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1.
Am J Gastroenterol ; 116(9): 1924-1928, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34465694

RESUMO

INTRODUCTION: We evaluated 8, 12, or 24 weeks of ledipasvir/sofosbuvir in patients with hepatitis C virus and end-stage renal disease undergoing dialysis. METHODS: Primary efficacy end point was sustained virologic response 12 weeks after treatment. Primary safety end point was treatment discontinuation because of adverse events (AEs). RESULTS: Ninety-four percent (89/95) achieved sustained virologic response 12 weeks after treatment. Six patients died during treatment (n = 4) or before study completion (n = 2); no deaths were related to treatment. No patients discontinued treatment because of AEs. Thirteen percent had serious AEs; none were related to treatment. DISCUSSION: Treatment with ledipasvir/sofosbuvir was safe and effective in patients with end-stage renal disease undergoing dialysis.


Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Fluorenos/uso terapêutico , Hepatite C/tratamento farmacológico , Falência Renal Crônica/terapia , Sofosbuvir/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/administração & dosagem , Benzimidazóis/administração & dosagem , Esquema de Medicação , Feminino , Fluorenos/administração & dosagem , Hepatite C/complicações , Humanos , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Sofosbuvir/administração & dosagem , Resposta Viral Sustentada , Resultado do Tratamento
2.
N Engl J Med ; 385(7): 595-608, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34379922

RESUMO

BACKGROUND: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection. METHODS: We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection. RESULTS: The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified. CONCLUSIONS: CAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 083 ClinicalTrials.gov number, NCT02720094.).


Assuntos
Infecções por HIV/prevenção & controle , Inibidores de Integrase de HIV/administração & dosagem , Profilaxia Pré-Exposição , Piridonas/administração & dosagem , Tenofovir/uso terapêutico , Administração Oral , Adulto , Idoso , Fármacos Anti-HIV/uso terapêutico , Preparações de Ação Retardada/administração & dosagem , Método Duplo-Cego , Esquema de Medicação , Resistência a Medicamentos/genética , Feminino , Inibidores de Integrase de HIV/efeitos adversos , Homossexualidade Masculina , Humanos , Injeções Intramusculares/efeitos adversos , Análise de Intenção de Tratamento , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Piridonas/efeitos adversos , Pessoas Transgênero , Adulto Jovem
3.
Medicine (Baltimore) ; 100(29): e26724, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34398046

RESUMO

ABSTRACT: To evaluate the duration of topical brimonidine therapy before the onset of brimonidine-related allergic conjunctivitis and the clinical characteristics associated with the development of brimonidine allergy.We retrospectively enrolled patients who presented brimonidine allergy from December 1, 2008 to November 30, 2020. The duration of brimonidine treatment, concomitant medications, benzalkonium chloride (BAK) exposure, change in IOP, and season of onset were evaluated.292 patients were included, among which 147 were female and 145 were male. The mean age was 58.3 ± 13.6 years old. The mean (median) duration of brimonidine therapy was 266.6 (196) days, with a peak at 60-120 days. The duration was similar whether the patients received brimonidine monotreatment or in combination with other glaucoma drugs, with or without BAK. The IOP increased by 5.6% after brimonidine allergy (P < .001), which was even higher in the brimonidine monotherapy group (9.2%, P < .001). There was no significant IOP elevation in patients treated with multiple glaucoma medications.Around half of brimonidine allergy occurred within 6 months, with a peak in 2 to 4 months. The duration did not differ in patients receiving brimonidine monotherapy or multiple glaucoma medications. The presence of BAK did not affect the duration either. When brimonidine allergy occurred, there was a loss of IOP control, especially in patients receiving brimonidine monotherapy. It is recommended to switch to other types of glaucoma medications for better IOP control.


Assuntos
Anti-Hipertensivos/efeitos adversos , Tartarato de Brimonidina/efeitos adversos , Conjuntivite Alérgica/epidemiologia , Soluções Oftálmicas/efeitos adversos , Anti-Hipertensivos/administração & dosagem , Tartarato de Brimonidina/administração & dosagem , Conjuntivite Alérgica/induzido quimicamente , Esquema de Medicação , Feminino , Seguimentos , Glaucoma/tratamento farmacológico , Humanos , Pressão Intraocular , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas/administração & dosagem , Estudos Retrospectivos
4.
Turk J Gastroenterol ; 32(6): 488-492, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34405814

RESUMO

The COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2, has resulted in high mortality and morbidity worldwide and is still a growing problem. Inflammatory bowel disease (IBD) is a chronic inflammatory disease for which a substantial number of patients are treated with immunosuppressive medications, either occasionally or long-term. Despite the accumulating evidence, there is still a lack of knowledge about the impact of COVID-19 on IBD patients, especially those who are under immunosuppressive treatment. Moreover, following the emergence of several COVID vaccines, there are concerns regarding vaccine effectiveness and possible side effects in such patients. In this context, we tried to briefly summarize the accumulating evidence and recommendations for the management of IBD in the context of the COVID-19 pandemic.


Assuntos
COVID-19/imunologia , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/imunologia , COVID-19/diagnóstico , COVID-19/terapia , Vacinas contra COVID-19/imunologia , Esquema de Medicação , Humanos , Doenças Inflamatórias Intestinais/complicações , Prognóstico , Fatores de Risco , Suspensão de Tratamento
5.
Lancet Haematol ; 8(9): e627-e636, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34363769

RESUMO

BACKGROUND: Current guidelines recommend a risk-adjusted treatment strategy for the management of acute pulmonary embolism. This is a particular patient category for whom optimal treatment (anticoagulant treatment, reperfusion strategies, and duration of hospitalisation) is currently unknown. We investigated whether treatment of acute intermediate-risk pulmonary embolism with parenteral anticoagulation for a short period of 72 h, followed by a switch to a direct oral anticoagulant (dabigatran), is effective and safe. METHODS: We did a multinational, multicentre, single-arm, phase 4 trial at 42 hospitals in Austria, Belgium, France, Germany, Italy, Netherlands, Romania, Slovenia, and Spain. Adult patients (aged ≥18 years) with symptomatic intermediate-risk pulmonary embolism, with or without deep-vein thrombosis, were enrolled. Patients received parenteral low-molecular-weight or unfractionated heparin for 72 h after diagnosis of pulmonary embolism before switching to oral dabigatran 150 mg twice per day following a standard clinical assessment. The primary outcome was recurrent symptomatic venous thromboembolism or pulmonary embolism-related death within 6 months. The primary and safety outcomes were assessed in the intention-to-treat population. The study was terminated early, as advised by the data safety and monitoring board, following sample size adaptation after the predefined interim analysis on Dec 18, 2018. This trial is registered with the EU Clinical Trials Register (EudraCT 2015-001830-12) and ClinicalTrials.gov (NCT02596555). FINDINGS: Between Jan 1, 2016, and July 31, 2019, 1418 patients with pulmonary embolism were screened, of whom 402 were enrolled and were included in the intention-to-treat analysis (median age was 69·5 years [IQR 60·0-78·0); 192 [48%] were women and 210 [52%] were men). Median follow-up was 217 days (IQR 210-224) and 370 (92%) patients adhered to the protocol. The primary outcome occurred in seven (2% [upper bound of right-sided 95% CI 3]; p<0·0001 for rejecting the null hypothesis) patients, with all events occurring in those with intermediate-high-risk pulmonary embolism (seven [3%; upper bound of right-sided 95% CI 5] of 283). At 6 months, 11 (3% [95% CI 1-5]) of 402 patients had at least one major bleeding event and 16 (4% [2-6]) had at least one clinically relevant non-major bleeding event; the only fatal haemorrhage occurred in one (<1%) patient before the switch to dabigatran. INTERPRETATION: A strategy of early switch from heparin to dabigatran following standard clinical assessment was effective and safe in patients with intermediate-risk pulmonary embolism. Our results can help to refine guideline recommendations for the initial treatment of acute intermediate-risk pulmonary embolism, optimising the use of resources and avoiding extended hospitalisation. FUNDING: German Federal Ministry of Education and Research, University Medical Center Mainz, and Boehringer Ingelheim.


Assuntos
Anticoagulantes/uso terapêutico , Dabigatrana/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Dabigatrana/efeitos adversos , Esquema de Medicação , Feminino , Seguimentos , Hemorragia/etiologia , Heparina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/complicações , Fatores de Risco , Resultado do Tratamento , Tromboembolia Venosa/complicações
7.
Nutrients ; 13(7)2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34371880

RESUMO

BACKGROUND: The nutritional status of vitamin A in lactating mothers and infants is still not optimistic. Due to the dietary habits and dietary restrictions of postpartum customs in China, vitamin A supplementation has been advocated as a potential strategy to improve vitamin A status of lactating mothers with inadequate dietary vitamin A intake. Existing clinical trials are limited to single or double high-dose maternal administrations. However, in China, vitamin A supplements are readily available in the form of daily oral low-dose supplements, and the effect of these is unknown. This study aimed to evaluate the effects of daily oral low-dose vitamin A supplementation on the retinol levels in the serum and breast milk of lactating mothers and the health status of infants in China. METHODS: Lactating mothers who met the inclusion criteria and planned to continue exclusive breastfeeding were randomly assigned to receive either daily oral vitamin A and D drops (one soft capsule of 1800 IU vitamin A and 600 IU vitamin D2), or a matching placebo for 2 months. Before and after the intervention, dietary intake was investigated by instant photography, and the retinol concentration in maternal serum and breast milk was determined by ultra-high performance liquid chromatography-tandem mass spectrometry. During the trial, the health status of infants was diagnosed by a paediatrician or reported by lactating mothers. A total of 245 participants completed the study, with 117 in the supplementation group and 128 in the control group. RESULTS: After the 2-month intervention, maternal serum retinol concentrations increased in the supplementation group with no change in the control group. Although breast milk retinol concentrations decreased significantly in both groups, the decrease in the supplementation group was significantly lower than that in the control group. However, maternal vitamin A supplementation was not associated with a lower risk of infant febrile illness, respiratory tract infection, diarrhoea, and eczema. CONCLUSIONS: Daily oral low-dose vitamin A supplementation is helpful in improving maternal vitamin A status, despite having no effect on infant health status through breast milk.


Assuntos
Suplementos Nutricionais , Lactação/metabolismo , Fenômenos Fisiológicos da Nutrição Materna , Leite Humano/metabolismo , Estado Nutricional , Vitamina A/administração & dosagem , Administração Oral , Adulto , China , Suplementos Nutricionais/efeitos adversos , Esquema de Medicação , Combinação de Medicamentos , Ergocalciferóis/administração & dosagem , Feminino , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido , Gravidez , Método Simples-Cego , Fatores de Tempo , Resultado do Tratamento , Vitamina A/efeitos adversos , Vitamina A/sangue , Adulto Jovem
9.
PLoS One ; 16(8): e0255644, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34347836

RESUMO

OBJECTIVES: In severe COVID-19 pneumonia, the appropriate timing and dosing of corticosteroids (CS) is not known. Patient subgroups for which CS could be more beneficial also need appraisal. The aim of this study was to assess the effect of early CS in COVID-19 pneumonia patients admitted to the ICU on the occurrence of 60-day mortality, ICU-acquired-bloodstream infections(ICU-BSI), and hospital-acquired pneumonia and ventilator-associated pneumonia(HAP-VAP). METHODS: We included patients with COVID-19 pneumonia admitted to 11 ICUs belonging to the French OutcomeReaTM network from January to May 2020. We used survival models with ponderation with inverse probability of treatment weighting (IPTW). RESULTS: The study population comprised 303 patients having a median age of 61.6 (53-70) years of whom 78.8% were male and 58.6% had at least one comorbidity. The median SAPS II was 33 (25-44). Invasive mechanical ventilation was required in 34.8% of the patients. Sixty-six (21.8%) patients were in the Early-C subgroup. Overall, 60-day mortality was 29.4%. The risks of 60-day mortality (IPTWHR = 0.86;95% CI 0.54 to 1.35, p = 0.51), ICU-BSI and HAP-VAP were similar in the two groups. Importantly, early CS treatment was associated with a lower mortality rate in patients aged 60 years or more (IPTWHR, 0.53;95% CI, 0.3-0.93; p = 0.03). In contrast, CS was associated with an increased risk of death in patients younger than 60 years without inflammation on admission (IPTWHR = 5.01;95% CI, 1.05, 23.88; p = 0.04). CONCLUSION: For patients with COVID-19 pneumonia, early CS treatment was not associated with patient survival. Interestingly, inflammation and age can significantly influence the effect of CS.


Assuntos
Corticosteroides/administração & dosagem , COVID-19/tratamento farmacológico , COVID-19/mortalidade , Adulto , Idoso , COVID-19/terapia , Estudos de Coortes , Redes Comunitárias , Estado Terminal/mortalidade , Estado Terminal/terapia , Esquema de Medicação , Intervenção Médica Precoce/métodos , Feminino , França/epidemiologia , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Respiração Artificial/mortalidade , Respiração Artificial/estatística & dados numéricos , Fatores de Tempo , Resultado do Tratamento
10.
Pediatr Ann ; 50(7): e268-e269, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34264795
11.
Expert Opin Drug Metab Toxicol ; 17(9): 1039-1048, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34225556

RESUMO

Introduction: Usage of ceftriaxone-based therapy to treat Methicillin-Susceptible Staphylococcus aureus (MSSA) infections is a controversial issue, from in vitro to clinical studies.Area covered: We conducted a literature review using PubMed of articles with ceftriaxone pharmacokinetics parameters and built a probability of target attainment (PTA) based on PK values from stable conditions (non-critically-ill patients) with goals of fT>55%, fT>75%, and fT>100%. Ceftriaxone's minimal inhibitory concentration from 31 MSSA strains (0.25-64 mg/L) was used to build the cumulative fraction response (CFR). The isolates were clinically relevant from blood, bronchoalveolar lavage, and soft tissue biopsy.Expert opinion: The results from controversies about using ceftriaxone for MSSA infections have been commonly addressed in the literature. However, variables such as (i) pharmacokinetic profile, (ii) pharmacodynamic target, (iii) site of infection, and (iv) MIC distributions may influence divergences. From this pharmacokinetics-pharmacodynamics perspective, ceftriaxone may be a reasonable option for MSSA infections when the MIC50 and MIC90 were 4 mg/L and 8 mg/L. CFR analysis demonstrated that ceftriaxone 1 g q24 h could be used if bacteriostasis is the aim (fT>55%), while 1 g q12h should be used for bactericidal effects (fT>75% or fT>100%). These dosing regimens should be considered in other clinical trials.


Assuntos
Antibacterianos/administração & dosagem , Ceftriaxona/administração & dosagem , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Ceftriaxona/farmacocinética , Ceftriaxona/farmacologia , Esquema de Medicação , Farmacorresistência Bacteriana , Humanos , Meticilina/farmacologia , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação
12.
Br J Anaesth ; 127(3): 458-469, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34243941

RESUMO

To meet the WHO vision of reducing medication errors by 50%, it is essential to know the current error rate. We undertook an integrative review of the literature, using a systematic search strategy. We included studies that provided an estimate of error rate (i.e. both numerator and denominator data), regardless of type of study (e.g. RCT or observational study). Under each method type, we categorised the error rate by type, by classification used by the primary studies (e.g. wrong drug, wrong dose, wrong time), and then pooled numerator and denominator data across studies to obtain an aggregate error rate for each method type. We included a total of 30 studies in this review. Of these, two studies were national audit projects containing relevant data, and for 28 studies we identified five discrete method types: retrospective recall (6), self-reporting (7), observational (5), large databases (7), and observing for drug calculation errors (3). Of these 28 studies we included 22 for a numerical analysis and used six to inform a narrative review. Drug error is recalled by ~1 in 5 anaesthetists as something that happened over their career; in self-reports there is an admitted rate of ~1 in 200 anaesthetics. In observed practice, error is seen in almost every anaesthetic. In large databases, drug error constitutes ~10% of anaesthesia incidents reported. Wrong drug or dose form the most common type of error across all five study method types (especially dosing error in paediatric studies). We conclude that medication error is common in anaesthetic practice, although we were uncertain of the precise frequency or extent of harm. Studies concerning medication error are very heterogenous, and we recommend consideration of standardised reporting as in other research domains.


Assuntos
Anestesia/efeitos adversos , Anestésicos/efeitos adversos , Projetos de Pesquisa Epidemiológica , Erros de Medicação , Anestésicos/administração & dosagem , Esquema de Medicação , Humanos , Incidência , Segurança do Paciente , Medição de Risco , Fatores de Risco , Análise de Causa Fundamental
14.
Eur J Endocrinol ; 185(4): 515-524, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34324430

RESUMO

Objective: In primary hyperparathyroidism (PHPT) with osteoporosis, bone mineral density (BMD) improves after parathyroidectomy. It is unclear whether combining surgery with postoperative bisphosphonate treatment can further improve bone health. Design: This randomized, placebo-controlled study compared the effects of surgery alone and surgery combined with zoledronic acid on bone metabolism in PHPT with osteoporosis. Methods: Fifty-six patients (f/m 47/9, mean age 68.4 years) with PHPT and osteoporosis were randomized 1-3 months after parathyroidectomy to receive a 2-year treatment of zoledronic acid or placebo. Dual-energy X-ray absorptiometry (DXA) and bone turnover markers (N-terminal propeptide of type 1 procollagen, C-terminal telopeptide of type 1 collagen, and alkaline phosphatase) were measured annually during the 2-year follow-up. Results: Two years after parathyroidectomy, BMD was significantly higher in the zoledronic acid (ZOL) group compared with the placebo (PBO) group at the femoral neck (P = 0.045 for Z-score) and lumbar spine (P = 0.039 and 0.017 for T- and Z-scores, respectively). Bone turnover markers were significantly lower in the ZOL group (P < 0.001 for all markers). Of the 18 patients who had received bisphosphonates for >1 year before surgery, BMD improved significantly in the ZOL group both in the femoral neck and lumbar spine (n = 10; all P < 0.001-0.01), but in the PBO group, only in the lumbar spine (n = 8, P = 0.03), (P = 0.08-0.95 for between-group changes). Conclusion: BMD increases after parathyroidectomy both with and without zoledronic acid but the increase is significantly higher with postoperative zoledronic acid.


Assuntos
Hiperparatireoidismo Primário , Osteoporose , Ácido Zoledrônico/administração & dosagem , Idoso , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/administração & dosagem , Terapia Combinada , Método Duplo-Cego , Esquema de Medicação , Feminino , Finlândia , Humanos , Hiperparatireoidismo Primário/complicações , Hiperparatireoidismo Primário/tratamento farmacológico , Hiperparatireoidismo Primário/cirurgia , Masculino , Pessoa de Meia-Idade , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Osteoporose/cirurgia , Paratireoidectomia , Período Pós-Operatório , Resultado do Tratamento
15.
J Fam Pract ; 70(3): E1-E3, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-34314342

RESUMO

MAYBE, but it's too soon to tell. There is limited evidence that ketamine by itself is effective in the very short term. Single-dose intravenous (IV) ketamine is more likely than placebo (odds ratio = 11-13) to produce improvement (> 50%) in standardized depression scores in 1 to 3 days, lasting up to a week. Twice- or thriceweekly IV ketamine improves symptom scores by 20%-25% over 2 weeks (strength of recommendation [SOR]: B, meta-analysis of small, low-quality, randomized controlled trials [RCTs] and a single small RCT).Augmentation of sertraline with daily oral ketamine moderately improves symptom scores for 6 weeks in patients with moderate depression (SOR: B, small, lowquality RCTs).Augmentation of oral antidepressants (duloxetine, escitalopram, sertraline, venlafaxine) with intranasal esketamine spray improves response and remission rates at 4 weeks (16% for both outcomes) in patients with predominantly treatment-resistant major depression (SOR: A, meta-analysis of RCTs).Ketamine therapy is associated with confusion, emotional blunting, headache, dizziness, and blurred vision (SOR: A, metaanalyses).Nasal esketamine spray produces the adverse effects of dizziness, vertigo, and blurred vision severe enough to cause discontinuation in 4% of patients; it also can produce transient elevation of blood pressure (SOR: A, meta-analyses).


Assuntos
Antidepressivos/efeitos adversos , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Ketamina/efeitos adversos , Administração Intranasal , Administração Oral , Adulto , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/prevenção & controle , Esquema de Medicação , Humanos , Ketamina/uso terapêutico , Indução de Remissão , Resultado do Tratamento
18.
JAMA ; 326(4): 324-331, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34313686

RESUMO

Importance: Determination of optimal treatment durations for common infectious diseases is an important strategy to preserve antibiotic effectiveness. Objective: To determine whether 7 days of treatment is noninferior to 14 days when using ciprofloxacin or trimethoprim/sulfamethoxazole to treat urinary tract infection (UTI) in afebrile men. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled noninferiority trial of afebrile men with presumed symptomatic UTI treated with ciprofloxacin or trimethoprim/sulfamethoxazole at 2 US Veterans Affairs medical centers (enrollment, April 2014 through December 2019; final follow-up, January 28, 2020). Of 1058 eligible men, 272 were randomized. Interventions: Participants continued the antibiotic prescribed by their treating clinician for 7 days of treatment and were randomized to receive continued antibiotic therapy (n = 136) or placebo (n = 136) for days 8 to 14 of treatment. Main Outcomes and Measures: The prespecified primary outcome was resolution of UTI symptoms by 14 days after completion of active antibiotic treatment. A noninferiority margin of 10% was selected. The as-treated population (participants who took ≥26 of 28 doses and missed no more than 2 consecutive doses) was used for the primary analysis, and a secondary analysis included all patients as randomized, regardless of treatment adherence. Secondary outcomes included recurrence of UTI symptoms and/or adverse events within 28 days of stopping study medication. Results: Among 272 patients (median [interquartile range] age, 69 [62-73] years) who were randomized, 100% completed the trial and 254 (93.4%) were included in the primary as-treated analysis. Symptom resolution occurred in 122/131 (93.1%) participants in the 7-day group vs 111/123 (90.2%) in the 14-day group (difference, 2.9% [1-sided 97.5% CI, -5.2% to ∞]), meeting the noninferiority criterion. In the secondary as-randomized analysis, symptom resolution occurred in 125/136 (91.9%) participants in the 7-day group vs 123/136 (90.4%) in the 14-day group (difference, 1.5% [1-sided 97.5% CI, -5.8% to ∞]) Recurrence of UTI symptoms occurred in 13/131 (9.9%) participants in the 7-day group vs 15/123 (12.9%) in the 14-day group (difference, -3.0% [95% CI, -10.8% to 6.2%]; P = .70). Adverse events occurred in 28/136 (20.6%) participants in the 7-day group vs 33/136 (24.3%) in the 14-day group. Conclusions and Relevance: Among afebrile men with suspected UTI, treatment with ciprofloxacin or trimethoprim/sulfamethoxazole for 7 days was noninferior to 14 days of treatment with regard to resolution of UTI symptoms by 14 days after antibiotic therapy. The findings support the use of a 7-day course of ciprofloxacin or trimethoprim/sulfamethoxazole as an alternative to a 14-day course for treatment of afebrile men with UTI. Trial Registration: ClinicalTrials.gov identifier: NCT01994538.


Assuntos
Antibacterianos/administração & dosagem , Ciprofloxacina/administração & dosagem , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Infecções Urinárias/tratamento farmacológico , Idoso , Antibacterianos/efeitos adversos , Ciprofloxacina/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Duração da Terapia , Humanos , Masculino , Pessoa de Meia-Idade , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Infecções Urinárias/microbiologia , Urina/microbiologia
20.
N Engl J Med ; 385(6): 503-515, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34170647

RESUMO

BACKGROUND: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist that is under development for the treatment of type 2 diabetes. The efficacy and safety of once-weekly tirzepatide as compared with semaglutide, a selective GLP-1 receptor agonist, are unknown. METHODS: In an open-label, 40-week, phase 3 trial, we randomly assigned 1879 patients, in a 1:1:1:1 ratio, to receive tirzepatide at a dose of 5 mg, 10 mg, or 15 mg or semaglutide at a dose of 1 mg. At baseline, the mean glycated hemoglobin level was 8.28%, the mean age 56.6 years, and the mean weight 93.7 kg. The primary end point was the change in the glycated hemoglobin level from baseline to 40 weeks. RESULTS: The estimated mean change from baseline in the glycated hemoglobin level was -2.01 percentage points, -2.24 percentage points, and -2.30 percentage points with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and -1.86 percentage points with semaglutide; the estimated differences between the 5-mg, 10-mg, and 15-mg tirzepatide groups and the semaglutide group were -0.15 percentage points (95% confidence interval [CI], -0.28 to -0.03; P = 0.02), -0.39 percentage points (95% CI, -0.51 to -0.26; P<0.001), and -0.45 percentage points (95% CI, -0.57 to -0.32; P<0.001), respectively. Tirzepatide at all doses was noninferior and superior to semaglutide. Reductions in body weight were greater with tirzepatide than with semaglutide (least-squares mean estimated treatment difference, -1.9 kg, -3.6 kg, and -5.5 kg, respectively; P<0.001 for all comparisons). The most common adverse events were gastrointestinal and were primarily mild to moderate in severity in the tirzepatide and semaglutide groups (nausea, 17 to 22% and 18%; diarrhea, 13 to 16% and 12%; and vomiting, 6 to 10% and 8%, respectively). Of the patients who received tirzepatide, hypoglycemia (blood glucose level, <54 mg per deciliter) was reported in 0.6% (5-mg group), 0.2% (10-mg group), and 1.7% (15-mg group); hypoglycemia was reported in 0.4% of those who received semaglutide. Serious adverse events were reported in 5 to 7% of the patients who received tirzepatide and in 3% of those who received semaglutide. CONCLUSIONS: In patients with type 2 diabetes, tirzepatide was noninferior and superior to semaglutide with respect to the mean change in the glycated hemoglobin level from baseline to 40 weeks. (Funded by Eli Lilly; SURPASS-2 ClinicalTrials.gov number, NCT03987919.).


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Polipeptídeo Inibidor Gástrico/administração & dosagem , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Hipoglicemiantes/administração & dosagem , Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Feminino , Polipeptídeo Inibidor Gástrico/efeitos adversos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Incretinas/uso terapêutico , Injeções Subcutâneas , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Perda de Peso/efeitos dos fármacos
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