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1.
Bull Cancer ; 107(1): 10-20, 2020 Jan.
Artigo em Francês | MEDLINE | ID: mdl-31982092

RESUMO

Papillomavirus (HPV), the first sexually transmitted disease in the world, is the main infectious agent responsible for cancer (6300 per year, in France). The cycle of HPV infection - >precancerous lesions - >cancer is well documented with regard to the cervix (cf. Nobel Prize in 2008). While this area is the most frequent (3000), it is far from being the only one. Other cancers include the anus, oropharyngeal sphere, glans and vulva. The sum of these other induced HPV cancers is greater than the total number of cervical cancers and also concerns boys. Screening is essential but insufficient and only concerns the cervix. Only vaccination can provide primary and general prevention. Since 2007, there have been many studies demonstrating its excellent efficacy and tolerance. However, France lags behind other countries with a vaccination coverage (<30 %) that does not allow for an epidemiological impact.


Assuntos
Neoplasias do Ânus/prevenção & controle , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Doenças Virais Sexualmente Transmissíveis/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Adolescente , Adulto , Neoplasias do Ânus/epidemiologia , Neoplasias do Ânus/virologia , Criança , Condiloma Acuminado/epidemiologia , Condiloma Acuminado/prevenção & controle , Condiloma Acuminado/virologia , Feminino , França/epidemiologia , Genótipo , Vacina Quadrivalente Recombinante contra HPV tipos 6, 11, 16, 18/administração & dosagem , Humanos , Masculino , Números Necessários para Tratar , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Vacinas contra Papillomavirus/imunologia , Lesões Pré-Cancerosas/complicações , Doenças Virais Sexualmente Transmissíveis/complicações , Doenças Virais Sexualmente Transmissíveis/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Adulto Jovem
3.
Br J Radiol ; 92(1102): 20190317, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31295011

RESUMO

OBJECTIVE: In this study, we used the concept of organ-equivalent dose (OED) to evaluate the excess absolute risk (EAR) for secondary cancer in various organs after radiation treatment for breast cancer. METHODS: Using CT data set of 12 patients, we generated three different whole-breast radiation treatment plans using 50 Gy in 2 Gy fractions: three-dimensional conformal radiotherapy with a field-in-field (FinF) technique, intensity modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT). The OEDs were calculated from differential dose-volume histograms on the basis of the "linear-exponential," "plateau," and "full mechanistic" dose-response models. Secondary cancer risks of the contralateral breast (CB), contralateral lung (CL), and ipsilateral lung (IL) were estimated and compared. RESULTS: The lowest EARs for the CB, CL, and IL were achieved with FinF, which reduced the EARs by 77%, 88%, and 56% relative to those with IMRT, and by 77%, 84%, and 58% relative to those with VMAT, respectively. The secondary cancer risk for FinF was significantly lower than those of IMRT and VMAT. OED-based secondary cancer risks for CB and IL were similar when IMRT and VMAT were used, but the risk for CL was statistically lower when VMAT was used. CONCLUSION: The overall estimation of EAR indicated that the radiation-induced cancer risk of breast radiation therapy was lower with FinF than with IMRT and VMAT. Therefore, when secondary cancer risk is a major concern, FinF is considered to be the preferred treatment option in irradiation of whole-breast. ADVANCES IN KNOWLEDGE: Secondary malignancy estimation after breast radiotherapy is becoming an important subject for comparative treatment planning.When secondary cancer risk a major concern, FinF technique is considered the preferred treatment option in whole breast patients.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias Induzidas por Radiação/etiologia , Segunda Neoplasia Primária/etiologia , Radioterapia Conformacional/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Mama/diagnóstico por imagem , Mama/efeitos da radiação , Fracionamento da Dose de Radiação , Relação Dose-Resposta à Radiação , Feminino , Coração/diagnóstico por imagem , Coração/efeitos da radiação , Humanos , Pulmão/diagnóstico por imagem , Pulmão/efeitos da radiação , Neoplasias Pulmonares/etiologia , Números Necessários para Tratar , Órgãos em Risco/diagnóstico por imagem , Órgãos em Risco/efeitos da radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Conformacional/métodos , Radioterapia de Intensidade Modulada/métodos , Medição de Risco/métodos , Tomografia Computadorizada por Raios X , Neoplasias Unilaterais da Mama/etiologia
4.
Cochrane Database Syst Rev ; 6: CD012673, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31220333

RESUMO

BACKGROUND: The presence of oesophageal varices is associated with the risk of upper gastrointestinal bleeding. Endoscopic variceal ligation is used to prevent this occurrence but the ligation procedure may be associated with complications. OBJECTIVES: To assess the beneficial and harmful effects of band ligation versus no intervention for primary prevention of upper gastrointestinal bleeding in adults with cirrhosis and oesophageal varices. SEARCH METHODS: We combined searches in the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, and Science Citation Index with manual searches. The last search update was 9 February 2019. SELECTION CRITERIA: We included randomised clinical trials comparing band ligation verus no intervention regardless of publication status, blinding, or language in the analyses of benefits and harms, and observational studies in the assessment of harms. Included participants had cirrhosis and oesophageal varices with no previous history of variceal bleeding. DATA COLLECTION AND ANALYSIS: Three review authors extracted data independently. The primary outcome measures were all-cause mortality, upper gastrointestinal bleeding, and serious adverse events. We undertook meta-analyses and presented results using risk ratios (RRs) with 95% confidence intervals (CIs) and I2 values as a marker of heterogeneity. In addition, we calculated the number needed to treat to benefit (NNTTB) for the primary outcomes . We assessed bias control using the Cochrane Hepato-Biliary domains; determined the certainty of the evidence using GRADE; and conducted sensitivity analyses including Trial Sequential Analysis. MAIN RESULTS: Six randomised clinical trials involving 637 participants fulfilled our inclusion criteria. One of the trials included an additional small number of participants (< 10% of the total) with non-cirrhotic portal hypertension/portal vein block. We classified one trial as at low risk of bias for the outcome, mortality and high risk of bias for the remaining outcomes; the five remaining trials were at high risk of bias for all outcomes. We downgraded the evidence to moderate certainty due to the bias risk. We gathered data on all primary outcomes from all trials. Seventy-one of 320 participants allocated to band ligation compared to 129 of 317 participants allocated to no intervention died (RR 0.55, 95% CI 0.43 to 0.70; I2 = 0%; NNTTB = 6 persons). In addition, band ligation was associated with reduced risks of upper gastrointestinal bleeding (RR 0.44, 95% CI 0.28 to 0.72; 6 trials, 637 participants; I2 = 61%; NNTTB = 5 persons), serious adverse events (RR 0.55, 95% CI 0.43 to 0.70; 6 trials, 637 participants; I2 = 44%; NNTTB = 4 persons), and variceal bleeding (RR 0.43, 95% CI 0.27 to 0.69; 6 trials, 637 participants; I² = 56%; NNTTB = 5 persons). The non-serious adverse events reported in association with band ligation included oesophageal ulceration, dysphagia, odynophagia, retrosternal and throat pain, heartburn, and fever, and in the one trial involving participants with either small or large varices, the incidence of non-serious side effects in the banding group was much higher in those with small varices, namely ulcers: small versus large varices 30.5% versus 8.7%; heartburn 39.2% versus 17.4%. No trials reported on health-related quality of life.Two trials did not receive support from pharmaceutical companies; the remaining four trials did not provide information on this issue. AUTHORS' CONCLUSIONS: This review found moderate-certainty evidence that, in patients with cirrhosis, band ligation of oesophageal varices reduces mortality, upper gastrointestinal bleeding, variceal bleeding, and serious adverse events compared to no intervention. It is unlikely that further trials of band ligation versus no intervention would be considered ethical.


Assuntos
Varizes Esofágicas e Gástricas/complicações , Hemorragia Gastrointestinal/prevenção & controle , Cirrose Hepática/complicações , Adulto , Varizes Esofágicas e Gástricas/mortalidade , Varizes Esofágicas e Gástricas/terapia , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/mortalidade , Humanos , Hipertensão Portal/complicações , Ligadura/efeitos adversos , Ligadura/instrumentação , Ligadura/métodos , Ligadura/mortalidade , Pessoa de Meia-Idade , Números Necessários para Tratar , Prevenção Primária/métodos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Conduta Expectante
5.
Med J Aust ; 210(9): 424-428, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30977152

RESUMO

Chronic obstructive pulmonary disease (COPD) is defined based on a reduced ratio of forced expiratory volume in one second (FEV1 ) to forced vital capacity (FVC) on spirometry. However, within this definition, there is significant heterogeneity of pathophysiological processes that lead to airflow obstruction and variation in phenotypic manifestations across patients. Current pharmacological treatments are based on large randomised clinical trials that apply to an "average" patient. Precision health enables tailoring of treatment for each individual patient by taking into account their unique characteristics. The number needed to treat (NNT) metric is often used to define implementation of precision health for specific interventions, with common endpoints requiring an NNT ≤ 5 to achieve precision therapy. Higher NNTs may be acceptable for rare but important endpoints such as mortality. Long-acting muscarinic antagonists and inhaled corticosteroids, which are commonly used in COPD, have 1-year treatment NNTs between 15 and 20 for exacerbation prevention in unselected patients with COPD. Subgroup identification using biomarkers or clinical traits may enable precision health. For example, NNT for inhaled corticosteroids is 9 in patients with a blood eosinophil count ≥ 300 cells/µL and 8 for long-acting muscarinic antagonists in patients with a body mass index ≤ 20 kg/m2 . Lung volume reduction surgery is associated with an NNT of 6 for survival over 5 years in patients with upper lobe-predominant disease and low exercise capacity (whereas the NNT is 245 when no bioimaging or exercise markers are used). Continuous domiciliary oxygen therapy (for at least 15 hours/day) has an NNT of 5 for survival over 5 years in patients with resting hypoxemia (PaO2  < 60 mmHg on room air). Emerging areas of precision health in COPD with potential for low NNTs in specific circumstances include anti-interleukin-5 therapy for eosinophilic COPD, and immunoglobulin replacement therapy for patients with severe immunoglobulin deficiency.


Assuntos
Biomarcadores , Números Necessários para Tratar , Medicina de Precisão , Doença Pulmonar Obstrutiva Crônica/terapia , Administração por Inalação , Corticosteroides/administração & dosagem , Broncodilatadores/administração & dosagem , Volume Expiratório Forçado , Humanos , Antagonistas Muscarínicos/administração & dosagem , Oxigenoterapia , Doença Pulmonar Obstrutiva Crônica/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Espirometria
6.
World J Surg ; 43(8): 2077-2085, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30863872

RESUMO

BACKGROUND: An aging population combined with an increased colorectal cancer (CRC) incidence in the older population will increase its prevalence in the elderly, questioning how many years of life are lost (YLLs) in these patients. PATIENTS AND METHODS: Data from 32,568 Dutch CRC patients ≥ 80 years were used to estimate the number of YLLs after diagnosis, using a reference age-, sex- and year-of-onset-matched cohort derived from national life tables. YLLs were additionally adjusted by comorbidities. Number needed to treat (NNT) was used as measure of surgical effect size. RESULTS: Surgery was applied in 74.9% of patients leading to 1.3 YLLs, being superior in 86.1% of cases with respect to alternative therapies (YLLs 4.8 years) and resulting in a number of two patients needed to operate to achieve one positive outcome. YLLs and NNTs depended on CRC stage, patient' age and comorbidities. For Stage I-II patients in the best clinical conditions (80-85 years without comorbidities), YLLs increased up to 4.1 years after surgery and up to 8.8 years without surgery (NNT 3). For Stage III patients, the NNT of surgery varied between 2 when they were in the best clinical conditions and 4 when they were older with high comorbidities. In Stage IV patients, the NNT ranged between 6 and 31. CONCLUSIONS: YLLs represents a novel approach to evaluate CRC prognosis. Stage I-III surgical patients can have a life expectancy similar to that of general population, being the NNT of surgery reasonably small compared with alternatives. Personalized comorbidity data are needed to confirm present findings.


Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/cirurgia , Expectativa de Vida , Números Necessários para Tratar/estatística & dados numéricos , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Comorbidade , Feminino , Humanos , Tábuas de Vida , Masculino , Estadiamento de Neoplasias , Prognóstico
7.
Cochrane Database Syst Rev ; 3: CD011268, 2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30883669

RESUMO

BACKGROUND: Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review - one of four reviews on efficacy and safety of interventions to prevent SAD - focuses on second-generation antidepressants (SGAs). OBJECTIVES: To assess the efficacy and safety of SGAs (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient-centred outcomes among adults with a history of SAD. SEARCH METHODS: We searched Ovid MEDLINE (1950- ), Embase (1974- ), PsycINFO (1967- ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD-CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library, the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. SELECTION CRITERIA: For efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter-type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non-randomised studies. Eligible studies compared a SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus placebo or the same comparator intervention as monotherapy. DATA COLLECTION AND ANALYSIS: Two review authors independently screened abstracts and full-text publications, extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random-effects (Mantel-Haenszel) meta-analyses. We assessed statistical heterogeneity by calculating the Chi2 statistic and the Cochran Q. We used the I2 statistic to estimate the magnitude of heterogeneity. We assessed publication bias by using funnel plots.We rated the strength of the evidence using the system developed by the GRADE Working Group. MAIN RESULTS: We identified 3745 citations after de-duplication of search results and excluded 3619 records during title and abstract reviews. We assessed 126 full-text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates.Overall, moderate-quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in people with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; 3 RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate-quality evidence), insomnia and nausea (both low-quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 50% and 60%, NNTBs are 5 (95% CI 4 to 7) and 4 (95% CI 3 to 6), respectively.We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest, such as light therapy, psychological therapies, melatonin or agomelatine. AUTHORS' CONCLUSIONS: Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high-risk population, three out of four people will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment, and might want to consider offering other potentially efficacious interventions, which might confer a lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences.Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non-pharmacological interventions.


Assuntos
Antidepressivos de Segunda Geração/uso terapêutico , Bupropiona/uso terapêutico , Transtorno Afetivo Sazonal/tratamento farmacológico , Adulto , Antidepressivos de Segunda Geração/efeitos adversos , Bupropiona/efeitos adversos , Diarreia/induzido quimicamente , Cefaleia/induzido quimicamente , Humanos , Incidência , Náusea/induzido quimicamente , Números Necessários para Tratar , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Transtorno Afetivo Sazonal/epidemiologia , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente
8.
Implement Sci ; 14(1): 31, 2019 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-30890160

RESUMO

BACKGROUND: People in close contact with tuberculosis should have screening and appropriate management, as an opportunity for active case detection and prevention. However, implementation of tuberculosis contact screening and management is limited in high-burden settings. Behaviour change is needed across three levels of the healthcare system-policymakers, healthcare providers, and patients. To bridge the wide policy-practice gap, this study draws on the Consolidated Framework for Implementation Research, the Behaviour Change Wheel, and the RE-AIM model (Reach, Effectiveness, Adoption, Implementation, Maintenance) to respectively understand barriers, implement change, and evaluate process and outcome. METHODS: This methods paper describes a mixed-methods intervention study in Eastern Indonesia. Quantitative data will be collected during baseline, intervention, and sustainability periods and analyzed using time series analysis. The primary outcome is the number of individuals completing tuberculosis preventive therapy by the end of the two-year intervention phase. Of an estimated 10,000 contacts during this period, we anticipate that a minimum of 416 will be found to have active TB or will complete preventive therapy. Qualitative data (semi-structured interviews, focus group discussions, and observations) will be collected from consenting healthcare providers, patients, and contacts. Activities to promote policy implementation include healthcare provider training, quarterly continuous quality improvement workshops, a social media discussion forum, and promotional materials. The Consolidated Framework for Implementation Research will be used to identify reasons for limited policy implementation at baseline. The Behaviour Change Wheel will be used to ensure that a suitable range of activities are implemented to facilitate change. The RE-AIM model will be used as the evaluation framework. DISCUSSION: Use of theoretical frameworks in combination can ensure a comprehensive understanding of, and robust response to, health policy underimplementation. The selected frameworks are highly applicable to this pragmatic intervention study, in a setting where End TB Strategy targets will not be met without substantial behavior change within health systems. Continuous quality improvement cycles will provide a way to engage staff and stakeholders in understanding local data to motivate behavior change. If successful, up to 500 people could be prevented from developing complications of tuberculosis through early case-finding or receiving preventive therapy over a two-year period. STUDY REGISTRATION: Australian New Zealand Clinical Trials Register 375803 .


Assuntos
Lacunas da Prática Profissional , Tuberculose/prevenção & controle , Pessoal Administrativo , Adulto , Busca de Comunicante , Estudos Controlados Antes e Depois , Efeitos Psicossociais da Doença , Coleta de Dados/métodos , Assistência à Saúde/organização & administração , Diagnóstico Precoce , Doenças Endêmicas , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde/normas , Política de Saúde , Humanos , Indonésia/epidemiologia , Masculino , Estudos Multicêntricos como Assunto , Números Necessários para Tratar , Ensaios Clínicos Pragmáticos como Assunto , Tamanho da Amostra , Tuberculose/epidemiologia
9.
Cochrane Database Syst Rev ; 3: CD010677, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30921478

RESUMO

BACKGROUND: Panic disorder is characterised by recurrent unexpected panic attacks consisting of a wave of intense fear that reaches a peak within a few minutes. Panic disorder is a common disorder, with an estimated lifetime prevalence of 1% to 5% in the general population and a 7% to 10% prevalence in primary care settings. Its aetiology is not fully understood and is probably heterogeneous.Panic disorder is treated with psychological and pharmacological interventions, often used in combination. Although benzodiazepines are frequently used in the treatment of panic disorder, guidelines recommend antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs), as first-line treatment for panic disorder, particularly due to their lower incidence of dependence and withdrawal reaction when compared to benzodiazepines. Despite these recommendations, benzodiazepines are widely used in the treatment of panic disorder, probably because of their rapid onset of action. OBJECTIVES: To assess the efficacy and acceptability of benzodiazepines versus placebo in the treatment of panic disorder with or without agoraphobia in adults. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR Studies and References), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1950-), Embase (1974-), and PsycINFO (1967-) up to 29 May 2018. We handsearched reference lists of relevant papers and previous systematic reviews. We contacted experts in the field for supplemental data. SELECTION CRITERIA: All double-blind (blinding of patients and personnel) controlled trials randomising adults with panic disorder with or without agoraphobia to benzodiazepine or placebo. DATA COLLECTION AND ANALYSIS: Two review authors independently checked the eligibility of studies and extracted data using a standardised form. Data were then entered data into Review Manager 5 using a double-check procedure. Information extracted included study characteristics, participant characteristics, intervention details, settings, and outcome measures in terms of efficacy, acceptability, and tolerability. MAIN RESULTS: We included 24 studies in the review with a total of 4233 participants, of which 2124 were randomised to benzodiazepines and 1475 to placebo. The remaining 634 participants were randomised to other active treatments in three-arm trials. We assessed the overall methodological quality of the included studies as poor. We rated all studies as at unclear risk of bias in at least three domains. In addition, we judged 20 of the 24 included studies as having a high risk of bias in at least one domain.Two primary outcomes of efficacy and acceptability showed a possible advantage of benzodiazepines over placebo. The estimated risk ratio (RR) for a response to treatment was 1.65 (95% confidence interval (CI) 1.39 to 1.96) in favour of benzodiazepines, which corresponds to an estimated number needed to treat for an additional beneficial outcome (NNTB) of 4 (95% CI 3 to 7). The dropout rate was lower among participants treated with benzodiazepines (RR 0.50, 95% CI 0.39 to 0.64); the estimated NNTB was 6 (95% CI 5 to 9). We rated the quality of the evidence as low for both primary outcomes. The possible advantage of benzodiazepine was also seen for remission (RR 1.61, 95% CI 1.38 to 1.88) and the endpoint data for social functioning (standardised mean difference (SMD) -0.53, 95% CI -0.65 to -0.42), both with low-quality evidence. We assessed the evidence for the other secondary outcomes as of very low quality. With the exception of the analyses of the change score data for depression (SMD -0.22, 95% CI -0.48 to 0.04) and social functioning (SMD -0.32, 95% CI -0.88 to 0.24), all secondary outcome analyses showed an effect in favour of benzodiazepines compared to placebo. However, the number of dropouts due to adverse effects was higher with benzodiazepines than with placebo (RR 1.58, 95% CI 1.16 to 2.15; low-quality evidence). Furthermore, our analyses of adverse events showed that a higher proportion of participants experienced at least one adverse effect when treated with benzodiazepines (RR 1.18, 95% CI 1.02 to 1.37; low-quality evidence). AUTHORS' CONCLUSIONS: Low-quality evidence shows a possible superiority of benzodiazepine over placebo in the short-term treatment of panic disorders. The validity of the included studies is questionable due to possible unmasking of allocated treatments, high dropout rates, and probable publication bias. Moreover, the included studies were only short-term studies and did not examine the long-term efficacy nor the risks of dependency and withdrawal symptoms. Due to these limitations, our results regarding the efficacy of benzodiazepines versus placebo provide only limited guidance for clinical practice. Furthermore, the clinician's choice is not between benzodiazepines and placebo, but between benzodiazepines and other agents, notably SSRIs, both in terms of efficacy and adverse effects. The choice of treatment should therefore be guided by the patient's preference and should balance benefits and harms from treatment in a long-term perspective.


Assuntos
Benzodiazepinas/uso terapêutico , Transtorno de Pânico/tratamento farmacológico , Adulto , Idoso , Agorafobia/complicações , Agorafobia/tratamento farmacológico , Buspirona/uso terapêutico , Humanos , Imipramina/uso terapêutico , Pessoa de Meia-Idade , Números Necessários para Tratar , Transtorno de Pânico/complicações , Paroxetina/uso terapêutico , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Placebos/uso terapêutico , Propranolol/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Adulto Jovem
10.
BMJ Evid Based Med ; 24(4): 133-136, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30837230

RESUMO

Many patient-relevant outcomes, particularly quality of life measures such as pain or function, are routinely measured on a continuous scale. However, the interpretation of continuous outcomes is difficult, particularly when considering application to clinical practice and shared decision-making. Making matters worse is the frequent existence of multiple scales for any given construct. Therefore, quantitative syntheses of literature must find a way to combine different scales into a 'common language', and the most frequently used and longest-standing method to do so is the standardised mean difference. Unfortunately, the standardised mean difference is even more difficult to interpret clinically. However, there are validated methods to make these measures easier to understand and apply clinically. This analysis explores these issues and offers a resource to help make these continuous measures more clinically useful.


Assuntos
Números Necessários para Tratar , Qualidade de Vida , Estudos Epidemiológicos , Humanos , Razão de Chances , Resultado do Tratamento
11.
Actas Dermosifiliogr ; 110(7): 546-553, 2019 Sep.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-30851873

RESUMO

BACKGROUND AND OBJECTIVES: Psoriasis is a chronic inflammatory skin disease with an estimated prevalence in Spain of 2.3% of the population. Approximately 30% of patients have moderate-to-severe forms. Treatment with biologic agents is proving to be a step forward in the management of the disease, although these treatments are very expensive. The objective of this study was to determine the efficiency, in terms of cost per number needed to treat (NNT), of the biologic drugs available in Spain for the treatment of moderate to severe plaque psoriasis. METHODS: NNT data were obtained from a network meta-analysis that included all randomized clinical trials of biologic drugs sold in Spain. The cost of each treatment was calculated based on the approved dosage for the first year of treatment, as indicated in the Summary of Product Characteristics. These data were used to calculate the cost per NNT of the drugs for various PASI scores (75, 90, and 100). A sensitivity analysis was performed taking into consideration only the PASI-response measurement time (after 10, 12, or 16 weeks, depending on the drug). RESULTS: The order of efficiency, from most to least efficient, in the case of a PASI 75 response was ixekizumab > ustekinumab 45mg > ustekinumab 90mg > secukinumab > infliximab > etanercept > adalimumab. The order for PASI 90 was ixekizumab >secukinumab >ustekinumab 45mg > ustekinumab 90mg > infliximab > adalimumab > etanercept. The order for PASI 100 was ixekizumab > secukinumab > infliximab > ustekinumab 90mg > ustekinumab 45mg > adalimumab > etanercept. The sensitivity analysis showed some changes in the order, depending on the response-assessment period. CONCLUSIONS: The findings show a link between the efficacy of the biologic therapies available in Spain for the treatment of moderate-to-severe plaque psoriasis and their efficiency. Ixekizumab had the lowest cost per NNT for all PASI-response scores (75, 90, and 100) during the first year of treatment.


Assuntos
Custos de Medicamentos , Números Necessários para Tratar , Psoríase/tratamento farmacológico , Adalimumab/administração & dosagem , Adalimumab/economia , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/economia , Etanercepte/administração & dosagem , Etanercepte/economia , Humanos , Infliximab/administração & dosagem , Infliximab/economia , Meta-Análise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Espanha , Resultado do Tratamento , Ustekinumab/administração & dosagem , Ustekinumab/economia
12.
BMJ Open ; 9(2): e022839, 2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30787076

RESUMO

OBJECTIVES: The primary objective was to assess the utility of the number needed to treat (NNT) to inform decision-making in the context of paediatric oncology and to calculate the NNT in all superiority, parallel, paediatric haematological cancer, randomised controlled trials (RCTs), with a comparison to the threshold NNT as a measure of clinical significance. DESIGN: Systematic review DATA SOURCES: MEDLINE, EMBASE and the Cochrane Childhood Cancer Group Specialized Register through CENTRAL from inception to August 2018. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Superiority, parallel RCTs of haematological malignancy treatments in paediatric patients that assessed an outcome related to survival, relapse or remission; reported a sample size calculation with a delta value to allow for calculation of the threshold NNT, and that included parameters required to calculate the NNT and associated CI. RESULTS: A total of 43 RCTs were included, representing 45 randomised questions, of which none reported the NNT. Among acute lymphoblastic leukaemia (ALL) RCTs, 29.2% (7/24) of randomised questions were found to have a NNT corresponding to benefit, in comparison to acute myeloid leukaemia (ALM) RCTs with 50% (3/6), and none in lymphoma RCTs (0/13). Only 28.6% (2/7) and 33.3% (1/3) had a NNT that was less than the threshold NNT for ALL and AML, respectively. Of these, 100% (2/2 ALL and 1/1 AML) were determined to be possibly clinically significant. CONCLUSIONS: We recommend that decision-makers in paediatric oncology use the NNT and associated confidence limits as a supportive tool to evaluate evidence from RCTs while placing careful attention to the inherent limitations of this measure.


Assuntos
Neoplasias Hematológicas/terapia , Números Necessários para Tratar , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Criança , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/normas
13.
Cochrane Database Syst Rev ; 1: CD012621, 2019 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-30701543

RESUMO

BACKGROUND: Pulmonary hypertension (PH) comprises a group of complex and heterogenous conditions, characterised by elevated pulmonary artery pressure, and which left untreated leads to right-heart failure and death. PH includes World Health Organisation (WHO) Group 1 pulmonary arterial hypertension (PAH); Group 2 consists of PH due to left-heart disease (PH-LHD); Group 3 comprises PH as a result of lung diseases or hypoxia, or both; Group 4 includes PH due to chronic thromboembolic occlusion of pulmonary vasculature (CTEPH), and Group 5 consists of cases of PH due to unclear and/or multifactorial mechanisms including haematological, systemic, or metabolic disorders. Phosphodiesterase type 5 (PDE5) inhibitors increase vasodilation and inhibit proliferation. OBJECTIVES: To determine the efficacy of PDE5 inhibitors for pulmonary hypertension in adults and children. SEARCH METHODS: We performed searches of CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science up to 26 September 2018. We handsearched review articles, clinical trial registries, and reference lists of retrieved articles. SELECTION CRITERIA: We included randomised controlled trials that compared any PDE5 inhibitor versus placebo, or any other PAH disease-specific therapies, for at least 12 weeks. We include separate analyses for each PH group. DATA COLLECTION AND ANALYSIS: We imported studies identified by the search into a reference manager database. We retrieved the full-text versions of relevant studies, and two review authors independently extracted data. Primary outcomes were: change in WHO functional class, six-minute walk distance (6MWD), and mortality. Secondary outcomes were haemodynamic parameters, quality of life/health status, dyspnoea, clinical worsening (hospitalisation/intervention), and adverse events. When appropriate, we performed meta-analyses and subgroup analyses by severity of lung function, connective tissue disease diagnosis, and radiological pattern of fibrosis. We assessed the evidence using the GRADE approach and created 'Summary of findings' tables. MAIN RESULTS: We included 36 studies with 2999 participants (with pulmonary hypertension from all causes) in the final review. Trials were conducted for 14 weeks on average, with some as long as 12 months. Two trials specifically included children.Nineteen trials included group 1 PAH participants. PAH participants treated with PDE5 inhibitors were more likely to improve their WHO functional class (odds ratio (OR) 8.59, 95% confidence interval (CI) 3.95 to 18.72; 4 trials, 282 participants), to walk 48 metres further in 6MWD (95% CI 40 to 56; 8 trials, 880 participants), and were 22% less likely to die over a mean duration of 14 weeks (95% CI 0.07 to 0.68; 8 trials, 1119 participants) compared to placebo (high-certainty evidence). The number needed to treat to prevent one additional death was 32 participants. There was an increased risk of adverse events with PDE5 inhibitors, especially headache (OR 1.97, 95% CI 1.33 to 2.92; 5 trials, 848 participants), gastrointestinal upset (OR 1.63, 95% CI 1.07 to 2.48; 5 trials, 848 participants), flushing (OR 4.12, 95% CI 1.83 to 9.26; 3 trials, 748 participants), and muscle aches and joint pains (OR 2.52, 95% CI 1.59 to 3.99; 4 trials, 792 participants).Data comparing PDE5 inhibitors to placebo whilst on other PAH-specific therapy were limited by the small number of included trials. Those PAH participants on PDE5 inhibitors plus combination therapy walked 19.66 metres further in six minutes (95% CI 9 to 30; 4 trials, 509 participants) compared to placebo (moderate-certainty evidence). There were limited trials comparing PDE5 inhibitors directly with other PAH-specific therapy (endothelin receptor antagonists (ERAs)). Those on PDE5 inhibitors walked 49 metres further than on ERAs (95% CI 4 to 95; 2 trials, 36 participants) (low-certainty evidence). There was no evidence of a difference in WHO functional class or mortality across both treatments.Five trials compared PDE5 inhibitors to placebo in PH secondary to left-heart disease (PH-LHD). The quality of data were low due to imprecision and inconsistency across trials. In those with PH-LHD there were reduced odds of an improvement in WHO functional class using PDE5 inhibitors compared to placebo (OR 0.53, 95% CI 0.32 to 0.87; 3 trials, 285 participants), and those using PDE5 inhibitors walked 34 metres further compared to placebo (95% CI 23 to 46; 3 trials, 284 participants). There was no evidence of a difference in mortality. Five trials compared PDE5 inhibitors to placebo in PH secondary to lung disease/hypoxia, mostly in COPD. Data were of low quality due to imprecision of effect and inconsistency across trials. There was a small improvement of 27 metres in 6MWD using PDE5 inhibitors compared to placebo in those with PH due to lung disease. There was no evidence of worsening hypoxia using PDE5 inhibitors, although data were limited. Three studies compared PDE5 inhibitors to placebo or other PAH-specific therapy in chronic thromboembolic disease. There was no significant difference in any outcomes. Data quality was low due to imprecision of effect and heterogeneity across trials. AUTHORS' CONCLUSIONS: PDE5 inhibitors appear to have clear beneficial effects in group 1 PAH. Sildenafil, tadalafil and vardenafil are all efficacious in this clinical setting, and clinicians should consider the side-effect profile for each individual when choosing which PDE5 inhibitor to prescribe.While there appears to be some benefit for the use of PDE5 inhibitors in PH-left-heart disease, it is not clear based on the mostly small, short-term studies, which type of left-heart disease stands to benefit. These data suggest possible harm in valvular heart disease. There is no clear benefit for PDE5 inhibitors in pulmonary hypertension secondary to lung disease or chronic thromboembolic disease. Further research is required into the mechanisms of pulmonary hypertension secondary to left-heart disease, and cautious consideration of which subset of these patients may benefit from PDE5 inhibitors. Future trials in PH-LHD should be sufficiently powered, with long-term follow-up, and should include invasive haemodynamic data, WHO functional class, six-minute walk distance, and clinical worsening.


Assuntos
Hipertensão Pulmonar/tratamento farmacológico , Inibidores da Fosfodiesterase 5/uso terapêutico , Adulto , Criança , Antagonistas dos Receptores de Endotelina/uso terapêutico , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/mortalidade , Números Necessários para Tratar , Inibidores da Fosfodiesterase 5/efeitos adversos , Placebos/uso terapêutico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Teste de Caminhada
14.
Cochrane Database Syst Rev ; 1: CD011825, 2019 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-30656650

RESUMO

BACKGROUND: Macrolide antibiotics (macrolides) are among the most commonly prescribed antibiotics worldwide and are used for a wide range of infections. However, macrolides also expose people to the risk of adverse events. The current understanding of adverse events is mostly derived from observational studies, which are subject to bias because it is hard to distinguish events caused by antibiotics from events caused by the diseases being treated. Because adverse events are treatment-specific, rather than disease-specific, it is possible to increase the number of adverse events available for analysis by combining randomised controlled trials (RCTs) of the same treatment across different diseases. OBJECTIVES: To quantify the incidences of reported adverse events in people taking macrolide antibiotics compared to placebo for any indication. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which includes the Cochrane Acute Respiratory Infections Group Specialised Register (2018, Issue 4); MEDLINE (Ovid, from 1946 to 8 May 2018); Embase (from 2010 to 8 May 2018); CINAHL (from 1981 to 8 May 2018); LILACS (from 1982 to 8 May 2018); and Web of Science (from 1955 to 8 May 2018). We searched clinical trial registries for current and completed trials (9 May 2018) and checked the reference lists of included studies and of previous Cochrane Reviews on macrolides. SELECTION CRITERIA: We included RCTs that compared a macrolide antibiotic to placebo for any indication. We included trials using any of the four most commonly used macrolide antibiotics: azithromycin, clarithromycin, erythromycin, or roxithromycin. Macrolides could be administered by any route. Concomitant medications were permitted provided they were equally available to both treatment and comparison groups. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted and collected data. We assessed the risk of bias of all included studies and the quality of evidence for each outcome of interest. We analysed specific adverse events, deaths, and subsequent carriage of macrolide-resistant bacteria separately. The study participant was the unit of analysis for each adverse event. Any specific adverse events that occurred in 5% or more of any group were reported. We undertook a meta-analysis when three or more included studies reported a specific adverse event. MAIN RESULTS: We included 183 studies with a total of 252,886 participants (range 40 to 190,238). The indications for macrolide antibiotics varied greatly, with most studies using macrolides for the treatment or prevention of either acute respiratory tract infections, cardiovascular diseases, chronic respiratory diseases, gastrointestinal conditions, or urogynaecological problems. Most trials were conducted in secondary care settings. Azithromycin and erythromycin were more commonly studied than clarithromycin and roxithromycin.Most studies (89%) reported some adverse events or at least stated that no adverse events were observed.Gastrointestinal adverse events were the most commonly reported type of adverse event. Compared to placebo, macrolides caused more diarrhoea (odds ratio (OR) 1.70, 95% confidence interval (CI) 1.34 to 2.16; low-quality evidence); more abdominal pain (OR 1.66, 95% CI 1.22 to 2.26; low-quality evidence); and more nausea (OR 1.61, 95% CI 1.37 to 1.90; moderate-quality evidence). Vomiting (OR 1.27, 95% CI 1.04 to 1.56; moderate-quality evidence) and gastrointestinal disorders not otherwise specified (NOS) (OR 2.16, 95% CI 1.56 to 3.00; moderate-quality evidence) were also reported more often in participants taking macrolides compared to placebo.The number of additional people (absolute difference in risk) who experienced adverse events from macrolides was: gastrointestinal disorders NOS 85/1000; diarrhoea 72/1000; abdominal pain 62/1000; nausea 47/1000; and vomiting 23/1000.The number needed to treat for an additional harmful outcome (NNTH) ranged from 12 (95% CI 8 to 23) for gastrointestinal disorders NOS to 17 (9 to 47) for abdominal pain; 19 (12 to 33) for diarrhoea; 19 (13 to 30) for nausea; and 45 (22 to 295) for vomiting.There was no clear consistent difference in gastrointestinal adverse events between different types of macrolides or route of administration.Taste disturbances were reported more often by participants taking macrolide antibiotics, although there were wide confidence intervals and moderate heterogeneity (OR 4.95, 95% CI 1.64 to 14.93; I² = 46%; low-quality evidence).Compared with participants taking placebo, those taking macrolides experienced hearing loss more often, however only four studies reported this outcome (OR 1.30, 95% CI 1.00 to 1.70; I² = 0%; low-quality evidence).We did not find any evidence that macrolides caused more cardiac disorders (OR 0.87, 95% CI 0.54 to 1.40; very low-quality evidence); hepatobiliary disorders (OR 1.04, 95% CI 0.27 to 4.09; very low-quality evidence); or changes in liver enzymes (OR 1.56, 95% CI 0.73 to 3.37; very low-quality evidence) compared to placebo.We did not find any evidence that appetite loss, dizziness, headache, respiratory symptoms, blood infections, skin and soft tissue infections, itching, or rashes were reported more often by participants treated with macrolides compared to placebo.Macrolides caused less cough (OR 0.57, 95% CI 0.40 to 0.80; moderate-quality evidence) and fewer respiratory tract infections (OR 0.70, 95% CI 0.62 to 0.80; moderate-quality evidence) compared to placebo, probably because these are not adverse events, but rather characteristics of the indications for the antibiotics. Less fever (OR 0.73, 95% 0.54 to 1.00; moderate-quality evidence) was also reported by participants taking macrolides compared to placebo, although these findings were non-significant.There was no increase in mortality in participants taking macrolides compared with placebo (OR 0.96, 95% 0.87 to 1.06; I² = 11%; low-quality evidence).Only 24 studies (13%) provided useful data on macrolide-resistant bacteria. Macrolide-resistant bacteria were more commonly identified among participants immediately after exposure to the antibiotic. However, differences in resistance thereafter were inconsistent.Pharmaceutical companies supplied the trial medication or funding, or both, for 91 trials. AUTHORS' CONCLUSIONS: The macrolides as a group clearly increased rates of gastrointestinal adverse events. Most trials made at least some statement about adverse events, such as "none were observed". However, few trials clearly listed adverse events as outcomes, reported on the methods used for eliciting adverse events, or even detailed the numbers of people who experienced adverse events in both the intervention and placebo group. This was especially true for the adverse event of bacterial resistance.


Assuntos
Antibacterianos/efeitos adversos , Macrolídeos/efeitos adversos , Dor Abdominal/induzido quimicamente , Doenças dos Ductos Biliares/induzido quimicamente , Diarreia/induzido quimicamente , Perda Auditiva/induzido quimicamente , Cardiopatias/induzido quimicamente , Humanos , Macrolídeos/uso terapêutico , Náusea/induzido quimicamente , Números Necessários para Tratar , Placebos , Ensaios Clínicos Controlados Aleatórios como Assunto , Distúrbios do Paladar/induzido quimicamente , Vômito/induzido quimicamente
15.
Heart Vessels ; 34(7): 1196-1202, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30607538

RESUMO

According to current guidelines prophylactic implantable cardioverter-defibrillator (ICD) therapy is recommended in patients with significantly impaired left ventricular systolic function. However, the recently published DANISH trial did not find a significantly lower long-term rate of death from any cause compared with usual clinical care in patients with non-ischemic cardiomyopathy. We investigated whether registry data from a multi-center 'real-life' registry on patients with non-ischemic cardiomyopathy are similar to this trial. The German Device Registry (DEVICE) is a nationwide, prospective registry with one-year follow-up investigating 5451 patients receiving device implantations in 50 German centers. The present analysis of DEVICE focused on patients with non-ischemic cardiomyopathy and a left ventricular ejection fraction ≤35% who received a prophylactic ICD. Out of 779 patients with symptomatic heart failure and nonischemic cardiomyopathy, 33.1% received a single chamber ICD (VVI), while 11.0% were implanted with a dual-chamber ICD (DDD), and 55.8% received a defibrillator system for cardiac resynchronization therapy. Median follow-up was 16.1 months. 90.7% were alive at follow-up, 9.3% had died during this period. Overall mortality after one year was 5.4%. Overall mortality one year after implantation was significantly increased in patients 68 years and older(7.9%) as compared to younger patients (59-68 years: 2.5%; < 59 years: 3.8%; p < 0.015). Data from the present registry support the recently published results of the DANISH trial. In particular the influence of an increased age as proven in the DANISH trial might also play a role in the present collective. This limits the potential beneficial effect of ICD therapy in particular in the elderly population.


Assuntos
Terapia de Ressincronização Cardíaca/efeitos adversos , Cardiomiopatias/terapia , Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis/efeitos adversos , Idoso , Cardiomiopatias/mortalidade , Causas de Morte , Feminino , Alemanha/epidemiologia , Insuficiência Cardíaca , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Números Necessários para Tratar , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistema de Registros , Taxa de Sobrevida
16.
Indian Heart J ; 70(6): 911-914, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30580865

RESUMO

The recently published Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial evaluated the hypothesis that rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary prevention. In India, stable cardiovascular disease occurs in a much younger age group relative to the rest of the world. Our critical analysis of COMPASS trial showed that the younger age group appeared to derive greater benefit from the rivaroxaban+aspirin combination (relative to aspirin alone) as seen with number needed to treat metrics as compared to the older age group.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Fibrinolíticos/uso terapêutico , Medição de Risco , Prevenção Secundária/métodos , Terapia Trombolítica/métodos , Doenças Cardiovasculares/epidemiologia , Humanos , Índia/epidemiologia , Morbidade/tendências , Números Necessários para Tratar
18.
Cochrane Database Syst Rev ; 12: CD012738, 2018 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-30537022

RESUMO

BACKGROUND: There is evidence that implantable cardioverter-defibrillator (ICD) for primary prevention in people with an ischaemic cardiomyopathy improves survival rate. The evidence supporting this intervention in people with non-ischaemic cardiomyopathy is not as definitive, with the recently published DANISH trial finding no improvement in survival rate. A systematic review of all eligible studies was needed to evaluate the benefits and harms of using ICDs for primary prevention in people with non-ischaemic cardiomyopathy. OBJECTIVES: To evaluate the benefits and harms of using compared to not using ICD for primary prevention in people with non-ischaemic cardiomyopathy receiving optimal medical therapy. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and the Web of Science Core Collection on 10 October 2018. For ongoing or unpublished clinical trials, we searched the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and the ISRCTN registry. To identify economic evaluation studies, we conducted a separate search to 31 March 2015 of the NHS Economic Evaluation Database, and from March 2015 to October 2018 on MEDLINE and Embase. SELECTION CRITERIA: We included randomised controlled trials involving adults with chronic non-ischaemic cardiomyopathy due to a left ventricular systolic dysfunction with an ejection fraction of 35% or less (New York Heart Association (NYHA) type I-IV). Participants in the intervention arm should have received ICD in addition to optimal medical therapy, while those in the control arm received optimal medical therapy alone. We included studies with cardiac resynchronisation therapy when it was appropriately balanced in the experimental and control groups. DATA COLLECTION AND ANALYSIS: The primary outcomes were all-cause mortality, cardiovascular mortality, sudden cardiac death, and adverse events associated with the intervention. The secondary outcomes were non-cardiovascular death, health-related quality of life, hospitalisation for heart failure, first ICD-related hospitalisation, and cost. We abstracted the log (hazard ratio) and its variance from trial reports for time-to-event survival data. We extracted the raw data necessary to calculate the risk ratio. We summarised data on quality of life and cost-effectiveness narratively. We assessed the certainty of evidence for all outcomes using GRADE. MAIN RESULTS: We identified six eligible randomised trials with a total of 3128 participants. The use of ICD plus optimal medical therapy versus optimal medical therapy alone decreases the risk of all-cause mortality (hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.66 to 0.92; participants = 3128; studies = 6; high-certainty evidence). An average of 24 patients need to be treated with ICD to prevent one additional death from any cause (number needed to treat for an additional beneficial outcome (NNTB) = 24). Individuals younger than 65 derive more benefit than individuals older than 65 (HR 0.51, 95% CI 0.29 to 0.91; participants = 348; studies = 1) (NNTB = 10). When added to medical therapy, ICDs probably decrease cardiovascular mortality compared to not adding them (risk ratio (RR) 0.75, 95% CI 0.46 to 1.21; participants = 1781; studies = 4; moderate-certainty evidence) (possibility of both plausible benefit and no effect). Implantable cardioverter-defibrillator was also found to decrease sudden cardiac deaths (HR 0.45, 95% CI 0.29 to 0.70; participants = 1677; studies = 3; high-certainty evidence). An average of 25 patients need to be treated with an ICD to prevent one additional sudden cardiac death (NNTB = 25). We found that ICDs probably increase adverse events (possibility of both plausible harm and benefit), but likely have little or no effect on non-cardiovascular mortality (RR 1.17, 95% CI 0.81 to 1.68; participants = 1781; studies = 4; moderate-certainty evidence) (possibility of both plausible benefit and no effect). Finally, using ICD therapy probably has little or no effect on quality of life, however shocks from the device cause a deterioration in quality of life. No study reported the outcome of first ICD-related hospitalisations. AUTHORS' CONCLUSIONS: The use of ICD in addition to medical therapy in people with non-ischaemic cardiomyopathy decreases all-cause mortality and sudden cardiac deaths and probably decreases mortality from cardiovascular causes compared to medical therapy alone. Their use probably increases the risk for adverse events. However, these devices come at a high cost, and shocks from ICDs cause a deterioration in quality of life.


Assuntos
Cardiomiopatias/terapia , Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis , Cardiomiopatias/mortalidade , Causas de Morte , Desfibriladores Implantáveis/efeitos adversos , Insuficiência Cardíaca , Hospitalização , Humanos , Números Necessários para Tratar , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida
19.
Cochrane Database Syst Rev ; 11: CD012125, 2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30480764

RESUMO

BACKGROUND: Septic arthritis is an acute infection of the joints characterised by erosive disruption of the articular space. It is the most common non-degenerative articular disease in developing countries. The most vulnerable population for septic arthritis includes infants and preschoolers, especially boys. Septic arthritis disproportionately affects populations of low socioeconomic status. Systemic corticosteroids and antibiotic therapy may be beneficial for treatment of septic arthritis. Even if the joint infection is eradicated by antibiotic treatment, the inflammatory process may produce residual joint damage and sequelae. OBJECTIVES: To determine the benefits and harms of corticosteroids as adjunctive therapy in children with a diagnosis of septic arthritis. SEARCH METHODS: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library, Latin American Caribbean Health Sciences Literature (LILACS), the World Health Organization (WHO) trials portal (www.who.int/ictrp/en/), ClinicalTrials.gov (www.ClinicalTrials.gov), and Google Scholar. We searched all databases from their inception to 17 April 2018, with no restrictions on language of publication. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with patients from two months to 18 years of age with a diagnosis of septic arthritis who were receiving corticosteroids in addition to antibiotic therapy or as an adjuvant to other therapies such as surgical drainage, intra-articular puncture, arthroscopic irrigation, or debridement. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility, data extraction, and evaluation of risk of bias. We considered as major outcomes the presence of pain, activities of daily living, normal physical joint function, days of antibiotic treatment, length of hospital stay, and numbers of total and serious adverse events. We used standard methodological procedures expected by Cochrane. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created a 'Summary of findings' table. MAIN RESULTS: We included two RCTs involving a total of 149 children between three months and 18 years of age who were receiving antibiotics for septic arthritis. The most commonly affected joints were hips and knees. These studies were performed in Costa Rica and Israel. In both studies, dexamethasone administered intravenously (ranging from 0.15 to 0.2 mg/kg/dose every six to eight hours) during four days was the corticosteroid, and the comparator was placebo. Trials excluded patients with any degree of immunodeficiency or immunosuppression. The longest follow-up was one year. Trials did not report activities of daily living nor length of hospital stay. Both studies used adequate processes for randomisation, allocation concealment, and blinding, and review authors judged them to have low risk of selection and performance bias. Losses to follow-up were substantive in both studies, and we judged them to have high risk of attrition bias and of selective outcome reporting. We graded all outcomes as low quality due to concerns about study limitations and imprecision.The risk ratio (RR) for absence of pain at 12 months of follow-up was 1.33, favouring corticosteroids (95% confidence interval (CI) 1.03 to 1.72; P = 0.03; number needed to treat for an additional beneficial outcome (NNTB) = 13, 95% CI 6 to 139; absolute risk difference 24%, 95% CI 5% to 43%).The RR for normal function of the affected joint at 12 months of follow-up was 1.32, favouring corticosteroids (95% CI 1.12 to 1.57; P = 0.001; NNTB = 13, 95% CI 7 to 33; absolute risk difference 24%, 95% CI 11% to 37%).We found a reduction in the number of days of intravenous antibiotic treatment favouring corticosteroids (mean difference (MD) -2.77, 95% CI -4.16 to -1.39) based on two trials with 149 participants.Researchers did not report length of hospital stay. One trial (49 participants) reported that treatment with dexamethasone was associated with a shorter duration of IV antibiotic treatment, leading to a shorter hospital stay, and although duration of hospitalisation was a primary outcome of the study, study authors did not provide data on the duration of hospitalisation. We downgraded the quality by one level for concerns about study limitations (high risk of attrition bias and selective reporting), and by another level for imprecision.In one trial of 49 participants, researchers followed 29 children for 12 months, and parents reported that no children demonstrated adverse effects of the intervention. AUTHORS' CONCLUSIONS: Evidence for corticosteroids as adjunctive therapy in children with a diagnosis of septic arthritis is of low quality and is derived from the findings of two trials (N = 149). Corticosteroids may increase the proportion of patients without pain and the proportion of patients with normal function of the affected joint at 12 months, and may also reduce the number of days of antibiotic treatment. However, we cannot draw strong conclusions based upon these trial results. Additional randomised clinical trials in children with relevant outcomes are needed.


Assuntos
Artrite Infecciosa/tratamento farmacológico , Dexametasona/uso terapêutico , Glucocorticoides/uso terapêutico , Articulação do Quadril , Articulação do Joelho , Doença Aguda , Adolescente , Antibacterianos/uso terapêutico , Artralgia/tratamento farmacológico , Quimioterapia Adjuvante , Criança , Pré-Escolar , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Lactente , Injeções Intravenosas , Números Necessários para Tratar , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Trials ; 19(1): 606, 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30400926

RESUMO

BACKGROUND: A key step in the design of a RCT is the estimation of the number of participants needed in the study. The most common approach is to specify a target difference between the treatments for the primary outcome and then calculate the required sample size. The sample size is chosen to ensure that the trial will have a high probability (adequate statistical power) of detecting a target difference between the treatments should one exist. The sample size has many implications for the conduct and interpretation of the study. Despite the critical role that the target difference has in the design of a RCT, the way in which it is determined has received little attention. In this article, we summarise the key considerations and messages from new guidance for researchers and funders on specifying the target difference, and undertaking and reporting a RCT sample size calculation. This article on choosing the target difference for a randomised controlled trial (RCT) and undertaking and reporting the sample size calculation has been dual published in the BMJ and BMC Trials journals METHODS: The DELTA2 (Difference ELicitation in TriAls) project comprised five major components: systematic literature reviews of recent methodological developments (stage 1) and existing funder guidance (stage 2); a Delphi study (stage 3); a two-day consensus meeting bringing together researchers, funders and patient representatives (stage 4); and the preparation and dissemination of a guidance document (stage 5). RESULTS AND DISCUSSION: The key messages from the DELTA2 guidance on determining the target difference and sample size calculation for a randomised caontrolled trial are presented. Recommendations for the subsequent reporting of the sample size calculation are also provided.


Assuntos
Ensaios Clínicos Controlados Aleatórios como Assunto , Tamanho da Amostra , Técnica Delfos , Guias como Assunto , Humanos , Números Necessários para Tratar , Relatório de Pesquisa
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