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1.
Theranostics ; 11(3): 1207-1231, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33391531

RESUMEN

Rationale: Coronavirus disease 2019 (COVID-19) has spread worldwide and poses a threat to humanity. However, no specific therapy has been established for this disease yet. We conducted a systematic review to highlight therapeutic agents that might be effective in treating COVID-19. Methods: We searched Medline, Medrxiv.org, and reference lists of relevant publications to identify articles of in vitro, in vivo, and clinical studies on treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19 published in English until the last update on October 11, 2020. Results: We included 36 studies on SARS, 30 studies on MERS, and 10 meta-analyses on SARS and MERS in this study. Through 12,200 title and 830 full-text screenings for COVID-19, eight in vitro studies, 46 randomized controlled trials (RCTs) on 6,886 patients, and 29 meta-analyses were obtained and investigated. There was no therapeutic agent that consistently resulted in positive outcomes across SARS, MERS, and COVID-19. Remdesivir showed a therapeutic effect for COVID-19 in two RCTs involving the largest number of total participants (n = 1,461). Other therapies that showed an effect in at least two RCTs for COVID-19 were sofosbuvir/daclatasvir (n = 114), colchicine (n = 140), IFN-ß1b (n = 193), and convalescent plasma therapy (n = 126). Conclusions: This review provides information to help establish treatment and research directions for COVID-19 based on currently available evidence. Further RCTs are required.


Asunto(s)
Antivirales/uso terapéutico , Infecciones por Coronavirus/terapia , Síndrome Respiratorio Agudo Grave/terapia , Adenosina Monofosfato/análogos & derivados , Adenosina Monofosfato/uso terapéutico , Alanina/análogos & derivados , Alanina/uso terapéutico , Animales , Carbamatos/uso terapéutico , Infecciones por Coronavirus/mortalidad , Modelos Animales de Enfermedad , Combinación de Medicamentos , Evaluación Preclínica de Medicamentos , Quimioterapia Combinada/métodos , Humanos , Imidazoles/uso terapéutico , Inmunización Pasiva/métodos , Pirrolidinas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Síndrome Respiratorio Agudo Grave/mortalidad , Sofosbuvir/uso terapéutico , Resultado del Tratamiento , Valina/análogos & derivados , Valina/uso terapéutico
2.
Trials ; 22(1): 4, 2021 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-33397429

RESUMEN

OBJECTIVES: We will evaluate the efficacy and safety of Ivermectin in patients with mild and moderately severe COVID-19. TRIAL DESIGN: This is a phase 3, single-center, randomized, open-label, controlled trial with a 2-arm parallel-group design (1:1 ratio). PARTICIPANTS: The Severe Acute Respiratory Syndrome Departments of the Shahid Mohammadi Hospital, Bandar Abbas, Iran, will screen for patients age ≥ 20 years and weight ≥35 kg for the following criteria: Inclusion criteria for patients with mild COVID-19 symptoms (outpatients) 1. Diagnosed mild pneumonia using computed tomography (CT) and/or chest X-ray (CX-R) imaging, not requiring hospitalization. 2. Signing informed consent. Inclusion criteria for patients with moderate COVID-19 symptoms (inpatients) 1. Confirmed infection using PCR. 2. Diagnosed moderate pneumonia using CT and/or CXR imaging, requiring hospitalization. 3. Hospitalized ≤ 48 hours. 4. Signing informed consent. Exclusion criteria 1. Severe and critical pneumonia due to COVID-19. 2. Underlying diseases, including AIDS, asthma, loiasis, and severe liver and kidney disease. 3. Use of anticoagulants (e.g., warfarin) and ACE inhibitors (e.g., captopril). 4. History of drug allergy to Ivermectin. 5. Pregnancy or breastfeeding. INTERVENTION AND COMPARATOR: Intervention groups: Outpatient and inpatient groups will receive the standard treatment regimen for mild and moderate COVID-19, based on the Iranian Ministry of Health and Medical Education's protocol, along with oral Ivermectin (MSD Company, France) at a single dose of 0.2 mg/kg. Control groups: The outpatient group will receive hydroxychloroquine sulfate (Amin Pharmaceutical Company, Iran) at a dose of 400 mg twice a day for the first day and 200 mg twice a day for seven subsequent days. The inpatient group will receive 200/50 mg Lopinavir/Ritonavir (Heterd Company, India) twice a day for the seven days, plus five doses of 44 mcg Interferon beta-1a (CinnaGen, Iran) every other day. Other supportive and routine care will be the same in both outpatient and inpatient groups. MAIN OUTCOME: The primary outcomes are composite and include the improvement of clinical symptoms and need for hospitalization for outpatient groups, and the length of hospital stay until discharge, the need for ICU admission until discharge, and the need for mechanical ventilation for inpatient groups within seven days of randomization. The secondary outcome is the incidence of serious adverse drug reactions within seven days of randomization. RANDOMIZATION: Patients in both outpatient (mild) and inpatient (moderate) groups will be randomized into the treatment and control groups based on the following method. A simple randomization method and table of random numbers will be used. If the selected number is even, the patient is allocated to the treatment group, and if it is odd, the patient is allocated to the control group in a 1:1 ratio. BLINDING (MASKING): This is an open-label study, and there is not blinding. Numbers to be randomized (sample size) A total number of 120 patients (60 outpatients and 60 patients) will be randomized into two groups (30 patients in each of the intervention groups and 30 patients in each of the control groups). TRIAL STATUS: The protocol is Version 1.0, November 17, 2020. Recruitment began November 25, 2020, and is anticipated to be completed by February 25, 2021. TRIAL REGISTRATION: This clinical trial has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is " IRCT20200506047323N6 ". The registration date is November 17, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting the dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.


Asunto(s)
Antivirales/administración & dosificación , Ivermectina/administración & dosificación , /aislamiento & purificación , Administración Oral , Adulto , Antivirales/efectos adversos , /virología , Ensayos Clínicos Fase III como Asunto , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Femenino , Humanos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/efectos adversos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Interferón beta-1a/administración & dosificación , Interferón beta-1a/efectos adversos , Irán , Ivermectina/efectos adversos , Tiempo de Internación/estadística & datos numéricos , Lopinavir/administración & dosificación , Lopinavir/efectos adversos , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Ritonavir/administración & dosificación , Ritonavir/efectos adversos , Índice de Severidad de la Enfermedad
3.
Trials ; 22(1): 3, 2021 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-33397457

RESUMEN

OBJECTIVES: To investigate the efficacy and safety of repurposed antiprotozoal and antiretroviral drugs, nitazoxanide and atazanavir/ritonavir, in shortening the time to clinical improvement and achievement of SARS-CoV-2 polymerase chain reaction (PCR) negativity in patients diagnosed with moderate to severe COVID-19. TRIAL DESIGN: This is a pilot phase 2, multicentre 2-arm (1:1 ratio) open-label randomised controlled trial. PARTICIPANTS: Patients with confirmed COVID-19 diagnosis (defined as SARS-CoV-2 PCR positive nasopharyngeal swab) will be recruited from four participating isolation and treatment centres in Nigeria: two secondary care facilities (Infectious Diseases Hospital, Olodo, Ibadan, Oyo State and Specialist State Hospital, Asubiaro, Osogbo, Osun State) and two tertiary care facilities (Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Osun State and Olabisi Onabanjo University Teaching Hospital, Sagamu, Ogun State). These facilities have a combined capacity of 146-bed COVID-19 isolation and treatment ward. INCLUSION CRITERIA: Confirmation of SARS-CoV-2 infection by PCR test within two days before randomisation and initiation of treatment, age bracket of 18 and 75 years, symptomatic, able to understand study information and willingness to participate. Exclusion criteria include the inability to take orally administered medication or food, known hypersensitivity to any of the study drugs, pregnant or lactating, current or recent (within 24 hours of enrolment) treatment with agents with actual or likely antiviral activity against SARS-CoV-2, concurrent use of agents with known or suspected interaction with study drugs, and requiring mechanical ventilation at screening. INTERVENTION AND COMPARATOR: Participants in the intervention group will receive 1000 mg of nitazoxanide twice daily orally and 300/100 mg of atazanvir/ritonavir once daily orally in addition to standard of care while participants in the control group will receive only standard of care. Standard of care will be determined by the physician at the treatment centre in line with the current guidelines for clinical management of COVID-19 in Nigeria. MAIN OUTCOME MEASURES: Main outcome measures are: (1) Time to clinical improvement (defined as time from randomisation to either an improvement of two points on a 10-category ordinal scale (developed by the WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection) or discharge from the hospital, whichever came first); (2) Proportion of participants with SARS-CoV-2 polymerase chain reaction (PCR) negative result at days 2, 4, 6, 7, 14 and 28; (3) Temporal patterns of SARS-CoV-2 viral load on days 2, 4, 6, 7, 14 and 28 quantified by RT-PCR from saliva of patients receiving standard of care alone versus standard of care plus study drugs. RANDOMISATION: Allocation of participants to study arm is randomised within each site with a ratio 1:1 based on randomisation sequences generated centrally at Obafemi Awolowo University. The model was implemented in REDCap and includes stratification by age, gender, viral load at diagnosis and presence of relevant comorbidities. BLINDING: None, this is an open-label trial. NUMBER TO BE RANDOMISED (SAMPLE SIZE): 98 patients (49 per arm). TRIAL STATUS: Regulatory approval was issued by the National Agency for Food and Drug Administration and Control on 06 October 2020 (protocol version number is 2.1 dated 06 August 2020). Recruitment started on 9 October 2020 and is anticipated to end before April 2021. TRIAL REGISTRATION: The trial has been registered on ClinicalTrials.gov (July 7, 2020), with identifier number NCT04459286 and on Pan African Clinical Trials Registry (August 13, 2020), with identifier number PACTR202008855701534 . FULL PROTOCOL: The full protocol is attached as an additional file which will be made available on the trial website. In the interest of expediting dissemination of this material, the traditional formatting has been eliminated, and this letter serves as a summary of the key elements in the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).


Asunto(s)
Antivirales/administración & dosificación , Sulfato de Atazanavir/administración & dosificación , Ritonavir/administración & dosificación , Tiazoles/administración & dosificación , Administración Oral , Adolescente , Adulto , Anciano , Antivirales/efectos adversos , Sulfato de Atazanavir/efectos adversos , /virología , Ensayos Clínicos Fase II como Asunto , Esquema de Medicación , Combinación de Medicamentos , Reposicionamiento de Medicamentos , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Nigeria , Proyectos Piloto , ARN Viral/aislamiento & purificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Ritonavir/efectos adversos , /aislamiento & purificación , Índice de Severidad de la Enfermedad , Nivel de Atención , Tiazoles/efectos adversos , Resultado del Tratamiento , Carga Viral/efectos de los fármacos , Adulto Joven
4.
Medicine (Baltimore) ; 99(50): e23195, 2020 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-33327236

RESUMEN

BACKGROUND: Angina pectoris in coronary heart disease (CHD) is a common ischemic heart disease clinically. During the onset, patients often have symptoms such as chest discomfort or paroxysmal crushing pain in the posterior sternum, which seriously affects the quality of life of patients, and even can lead to myocardial infarction and endanger the lives of patients. Clinical studies have shown that the compound Chinese prescription Xuefu Zhuyu decoction combined with western medicine has a certain therapeutic effect on angina pectoris in CHD, but lack of evidence of evidence-based medicine. The purpose of this study is to evaluate the efficacy and safety of Xuefu Zhuyu decoction combined with western medicine in the treatment of angina pectoris in CHD. METHODS: Use computer to retrieve English databases (PubMed, Embase, Web of Science, the Cochrane Library) and Chinese databases (CNKI, Wan Fang, VIP, Chinese biomedical database), from the establishment of database to October 2020, for randomized controlled trials (RCTs) of Xuefu Zhuyu decoction combined with Western medicine for angina pectoris in CHD. Two investigators independently conducted data extraction and assessed the literature quality of the included studies. The Revman5.3 software was used for meta-analysis of the included literatures. RESULTS: The efficacy and safety of Xuefu Zhuyu decoction combined with western medicine in the treatment of angina pectoris in CHD were evaluated by total effective rate, angina pectoris pain score, TCM syndrome score, electrocardiogram effect, hemorheology index (including whole blood viscosity, plasma viscosity, hematocrit, and fibrinogen), and the incidence of adverse reactions. CONCLUSION: This study will provide reliable evidence-based evidence for the clinical application of Xuefu Zhuyu decoction combined with western medicine in the treatment of angina pectoris in CHD. ETHICS AND DISSEMINATION: Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval was not required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605 / OSF.IO / GFEQ7.


Asunto(s)
Angina de Pecho/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos bajo Prescripción/uso terapéutico , Angina de Pecho/etiología , Estudios de Casos y Controles , Enfermedad Coronaria/complicaciones , Enfermedad Coronaria/diagnóstico , Enfermedad Coronaria/epidemiología , Quimioterapia Combinada/métodos , Femenino , Humanos , Masculino , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Seguridad , Resultado del Tratamiento
5.
PLoS One ; 15(12): e0239964, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33362271

RESUMEN

BACKGROUND: Autoimmune hepatitis (AIH) is a progressive inflammatory liver disease of unknown aetiology. The number of reported AIH cases is increasing in the developed countries but the same cannot be said about sub Saharan Africa (SSA). Paediatric AIH diagnosis is usually missed and patients present with decompensated liver disease. Our study highlights the clinical profile of paediatric AIH cases at a referral hospital in Ghana. METHODS: This is a retrospective review of all cases of children diagnosed with autoimmune hepatitis at the gastroenterology clinic in Korle Bu Teaching Hospital, Accra, Ghana. Data was extracted from the patients' records from April 2016 to October 2019. These children were diagnosed based on the presence of autoantibodies, elevated immunoglobulin G and histologic presence of interphase hepatitis with the exclusion of hepatitis A, B, C and E depending on their clinical presentation, Wilson's disease, HIV, Schistosomiasis and sickle cell disease. RESULTS: Thirteen patients aged between 5 years to 13 years with a mean age of 10 years were diagnosed with AIH. All the patients had type 1 AIH with majority 8 (61.5%) being females. Most of the children presented with advanced liver disease with complications. Three patients had other associated autoimmune diseases. The patients were treated with prednisolone with or without azathioprine depending on the severity of the liver disease. CONCLUSION: Majority of paediatric AIH presents with advanced liver disease. There is the need for early detection to change the natural history of AIH in SSA.


Asunto(s)
Hepatitis Autoinmune/diagnóstico , Inmunosupresores/uso terapéutico , Adolescente , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Azatioprina/uso terapéutico , Niño , Preescolar , Quimioterapia Combinada/métodos , Femenino , Ghana , Hepatitis Autoinmune/sangre , Hepatitis Autoinmune/tratamiento farmacológico , Hepatitis Autoinmune/inmunología , Humanos , Masculino , Prednisolona/uso terapéutico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
6.
Cochrane Database Syst Rev ; 12: CD012965, 2020 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-33316083

RESUMEN

BACKGROUND: Acute bronchiolitis is a significant burden on children, their families and healthcare facilities. It mostly affects children younger than two years of age. Treatment involves adequate hydration, humidified oxygen supplementation, and nebulisation of medications, such as salbutamol, epinephrine, and hypertonic saline. The effectiveness of magnesium sulphate for acute bronchiolitis is unclear. OBJECTIVES: To assess the effects of magnesium sulphate in acute bronchiolitis in children up to two years of age. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, CINAHL, and two trials registries to 30 April 2020. We contacted trial authors to identify additional studies. We searched conference proceedings and reference lists of retrieved articles. Unpublished and published studies were eligible for inclusion. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs, comparing magnesium sulphate, alone or with another treatment, with placebo or another treatment, in children up to two years old with acute bronchiolitis. Primary outcomes were time to recovery, mortality, and adverse events. Secondary outcomes were duration of hospital stay, clinical severity score at 0 to 24 hours and 25 to 48 hours after treatment, pulmonary function test, hospital readmission within 30 days, duration of mechanical ventilation, and duration of intensive care unit stay. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We used GRADE methods to assess the certainty of the evidence. MAIN RESULTS: We included four RCTs (564 children). One study received funding from a hospital and one from a university; two studies did not report funding sources. Comparator interventions differed among all four trials. Studies were conducted in Qatar, Turkey, Iran, and India. We assessed two studies to be at an overall low risk of bias, and two to be at unclear risk of bias, overall. The certainty of the evidence for all outcomes and comparisons was very low except for one: hospital re-admission rate within 30 days of discharge for magnesium sulphate versus placebo. None of the studies measured time to recovery, duration of mechanical ventilation, duration of intensive care unit stay, or pulmonary function. There were no events of mortality or adverse effects for magnesium sulphate compared with placebo (1 RCT, 160 children). The effects of magnesium sulphate on clinical severity are uncertain (at 0 to 24 hours: mean difference (MD) on the Wang score 0.13, 95% confidence interval (CI) -0.28 to 0.54; and at 25 to 48 hours: MD on the Wang score -0.42, 95% CI -0.84 to -0.00). Magnesium sulphate may increase hospital re-admission rate within 30 days of discharge (risk ratio (RR) 3.16, 95% CI 1.20 to 8.27; 158 children; low-certainty evidence). None of our primary outcomes were measured for magnesium sulphate compared with hypertonic saline (1 RCT, 220 children). Effects were uncertain on the duration of hospital stay in days (MD 0.00, 95% CI -0.28 to 0.28), and on clinical severity on the Respiratory Distress Assessment Instrument (RDAI) score at 25 to 48 hours (MD 0.10, 95% CI -0.39 to 0.59). There were no events of mortality or adverse effects for magnesium sulphate, with or without salbutamol, compared with salbutamol (1 RCT, 57 children). Effects on the duration of hospital stay were uncertain (magnesium sulphate: 24 hours (95% CI 25.8 to 47.4), magnesium sulphate + salbutamol: 20 hours (95% CI 15.3 to 39.0), and salbutamol: 24 hours (95% CI 23.4 to 76.9)). None of our primary outcomes were measured for magnesium sulphate + epinephrine compared with no treatment or normal saline + epinephrine (1 RCT,120 children). Effects were uncertain for the duration of hospital stay in hours (MD -0.40, 95% CI -3.94 to 3.14), and for RDAI scores (0 to 24 hours: MD -0.20, 95% CI -1.06 to 0.66; and 25 to 48 hours: MD -0.90, 95% CI -1.75 to -0.05). AUTHORS' CONCLUSIONS: There is insufficient evidence to establish the efficacy and safety of magnesium sulphate for treating children up to two years of age with acute bronchiolitis. No evidence was available for time to recovery, duration of mechanical ventilation and intensive care unit stay, or pulmonary function. There was no information about adverse events for some comparisons. Well-designed RCTs to assess the effects of magnesium sulphate for children with acute bronchiolitis are needed. Important outcomes, such as time to recovery and adverse events should be measured.


Asunto(s)
Bronquiolitis/tratamiento farmacológico , Broncodilatadores/uso terapéutico , Sulfato de Magnesio/uso terapéutico , Enfermedad Aguda , Albuterol/uso terapéutico , Sesgo , Broncodilatadores/administración & dosificación , Quimioterapia Combinada/métodos , Epinefrina/uso terapéutico , Humanos , Lactante , Recién Nacido , Tiempo de Internación , Sulfato de Magnesio/administración & dosificación , Readmisión del Paciente/estadística & datos numéricos , Placebos/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Solución Salina/uso terapéutico , Índice de Severidad de la Enfermedad
7.
Cochrane Database Syst Rev ; 12: CD012980, 2020 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-33341943

RESUMEN

BACKGROUND: Frostbite is a thermal injury caused when tissue is exposed to sub-zero temperatures (in degrees Celsius) long enough for ice crystals to form in the affected tissue. Depending on the degree of tissue damage, thrombosis, ischaemia, necrosis (tissue death), gangrene and ultimately amputation may occur. Several interventions for frostbite injuries have been proposed, such as hyperbaric oxygen therapy, sympathectomy (nerve block), thrombolytic (blood-thinning) therapy and vasodilating agents such as iloprost, reserpine, pentoxifylline and buflomedil, but the benefits and harms of these interventions are unclear. OBJECTIVES: To assess the benefits and harms of the different management options for frostbite injuries. SEARCH METHODS: On 25 February 2020, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase (OvidSP), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED), Conference Proceedings Citation Index-Science (CPCI-S), as well as trials registers. Shortly before publication, we searched Clinicaltrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform, OpenGrey and GreyLit (9 November 2020) again. We investigated references from relevant articles, and corresponded with a trial author. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared any medical intervention, e.g. pharmacological therapy, topical treatments or rewarming techniques, for frostbite injuries to another treatment, placebo or no treatment. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data. We used Review Manager 5 for statistical analysis of dichotomous data with risk ratio (RR) with 95% confidence intervals (CIs). We used the Cochrane 'Risk of bias' tool to assess bias in the included trial. We assessed incidence of amputations, rates of serious and non-serious adverse events, acute pain, chronic pain, ability to perform activities of daily living, quality of life, withdrawal rate from medical therapy due to adverse events, occupational effects and mortality. We used GRADE to assess the quality of the evidence. MAIN RESULTS: We included one, open-label randomised trial involving 47 participants with severe frostbite injuries. We judged this trial to be at high risk of bias for performance bias, and uncertain risk for attrition bias; all other risk of bias domains we judged as low. All participants underwent rapid rewarming, received 250 mg of aspirin and 400 mg intravascular (IV) buflomedil (since withdrawn from practice), and were then randomised to one of three treatment groups for the following eight days. Group 1 received additional IV buflomedil 400 mg for one hour per day. Group 2 received the prostacyclin, iloprost, 0.5 ng to 2 ng/kg/min IV for six hours per day. Group 3 received IV iloprost 2 ng/kg/min for six hours per day plus fibrinolysis with 100 mg recombinant tissue plasminogen activator (rtPA) for the first day only. The results suggest that iloprost and iloprost plus rtPA may reduce the rate of amputations in people with severe frostbite compared to buflomedil alone, RR 0.05 (95% CI 0.00 to 0.78; P = 0.03; very low-quality evidence) and RR 0.31 (95% CI 0.10 to 0.94; P = 0.04; very low-quality evidence), respectively. Iloprost may be as effective as iloprost plus rtPA at reducing the amputation rate, RR 0.14 (95% CI 0.01 to 2.56; P = 0.19; very low-quality evidence). There were no reported deaths or withdrawals due to adverse events in any of the groups; we assessed evidence for both outcomes as being of very low quality. Adverse events (including flushing, nausea, palpitations and vomiting) were common, but not reported separately by comparator arm (very low-quality evidence). The included study did not measure the outcomes of acute pain, chronic pain, ability to perform activities of daily living, quality of life or occupational effects. AUTHORS' CONCLUSIONS: There is a paucity of evidence regarding interventions for frostbite injuries. Very low-quality evidence from a single small trial indicates that iloprost, and iloprost plus rtPA, in combination with buflomedil may reduce the need for amputation in people with severe frostbite compared to buflomedil alone. However, buflomedil has been withdrawn from use. High quality randomised trials are needed to establish firm evidence for the treatment of frostbite injuries.


Asunto(s)
Congelación de Extremidades/terapia , Amputación/estadística & datos numéricos , Aspirina/administración & dosificación , Sesgo , Quimioterapia Combinada/métodos , Epoprostenol/administración & dosificación , Fibrinolíticos/administración & dosificación , Humanos , Iloprost/administración & dosificación , Inhibidores de Agregación Plaquetaria/administración & dosificación , Pirrolidinas/administración & dosificación , Proteínas Recombinantes/administración & dosificación , Recalentamiento/métodos , Activador de Tejido Plasminógeno/administración & dosificación , Vasodilatadores/administración & dosificación
8.
Medicine (Baltimore) ; 99(52): e23771, 2020 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-33350762

RESUMEN

BACKGROUND: Lesional and symptomatic causes of epilepsy are the most common neurological disorders of the brain. Topiramate effectively controls newly diagnosed epilepsy and refractory focal seizures, but high-dose topiramate does not improve seizure control. This study aimed to evaluate the clinical efficacy and safety of dose-escalated topiramate as first-line monotherapy and add-on therapy in patients with neurosurgery-related epilepsy. MATERIAL AND METHODS: A total of 55 neurosurgical patients with epilepsy were divided into monotherapy and add-on therapy groups and both groups received topiramate via the dose-escalation method. The primary efficacy outcomes were seizure-free rate and seizure response rate. Adverse events and seizure frequency were recorded. RESULTS: The seizure response rate in the first month of monotherapy was significantly better than that of add-on therapy (89% vs 65%, P < .05), but no significant differences were found in seizure response rates between the 2 groups after 2 months of treatment. Both monotherapy and add-on therapy were effective in controlling seizures, with mean seizure frequency of 0.725 vs 0.536 and seizure-free rate of 88% vs 78.6%. Both treatments showed good improvement of seizure frequency in patients without tumor. The efficacy of monotherapy was better than that of add-on therapy (80% vs 29.2%) in patients with body mass index (BMI) ≤24. However, add-on therapy was better than monotherapy (76.7% vs 21.4%) in patients with BMI > 24. Dizziness (25.5%) and headache (16.4%) were the most common adverse events. No severe adverse event such as cognitive impairment was observed. CONCLUSIONS: Dose-escalated topiramate monotherapy and add-on therapy demonstrate good efficacy and safety, with fewer adverse events in seizure control in neurosurgical patients.


Asunto(s)
Relación Dosis-Respuesta a Droga , Quimioterapia Combinada/métodos , Epilepsia , Procedimientos Neuroquirúrgicos/efectos adversos , Complicaciones Posoperatorias , Topiramato , Adulto , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/efectos adversos , Monitoreo de Drogas/métodos , Epilepsia/diagnóstico , Epilepsia/tratamiento farmacológico , Epilepsia/etiología , Femenino , Humanos , Masculino , Evaluación de Procesos y Resultados en Atención de Salud , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/tratamiento farmacológico , Topiramato/administración & dosificación , Topiramato/efectos adversos , Resultado del Tratamiento
9.
Medicine (Baltimore) ; 99(52): e23844, 2020 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-33350773

RESUMEN

BACKGROUND: Pain on injection is a well-recognized adverse event of propofol administration for the stimulation of general anesthesia. Pre-treatment with lidocaine or flurbiprofen axetil has proven to be effectual in the reduction propofol-induced pain in adults. Nonetheless, only few studies have evaluated the clinical therapeutic effects of lidocaine combination with flurbiprofen axetil to prevent pain on injection of propofol. The current study aims to evaluate the clinical therapeutic effects of lidocaine combination with flurbiprofen axetil to reduce pain on injection of propofol among adult patients. METHODS: The literature search will be conducted from their inception to November 2020 from MEDLINE, EMBASE, Web of Science, and Cochrane Library databases without date or geographical restrictions. However, language will be restricted to publications in English and Chinese. Two authors will independently screen abstracts and titles of all papers to determine whether to include or exclude them. The authors will also study characteristic and outcomes of data extraction and carry out risk of bias assessment. We plan to use either a fixed-effects or random-effects model to estimate the risk ratios (RR) or mean difference (MD) or standardized mean difference (SMD) together with 95% confidence interval (CI). RESULTS: This study will provide high-quality evidence for the clinical therapeutic effects of lidocaine combination with flurbiprofen axetil for reducing pain on injection of propofol in adult patients. CONCLUSION: This study will summarize current evidence for the management of pain on injection of propofol in adult patients and provide guidance for both intervention and future research. ETHICS AND DISSEMINATION: Since no data collection will be involved, there is no need for an ethics approval. REGISTRATION NUMBER: November 17, 2020.osf.io/72tpj/. (https://osf.io/72tpj/).


Asunto(s)
Flurbiprofeno/análogos & derivados , Lidocaína/farmacología , Dolor Asociado a Procedimientos Médicos , Propofol/efectos adversos , Adulto , Anestésicos Intravenosos/administración & dosificación , Anestésicos Intravenosos/efectos adversos , Anestésicos Locales/farmacología , Quimioterapia Combinada/métodos , Flurbiprofeno/farmacología , Humanos , Metaanálisis como Asunto , Dolor Asociado a Procedimientos Médicos/etiología , Dolor Asociado a Procedimientos Médicos/prevención & control , Propofol/administración & dosificación , Proyectos de Investigación , Revisiones Sistemáticas como Asunto , Resultado del Tratamiento
10.
Lancet Glob Health ; 8(12): e1512-e1523, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33137287

RESUMEN

BACKGROUND: Prevention of malaria infection during pregnancy in HIV-negative women currently relies on the use of long-lasting insecticidal nets together with intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP). Increasing sulfadoxine-pyrimethamine resistance in Africa threatens current prevention of malaria during pregnancy. Thus, a replacement for IPTp-SP is urgently needed, especially for locations with high sulfadoxine-pyrimethamine resistance. Dihydroartemisinin-piperaquine is a promising candidate. We aimed to estimate the cost-effectiveness of intermittent preventive treatment in pregnancy with dihydroartemisinin-piperaquine (IPTp-DP) versus IPTp-SP to prevent clinical malaria infection (and its sequelae) during pregnancy. METHODS: We did a cost-effectiveness analysis using meta-analysis and individual trial results from three clinical trials done in Kenya and Uganda. We calculated disability-adjusted life-years (DALYs) arising from stillbirths, neonatal death, low birthweight, mild and moderate maternal anaemia, and clinical malaria infection, associated with malaria during pregnancy. Cost estimates were obtained from data collected in observational studies, health-facility costings, and from international drug procurement databases. The cost-effectiveness analyses were done from a health-care provider perspective using a decision tree model with a lifetime horizon. Deterministic and probabilistic sensitivity analyses using appropriate parameter ranges and distributions were also done. Results are presented as the incremental cost per DALY averted and the likelihood that an intervention is cost-effective for different cost-effectiveness thresholds. FINDINGS: Compared with three doses of sulfadoxine-pyrimethamine, three doses of dihydroartemisinin-piperaquine, delivered to a hypothetical cohort of 1000 pregnant women, averted 892 DALYs (95% credibility interval 274 to 1517) at an incremental cost of US$7051 (2653 to 13 038) generating an incremental cost-effectiveness ratio (ICER) of $8 (2 to 29) per DALY averted. Compared with monthly doses of sulfadoxine-pyrimethamine, monthly doses of dihydroartemisinin-piperaquine averted 534 DALYS (-141 to 1233) at a cost of $13 427 (4994 to 22 895), resulting in an ICER of $25 (-151 to 224) per DALY averted. Both results were highly robust to most or all variations in the deterministic sensitivity analysis. INTERPRETATION: Our findings suggest that among HIV-negative pregnant women with high uptake of long-lasting insecticidal nets, IPTp-DP is cost-effective in areas with high malaria transmission and high sulfadoxine-pyrimethamine resistance. These data provide a comprehensive overview of the current evidence on the cost-effectiveness of IPTp-DP. Nevertheless, before a policy change is advocated, we recommend further research into the effectiveness and costs of different regimens of IPTp-DP in settings with different underlying sulfadoxine-pyrimethamine resistance. FUNDING: Malaria in Pregnancy Consortium, which is funded through a grant from the Bill & Melinda Gates Foundation to the Liverpool School of Hygiene and Tropical Medicine.


Asunto(s)
Antimaláricos/economía , Artemisininas/economía , Análisis Costo-Beneficio/economía , Malaria/prevención & control , Complicaciones Parasitarias del Embarazo/prevención & control , Quinolinas/economía , Adulto , Antimaláricos/administración & dosificación , Antimaláricos/uso terapéutico , Artemisininas/administración & dosificación , Artemisininas/uso terapéutico , Análisis Costo-Beneficio/métodos , Análisis Costo-Beneficio/estadística & datos numéricos , Esquema de Medicación , Quimioterapia Combinada/economía , Quimioterapia Combinada/métodos , Femenino , Humanos , Kenia , Malaria/economía , Embarazo , Complicaciones Parasitarias del Embarazo/economía , Quinolinas/administración & dosificación , Quinolinas/uso terapéutico , Terapéutica , Uganda , Adulto Joven
11.
Cochrane Database Syst Rev ; 11: CD012754, 2020 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-33232518

RESUMEN

BACKGROUND: Postpartum haemorrhage (PPH), defined as a blood loss of 500 mL or more after birth, is the leading cause of maternal death worldwide. The World Health Organization (WHO) recommends that all women giving birth should receive a prophylactic uterotonic agent. Despite the routine administration of a uterotonic agent for prevention, PPH remains a common complication causing one-quarter of all maternal deaths globally. When prevention fails and PPH occurs, further administration of uterotonic agents as 'first-line' treatment is recommended. However, there is uncertainty about which uterotonic agent is best for the 'first-line' treatment of PPH. OBJECTIVES: To identify the most effective uterotonic agent(s) with the least side-effects for PPH treatment, and generate a meaningful ranking among all available agents according to their relative effectiveness and side-effect profile. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (5 May 2020), and the reference lists of all retrieved studies. SELECTION CRITERIA: All randomised controlled trials or cluster-randomised trials comparing the effectiveness and safety of uterotonic agents with other uterotonic agents for the treatment of PPH were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed all trials for inclusion, extracted data and assessed each trial for risk of bias. Our primary outcomes were additional blood loss of 500 mL or more after recruitment to the trial until cessation of active bleeding and the composite outcome of maternal death or severe morbidity. Secondary outcomes included blood loss-related outcomes, morbidity outcomes, and patient-reported outcomes. We performed pairwise meta-analyses and indirect comparisons, where possible, but due to the limited number of included studies, we were unable to conduct the planned network meta-analysis. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: Seven trials, involving 3738 women in 10 countries, were included in this review. All trials were conducted in hospital settings. Randomised women gave birth vaginally, except in one small trial, where women gave birth either vaginally or by caesarean section. Across the seven trials (14 trial arms) the following agents were used: six trial arms used oxytocin alone; four trial arms used misoprostol plus oxytocin; three trial arms used misoprostol; one trial arm used Syntometrine® (oxytocin and ergometrine fixed-dose combination) plus oxytocin infusion. Pairwise meta-analysis of two trials (1787 participants), suggests that misoprostol, as first-line treatment uterotonic agent, probably increases the risk of blood transfusion (risk ratio (RR) 1.47, 95% confidence interval (CI) 1.02 to 2.14, moderate-certainty) compared with oxytocin. Low-certainty evidence suggests that misoprostol administration may increase the incidence of additional blood loss of 1000 mL or more (RR 2.57, 95% CI 1.00 to 6.64). The data comparing misoprostol with oxytocin is imprecise, with a wide range of treatment effects for the additional blood loss of 500 mL or more (RR 1.66, 95% CI 0.69 to 4.02, low-certainty), maternal death or severe morbidity (RR 1.98, 95% CI 0.36 to 10.72, low-certainty, based on one study n = 809 participants, as the second study had zero events), and the use of additional uterotonics (RR 1.30, 95% CI 0.57 to 2.94, low-certainty). The risk of side-effects may be increased with the use of misoprostol compared with oxytocin: vomiting (2 trials, 1787 participants, RR 2.47, 95% CI 1.37 to 4.47, high-certainty) and fever (2 trials, 1787 participants, RR 3.43, 95% CI 0.65 to 18.18, low-certainty). According to pairwise meta-analysis of four trials (1881 participants) generating high-certainty evidence, misoprostol plus oxytocin makes little or no difference to the use of additional uterotonics (RR 0.99, 95% CI 0.94 to 1.05) and to blood transfusion (RR 0.95, 95% CI 0.77 to 1.17) compared with oxytocin. We cannot rule out an important benefit of using the misoprostol plus oxytocin combination over oxytocin alone, for additional blood loss of 500 mL or more (RR 0.84, 95% CI 0.66 to 1.06, moderate-certainty). We also cannot rule out important benefits or harms for additional blood loss of 1000 mL or more (RR 0.76, 95% CI 0.43 to 1.34, moderate-certainty, 3 trials, 1814 participants, one study reported zero events), and maternal mortality or severe morbidity (RR 1.09, 95% CI 0.35 to 3.39, moderate-certainty). Misoprostol plus oxytocin increases the incidence of fever (4 trials, 1866 participants, RR 3.07, 95% CI 2.62 to 3.61, high-certainty), and vomiting (2 trials, 1482 participants, RR 1.85, 95% CI 1.16 to 2.95, high-certainty) compared with oxytocin alone. For all outcomes of interest, the available evidence on the misoprostol versus Syntometrine® plus oxytocin combination was of very low-certainty and these effects remain unclear. Although network meta-analysis was not performed, we were able to compare the misoprostol plus oxytocin combination with misoprostol alone through the common comparator of oxytocin. This indirect comparison suggests that the misoprostol plus oxytocin combination probably reduces the risk of blood transfusion (RR 0.65, 95% CI 0.42 to 0.99, moderate-certainty) and may reduce the risk of additional blood loss of 1000 mL or more (RR 0.30, 95% CI 0.10 to 0.89, low-certainty) compared with misoprostol alone. The combination makes little or no difference to vomiting (RR 0.75, 95% CI 0.35 to 1.59, high-certainty) compared with misoprostol alone. Misoprostol plus oxytocin compared to misoprostol alone are compatible with a wide range of treatment effects for additional blood loss of 500 mL or more (RR 0.51, 95% CI 0.20 to 1.26, low-certainty), maternal mortality or severe morbidity (RR 0.55, 95% CI 0.07 to 4.24, low-certainty), use of additional uterotonics (RR 0.76, 95% CI 0.33 to 1.73, low-certainty), and fever (RR 0.90, 95% CI 0.17 to 4.77, low-certainty). AUTHORS' CONCLUSIONS: The available evidence suggests that oxytocin used as first-line treatment of PPH probably is more effective than misoprostol with less side-effects. Adding misoprostol to the conventional treatment of oxytocin probably makes little or no difference to effectiveness outcomes, and is also associated with more side-effects. The evidence for most uterotonic agents used as first-line treatment of PPH is limited, with no evidence found for commonly used agents, such as injectable prostaglandins, ergometrine, and Syntometrine®.


Asunto(s)
Ergonovina/uso terapéutico , Misoprostol/uso terapéutico , Metaanálisis en Red , Oxitócicos/uso terapéutico , Oxitocina/uso terapéutico , Hemorragia Posparto/tratamiento farmacológico , Sesgo , Transfusión Sanguínea/estadística & datos numéricos , Intervalos de Confianza , Quimioterapia Combinada/métodos , Femenino , Humanos , Misoprostol/efectos adversos , Oxitócicos/efectos adversos , Oxitocina/efectos adversos , Hemorragia Posparto/inducido químicamente , Hemorragia Posparto/mortalidad , Embarazo , Ensayos Clínicos Controlados Aleatorios como Asunto
12.
Seizure ; 83: 197-202, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33197757

RESUMEN

PURPOSE: Although levetiracetam (LEV) is globally established as a leading antiseizure medication (ASM) it is still a controversial matter whether dose increases correspond with an increased efficacy if LEV in the recommended dose range did not show satisfying efficacy. In our clinical perception we questioned the value of dose increases in such non-responders. METHODS: In this retrospective monocenter study we analyzed the data of adult people with epilepsies (PWE) with focal-onset seizures who had been treated at the department of adults of the Kork Epilepsy Center between 2009 and 2019, who had been on a stable daily LEV dose and in whom LEV was further increased due to further seizures in spite of baseline LEV in a recommended daily dose range. For reasons of data homogeneity, we included only PWE with at least two definite seizures during the hospital stay under the baseline LEV dose who were treated and observed as in-patients after the increase of LEV for a period at least three-fold longer than the baseline interval before. Additional data acquisition comprised clinical data including adverse events, serum concentrations of LEV and other ASMs, and additional laboratory findings. The primary outcome variable was the change of seizure frequency prior to and after the increase of LEV. RESULTS: Out of 518 PWE who had been on LEV during their hospital stay, a total of 61 PWE fulfilled the inclusion criteria. After a gradual dose increment, 91,8 % of PWE showed a reduced seizure frequency, 73,8 % had a reduction of seizures of 50 % or more, and 21,3 % were seizure-free during the observation period. A significant seizure reduction could be shown with a seizure count of 2,5/week prior to the increment and 0,7/week after dose increment (p < 0,00001). Seven PWE reported minor adverse events and ten PWE showed slight laboratory changes (within normal levels). CONCLUSION: Contrary to our long-term clinical impression, LEV dose increments were reasonable and improved the seizure situation in PWE, usually without additional safety hazards.


Asunto(s)
Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Levetiracetam/uso terapéutico , Convulsiones/tratamiento farmacológico , Adulto , Quimioterapia Combinada/métodos , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven
13.
Isr Med Assoc J ; 11(22): 665-672, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33249784

RESUMEN

BACKGROUND: The coronavirus disease-2019 (COVID-19) and its management in patients with epilepsy can be complex. Prescribers should consider potential effects of investigational anti-COVID-19 drugs on seizures, immunomodulation by anti-seizure medications (ASMs), changes in ASM pharmacokinetics, and the potential for drug-drug interactions (DDIs). The goal of the Board of the Israeli League Against Epilepsy (the Israeli Chapter of the International League Against Epilepsy, ILAE) was to summarize the main principles of the pharmacological treatment of COVID-19 in patients with epilepsy. This guide was based on current literature, drug labels, and drug interaction resources. We summarized the available data related to the potential implications of anti-COVID-19 co-medication in patients treated with ASMs. Our recommendations refer to drug selection, dosing, and patient monitoring. Given the limited availability of data, some recommendations are based on general pharmacokinetic or pharmacodynamic principles and might apply to additional future drug combinations as novel treatments emerge. They do not replace evidence-based guidelines, should those become available. Awareness to drug characteristics that increase the risk of interactions can help adjust anti-COVID-19 and ASM treatment for patients with epilepsy.


Asunto(s)
Anticonvulsivantes , Antivirales , Interacciones Farmacológicas , Quimioterapia Combinada , Epilepsia , Administración del Tratamiento Farmacológico , Anticonvulsivantes/clasificación , Anticonvulsivantes/farmacología , Antivirales/clasificación , Antivirales/farmacología , Comorbilidad , Monitoreo de Drogas/métodos , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Quimioterapia Combinada/normas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Epilepsia/diagnóstico , Epilepsia/tratamiento farmacológico , Epilepsia/epidemiología , Humanos , Israel/epidemiología , Administración del Tratamiento Farmacológico/normas , Administración del Tratamiento Farmacológico/tendencias , Selección de Paciente , Guías de Práctica Clínica como Asunto , Ajuste de Riesgo/métodos , Ajuste de Riesgo/tendencias
14.
Reumatismo ; 72(3): 173-177, 2020 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-33213130

RESUMEN

The outbreak of coronavirus disease 2019 (COVID-19) has involved more than 159 countries and more than 5 million people worldwide. A 40-year-old man with a history of rheumatoid arthritis treated with prednisolone, Disease-Modifying Anti-Rheumatic Drugs (DMARDs), and biologic agents was admitted with chief complaints of fever, chills, malaise, myalgia, and dyspnea. Chest computed tomography showed bilateral subsegmental atelectasis and diffuse ground-glass opacities in both lungs inducing the suspicion of COVID-19 infection. The oro-nasopharynx swab sample for COVID-19 polymerase chain reaction was positive. In addition to supportive care, lopinavir/ritonavir 400/100 mg twice daily and oseltamivir (75 mg) twice daily were started in combination with a starting dose of hydroxychloroquine (400 mg). The methotrexate dose was decreased, and the dose of prednisolone was increased to 30 mg for 10 days. Azathioprine and adalimumab were continued at previous doses. The use of biologic agents and DMARDs in rheumatic patients is a serious challenge in the COVID-19 pandemic. In conclusion, during the COVID-19 pandemic, due to the key roles of cytokines in the promotion of the disease, the rheumatic patients may benefit from continuing their previous treatment, which may have protective effects.


Asunto(s)
Antirreumáticos/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Adalimumab/administración & dosificación , Adulto , Antivirales/administración & dosificación , Artritis Reumatoide/complicaciones , Azatioprina/administración & dosificación , Terapia Biológica , Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Combinación de Medicamentos , Quimioterapia Combinada/métodos , Humanos , Lopinavir/administración & dosificación , Masculino , Metotrexato/administración & dosificación , Oseltamivir/administración & dosificación , Pandemias , Neumonía Viral/complicaciones , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Prednisolona/administración & dosificación , Ritonavir/administración & dosificación
15.
Cochrane Database Syst Rev ; 11: CD013138, 2020 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-33251587

RESUMEN

BACKGROUND: Gender dysphoria is described as a mismatch between an individual's experienced or expressed gender and their assigned gender, based on primary or secondary sexual characteristics. Gender dysphoria can be associated with clinically significant psychological distress and may result in a desire to change sexual characteristics. The process of adapting a person's sexual characteristics to their desired sex is called 'transition.' Current guidelines suggest hormonal and, if needed, surgical intervention to aid transition in transgender women, i.e. persons who aim to transition from male to female. In adults, hormone therapy aims to reverse the body's male attributes and to support the development of female attributes. It usually includes estradiol, antiandrogens, or a combination of both. Many individuals first receive hormone therapy alone, without surgical interventions. However, this is not always sufficient to change such attributes as facial bone structure, breasts, and genitalia, as desired. For these transgender women, surgery may then be used to support transition. OBJECTIVES: We aimed to assess the efficacy and safety of hormone therapy with antiandrogens, estradiol, or both, compared to each other or placebo, in transgender women in transition. SEARCH METHODS: We searched MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, Biosis Preview, PsycINFO, and PSYNDEX. We carried out our final searches on 19 December 2019. SELECTION CRITERIA: We aimed to include randomised controlled trials (RCTs), quasi-RCTs, and cohort studies that enrolled transgender women, age 16 years and over, in transition from male to female. Eligible studies investigated antiandrogen and estradiol hormone therapies alone or in combination, in comparison to another form of the active intervention, or placebo control. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane to establish study eligibility. MAIN RESULTS: Our database searches identified 1057 references, and after removing duplicates we screened 787 of these. We checked 13 studies for eligibility at the full text screening stage. We excluded 12 studies and identified one as an ongoing study. We did not identify any completed studies that met our inclusion criteria. The single ongoing study is an RCT conducted in Thailand, comparing estradiol valerate plus cyproterone treatment with estradiol valerate plus spironolactone treatment. The primary outcome will be testosterone level at three month follow-up. AUTHORS' CONCLUSIONS: We found insufficient evidence to determine the efficacy or safety of hormonal treatment approaches for transgender women in transition. This lack of studies shows a gap between current clinical practice and clinical research. Robust RCTs and controlled cohort studies are needed to assess the benefits and harms of hormone therapy (used alone or in combination) for transgender women in transition. Studies should specifically focus on short-, medium-, and long-term adverse effects, quality of life, and participant satisfaction with the change in male to female body characteristics of antiandrogen and estradiol therapy alone, and in combination. They should also focus on the relative effects of these hormones when administered orally, transdermally, and intramuscularly. We will include non-controlled cohort studies in the next iteration of this review, as our review has shown that such studies provide the highest quality evidence currently available in the field. We will take into account methodological limitations when doing so.


Asunto(s)
Antagonistas de Andrógenos/uso terapéutico , Estradiol/uso terapéutico , Estrógenos/uso terapéutico , Procedimientos de Reasignación de Sexo/métodos , Personas Transgénero , Quimioterapia Combinada/métodos , Femenino , Humanos , Masculino , Placebos/uso terapéutico
16.
PLoS One ; 15(11): e0242028, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33152046

RESUMEN

In recent years, the development of diagnostics using artificial intelligence (AI) has been remarkable. AI algorithms can go beyond human reasoning and build diagnostic models from a number of complex combinations. Using next-generation sequencing technology, we identified hepatitis C virus (HCV) variants resistant to directing-acting antivirals (DAA) by whole genome sequencing of full-length HCV genomes, and applied these variants to various machine-learning algorithms to evaluate a preliminary predictive model. HCV genomic RNA was extracted from serum from 173 patients (109 with subsequent sustained virological response [SVR] and 64 without) before DAA treatment. HCV genomes from the 109 SVR and 64 non-SVR patients were randomly divided into a training data set (57 SVR and 29 non-SVR) and a validation-data set (52 SVR and 35 non-SVR). The training data set was subject to nine machine-learning algorithms selected to identify the optimized combination of functional variants in relation to SVR status following DAA therapy. Subsequently, the prediction model was tested by the validation-data set. The most accurate learning method was the support vector machine (SVM) algorithm (validation accuracy, 0.95; kappa statistic, 0.90; F-value, 0.94). The second-most accurate learning algorithm was Multi-layer perceptron. Unfortunately, Decision Tree, and Naive Bayes algorithms could not be fitted with our data set due to low accuracy (< 0.8). Conclusively, with an accuracy rate of 95.4% in the generalization performance evaluation, SVM was identified as the best algorithm. Analytical methods based on genomic analysis and the construction of a predictive model by machine-learning may be applicable to the selection of the optimal treatment for other viral infections and cancer.


Asunto(s)
Variación Genética/genética , Genoma Viral/genética , Hepacivirus/genética , Anciano , Algoritmos , Antivirales/uso terapéutico , Inteligencia Artificial , Teorema de Bayes , Quimioterapia Combinada/métodos , Femenino , Hepacivirus/efectos de los fármacos , Hepatitis C/tratamiento farmacológico , Hepatitis C/virología , Humanos , Aprendizaje Automático , Masculino , Redes Neurales de la Computación , ARN Viral/genética , Máquina de Vectores de Soporte , Respuesta Virológica Sostenida
17.
Cancer Sci ; 111(12): 4326-4335, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33006786

RESUMEN

PD-1/PD-L1 immune checkpoint inhibitors are promising cancer immunotherapies however responses are still limited and the development of more effective combination immunotherapy is needed. We previously reported that STAT3 activation in cancer cells and immune cells was involved in immune-resistant mechanisms. In this study, we evaluated the effect of highly absorptive forms of curcumin extracts and synthetic curcumin on anti-tumor T cell responses. The curcumin po administration resulted in the significant augmentation of in vivo induction of tumor antigen-specific T cells through restoration of dendritic cells (DCs) by inhibiting directly STAT3 in DCs and indirectly via reduced IL-6 production from STAT3 activated cancer cells in 2 syngeneic MC38 and CT26 murine tumor models. Curcumin also showed direct DC enhancing activity and enhanced T cell induction for the immunized antigens in non-tumor-bearing mice and human hosts. Curcumin restored DC functions in xenogeneic nude mouse model implanted with high IL-6-producing human clear cell ovarian cancer cells. The combination of curcumin and PD-1/PD-L1 Abs demonstrated a synergistic anti-tumor activity in MC38 murine tumor models. These results indicated that curcumin augments the induction of tumor antigen-specific T cells by restoring the T cell stimulatory activity of DCs targeting activated STAT3 in both cancer cells and immune cells. Combination immunotherapy with curcumin and PD-1/PD-L1 Ab is an attractive strategy in the development of effective immunotherapy against various cancers.


Asunto(s)
Antineoplásicos/uso terapéutico , Curcumina/uso terapéutico , Células Dendríticas/metabolismo , Neoplasias/terapia , Factor de Transcripción STAT3/antagonistas & inhibidores , Animales , Células Dendríticas/inmunología , Quimioterapia Combinada/métodos , Femenino , Humanos , Inmunoterapia/métodos , Interferón gamma/metabolismo , Interleucina-6/biosíntesis , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Desnudos , FN-kappa B/análisis , Neoplasias/inmunología , Extractos Vegetales/uso terapéutico , Factor de Transcripción STAT3/análisis , Factor de Transcripción STAT3/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo
18.
Medicine (Baltimore) ; 99(44): e22897, 2020 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-33126343

RESUMEN

Inflammatory bowel disease (IBD) in Asia has become increasingly prevalent. As a treatment of IBD, many immunomodulators and biological agents were introduced and shown to be effective in inducing and maintaining remission. However, many cases with treatment failure were reported. To overcome the failure, combination therapy of immunomodulatory and biologics have emerged, showing better outcomes by optimizing biologic pharmacokinetics and minimizing immunogenicity. Adversely, rates of tuberculosis (TB) have been increased as a result. The aim of this study is to compare the risk of TB according to the therapy using large population data.We used data from the South Korean Health Insurance and Review Agency over the period 2008-2016 and calculated the hazard ratio (HR) for TB in IBD. We compared the risk of TB according to the medication: infliximab only, azathioprine only (AZA), combination of azathioprine and infliximab (CAI), azathioprine monotherapy and infliximab monotherapy (AIM), and azathioprine and infliximab whether simultaneously or separately (AISS).In IBD patients, a total of 249 patients were identified as active TB. After one-to-one matching with age, sex and disease duration, the risks of TB were significantly higher in AZA group (HR, 2.06; 95% CI, 1.35-3.12, P < .001), AIM group (HR, 3.26; 95% CI, 1.18-9.05, P = .02), AISS group (HR, 3.50; 95% CI, 1.92-6.37, P < .001), and CAI group (HR, 5.67; 95% CI, 2.42-10.21, P < .001), and the HR increased gradually in this order. In UC patients, the results were in similar pattern, but this pattern was not observed in CD patients in our study.Our study shows that Korean IBD patients are at risk of TB, and the risk increases with usage of IBD medication; moreover, the risk is the highest if combination therapy is used. These results highlight the importance of screening for TB in IBD patients, especially in combination therapy.


Asunto(s)
Azatioprina/uso terapéutico , Quimioterapia Combinada/métodos , Infliximab/uso terapéutico , Tuberculosis , Inmunidad Adaptativa/efectos de los fármacos , Productos Biológicos/uso terapéutico , Estudios de Cohortes , Femenino , Humanos , Factores Inmunológicos/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedades Inflamatorias del Intestino/inmunología , Quimioterapia de Mantención/efectos adversos , Quimioterapia de Mantención/métodos , Masculino , Persona de Mediana Edad , República de Corea/epidemiología , Medición de Riesgo , Factores de Riesgo , Tuberculosis/diagnóstico , Tuberculosis/epidemiología , Tuberculosis/prevención & control
19.
Proc Natl Acad Sci U S A ; 117(42): 26356-26365, 2020 10 20.
Artículo en Inglés | MEDLINE | ID: mdl-33020270

RESUMEN

Understanding differences in DNA double-strand break (DSB) repair between tumor and normal tissues would provide a rationale for developing DNA repair-targeted cancer therapy. Here, using knock-in mouse models for measuring the efficiency of two DSB repair pathways, homologous recombination (HR) and nonhomologous end-joining (NHEJ), we demonstrated that both pathways are up-regulated in hepatocellular carcinoma (HCC) compared with adjacent normal tissues due to altered expression of DNA repair factors, including PARP1 and DNA-PKcs. Surprisingly, inhibiting PARP1 with olaparib abrogated HR repair in HCC. Mechanistically, inhibiting PARP1 suppressed the clearance of nucleosomes at DNA damage sites by blocking the recruitment of ALC1 to DSB sites, thereby inhibiting RPA2 and RAD51 recruitment. Importantly, combining olaparib with NU7441, a DNA-PKcs inhibitor that blocks NHEJ in HCC, synergistically suppressed HCC growth in both mice and HCC patient-derived-xenograft models. Our results suggest the combined inhibition of both HR and NHEJ as a potential therapy for HCC.


Asunto(s)
Carcinoma Hepatocelular/tratamiento farmacológico , Cromonas/farmacología , Morfolinas/farmacología , Ftalazinas/farmacología , Piperazinas/farmacología , Animales , Roturas del ADN de Doble Cadena/efectos de los fármacos , Daño del ADN , Reparación del ADN por Unión de Extremidades/efectos de los fármacos , Reparación del ADN/efectos de los fármacos , Proteínas de Unión al ADN/metabolismo , Quimioterapia Combinada/métodos , Técnicas de Sustitución del Gen , Recombinación Homóloga , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Ratones , Ratones Desnudos , Poli(ADP-Ribosa) Polimerasa-1/antagonistas & inhibidores , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Reparación del ADN por Recombinación/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
20.
PLoS One ; 15(10): e0240161, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33057407

RESUMEN

BACKGROUNDS: We investigated the prognostic impact of antithrombotic regimens at 1-year after percutaneous coronary intervention (PCI) among patients with atrial fibrillation (AF). METHOD AND RESULTS: A total of 13,278 AF patients who underwent PCI from 2009 to 2013 were selected from Korean National Health Insurance Service database. Patients were categorized by antithrombotic regimens at 1-year after PCI: (1) OAC with or without single antiplatelet (OAC±SAPT); (2) triple therapy (TT) and (3) antiplatelets (APT) only. After propensity score matching, composite ischaemia (death, myocardial infarction, and stroke), composite bleeding (intracranial hemorrhage and gastrointestinal bleeding), and a composite clinical outcome (composite ischaemia and bleeding) were compared. Of total population, 1,100 (8.3%), 746 (5.6%), and 11,432 (86.1%) were treated with OAC±SAPT, TT, and APT only, respectively. Compared to OAC±SAPT group, the TT group had significantly higher risk of the composite clinical outcome (hazard ratio [HR] 1.46, 95% confidence interval [CI] 1.00-2.13) attributed to a higher trend in both ischaemia (HR 1.63, 95% CI 0.99-2.67) and bleeding (HR 1.22, 95% CI 0.69-2.13). The APT only group showed a higher risk of ischaemia (HR 1.85, 95% CI 1.25-2.74), despite a lower risk of bleeding (HR 0.55, 95% CI 0.32-0.94) compared to OAC±SAPT group. CONCLUSIONS: OAC±SAPT was associated with better clinical outcomes compared to TT or APT only treatments, beyond 1-year after PCI among Asians with AF.


Asunto(s)
Anticoagulantes/administración & dosificación , Fibrilación Atrial/cirugía , Enfermedad de la Arteria Coronaria/cirugía , Intervención Coronaria Percutánea/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Complicaciones Posoperatorias/epidemiología , Anciano , Anticoagulantes/efectos adversos , Fibrilación Atrial/etiología , Fibrilación Atrial/mortalidad , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/mortalidad , Quimioterapia Combinada/métodos , Femenino , Hemorragia Gastrointestinal/epidemiología , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/prevención & control , Humanos , Hemorragias Intracraneales/epidemiología , Hemorragias Intracraneales/etiología , Hemorragias Intracraneales/prevención & control , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Infarto del Miocardio/etiología , Infarto del Miocardio/prevención & control , Inhibidores de Agregación Plaquetaria/efectos adversos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Prevalencia , Pronóstico , República de Corea/epidemiología , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Resultado del Tratamiento
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