Cystic Fibrosis and non-Cystic Fibrosis donors.
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Regulador de Conductancia de Transmembrana de Fibrosis Quística , Fibrosis Quística , Espectrometría Raman , Humanos , Espectrometría Raman/métodos , Concentración de Iones de Hidrógeno , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Compuestos de Sulfhidrilo/química , Benzoatos/químicaRESUMEN
Broadly neutralising antibodies (bNAbs) targeting HIV show promise for both prevention of infection and treatment. Among these, 10-1074 has shown potential in neutralising a wide range of HIV strains. However, resistant viruses may limit the clinical efficacy of 10-1074. The prevalence of both de novo and emergent 10-1074 resistance will determine its use at a population level both to protect against HIV transmission and as an option for treatment. To help understand this further, we report the prevalence of pre-existing mutations associated with 10-1074 resistance in a bNAb-naive population of 157 individuals presenting to UK HIV centres with primary HIV infection, predominantly B clade, receiving antiretroviral treatment. Single genome analysis of HIV proviral envelope sequences showed that 29% of participants' viruses tested had at least one sequence with 10-1074 resistance-associated mutations. Mutations interfering with the glycan binding site at HIV Env position 332 accounted for 95% of all observed mutations. Subsequent analysis of a larger historic dataset of 2425 B-clade envelope sequences sampled from 1983 to 2019 revealed an increase of these mutations within the population over time. Clinical studies have shown that the presence of pre-existing bNAb mutations may predict diminished therapeutic effectiveness of 10-1074. Therefore, we emphasise the importance of screening for these mutations before initiating 10-1074 therapy, and to consider the implications of pre-existing resistance when designing prevention strategies.
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Infecciones por VIH , VIH-1 , Humanos , Anticuerpos ampliamente neutralizantes , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Anticuerpos Neutralizantes , Prevalencia , Epítopos , VIH-1/genética , Productos del Gen env del Virus de la Inmunodeficiencia Humana/genética , Anticuerpos Anti-VIH , Reino Unido/epidemiologíaRESUMEN
INTRODUCTION: Acupuncture and related acupoint therapies have been widely used for smoking cessation. Some relevant systematic reviews (SRs) have been published. There is a need to summarize and update the evidence to inform practice and decision-making. METHODS: Eight databases were searched from their inception to December 2023. SRs, any randomized controlled trials (RCTs) comparing acupuncture therapies with sham acupuncture, pharmacotherapy, behavioral therapy, or no treatment, were included. The primary outcome was the abstinence rate. AMSTAR-2 was employed to assess the quality of SRs. An updated meta-analysis was conducted based on SRs and RCTs. Data were synthesized using risk ratios (RR) with 95% confidence intervals (CIs). The GRADE approach was employed to assess the certainty of the updated evidence. RESULTS: Thirteen SRs and 20 RCTs outside of the SRs were identified. The SRs were of low or very low quality by AMSTAR-2. Sixteen (80%) RCTs were at high risk of performance bias. Eight acupuncture and related acupoint therapies were involved. The short-term (≤6 months) abstinence rate outcome was summarized as follows. Most SRs suggested that filiform needle acupuncture or acupressure had a better effect than sham acupuncture, but the findings were inconsistent. The updated meta-analysis also suggested that filiform needle acupuncture was more effective than sham acupuncture (RR=1.44; 95% CI: 1.02-2.02; I2 = 66%; low certainty; 9 RCTs, n=1358). Filiform needle acupuncture combined with acupressure was comparable to nicotine patches (RR=0.99; 95% CI: 0.74-1.32; low certainty; 6 RCTs, n= 524). Acupressure was superior to counseling (RR=1.46; 95% CI: 1.14-1.87; I2=5%; low certainty; 8 RCTs, n=595). No serious adverse events were reported in these SRs or RCTs. CONCLUSIONS: Low certainty evidence suggests that filiform needle acupuncture and auricular acupressure appear to be safe and effective in achieving short-term smoking cessation. However, long-term follow-up data are needed.
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[This corrects the article DOI: 10.3389/fendo.2024.1351281.].
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Background: Unexplained recurrent implantation failure and the high cost of assisted reproductive techniques for those experiencing infertility have increasingly resulted in the use of acupuncture. However, the trends and research status of acupuncture on infertility resulting in natural conception have not been systematically summarized. This scoping review and knowledge graph analysis aimed to summarize existing clinical studies on acupuncture for infertility that resulted in natural conception. Methods: Seven databases, namely, PubMed, Embase, the Cochrane Library, CNKI, VIP, Wanfang Data, and SinoMed, were searched up to August 2023 (updated on 1 April). Two authors independently identified related clinical studies and systematic reviews, and extracted data from included studies on acupuncture for infertility; any discrepancies were resolved by discussion or judged by a third author. A meta-analysis was conducted based on randomized controlled trials (RCTs), and data were synthesized using risk ratios with 95% confidence intervals. Results: Of the 310 articles meeting the inclusion criteria, 274 were primary studies, 7 were systematic reviews, and 29 were case reports. Reported adverse events included mild ovarian irritation and early signs of miscarriage. Out of the 274 primary studies, there were 40 (14.60%) cases of male infertility and 234 (85.40%) cases of female infertility. Current research highlights on acupuncture for infertility focused on female infertility caused by polycystic ovary syndrome, ovulation disorder, and luteinized unruptured follicle syndrome (LUFS), while acupuncture for male infertility was a hotspot in the early research stage. The meta-analysis also suggested that acupuncture was more effective than human chorionic gonadotropin (HCG) [RR = 1.89, 95% CI (1.47, 2.42), 11 RCTs, 662 participants]. Acupuncture combined with HCG was comparable to HCG [RR = 2.33, 95% CI (1.53, 3.55), four RCTs, 259 participants]. Compared with no treatment, acupuncture resulted in a higher pregnancy rate [RR = 22.12, 95% CI (1.39, 353.09), one RCT, 47 participants]. There was no statistical difference between acupuncture combined with HCG plus letrozole and HCG plus letrozole [RR = 1.56, 95% CI (0.84, 2.89), one RCT, 84 participants]. Conclusion: Current research highlights on acupuncture for infertility resulting in natural conception focused on female infertility caused by polycystic ovary syndrome, ovulation disorder, and LUFS, while studies on male infertility and female infertility caused by blockage in the fallopian tube, thin endometrium, and other factors were insufficient. Well-designed confirmatory clinical studies are still needed as the research hypotheses of most studies were unclear.
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Terapia por Acupuntura , Bibliometría , Infertilidad Femenina , Humanos , Terapia por Acupuntura/métodos , Terapia por Acupuntura/tendencias , Femenino , Infertilidad Femenina/terapia , Masculino , Infertilidad/terapia , Embarazo , Infertilidad Masculina/terapiaRESUMEN
OBJECTIVE: We present findings from a large cohort of individuals treated during primary HIV infection (PHI) and examine the impact of time from HIV-1 acquisition to antiretroviral therapy (ART) initiation on clinical outcomes. We also examine the temporal changes in the demographics of individuals presenting with PHI to inform HIV-1 prevention strategies. METHODS: Individuals who fulfilled the criteria of PHI and started ART within 3 months of confirmed HIV-1 diagnosis were enrolled between 2009 and 2020. Baseline demographics of those diagnosed between 2009 and 2015 (before preexposure prophylaxis (PrEP) and universal ART availability) and 2015-2020 (post-PrEP and universal ART availability) were compared. We examined the factors associated with immune recovery and time to viral suppression. RESULTS: Two hundred four individuals enrolled, 144 from 2009 to 2015 and 90 from 2015 to 2020; median follow-up was 33âmonths. At PHI, the median age was 33âyears; 4% were women, 39% were UK-born, and 84% were MSM. The proportion of UK-born individuals was 47% in 2009-2015, compared with 29% in 2015-2020. There was an association between earlier ART initiation after PHI diagnosis and increased immune recovery; each day that ART was delayed was associated with a lower likelihood of achieving a CD4 + cell count more than 900âcells/µl [hazard ratio 0.99 (95% confidence interval, 95% CI 0.98-0.99), P â=â0.02) and CD4/CD8 more than 1.0 (hazard ratio 0.98 (95% CI 0.97-0.99). CONCLUSION: Early initiation of ART at PHI diagnosis is associated with enhanced immune recovery, providing further evidence to support immediate ART in the context of PHI. Non-UK-born MSM accounts for an increasing proportion of those with primary infection; UK HIV-1 prevention strategies should better target this group.
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Fármacos Anti-VIH , Infecciones por VIH , Seropositividad para VIH , VIH-1 , Minorías Sexuales y de Género , Masculino , Humanos , Femenino , Adulto , Infecciones por VIH/tratamiento farmacológico , Homosexualidad Masculina , Recuento de Linfocito CD4 , Seropositividad para VIH/tratamiento farmacológico , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente ActivaRESUMEN
Background: The COVID-19 pandemic has had a profound global impact, although the majority of recently infected cases have presented with mild to moderate symptoms. Previous clinical studies have demonstrated that Shufeng Jiedu (SFJD) capsule, a Chinese herbal patent medicine, effectively alleviates symptoms associated with the common cold, H1N1 influenza, and COVID-19. This study aimed to assess the efficacy and safety of SFJD capsules in managing symptoms of mild to moderate COVID-19 infection. Methods: A randomized, double-blind, placebo-controlled trial was conducted from May to December 2022 at two hospitals in China. Mild and moderate COVID-19-infected patients presenting respiratory symptoms within 3 days from onset were randomly assigned to either the SFJD or placebo groups in a 1:1 ratio. Individuals received SFJD capsules or a placebo three times daily for five consecutive days. Participants were followed up for more than 14 days after their RT-PCR nucleoid acid test for SARS-CoV-2 turned negative. The primary outcome measure was time to alleviate COVID-19 symptoms from baseline until the end of follow-up. Results: A total of 478 participants were screened; ultimately, 407 completed the trial after randomization (SFJD, n = 203; placebo, n = 204). No statistically significant difference in baseline parameters was observed between the two groups. The median time to alleviate all symptoms was 7 days in the SFJD group compared to 8 days in the placebo group (p = 0.037). Notably, the SFJD group significantly attenuated fever/chills (p = 0.04) and headache (p = 0.016) compared to the placebo group. Furthermore, the median time taken to reach normal body temperature within 24 h was reduced by 7 hours in the SFJD group compared to the placebo group (p = 0.033). No deaths or instances of serious or critical conditions occurred during this trial period; moreover, no serious adverse events were reported. Conclusion: The trial was conducted in a unique controlled hospital setting, and the 5-day treatment with SFJD capsules resulted in a 1-day reduction in overall symptoms, particularly headache and fever/chills, among COVID-19-infected participants with mild or moderate symptoms. Compared to placebo, SFJD capsules were found to be safe with fewer side effects. SFJD capsules could potentially serve as an effective treatment for alleviating mild to moderate symptoms of COVID-19. Clinical Trial Registration: https://www.isrctn.com/, identifier ISRCTN14236594.
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Traditional Chinese medicine (TCM) is an integral part of mainstream medicine in China. Due to its worldwide use, potential impact on healthcare and opportunities for new drug development, TCM is also of great international interest. Recently, a new era for modernisation of TCM was launched with the successful completion of the Good Practice in Traditional Chinese Medicine Research in the Post-genomic Era (GP-TCM) project, the European Union's Seventh Framework Programme (FP7) coordination action on TCM research. This 3.5-year project that involved inputs from over 200 scientists resulted in the production of 20 editorials and in-depth reviews on different aspects of TCM that were published in a special issue of Journal of Ethnopharmacology (2012; volume 140, issue 3). In this narrative review, we aim to summarise the findings of the FP7 GP-TCM project and highlight the relevance of TCM to modern medicine within a historical and international context. Advances in TCM research since the 1950s can be characterised into three phases: Phase I (1950s-1970s) was fundamental for developing TCM higher education, research and hospital networks in China; Phase II (1980s-2000s) was critical for developing legal, economic and scientific foundations and international networks for TCM; and Phase III (2011 onwards) is concentrating on consolidating the scientific basis and clinical practice of TCM through interdisciplinary, interregional and intersectoral collaborations. Taking into account the quality and safety requirements newly imposed by a globalised market, we especially highlight the scientific evidence behind TCM, update the most important milestones and pitfalls, and propose integrity, integration and innovation as key principles for further modernisation of TCM. These principles will serve as foundations for further research and development of TCM, and for its future integration into tomorrow's medicine.
Asunto(s)
Medicina Tradicional China/historia , Medicina Tradicional China/normas , Animales , Bases de Datos Bibliográficas , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Internacionalidad/historia , Medicina Tradicional China/métodos , Medicina Tradicional China/tendenciasRESUMEN
Background: To explore the effectiveness and safety of Chinese herbal medicine (CHM) for drug-induced liver injury (DILI) in patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Methods: A systematic search was made of eight databases (Pubmed, Cochrane Library, Web of Science, Embase, CNKI, Wanfang, VIP, Sinomed) and two trial registries (WHO ICTRP, ClinicalTrials.gov) from inception to September 2022. The effect size was presented as risk ratio (RR) or mean difference (MD) with their 95% confidence interval (CI). The Cochrane Risk of Bias and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tools were used for quality appraisal. Results: Ten randomized controlled trials (RCTs) involving 732 participants were included. Comparing CHM alone with routine treatment, the CHM group showed lower aspartate aminotransferase (MD=-11.47 U/L, 95%CI[-13.05, -9.89], low certainty), lower alanine aminotransferase (MD=-2.68 U/L, 95%CI[-4.27, -1.08], low certainty), lower total bilirubin (MD=-4.31 mmol/L, 95%CI[-5.66, -2.96], low certainty), lower bilirubin direct (MD=-3.19 mmol/L, 95%CI[-3.87, -2.51], low certainty), and higher effective rate (assessed by symptoms and liver indicators) (RR=1.13, 95%CI[1.06, 1.20], low certainty). A significant difference was also found in CHM plus routine treatment versus routine treatment in the previous outcomes. No significant difference was found on helper T cells among these comparisons. Only one RCT reported safety of CHM and found no adverse reaction during the trial. Conclusions: CHM may improve the liver function indices and effective rate for HIV/AIDS patients with DILI. However, the sample size was small and quality was low. Larger-samples of high-quality trials are needed.
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Patient derived organoids have the potential to improve the physiological relevance of in vitro disease models. However, the 3D architecture of these self-assembled cellular structures makes probing their biochemistry more complex than in traditional 2D culture. We explore the application of surface enhanced Raman scattering microsensors (SERS-MS) to probe local pH gradients within patient derived airway organoid cultures. SERS-MS consist of solid polymer cores decorated with surface immobilised gold nanoparticles which are functionalised with pH sensitive reporter molecule 4-mercaptobenzoic acid (MBA). We demonstrate that by mixing SERS-MS into the extracellular matrix (ECM) of airway organoid cultures the probes can be engulfed by expanding organoids and report on local pH in the organoid lumen and ECM.