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Transfusion-dependent patients typically develop iron-induced cardiomyopathy, liver disease, and endocrine complications. We aimed to estimate the incidence of endocrine disorders in transfusiondependent thalassemia (TDT) patients during long-term iron-chelation therapy with deferasirox (DFX). We developed a multi-center follow-up study of 426 TDT patients treated with once-daily DFX for a median duration of 8 years, up to 18.5 years. At baseline, 118, 121, and 187 patients had 0, 1, or ≥2 endocrine diseases respectively. 104 additional endocrine diseases were developed during the follow-up. The overall risk of developing a new endocrine complication within 5 years was 9.7% (95% Confidence Interval [CI]: 6.3-13.1). Multiple Cox regression analysis identified three key predictors: age showed a positive log-linear effect (adjusted hazard ratio [HR] for 50% increase 1.2, 95% CI: 1.1-1.3, P=0.005), the serum concentration of thyrotropin showed a positive linear effect (adjusted HR for 1 mIU/L increase 1.3, 95% CI: 1.1-1.4, P<0.001) regardless the kind of disease incident, while the number of previous endocrine diseases showed a negative linear effect: the higher the number of diseases at baseline the lower the chance of developing further diseasess (adjusted HR for unit increase 0.5, 95% CI: 0.4-0.7, P<0.001). Age and thyrotropin had similar effect sizes across the categories of baseline diseases. The administration of levothyroxine as a covariate did not change the estimates. Although in DFX-treated TDT patients the risk of developing an endocrine complication is generally lower than the previously reported risk, there is considerable risk variation and the burden of these complications remains high. We developed a simple risk score chart enabling clinicians to estimate their patients' risk. Future research will look at increasing the amount of variation explained from our model and testing further clinical and laboratory predictors, including the assessment of direct endocrine magnetic resonance imaging.
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Sobrecarga de Hierro , Talasemia , Talasemia beta , Benzoatos/efectos adversos , Terapia por Quelación/efectos adversos , Deferasirox/efectos adversos , Estudios de Seguimiento , Humanos , Quelantes del Hierro/efectos adversos , Sobrecarga de Hierro/tratamiento farmacológico , Sobrecarga de Hierro/epidemiología , Sobrecarga de Hierro/etiología , Medición de Riesgo , Factores de Riesgo , Talasemia/complicaciones , Talasemia/epidemiología , Talasemia/terapia , Triazoles/efectos adversos , Talasemia beta/complicacionesRESUMEN
INTRODUCTION: Chemical matricectomy using phenol (CMP) is a recognized treatment option for onychocryptosis. However, the appropriate phenol application time to achieve nail matrix destruction is still unknown. Optimal ablation leads to low recurrence rates. The aim of this research was to assess the recurrence rate of onychocryptosis in a cohort of 622 consecutive patients treated with a 4-min CMP. METHODS: We recruited all patients undergoing a 4-min CMP for onychocryptosis at the Istituto Podologico Italiano, Rome, Italy, in 2008-2017. Postoperative follow-up visits were set at 24 h, 7, 14, 21, and 28 days, 6 months, and 1 year after surgery. We used adjusted logistic regression to evaluate the potential risk factors for the disease recurrence including age, gender, toe shape, comorbidities, and disease localization. RESULTS: The risk of recurrence in all patients treated with a 4-min CMP was 1.1% (n = 622, 95% CI = 0.5%-2.3%). In the subgroup of patients with cardiovascular disease (n = 39) the recurrence risk was 5.1% (95% CI = 0.61-7.3). Young age was also associated with increased odds of recurrence (p = 0.036). CONCLUSION: In this observational study, 4 min with no interruptions seems to be the appropriate application time of phenol when using CMP for the treatment of onychocryptosis. A randomized controlled trial should be carried out to confirm our results.
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Fármacos Dermatológicos/administración & dosificación , Uñas Encarnadas/tratamiento farmacológico , Fenoles/administración & dosificación , Adolescente , Adulto , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Factores de Tiempo , Adulto JovenRESUMEN
PURPOSE OF REVIEW: The prediction of cardiovascular disease (CVD) events is of strategic importance for the primary prevention of one of the big killers in the world. Predictive models have a history of decades, but still the desired accuracy is not reached by any of the existing models. The inclusion of inflammatory factors in the models did not increase their accuracy. In this review, we discuss the possible reasons for that failure and we propose a paradigm shift. RECENT FINDINGS: Systemic inflammation is a very volatile phenomenon. The blood concentration of inflammatory biomarkers may change considerably in one individual with a timescale of seconds. Sudden changes in environmental conditions can trigger rapid modifications in the inflammatory profile of an individual. In routine clinical practice, the blood tests for inflammation are carried out at one point in time, not in standard environmental conditions, and are therefore inadequate. SUMMARY: We have to direct CVD research toward the understanding of the synchronic relationship between external environmental conditions and internal physiological reactions. CVD risk assessment must be carried out by using continuous real-time monitoring of external and internal parameters together, something that may become possible with the advent of new technological devices.
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Biomarcadores/análisis , Enfermedades Cardiovasculares/prevención & control , Inflamación/sangre , Prevención Primaria , Humanos , Inflamación/metabolismoRESUMEN
We have previously shown that there is a complex and dynamic biological interaction between acute mental stress and acute release of inflammatory factors into the blood stream in relation to heart disease. We now hypothesize that the presence of chronic psychosocial stress may modify the weight of single test results for inflammation as a predictor of heart disease. Using a cross-sectional design, 500 participants free from heart disease drawn from the Whitehall II study in UK in 2006-2008 were tested for plasma fibrinogen as an inflammatory factor, financial strain as a marker of chronic psychosocial stress, coronary calcification measured using computed tomography, and for plasma high-sensitivity cardiac troponin T (HS-CTnT) as a marker of cardiac risk. Fibrinogen concentration levels above the average were associated with a 5-fold increase in the odds of HS-CTnT positivity only among individuals with financial strain (N=208, OR=4.73, 95%CI=1.67 to 13.40, P=0.003). Fibrinogen was in fact not associated with HS-CTnT positivity in people without financial strain despite the larger size of that subsample (n=292, OR=0.84, 95%CI=0.42 to 1.67, P=0.622). A test for interaction on the full sample (N=500) showed a P value of 0.010 after adjusting for a range of demographics, health behaviours, traditional cardiovascular risk factors, psychosocial stressors, inflammatory cytokines, and coronary calcification. In conclusion, elevated fibrinogen seems to be cardio-toxic only when is combined with financial strain. Chronic psychosocial stress may modify the meaning that we should give to single test results for inflammation. Further research is needed to confirm our results.
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Inflamación , Estrés Psicológico/sangre , Troponina T/sangre , Biomarcadores/sangre , Calcinosis , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/prevención & control , Estudios Transversales , Fibrinógeno/metabolismo , Humanos , Medición de Riesgo , Estrés Psicológico/psicología , Reino UnidoRESUMEN
BACKGROUND: Conventional cardiac risk scores may not be completely accurate in predicting acute events because they only include factors associated with atherosclerosis, considered as the fundamental precursor of cardiovascular disease. In UK in 2006-2008 (Whitehall II study) we tested the ability of several risk scores to identify individuals with cardiac cell damage and assessed to what extent their estimates were mediated by the presence of atherosclerosis. METHODS: 430 disease-free, low-risk participants were tested for high-sensitivity cardiac troponin-T (HS-CTnT) and for coronary calcification using electron-beam, dual-source, computed tomography (CAC). We analysed the data cross-sectionally using ROC curves and mediation tests. RESULTS: When the risk scores were ranked according to the magnitude of ROC areas for HS-CTnT prediction, a score based only on age and gender came first (ROC area=0.79), followed by Q-Risk2 (0.76), Framingham (0.70), Joint-British-Societies (0.69) and Assign (0.68). However, when the scores were ranked according to the extent of mediation by CAC (proportion of association mediated), their order was essentially reversed (age&gender=6.8%, Q-Risk2=9.7%, Framingham=16.9%, JBS=17.8%, Assign=17.7%). Therefore, the more accurate a score is in predicting detectable HS-CTnT, the less it is mediated by CAC; i.e. the more able a score is in capturing atherosclerosis the less it is able to predict cardiac damage. The P for trend was 0.009. CONCLUSIONS: The dynamics through which cardiac cell damage is caused cannot be explained by 'classic' heart disease risk factors alone. Further research is needed to identify precursors of heart disease other than atherosclerosis.
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Aterosclerosis/complicaciones , Calcinosis/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Troponina T/sangre , Factores de Edad , Anciano , Aterosclerosis/sangre , Enfermedades Cardiovasculares , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/etiología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Medición de Riesgo , Factores Sexuales , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Most research on the influence of psychosocial job characteristics on health status has been conducted within affluent Western economies. This research addresses the same topic in a middle-income Southeast Asian country, enabling comparison with a Western benchmark. METHODS: We analysed and compared the Health Survey for England conducted in 2010 and the Thai Cohort Study data at 2005 baseline for workers aged 35-45 years. Multivariate logistic regression was used to assess relationships between psychosocial job characteristics and health, measured as Adjusted Odd Ratios (AOR), controlling for potential covariates in final analyses. RESULTS: In both UK and Thai working adults, psychological distress was associated with job insecurity (AOR 2.58 and 2.32, respectively), inadequate coping with job demands (AOR 2.57 and 2.42), and low support by employers (AOR 1.93 and 1.84). Job autonomy was associated with psychological distress in the UK samples (AOR 2.61) but no relationship was found among Thais after adjusting for covariates (AOR 0.99). Low job security, inability to cope with job demands, and low employer support were associated with psychological distress both among Thai and UK workers. CONCLUSIONS: Job autonomy was an important part of a healthy work environment in Western cultures, but not in Thailand. This finding could reflect cultural differences with Thais less troubled by individualistic expression at work. Our study also highlights the implications for relevant workplace laws and regulations to minimise the adverse job effects. These public health strategies would promote mental health and wellbeing in the population.
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Empleo/psicología , Salud Mental , Cultura Organizacional , Adaptación Psicológica , Adulto , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estrés Psicológico , Tailandia , Reino UnidoRESUMEN
BACKGROUND: Socioeconomic status is a recognised determinant of health status, and the association may be mediated by unhealthy behaviours and psychosocial adversities, which, in developed countries, both aggregate in low socioeconomic sectors of the population. We explored the hypothesis that unhealthy behavioural choices and psychological distress do not both aggregate in low socioeconomic status groups in developing countries. METHODS: Our study is based on a cross-sectional comparison between national population samples of adults in England and Thailand. Psychological distress was assessed using the General Health Questionnaire (GHQ-12) or three anxiety-oriented items from the Kessler scale (K6). Socioeconomic status was assessed on the basis of occupational status. We computed a health-behaviour score using information about smoking, alcohol consumption, fruit and vegetable consumption, and physical activity. RESULTS: The final sample comprised 40,679 participants. In both countries and in both genders separately, there was a positive association between poor health-behaviour and high psychological distress, and between high psychological distress and low socioeconomic status. In contrast, the association between low socioeconomic status and poor health-behaviour was positive in both English men and women, flat in Thai men, and was negative in Thai women (likelihood ratio test P <0.001). CONCLUSION: The associations between socioeconomic status, behavioural choices, and psychological distress are different at the international level. Psychological distress may be consistently associated with low socioeconomic status, whereas poor health-behaviour is not. Future analyses will test whether psychological distress is a more consistent determinant of socioeconomic differences in health across countries.
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Comparación Transcultural , Conductas Relacionadas con la Salud , Disparidades en el Estado de Salud , Clase Social , Estrés Psicológico/psicología , Adulto , Anciano , Consumo de Bebidas Alcohólicas/psicología , Conducta de Elección , Estudios de Cohortes , Estudios Transversales , Ingestión de Alimentos/psicología , Inglaterra , Femenino , Frutas , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Actividad Motora , Escalas de Valoración Psiquiátrica , Factores de Riesgo , Fumar/psicología , Tailandia , VerdurasRESUMEN
BACKGROUND: The purpose of this study was to test whether lower socioeconomic status (SES) augments the effect of psychological distress on mortality from stroke or coronary heart disease (CHD). METHODS: We prospectively linked data from 66,500 participants 35 years or older in the Health Survey for England, selected using stratified random sampling from 1994 to 2004, and free of cardiovascular disease and cancer at baseline, with mortality records. The median follow-up time was 7.9 years. SES was indexed by occupational class, and psychological distress was assessed using the 12-item General Health Questionnaire (GHQ-12). RESULTS: After adjustment for demographic and clinical variables, both psychological distress and low SES were associated with increased mortality: the hazard ratios (HR) for one-category increase in low SES (three categories in total) were 1.15 for stroke-death (95% confidence interval [CI] = 1.00-1.31, p = .043) and 1.24 for CHD-death (95% CI = 1.09-1.41, p = .001); the HR for one-category increase in GHQ-12 (three categories in total) was 1.18 for stroke-death (95% CI = 1.07-1.30, p = .001) and 1.24 for CHD-death (95% CI = 1.13-1.36, p < .001). In stratified analyses, the strongest associations were found in the lowest SES categories: the HR for GHQ-12 toward stroke-death was 1.15 in high-SES participants (95% CI = 0.97-1.37, p = .107) and 1.31 in low-SES ones (95% CI = 1.13-1.51, p < .001); the HR for GHQ-12 toward CHD-death was 1.10 in high-SES participants (95% CI = 0.97-1.25, p = .129) and 1.33 in low-SES ones (95% CI = 1.19-1.48, p < .001). CONCLUSIONS: People in low socioeconomic circumstances are more vulnerable to the adverse effect of psychological distress. This pattern should be taken into account when evaluating the association between psychosocial variables and health outcomes.
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Enfermedad Coronaria/mortalidad , Enfermedad Coronaria/psicología , Clase Social , Estrés Psicológico/mortalidad , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/psicología , Adulto , Anciano , Inglaterra/epidemiología , Femenino , Estudios de Seguimiento , Encuestas Epidemiológicas/métodos , Encuestas Epidemiológicas/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Estrés Psicológico/psicología , Encuestas y CuestionariosRESUMEN
BACKGROUND: While efavirenz-associated adverse drug events (ADEs) were widely established, the clinical relevance is uncertain. OBJECTIVES: We aimed to assess the extent of treatment interruption caused by efavirenz-associated ADEs. METHODS: A case-control study of efavirenz recipients who did, versus did not (control) develop adverse drug events (ADE), and who were matched for baseline CD4 + at a ratio of 1:1.3 was conducted. Antiretroviral -naïve patients who were started on efavirenz were followed up retrospectively, and their records scrutinized every month for 2 years. Demographic and clinical predictors of treatment interruption were computed using Cox proportional hazard models. Kaplan- Meier curves were plotted to assess time to treatment interruption for the two groups. Clinical endpoints were: i) efficacy -improved CD4 + counts and/or viral load (VL) suppression, ii) safety -absence of treatment-limiting toxicities, and iii) durability - no interruption until follow-up ended. RESULTS: Both groups had comparable CD4 + counts at baseline (p = 0.15). At t = 24-months, VL in both groups were suppressed to undetectable levels (<20 copies/mL) while median CD4 + was 353 cells/µL (IQR: 249-460). The mean time on treatment was 23 months (95% CI, 22.3 -23.4) in the control group without ADE and 20 months (95% CI, 18.9 - 21.6) in the ADE group (p = 0.001). Kaplan-Meier plots demonstrated that 59.5% of patients who experienced ≥ 1 ADE versus 81% of those who did not experience any ADE were estimated to continue treatment for up to 24 months with no interruption (p = 0.001). Most interruptions to EFV treatment occurred in the presence of opportunistic infections and these were detected within the first 5 months of treatment initiation. Independent predictors which negatively impacted the dependent variable i.e., treatment durability, were intravenous drug use (adjusted hazard ratio, aHR 2.17, 95% CI, 1.03-4.61, p = 0.043), presence of ≥ 1 opportunistic infection(s) (aHR 2.2, 95% CI, 1.13-4.21, p = 0.021), and presence of ≥ 1 serious ADE(s) (aHR 4.18, 95% CI, 1.98-8.85, p = 0.00). CONCLUSION: Efavirenz' role as the preferred first-line regimen for South-East Asia's resource-limited regions will need to be carefully tailored to suit the regional population. Findings have implications to policy-makers and clinicians, particularly for the treatment of patients who develop ADEs and opportunistic infections, and for intravenous drug user subgroups.
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Fármacos Anti-VIH , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Infecciones por VIH , Infecciones Oportunistas , Abuso de Sustancias por Vía Intravenosa , Humanos , Fármacos Anti-VIH/efectos adversos , Estudios de Casos y Controles , Estudios Retrospectivos , Abuso de Sustancias por Vía Intravenosa/tratamiento farmacológico , Infecciones por VIH/tratamiento farmacológico , Recuento de Linfocito CD4 , Antirretrovirales/uso terapéutico , Carga Viral , Infecciones Oportunistas/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND: Mental healthcare services for children and young people (CYP) are a very limited resource in the UK. To prevent health inequalities, measures to increase overall capacity must sit alongside measures that ensure utilisation matches need. AIM: Our aim was to identify subgroups of CYP with unexpectedly low mental health service utilisation, presumably representing unmet need, and to assess whether there is area variation in the socioeconomic gradient of mental healthcare use. METHODS: This is a cross-sectional population survey of CYP (aged 5-24 years) using electronic health records from the Discover Now research platform, covering approximately 95% of the Northwest London resident population of 2.4 million people. RESULTS: The total sample comprised 764 327 CYP, of whom 2.1% attended a mental healthcare appointment in 2021 (95% CI 2.1% to 2.2%), our outcome measure. Lower socioeconomic status (our main exposure factor) was related to higher occurrence of mental healthcare appointments (+5% for each quintile increase in deprivation (95% CI 2% to 7%, p<0.001]). However, interaction analyses showed that the boroughs with unexpectedly low utilisation rates were also those not showing a clear trend between socioeconomic conditions and services utilisation (interaction p<0.001), suggesting that in these boroughs the occurrence of mental disorders in disadvantaged people was not captured by our analysis based on service utilisation. In some London boroughs, we found lower-than-expected activity for the most disadvantaged CYP. CONCLUSIONS: The mental healthcare needs of many CYP from socioeconomically deprived areas of Northwest London may be unmet. More information is needed to confirm our results.
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Although human monkeypox infections had not been recorded in the Kurdistan region of Iraq as of August 2023, the rapid growth of cases worldwide and the detection of monkeypox in neighboring Middle Eastern nations call for careful planning and timely response measures. Educating and empowering frontline healthcare workers (HCWs) so that they can act to curb the spread of monkeypox infections are core elements of primary prevention and protecting public health. Therefore, this study aimed to assess HCWs' knowledge and attitudes about monkeypox and their willingness to vaccinate against monkeypox. By employing a convenience sampling method, an online survey was disseminated via Google Forms between 1 November 2022 and 15 January 2023. The researchers utilized regression analyses to ascertain the factors associated with the three parameters: knowledge, attitude, and the willingness to vaccinate. A total of 637 HCWs were included in the analysis (ages ranged between 21 and 51 years). The mean overall scores were 8.18 of a max score of 16 (SD 3.37), 3.4 of 5 (SD 1.37), and 2.41 of 5 (SD 1.25) for knowledge, attitude, and willingness to vaccinate, respectively. A multivariate logistic regression analysis demonstrated that HCWs who had heard about monkeypox before 2022 rather than later had a higher level of knowledge (AOR: 4.85; 95% CI: 2.81-8.36; p < 0.001). In addition, those who had newly joined the workforce or had less than 1 year experience in practice had more positive attitudes about curbing monkeypox (AOR: 0.35; 95% CI: 0.20-0.59; p < 0.01) than those who practiced for longer. No significant predictors of willingness to vaccinate against monkeypox were identified. The research revealed that HCWs exhibited a relatively low level of monkeypox knowledge. They also had poor attitudes towards monkeypox vaccination and were therefore reluctant to receive the vaccines. Imparting knowledge about the infectious disease can cultivate better awareness and attitudes among HCWs as to their roles in mitigating the spread of an epidemic in the foreseeable future.
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The coronavirus disease 2019 (COVID-19) that can cause extreme acute respiratory syndrome has posed a catastrophic threat to public health. The vaccines had indeed restored optimism and, after more than two years of battling the pandemic, there is renewed hope for the transition to endemicity. At the start of vaccination efforts, when supply shortages of vaccines were inevitable, every nation determined the high-risk population groups to be given priority for the COVID-19 vaccines. In this paper, the characteristics of the initial COVID-19 vaccine recipients in Malaysia are described. In line with the policies of many other countries, Malaysia firstly inoculated frontline healthcare workers, and subsequently the list of front liners grew to include defense and security personnel and those involved in the provision of essential services. People with disabilities or those with special needs and several underlying medical conditions that increased their risk of developing severe COVID-related illnesses were included in the priority categories. These included patients with severe lung disease, chronic heart disease, chronic kidney disease, chronic liver disease, neurological disease, diabetes mellitus and obesity in adults, splenic dysfunction, and severe mental illness. With little information and under circumstances of great uncertainty, the Health Ministry of a middle-income country had developed a vaccination priority-list based on the disease's epidemiology and clinical data, vaccine type, operational considerations, and risk evaluation. Early evidence was presented and suggested that the full vaccination with any of the three predominant vaccines (AZD1222, BNT162b2, and CoronaVac) in the country had been highly effective in preventing COVID-19 infections, COVID-19-related ICU admissions, and death. As many SARS-CoV-2 variants of concern (VoC), such as the Omicron BA.2/4/5, are emerging, future vaccination strategies may necessitate the need to change the immunogen of the vaccine, as well as considerations for when to give high-risk groups booster injections. These considerations are valuable for future planning by policymakers and healthcare providers to make vaccination policy and decisions, especially for the inclusion of the COVID-19 vaccines into national immunization programs.
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COVID-19 vaccines are possibly the most effective medical countermeasures to mitigate and ultimately bring to a halt the COVID-19 pandemic. As we transition to endemicity, inequitable access to vaccines, and particularly in low- and middle-income countries (LMICs), still poses risks of unprecedented disruptions and the emergence of viral mutations, which potentially lead to notorious vaccine-resistant variants. The missteps learned from the previous responses to the human immunodeficiency virus (HIV) and influenza outbreaks founded the hypothetical plan to ensure that vaccine accessibility to LMICs is not impeded. The SARS-CoV-2 vaccines' social promise was to lessen the underlying racial, ethnic, and geographic inequities that COVID-19 has both made apparent and intensified. Vaccine nationalism was evident throughout the COVID-19 crisis. Many high-income countries directly negotiated large advance orders for the vaccines, leaving resource-limited countries scrambling for access. This occurred despite international initiatives to structure the development and equitable distribution of vaccines, channeled through a vaccine pillar: COVID-19 Vaccines Global Access (COVAX). The serious supply shortages and national procurement methods of some countries that bypassed the vaccine pillar hindered the optimal function of COVAX in delivering timely and adequate doses to participating countries. COVAX strategized its approach by promoting fundraising, coordinating vaccine donations from countries with surplus doses, expediting reviews of vaccine candidates, and facilitating the expansion of the manufacturing capacity. While increasing capacity for production, technology transfer led to lesser siloes, enhanced manufacturing standardization, and less secrecy over production data. Ultracold storage requirements for leading vaccines were a considerable hurdle to the global immunization efforts, and particularly in LMICs with limited equipment and resources to support sophisticated cold-chain systems. Manufacturers strived to ease cold-chain restrictions on the basis of stability data submitted to national regulatory bodies. The development of single-dose vaccines offered promising solutions to simplify the administrative and logistic complexities that existed within the COVID-19 vaccination programs. As such, the requirements for both ultracold storage conditions were eased, and concerns over booster doses were addressed. To expand coverage, the dosing intervals of the Oxford/AstraZeneca vaccines were extended according to data from Phase III clinical trials on effectiveness. In addition, with the recent outbreak of monkeypox, the lessons from past experiences of curbing infectious diseases, including COVID-19, must be learned and acted upon. The review summarizes the global efforts with respect to vaccine development, production, allocation, and deployment to achieve equitable access.
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OBJECTIVE: To assess the trends in uptake of minimal invasive esophagectomy in England over the last 12 years (1996/1997-2007/2008) and to compare their clinical outcomes with those after open esophagectomy. SUMMARY OF BACKGROUND DATA: Around 7400 people are affected each year in the United Kingdom. Prognosis following esophageal resection is, however, poor. Even after "curative" surgery, 5-year survival rates do not exceed 25%. The minimally invasive approach to esophagectomy has attracted attention as a potentially less invasive alternative to conventional surgery. METHODS: Data on patients undergoing esophagectomy for esophageal cancer were extracted from a national administrative database. The outcomes of interest were in-hospital mortality, 30-day in-hospital mortality, 30-day total (ie, in and out of hospital) mortality, 365-day total mortality, 28-day emergency readmission rates, and length of hospital stay. Hierarchical logistic regression was used to identify the effect of minimal invasive esophagectomy (MIE) on the outcomes after adjustment for age, gender, socioeconomic deprivation, and comorbidity. RESULTS: A total of 18,673 esophagectomies were performed over the 12-year study period. The use of minimal access surgery increased exponentially over time (from 0.6% in 1996/1997 to 16.0% in 2007/2008). There was a suggestion that patients undergoing MIE had better 1-year survival rates than patients receiving open esophagectomy (OR = 0.68, 95% CI = 0.46-1.01, P = 0.058). CONCLUSION: The uptake of MIE in England is increasing exponentially. With the possible exception of 1-year survival, patients selected for MIE demonstrated similar mortality and length of stay outcomes when compared with those undergoing conventional surgery. These results need to be confirmed in large-scale randomized controlled trials.
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Neoplasias Esofágicas/cirugía , Esofagectomía/métodos , Evaluación de Procesos y Resultados en Atención de Salud , Pautas de la Práctica en Medicina/estadística & datos numéricos , Anciano , Neoplasias Esofágicas/mortalidad , Esofagectomía/mortalidad , Femenino , Mortalidad Hospitalaria , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos , Pronóstico , Tasa de Supervivencia , Reino UnidoRESUMEN
In the context of the current SARS-CoV-2 pandemic, patients affected by chronic obstructive pulmonary disease (COPD) should be more vulnerable to Covid-19, whereas they seem to be protected against severe Covid-19. That paradox has important practical implications for the use of the drug Tocilizumab in Covid-19. Interleukin-6 (IL-6) orchestrates the so-called cytokine storm leading to the Acute Respiratory Distress Syndrome (ARDS), the life-threatening condition that is responsible for Covid-19 deaths. However, IL-6 has a paradoxical effect in many viral infections. For pathogens such as HIV and Hepatitis B for example, high elevations show a toxic effect and are associated with higher mortality (e.g. they promote progression to AIDS in HIV patients), whereas mild elevations show a protective effect. IL-6 can be therefore considered as being both a pro-inflammatory and an anti-inflammatory cytokine. Several studies have shown that severe COPD is associated with extremely-high levels of IL-6, whereas mild COPD is associated with mild elevations of IL-6. It is plausible that the chronic, mildly-elevated concentrations of IL-6 found in mild COPD patients is protective against the deterioration of Covid-19, as it is the case for other viral diseases. That may explain why COPD is surprisingly an uncommon comorbidity in Covid-19 intensive care units. This may have an important practical implication for the treatment of Covid-19 patients: our hypothesis is that Tocilizumab must be used exclusively in patients with an ongoing cytokine storm. Otherwise, an early use of Tocilizumab can be harmful, especially in patients affected by COPD or other conditions with mildly-elevated IL-6.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Tratamiento Farmacológico de COVID-19 , COVID-19/inmunología , Interleucina-6/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Antiinflamatorios/uso terapéutico , COVID-19/complicaciones , Citocinas/metabolismo , Infecciones por VIH/complicaciones , Hepatitis B/complicaciones , Humanos , Inflamación , Modelos Teóricos , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Síndrome de Dificultad Respiratoria/inmunología , Síndrome de Dificultad Respiratoria/virología , Resultado del TratamientoRESUMEN
We reviewed the literature concerning the innate response from nasal and oral epithelial cells and their reaction to hydrogen peroxide (H2O2). Hydrogen peroxide is produced physiologically by oral bacteria and plays a significant role in the balance of oral microecology since it is an important antimicrobial agent. In the epithelial cells, the enzyme superoxide dismutase catalyzes a reaction leading from hydrogen peroxide to the ion superoxide. The induced oxidative stress stimulates a local innate response via activation of the toll-like receptors and the NF-κB. Those kinds of reactions are also activated by viral infections. Virus-induced oxidative stress plays an important role in the regulation of the host immune system and the specific oxidant-sensitive pathway is one of the effective strategies against viral infections. Therefore, nose/mouth/throat washing with hydrogen peroxide may enhance those local innate responses to viral infections and help protect against the current coronavirus pandemic. We strongly encourage the rapid development of randomized controlled trials in both SARS-CoV-2 positive and negative subjects to test the preliminary findings from the in-vitro and in-vivo observational studies that we identified.
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Tratamiento Farmacológico de COVID-19 , Peróxido de Hidrógeno/administración & dosificación , Virosis/tratamiento farmacológico , COVID-19/inmunología , COVID-19/virología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/inmunología , Células Epiteliales/virología , Humanos , Inmunidad Innata/efectos de los fármacos , Técnicas In Vitro , Modelos Inmunológicos , Antisépticos Bucales/administración & dosificación , Rociadores Nasales , Pandemias , SARS-CoV-2/efectos de los fármacos , Virosis/inmunología , Virosis/virologíaRESUMEN
RATIONALE: Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis has been widely reported in depression, and evidence suggests that selective serotonin reuptake inhibitors (SSRIs) might exert their therapeutic effects through altering cortisol secretion. OBJECTIVE: This study assessed the effects of SSRI administration on diurnal cortisol secretion in healthy volunteers. METHODS: Sixty-four healthy men and women were randomised to receive either 10 mg escitalopram or placebo for six days in a double-blind fashion. On day six of medication, saliva samples were obtained at home for measurement of diurnal cortisol parameters (cortisol slope, cortisol awakening response, total daily cortisol output). RESULTS: Women receiving escitalopram had significantly steeper cortisol slopes across the day compared with those receiving placebo (F(1, 36) = 7.54, p = 0.009). This alteration in cortisol slope was driven by increases in waking cortisol levels (F(1, 35) = 9.21, p = 0.005). Escitalopram did not have any significant effect on the cortisol awakening response or the total daily cortisol output. CONCLUSIONS: Flattened cortisol slopes have been seen in depression. The results of this study suggest that escitalopram might exert its therapeutic effect in women in part through correction of a flattened diurnal cortisol rhythm.
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Ritmo Circadiano/fisiología , Citalopram/administración & dosificación , Hidrocortisona/metabolismo , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Adulto , Ritmo Circadiano/efectos de los fármacos , Método Doble Ciego , Femenino , Voluntarios Sanos , Humanos , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/metabolismo , Masculino , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/metabolismo , Saliva/efectos de los fármacos , Saliva/metabolismo , Adulto JovenRESUMEN
INTRODUCTION: The blood test for high-sensitivity cardiac troponin T (HS-CTnT) has been proposed as a marker of cardiovascular risk in the general population, as it is associated with subsequent incidence of cardiovascular events and mortality. We aimed at evaluating the feasibility of HS-CTnT testing within large nationally-representative population surveys in which blood samples are collected during household visits, shipped using the standard civil postal service, and then frozen for subsequent analyses. METHODS: The Health Survey for England (HSE) consists of a series of annual surveys beginning in 1991. It is designed to provide regular information on various aspects of the nation's health and risk factors. We measured HS-CTnT in the blood of 200 people from the HSE 2016 wave, then froze and stored their blood samples at -40°C for 5-10 weeks, and then thawed and retested them to appreciate the extent of within-person agreement or test-retest reliability of the two measurements. RESULTS: The Cronbach's Alpha (Scale Reliability Coefficient) and the Interclass Correlation Coefficient (two-way mixed-effects model for consistency of agreement at individual level) were 0.97 (95%CI = 0.96-0.99) and 0.95 (95%CI = 0.94-0.96) respectively. The time delay from blood withdrawal to analysis and storage (1-4 days) did not affect the results, nor did the freezing time before the retest (5-10 weeks). CONCLUSION: The measurement of HS-CTnT plasma concentration within large nationally-representative surveys such as the Health Survey for England is feasible.
Asunto(s)
Encuestas Epidemiológicas , Troponina T/sangre , Inglaterra/epidemiología , Humanos , Reproducibilidad de los ResultadosRESUMEN
This study was conducted on a sample of physicians training in Hygiene and Preventive medicine to evaluate their: smoking habits, awareness of the effects of cigarette smoke on health and attitudes regarding antismoking legislation. Data was obtained through administration of an anonymous questionnaire. A total of 220 physicians were interviewed: 27% was found to be a smoker while 45% of smokers stated that they did not want to quit smoking. These results are similar to those obtained for the general population. Amongst the residents of the various schools of specialisation, there are large differences in habits, awareness and attitudes towards smoke: a lack of professional training on the subject is present.