Botulinum toxin for the treatment of strabismus.

BACKGROUND: The use of botulinum toxin as an investigative and treatment modality for strabismus is well reported in the medical literature. However, it is unclear how effective it is in comparison with other treatment options for strabismus. OBJECTIVES: The primary objective was to examine the efficacy of botulinum toxin therapy in the treatment of strabismus compared with alternative conservative or surgical treatment options. This review sought to ascertain those types of strabismus that particularly benefit from the use of botulinum toxin as a treatment option (such as small angle strabismus or strabismus with binocular potential, i.e. the potential to use both eyes together as a pair). The secondary objectives were to investigate the dose effect and complication rates associated with botulinum toxin. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS and three trials registers on 6 July 2022, together with reference checking to identify additional studies. We did not use any date or language restrictions in the electronic searches for trials. SELECTION CRITERIA: We planned to include randomized controlled trials (RCTs) comparing botulinum toxin with strabismus surgery, botulinum toxin alternatives (i.e. bupivacaine) and conservative therapy such as orthoptic exercises, prisms, or lens therapy for people of any age with strabismus. All relevant RCTs identified in this update compared botulinum toxin with strabismus surgery. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane and assessed the certainty of the body of evidence using GRADE. MAIN RESULTS: We included four RCTs with 242 participants that enrolled adults with esotropia or exotropia, children with acquired esotropia, and children with infantile esotropia. The follow-up period ranged from six to 36 months. Two studies were conducted in Spain, and one each in Canada and South Africa. We judged the included studies to have a mixture of low, unclear and high risk of bias. We did not consider any of the included studies to be at low risk of bias for all domains. All four studies reported the proportion of participants who improved or corrected strabismus, defined as ≤ 10 prism diopters (PD) at six months (two studies) or ≤ 8 PD at one year (two studies). Low-certainty evidence suggested that participants treated with the surgery may be more likely to improve or correct strabismus compared with those who treated with botulinum toxin (risk ratio (RR) 0.72, 95% confidence interval (CI) 0.53 to 0.99; I² = 50%; 4 studies, 242 participants; low-certainty evidence). One study, which enrolled 110 children with infantile esotropia, suggested that surgery may reduce the incidence of additional surgical intervention required, but the evidence was very uncertain (RR 3.05, 95% CI 1.34 to 6.91; 1 study, 101 participants; very low-certainty evidence). Two studies conducted in Spain compared botulinum toxin with surgery in children who required retreatment for acquired or infantile esotropia. These two studies provided low-certainty evidence that botulinum toxin may have little to no effect on achieving sensory fusion (RR 0.88, 95% CI 0.63 to 1.23; I² = 0%; 2 studies, 102 participants) and stereopsis (RR 0.86, 95% CI 0.59 to 1.25; I² = 0%; 2 studies, 102 participants) compared with surgery. Three studies reported non-serious adverse events. Partial transient ptosis (range 16.7% to 37.0%) and transient vertical deviation (range 5.6% to 18.5%) were observed among participants treated with botulinum toxin in three studies. In one study, 44.7% participants in the surgery group experienced discomfort. No studies reported serious adverse events or postintervention quality of life. AUTHORS' CONCLUSIONS: It remains unclear whether botulinum toxin may be an alternative to strabismus surgery as an independent treatment modality among certain types of strabismus because we found only low and very low-certainty evidence in this review update. Low-certainty evidence suggests that strabismus surgery may be preferable to botulinum toxin injection to improve or correct strabismus when types of strabismus and different age groups are combined. We found low-certainty evidence suggesting botulinum toxin may have little to no effect on achievement of binocular single vision compared with surgery in children with acquired or infantile esotropia. We did not find sufficient evidence to draw any meaningful conclusions with respect to need for additional surgery, quality of life, and serious adverse events. We identified three ongoing trials comparing botulinum toxin with conventional surgeries in the varying types of strabismus, whose results will provide relevant evidence for our stated objectives. Future trials should be rigorously designed, and investigators should analyze outcome data appropriately and report adequate information to provide evidence of high certainty. Quality of life and cost-effectiveness should be examined in addition to clinical and safety outcomes.

Heparin versus 0.9% sodium chloride locking for prevention of occlusion in central venous catheters in adults.

BACKGROUND: Intermittent locking of central venous catheters (CVCs) is undertaken to help maintain their patency and performance. There are systematic variations in care: some practitioners use heparin (at different concentrations), whilst others use 0.9% sodium chloride (normal saline). This review looks at the effectiveness and safety of intermittent locking with heparin compared to normal saline, to see if the evidence establishes whether one is better than the other. This is an update of an earlier Cochrane Review. OBJECTIVES: To evaluate the benefits and harms of intermittent locking of CVCs with heparin versus normal saline in adults to prevent occlusion. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 20 October 2021. SELECTION CRITERIA: We included randomised controlled trials in adults ≥ 18 years of age with a CVC that compared intermittent locking with heparin at any concentration versus normal saline. We excluded studies on infants and children from this review. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were occlusion of CVCs and duration of catheter patency. Our secondary outcomes were CVC-related bloodstream infections and CVC-related colonisation, mortality, haemorrhage, heparin-induced thrombocytopaenia, CVC-related thrombosis, number of additional CVC insertions, abnormality of coagulation profile and allergic reactions to heparin. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified one new RCT with 30 participants for this update. We included a total of 12 RCTs with 2422 participants. Data for meta-analysis were available from all RCTs. We noted differences in methods used by the included studies and variation in heparin concentrations (10 to 5000 IU/mL), time to follow-up (1 to 251.8 days), and the unit of analysis used (participant, catheter, line access). Five studies included ICU (intensive care unit) patients, two studies included oncology patients, and the remaining studies included miscellaneous patients (chronic kidney disease, haemodialysis, home care patients, etc.). Primary outcomes Overall, combined results may show fewer occlusions with heparin compared to normal saline but this is uncertain (risk ratio (RR) 0.70, 95% confidence interval (CI) 0.51 to 0.95; 10 studies; 1672 participants; low-certainty evidence). We pooled studies that used participant or catheter as the unit of analysis. We carried out subgroup analysis by unit of analysis. No clear differences were detected after testing for subgroup differences (P = 0.23). We found no clear evidence of a difference in the duration of catheter patency with heparin compared to normal saline (mean difference (MD) 0.44 days, 95% CI -0.10 to 0.99; 6 studies; 1788 participants; low-certainty evidence). Secondary outcomes We found no clear evidence of a difference in the following outcomes: CVC-related bloodstream infections (RR 0.66, 95% CI 0.08 to 5.80; 3 studies; 1127 participants; very low-certainty evidence); mortality (RR 0.76, 95% CI 0.44 to 1.31; 3 studies; 1100 participants; very low-certainty evidence); haemorrhage (RR 1.54, 95% CI 0.41 to 5.74; 3 studies; 1197 participants; very low-certainty evidence); or heparin-induced thrombocytopaenia (RR 0.21, 95% CI 0.01 to 4.27; 3 studies; 443 participants; very low-certainty evidence). The main reasons for downgrading the certainty of evidence for the primary and secondary outcomes were unclear allocation concealment, suspicion of publication bias, imprecision and inconsistency. AUTHORS' CONCLUSIONS: Given the low-certainty evidence, we are uncertain whether intermittent locking with heparin results in fewer central venous catheter occlusions than intermittent locking with normal saline in adults. Low-certainty evidence suggests that heparin may have little or no effect on catheter patency duration. Although we found no evidence of differences in safety (CVC-related bloodstream infections, mortality, or haemorrhage), the combined studies were not powered to detect rare adverse events such as heparin-induced thrombocytopaenia. Further research conducted over longer periods would reduce the current uncertainties.

A systematic review and meta-analysis of the effectiveness and adverse events of gabapentin and pregabalin for sciatica pain / Revisión sistemática y metaanálisis sobre la efectividad y eventos adversos de gabapentina y pregabalina para el dolor de ciática

Aim: This SR aims to assess the effectiveness of pregabalin and gabapentin on pain and disability caused by acute sciatica and the adverse events associated with their clinical use.DesignSystematic review.DatabasesElectronic databases of Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Clinical Trials.gov were searched from their inception until March 1st of 2021.Selection criteriaRandomized trials (RCT) with adults>18 years old with acute sciatica for a minimum of 1 week and a maximum of 1 year (at least moderate pain).Data treatmentThe outcomes were pain, disability and adverse events. Data was summarized using odds ratio and mean difference. GRADE was used to calculate the level of evidence.ResultsEight RCT involving 747 participants were included. The effect of pregabalin was assessed in 3 RCT and in one three-arm trial (pregabalin vs limaprost vs a combination of limaprost and pregabalin). Two trials assessed the effect of gabapentin compared with placebo and one compared with tramadol. One study assessed the effect of gabapentin vs pregabalin in a crossover head-to-head trial.A statistically significant improvement on leg pain at 2 weeks and leg pain with movement at 3 and 4 months was found in a RCT comparing gabapentin with placebo. There were no statistically differences on the remaining time periods assessed for leg pain, low back pain and functional disability.ConclusionsThis SR provides clear evidence for lack of effectiveness of pregabalin and gabapentin for sciatica pain management. In view of this, its routine clinical use cannot be supported.

Objetivo: Esta revisión sistemática evalúa la efectividad de pregabalina y gabapentina sobre el dolor y la discapacidad producidas por el dolor agudo causado por ciática, y los eventos adversos asociados al uso clínico.DiseñoRevisión sistemática.Bases de datosSe buscó en Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, y en Clinical Trials.gov desde su inicio hasta el 1 de marzo del 2021.Criterios de selecciónEnsayos clínicos aleatorizados (ECA) sobre adultos > 18 años con ciática aguda establecida entre una semana como mínimo y un año como máximo (al menos con dolor moderado).Tratamiento de datosLos resultados fueron dolor, discapacidad y eventos adversos. Los datos fueron resumidos usando odds ratio y diferencia de medias. Para calcular el nivel de evidencia se empleó GRADE.ResultadosSe incluyeron 8 ECA con un total de 747 participantes. El efecto de la pregabalina fue evaluado en 3 ECA y en un ensayo de 3 brazos (pregabalina vs. limaprost vs. una combinación de limaprost y pregabalina). Dos ensayos evaluaron el efecto de gabapentina comparado con placebo y uno lo comparó con tramadol. Un estudio evaluó el efecto de gabapentina vs. pregabalina en un ensayo cruzado.En un ECA se encontró una diferencia estadísticamente significativa en la mejora del dolor de piernas a las 2 semanas y en el dolor de piernas con el movimiento a los 3 y 4 meses, con gabapentina comparado frente a placebo. No hubo diferencias en el resto de los periodos estudiados para el dolor de piernas, dolor en la zona lumbar o en la discapacidad funcional.ConclusionesEsta revisión sistemática ofrece evidencia clara de la falta de pruebas sobre la efectividad de pregabalina o gabapentina para el manejo del dolor derivado de la ciática. Por tanto, su uso clínico rutinario no está avalado.

A systematic review and meta-analysis of the effectiveness and adverse events of gabapentin and pregabalin for sciatica pain.

AIM: This SR aims to assess the effectiveness of pregabalin and gabapentin on pain and disability caused by acute sciatica and the adverse events associated with their clinical use. DESIGN: Systematic review. DATABASES: Electronic databases of Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Clinical Trials.gov were searched from their inception until March 1st of 2021. SELECTION CRITERIA: Randomized trials (RCT) with adults>18 years old with acute sciatica for a minimum of 1 week and a maximum of 1 year (at least moderate pain). DATA TREATMENT: The outcomes were pain, disability and adverse events. Data was summarized using odds ratio and mean difference. GRADE was used to calculate the level of evidence. RESULTS: Eight RCT involving 747 participants were included. The effect of pregabalin was assessed in 3 RCT and in one three-arm trial (pregabalin vs limaprost vs a combination of limaprost and pregabalin). Two trials assessed the effect of gabapentin compared with placebo and one compared with tramadol. One study assessed the effect of gabapentin vs pregabalin in a crossover head-to-head trial. A statistically significant improvement on leg pain at 2 weeks and leg pain with movement at 3 and 4 months was found in a RCT comparing gabapentin with placebo. There were no statistically differences on the remaining time periods assessed for leg pain, low back pain and functional disability. CONCLUSIONS: This SR provides clear evidence for lack of effectiveness of pregabalin and gabapentin for sciatica pain management. In view of this, its routine clinical use cannot be supported.

Design of 1-year mortality forecast at hospital admission: A machine learning approach.

Palliative care is referred to a set of programs for patients that suffer life-limiting illnesses. These programs aim to maximize the quality of life (QoL) for the last stage of life. They are currently based on clinical evaluation of the risk of 1-year mortality. The main aim of this work is to develop and validate machine-learning-based models to predict the exitus of a patient within the next year using data gathered at hospital admission. Five machine-learning techniques were applied using a retrospective dataset. The evaluation was performed with five metrics computed by a resampling strategy: Accuracy, the area under the ROC curve, Specificity, Sensitivity, and the Balanced Error Rate. All models reported an AUC ROC from 0.857 to 0.91. Specifically, Gradient Boosting Classifier was the best model, producing an AUC ROC of 0.91, a sensitivity of 0.858, a specificity of 0.808, and a BER of 0.1687. Information from standard procedures at hospital admission combined with machine learning techniques produced models with competitive discriminative power. Our models reach the best results reported in the state of the art. These results demonstrate that they can be used as an accurate data-driven palliative care criteria inclusion.

Conocimiento y valoración de las voluntades anticipadas del personal sanitario de unidades de hospitalización a domicilio, oncología médica, hospitales de día y servicios de urgencias / Knowledge and assessment of living wills by health professionals at home hospitalization units, medical oncology departments, daytime hospital services and emergency romos

OBJETIVO: Describir el conocimiento del personal sanitario de servicios implicados en el manejo de enfermos paliativos en situación avanzada, sobre el Documento de Voluntades Anticipadas (DVA) y su Registro Nacional. Conocer cómo valoran su uso y si lo consultan habitualmente. MATERIAL Y MÉTODO: Estudio multicéntrico, transversal descriptivo, mediante cuestionario anónimo cumplimentado por personal médico y de enfermería en tres centros hospitalarios. Se recogieron un total de 160 cuestionarios correspondientes a 58 médicos y 102 enfermeros, pertenecientes a Servicios de Urgencias (SU), Oncología, Unidades de Hospitalización a Domicilio (HaD) y Hospital de Día. El cuestionario constaba de 14 preguntas tipo test de respuesta única, además de las variables demográficas y laborales pertinentes para el estudio. RESULTADOS: Las medias de edad de la muestra fueron de 42 ± 9 años, y la experiencia profesional de 17 ± 9,3 años. El 83,1 % de los encuestados afirmaron conocer el DVA y el 53,7 % que sabrían cumplimentarlo, pero solo un 8,1 % de ellos contestaron correctamente a la pregunta de dónde localizar dicho documento. El 92,5 % de los encuestados no lo consultan nunca. Los dos encuestados que afirmaban consultarlo habitualmente, no supieron localizarlo. CONCLUSIONES: Existe un desconocimiento generalizado del DVA, siendo este independiente tanto de la categoría profesional como de los años de experiencia o del servicio en el que se trabaja. Incluso en los casos que dicen conocerlo, sus respuestas no corroboran tal afirmación

OBJECTIVE: To describe the knowledge healthcare providers at the units involved in the management of advanced palliatiave care patients have of the advance directives document (ADD). To find out how do they value its use, and whether they check it out regularly. MATERIAL AND METHODS: A multicenter, cross-sectional, descriptive study using an anonymous questionnaire to be completed by doctors and nurses in three hospitals. A total of 160 questionnaires were collected from 58 doctors and 102 nurses working at emergency rooms (ERs), oncology departments, home hospitalization units (HHUs), and day hospital services. Questionnaires included 14 multiple choice questions with only one valid option, and also collected the demographic and labor variables required by the study. RESULTS: Mean age in the sample was 42 ± 9 years, and professional experience was 17 ± 9.3 years. Among responders, 83.1 % claimed knowledge of the ADD, and 53.7 % said they could complete it, but only 8.1 % knew where to find it; 92.5 % of respondents never consult it. The two respondents who claimed they usually checked it out were eventually unable to locate it. CONCLUSIONS: Lack of knowledge about ADDs and their related National Registry is widespread, and occurs regardless of professional category or years of experience. Even in providers who claim awareness of this document the answers provided belie it

Heparin versus 0.9% sodium chloride locking for prevention of occlusion in central venous catheters in adults.

BACKGROUND: Intermittent locking of central venous catheters (CVCs) is undertaken to help maintain their patency. There are systematic variations in care: some practitioners use heparin (at different concentrations), whilst others use 0.9% NaCl (normal saline). This review looks at the effectiveness and safety of intermittent locking with heparin compared to 0.9% NaCl to see if the evidence establishes whether one is better than the other. This work is an update of a review first published in 2014. OBJECTIVES: To assess the effectiveness and safety of intermittent locking of CVCs with heparin versus normal saline (NS) in adults to prevent occlusion. SEARCH METHODS: The Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (last searched 11 June 2018) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 5). Searches were also carried out in MEDLINE, Embase, CINAHL, and clinical trials databases (11 June 2018). SELECTION CRITERIA: We included randomised controlled trials in adults ≥ 18 years of age with a CVC that compared intermittent locking with heparin at any concentration versus NS. We applied no restriction on language. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed quality, and extracted data. We contacted trial authors to retrieve additional information, when necessary. We carried out statistical analysis using Review Manager 5 and assessed the overall quality of the evidence supporting assessed outcomes using GRADE. We carried out prespecified subgroup analysis. MAIN RESULTS: We identified five new studies for this update (six prior studies were included in the original review), bringing the number of eligible studies to 11, with a total of 2392 participants. We noted differences in methods used by the included studies and variation in heparin concentrations (10 to 5000 IU/mL), time to follow-up (1 to 251.8 days), and the unit of analysis used (participant, catheter, line access).Combined results from these studies showed fewer occlusions with heparin than with NS (risk ratio (RR) 0.70, 95% confidence interval (CI) 0.51 to 0.95; P = 0.02; 1672 participants; 1025 catheters from 10 studies; I² = 14%) and provided very low-quality evidence.We carried out subgroup analysis by unit of analysis (testing for subgroup differences (P = 0.23; I² = 30.3%). When the unit of analysis was the participant, results show no clear differences in all occlusions between heparin and NS (RR 0.79, 95% CI 0.58 to 1.08; P = 0.15; 1672 participants; seven studies). Subgroup analysis using the catheter as the unit of analysis shows fewer occlusions with heparin use (RR 0.53, 95% CI 0.29 to 0.95; P = 0.03; 1025 catheters; three studies). When the unit of analysis was line access, results show no clear differences in occlusions between heparin and NS (RR 1.08, 95% CI 0.84 to 1.40; 770 line accesses; one study).We found no clear differences in the duration of catheter patency (mean difference (MD) 0.44 days, 95% CI -0.10 to 0.99; P = 0.11; 1036 participants; 752 catheters; six studies; low-quality evidence).We found no clear evidence of a difference in the following: CVC-related sepsis (RR 0.74, 95% CI 0.03 to 19.54; P = 0.86; 1097 participants; two studies; low-quality evidence); mortality (RR 0.76, 95% CI 0.44 to 1.31; P = 0.33; 1100 participants; three studies; low-quality evidence); haemorrhage at any site (RR 1.32, 95% CI 0.57 to 3.07; P = 0.52; 1245 participants; four studies; moderate-quality evidence); or heparin-induced thrombocytopaenia (RR 0.21, 95% CI 0.01 to 4.27; P = 0.31; 443 participants; three studies; low-quality evidence).The main reasons for downgrading the quality of evidence were unclear allocation concealment, imprecision, and suspicion of publication bias. AUTHORS' CONCLUSIONS: Given the very low quality of the evidence, we are uncertain whether intermittent locking with heparin results in fewer occlusions than intermittent locking with NS. Low-quality evidence suggests that heparin may have little or no effect on catheter patency. Although we found no evidence of differences in safety (sepsis, mortality, or haemorrhage), the combined trials are not powered to detect rare adverse events such as heparin-induced thrombocytopaenia.

Megestrol acetate for cachexia-anorexia syndrome. A systematic review.

In 1993, megestrol acetate (MA) was approved by the US Food and Drug Administration for the treatment of anorexia, cachexia, or unexplained weight loss in patients with acquired immunodeficiency syndrome. The mechanism by which MA increases appetite is unknown, and its effectiveness for anorexia and cachexia in neoplastic, elderly, and acquired immunodeficiency syndrome patients is under investigation. This is an updated version of a Cochrane systematic review first published in 2005 and later updated in 2013 entitled 'Megestrol acetate for the treatment of anorexia-cachexia syndrome'. MA vs. placebo: in studies where MA was compared with placebo, the overall results showed that MA patients gained weight (mean difference, MD 2.25 kg, 95% CI [1.19, 3.3]) but did not gain quality of life (QOL) (standarized mean difference, SMD 0.5, 95% CI [-0.13, 1.13]), with more adverse events (relative risk, RR 1.46, 95% CI [1.05, 2.04]), but no difference in deaths (RR 1.26, 95% CI [0.70, 2.27]). MA vs. no treatment: MA patients gained weight (MD 1.45 kg, 95% CI [0.15, 2.75]) but did not gain QOL (standardized mean difference 3.89 95% CI [-14, 6.28]). There was no increase in adverse events (RR 0.90, 95% CI [0.39, 2.08]) or deaths (RR 1.01, 95% CI [0.42, 2.45]). MA vs. active drugs: MA patients gained weight (MD 2.5 kg, 95% CI [0.37, 4.64]) but did not gain QOL (MD 0.20 95% CI [-0.02, 0.43]) and did not report an increase in adverse events (RR 1.05 95% CI [0.95, 1.16]) or in deaths (RR 1.53, 95% CI [1.02, 2.29]) Different doses of MA: in studies where lower doses of MA were compared with higher doses of MA, we did not find differences either in weight gain (MD -0.94 kg, 95% CI [-3.33, 1.45]), QOL (MD 0.31 95% CI [-0.19, 0.81]), or adverse events (RR 1.34, 95% CI [0.65, 2.76]). Thus, we cannot reach a conclusion for an optimal dose of MA.

Certolizumab pegol (CDP870) for rheumatoid arthritis in adults.

BACKGROUND: Tumour necrosis factor (TNF)-alpha inhibitors are beneficial for the treatment of rheumatoid arthritis (RA) for reducing the risk of joint damage, improving physical function and improving the quality of life. This review is an update of the 2014 Cochrane Review of the treatment of RA with certolizumab pegol. OBJECTIVES: To assess the clinical benefits and harms of certolizumab pegol (CZP) in people with RA who have not responded well to conventional disease-modifying anti-rheumatic drugs (DMARDs). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL: Cochrane Library 2016, Issue 9), MEDLINE, Embase, Web of Knowledge, reference lists of articles, clinicaltrials.gov and ICTRP of WHO. The searches were updated from 2014 (date of the last search for the previous version) to 26 September 2016. SELECTION CRITERIA: Randomised controlled trials that compared certolizumab pegol with any other agent, including placebo or methotrexate (MTX), in adults with active RA, regardless of current or prior treatment with conventional disease-modifying anti-rheumatic drugs (DMARDs), such as MTX. DATA COLLECTION AND ANALYSIS: Two review authors independently checked search results, extracted data and assessed trial quality. We resolved disagreements by discussion or referral to a third review author. MAIN RESULTS: We included 14 trials in this update, three more than previously. Twelve trials (5422 participants) included measures of benefit. We pooled 11 of them, two more than previously. Thirteen trials included information on harms, (5273 participants). The duration of follow-up varied from 12 to 52 weeks and the range of doses of certolizumab pegol varied from 50 to 400 mg given subcutaneously. In Phase III trials, the comparator was placebo plus MTX in seven trials and placebo in five. In the two Phase II trials the comparator was only placebo.The approved dose of certolizumab pegol, 200 mg every other week, produced clinically important improvements at 24 weeks for the following outcomes:- American College of Rheumatology (ACR) 50% improvement (pain, function and other symptoms of RA): 25% absolute improvement (95% confidence interval (CI) 20% to 33%); number need to treat for an additional beneficial outcome (NNTB) of 4 (95% CI 3 to 5); risk ratio (RR) 3.80 (95% CI 2.42 to 5.95), 1445 participants, 5 studies.- The Health Assessment Questionnaire (HAQ): -12% absolute improvement (95% CI -9% to -14%); NNTB of 8 (95% CI 7 to 11); mean difference (MD) - 0.35 (95% CI -0.43 to -0.26; 1268 participants, 4 studies) (scale 0 to 3; lower scores mean better function).- Proportion of participants achieving remission (Disease Activity Score (DAS) < 2.6) absolute improvement 10% (95% CI 8% to 16%); NNTB of 8 (95% CI 6 to 12); risk ratio (RR) 2.94 (95% CI 1.64 to 5.28), 2420 participants, six studies.- Radiological changes: erosion score (ES) absolute improvement -0.29% (95% CI -0.42% to -0.17%); NNTB of 6 (95% CI 4 to 10); MD -0.67 (95% CI -0.96 to -0.38); 714 participants, two studies (scale 0 to 230), but not a clinically important difference.-Serious adverse events (SAEs) were statistically but not clinically significantly more frequent for certolizumab pegol (200 mg every other week) with an absolute rate difference of 3% (95% CI 1% to 4%); number needed to treat for an additional harmful outcome (NNTH) of 33 (95% CI 25 to 100); Peto odds ratio (OR) 1.47 (95% CI 1.13 to 1.91); 3927 participants, nine studies.There was a clinically significant increase in all withdrawals in the placebo groups (for all doses and at all follow-ups) with an absolute rate difference of -29% (95% CI -16% to -42%), NNTH of 3 (95% CI 2 to 6), RR 0.47 (95% CI 0.39 to 0.56); and there was a clinically significant increase in withdrawals due to adverse events in the certolizumab groups (for all doses and at all follow-ups) with an absolute rate difference of 2% (95% CI 0% to 3%); NNTH of 58 (95% CI 28 to 329); Peto OR 1.45 (95% CI 1.09 to 1.94) 5236 participants Twelve studies.We judged the quality of evidence to be high for ACR50, DAS remission, SAEs and withdrawals due to adverse events, and moderate for HAQ and radiological changes, due to concerns about attrition bias. For all withdrawals we judged the quality of evidence to be moderate, due to inconsistency. AUTHORS' CONCLUSIONS: The results and conclusions did not change from the previous review. There is a moderate to high certainty of evidence from randomised controlled trials that certolizumab pegol, alone or combined with methotrexate, is beneficial in the treatment of RA for improved ACR50 and health-related quality of life, an increased chance of remission of RA, and reduced joint damage as seen on x-ray. Fewer people stopped taking their treatment, but most of these who did stopped due to serious adverse events. Adverse events were more frequent with active treatment. We found a clinically but not statistically significant risk of serious adverse events.

Heparin versus 0.9% sodium chloride intermittent flushing for prevention of occlusion in central venous catheters in adults.

BACKGROUND: Heparin intermittent flushing is a standard practice in the maintenance of patency in central venous catheters. However, we could find no systematic review examining its effectiveness and safety. OBJECTIVES: To assess the effectiveness of intermittent flushing with heparin versus 0.9% sodium chloride (normal saline) solution in adults with central venous catheters in terms of prevention of occlusion and overall benefits versus harms. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched December 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 11). Searches were also carried out in MEDLINE, EMBASE, CINAHL and clinical trials databases (December 2013). SELECTION CRITERIA: Randomised controlled trials (RCTs) in adults 18 years of age and older with a central venous catheter (CVC) in which intermittent flushing with heparin (any dose with or without other drugs) was compared with 0.9% normal saline were included. No restriction on language was applied. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed trial quality and extracted data. Trial authors were contacted to retrieve additional information, when necessary. MAIN RESULTS: Six eligible studies with a total of 1433 participants were included. The heparin concentrations used in these studies were very different (10-5000 IU/mL), and follow-up varied from 20 days to 180 days. The overall risk of bias in the studies was low. The quality of the evidence ranged from very low to moderate for the main outcomes (occlusion of CVC, duration of catheter patency, CVC-related sepsis, mortality and haemorrhage at any site).Combined findings from three trials in which the unit of analysis was the catheter suggest that heparin was associated with reduced CVC occlusion rates (risk ratio (RR) 0.53, 95% confidence interval (CI) 0.29 to 0.94). However, no clear evidence of a similar effect was found when the results of two studies in which the unit of analysis was the participant were combined (RR 0.21, 95% CI 0.03 to 1.70), nor when findings were derived from one study, which considered total line accesses (RR 1.08, 95% CI 0.84 to 1.40). Furthermore, results for other estimated effects were found to be imprecise and compatible with benefit and harm: catheter duration in days (mean difference (MD) 0.41, 95% CI -1.29 to 2.12), CVC-related thrombosis (RR 1.22, 95% CI 0.74 to 1.99), CVC-related sepsis (RR 1.02, 95% CI 0.34 to 3.03), mortality (RR 0.77, 95% CI 0.45 to 1.32) and haemorrhage at any site (RR 1.37, 95% CI 0.49 to 3.85). AUTHORS' CONCLUSIONS: We found no conclusive evidence of important differences when heparin intermittent flushing was compared with 0.9% normal saline flushing for central venous catheter maintenance in terms of efficacy or safety. As heparin is more expensive than normal saline, our findings challenge its continued use in CVC flushing outside the context of clinical trials.

Certolizumab pegol (CDP870) for rheumatoid arthritis in adults.

BACKGROUND: Tumour necrosis factor (TNF)-alpha inhibitors are beneficial for the treatment of rheumatoid arthritis (RA) in terms of reducing the risk of joint damage, improving physical function and improving quality of life. This Cochrane review is an update of a review of the treatment of RA with certolizumab pegol that was first published in 2011. OBJECTIVES: To assess the clinical benefits and harms of certolizumab pegol (CDP870) in patients with RA who have not responded well to conventional disease-modifying anti-rheumatic drugs (DMARDs). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2014, Issue 5), MEDLINE, EMBASE, Scopus, TOXLINE, Web of Knowledge; websites of the US Food and Drug Administration (FDA) and European Medicines Evaluation Agency (EMEA); reference lists of articles; and searched http/clinicaltrials.gov. The searches were updated from 2009 (date of last search for the original review) to 5 June 2014. SELECTION CRITERIA: Randomised controlled trials that compared certolizumab pegol with any other agent including placebo or methotrexate (MTX) in adult patients with active RA despite current or prior treatment with conventional disease-modifying anti-rheumatic drugs (DMARDs), such as MTX. DATA COLLECTION AND ANALYSIS: Two authors independently assessed search results, trial quality and extracted data. Disagreements were resolved by discussion or referral to a third author. MAIN RESULTS: Eleven trials were included in this update. Ten (4324 patients) were included in the pooled analysis for benefits, five more than previously, and 10 (3711 patients) in the pooled analysis for harms, four more trials (1930 patients) than previously. The duration of follow-up varied from 12 to 52 weeks and the range of doses of certolizumab pegol varied from 50 to 400 mg given subcutaneously (sc). In phase III trials, the control was placebo plus MTX in five trials and placebo in four trials. The risk of bias of the included studies was assessed as low but there may have been a risk of attrition bias.Statistically significant improvements were observed at 24 weeks with the approved dose of 200 mg certolizumab pegol every other week, in 1) American College of Rheumatology (ACR) 50% improvement: 27% absolute improvement (95% CI 20% to 33%), NNT of 4 (95% CI 3 to 8), risk ratio (RR) 3.80 (95% CI 2.42 to 5.95); 2) the Health Assessment Questionnaire (HAQ): -12% absolute improvement (95% CI -9% to -14%), NNT of 6 (95% CI 5 to 8), mean difference (MD) - 0.35 (95% CI -0.43 to -0.26) (scale 0 to 3); 3) Disease Activity Score (DAS) remission improvement: absolute improvement 11% (95% CI 8% to 15%), NNT of 9 (95% CI 4 to 20), RR 8.47 (95% CI 4.15-17.28); and 4) radiological changes: erosion score (ES) absolute improvement -0.29% (95% CI -0.42% to -0.17%), NNT of 6 (95% CI 4 to 10), MD -0.67 (95% CI -0.96 to -0.38) (scale 0 to 230). Serious adverse events were statistically significantly more frequent for certolizumab pegol (200 mg every other week) with an absolute rate difference of 4% (95% CI 2% to 6%), NNTH of 32 (95% CI 17 to 88), Peto odds ratio (OR) 1.77 (95% CI 1.27 to 2.46). There was a statistically significant increase in all withdrawals in the placebo groups (for all doses and all follow-ups) with an absolute rate difference of -34% (95% CI -18% to -50%), NNTH of 4 (95% CI 3 to 5), NNTH of 4 (95% CI 3 to 5), RR 0.42 (95% CI 0.36 to 0.50); and there was a statistically significant increase in all withdrawals due to adverse events in the certolizumab groups (for all doses and all follow-up) with an absolute rate difference of 2% (95% CI 1% to 3%), NNTH of 55 (95% CI 27 to 238), Peto OR 1.66 (95% CI 1.15 to 2.37).The risk of bias was low and the quality of evidence was downgraded to moderate because of high rates of dropouts (> 20%) in most of the trials. We did not find any problems with inconsistency, indirectness, imprecision or publication bias. AUTHORS' CONCLUSIONS: The results and conclusions did not change from the previous review. There is moderate-level evidence from randomised controlled trials that certolizumab pegol alone or combined with methotrexate is beneficial in the treatment of RA. Adverse events were more frequent with active treatment. We found a potential risk of serious adverse events.

Megestrol acetate for treatment of anorexia-cachexia syndrome.

BACKGROUND: This is an updated version of a previously published review in The Cochrane Library (2005, Issue 2) on 'Megestrol acetate for the treatment of anorexia-cachexia syndrome'. Megestrol acetate (MA) is currently used to improve appetite and to increase weight in cancer-associated anorexia. In 1993, MA was approved by the US Food and Drug Administration for the treatment of anorexia, cachexia or unexplained weight loss in patients with AIDS. The mechanism by which MA increases appetite is unknown and its effectiveness for anorexia and cachexia in neoplastic and AIDS (acquired immunodeficiency syndrome) patients is under investigation. OBJECTIVES: To evaluate the efficacy, effectiveness and safety of MA in palliating anorexia-cachexia syndrome in patients with cancer, AIDS and other underlying pathologies. SEARCH METHODS: We sought studies through an extensive search of electronic databases, journals, reference lists, contact with investigators and other search strategies outlined in the methods. The most recent search for this update was carried out in May 2012. SELECTION CRITERIA: Studies were included in the review if they assessed MA compared to placebo or other drug treatments in randomised controlled trials of patients with a clinical diagnosis of anorexia-cachexia syndrome related to cancer, AIDS or any other underlying pathology. DATA COLLECTION AND ANALYSIS: Two independent review authors conducted data extraction and evaluated methodological quality. We performed quantitative analyses using appetite and quality of life as a dichotomous variable, and analysed weight gain as continuous and dichotomous variables. MAIN RESULTS: We included 35 trials in this update, the same number but not the same trials as in the previous version of the review. The trials comprised 3963 patients for effectiveness and 3180 for safety. Sixteen trials compared MA at different doses with placebo, seven trials compared different doses of MA with other drug treatments and 10 trials compared different doses of MA. Meta-analysis showed a benefit of MA compared with placebo, particularly with regard to appetite improvement and weight gain in cancer, AIDS and other underlying conditions, and lack of benefit in the same patients when MA was compared to other drugs. There was insufficient information to define the optimal dose of MA, but higher doses were more related to weight improvement than lower doses. Quality of life improvement in patients was seen only when comparing MA versus placebo but not other drugs in both subcategories: cancer and AIDS. Oedema, thromboembolic phenomena and deaths were more frequent in the patients treated with MA. More than 40 side effects were studied. AUTHORS' CONCLUSIONS: This review shows that MA improves appetite and is associated with slight weight gain in cancer, AIDS and in patients with other underlying pathology. Despite the fact that these patients are receiving palliative care they should be informed of the risks involved in taking MA.

Riesgo de neumonía en pacientes con enfermedad pulmonar obstructiva crónica estable en tratamiento con terapia inhalada con glucocorticoides / Risk of pneumonia with inhaled corticosteroids for stable chronic obstructive pulmonary disease patients

Fundamento y objetivo: El uso de los corticoides inhalados se asocia a neumonías e infecciones agudas respiratorias. El objetivo de esta revisión es cuantificar el efecto sobre las neumonías en enfermos con enfermedad pulmonar obstructiva crónica (EPOC) estable.Material y método: Revisión sistemática de las revisiones sistemáticas existentes que analizan este efecto adverso.Resultados: El número de tratamientos necesarios para dañar (NNTH) de las diferentes revisiones sistemáticas oscila desde 12, en sujetos expuestos a más de tres años, hasta 80 en sujetos con un año de seguimiento. Budesonida parece no verse afectada por este efecto secundario. Conclusión: Sería aconsejable informar al paciente sobre el riesgo/beneficio de estas terapias tan habituales (AU)

Background and objective: Treatment with inhaled steroids is related to pneumonia and acute respiratory infection. The aim of this review is to quantify the effect inhaled steroids in pneumonia in stable chronic obstructive pulmonary disease (COPD) patients.Material and method: We performed a systematic review of the systematic reviews that have studied inhaled corticosteroids in stable COPD patients. Results: Inhaled steroid therapy in patients with clinically stable COPD causes an increase in the number of pneumonia. The NNTH of the analysed systematic reviews ranged from 12 subjects exposed to more than three years, to 80 subjects with one year follow up. Budesonide did not show this side effect. Conclusion: It would be advisable to inform patients about the risk/benefit of these therapies (AU)

Fentanilo transmucoso oral y dolor irruptivo en cáncer / Oral transmucosal fentanyl and breakthrough cancer pain

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[Risk of pneumonia with inhaled corticosteroids for stable chronic obstructive pulmonary disease patients]. / Riesgo de neumonía en pacientes con enfermedad pulmonar obstructiva crónica estable en tratamiento con terapia inhalada con glucocorticoides.

BACKGROUND AND OBJECTIVE: Treatment with inhaled steroids is related to pneumonia and acute respiratory infection. The aim of this review is to quantify the effect inhaled steroids in pneumonia in stable chronic obstructive pulmonary disease (COPD) patients. MATERIAL AND METHOD: We performed a systematic review of the systematic reviews that have studied inhaled corticosteroids in stable COPD patients. RESULTS: Inhaled steroid therapy in patients with clinically stable COPD causes an increase in the number of pneumonia. The NNTH of the analysed systematic reviews ranged from 12 subjects exposed to more than three years, to 80 subjects with one year follow up. Budesonide did not show this side effect. CONCLUSION: It would be advisable to inform patients about the risk/benefit of these therapies.

Certolizumab pegol (CDP870) for rheumatoid arthritis in adults.

BACKGROUND: TNF-alpha inhibitors have been shown to reduce the risk of joint damage and improve physical function and quality of life in people with rheumatoid arthritis (RA). This is the first Cochrane review of certolizumab pegol, a new TNF-alpha inhibitor. OBJECTIVES: To assess the effectiveness and safety of certolizumab pegol (CDP870) in patients with RA who have not responded well to conventional disease modifying anti-rheumatic drugs (DMARDs). SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 3),  MEDLINE (1966 to November 2009), EMBASE (1966 to November 2009), Scopus (January 2004 to November 2009), TOXLINE (until November 2009), Web of Knowledge (until November 2009); websites of the US Food and Drug Administration (FDA) and European Medicines Evaluation Agency (EMEA) (until November 2009), and reference lists of articles. SELECTION CRITERIA: Randomised controlled trials that compared certolizumab pegol with any other agent including placebo or methotrexate (MTX) in adult RA patients with active rheumatoid arthritis despite current or prior treatment with conventional DMARDs, such as methotrexate (MTX). DATA COLLECTION AND ANALYSIS: Two authors independently assessed search results, trial quality and extracted data. MAIN RESULTS: Five trials were included. We included in the analysis 2394 people for effectiveness and 2094 people for safety. The duration of follow-up was from 12 to 52 weeks, and the range of doses of certolizumab pegol were from 50 to 400 mg subcutaneously (sc). In three trials the control was placebo plus methotrexate (MTX) and in two trials it was just placebo. Significant improvements were observed at 24 weeks with the approved dose of 200 mg certolizumab pegol: American College of Rheumatology (ACR) 50% improvement: risk ratio (RR) 6.01 (95% CI 3.84 to 9.40) with an absolute benefit of 29% (95% CI 25% to 34%), number needed to treat to benefit (NNTB) of 4 (3 to 5) and the Health Assessment Questionnaire (HAQ) mean difference (MD) - 0.39 (95% CI -0.45 to -0.32) (scale 0 to 3). At 52 weeks the results were quite similar: ACR 50% improvement RR 5.27 (95% CI 3.19 to 8.71), HAQ mean difference (MD) - 0.42 (95% CI -0.52 to -0.32). Serious adverse events were more frequent for certolizumab pegol 200 mg, Peto OR 2.02 (95% CI 1.24 to 3.30). The most common adverse events with certolizumab pegol 200 mg were: upper respiratory tract infections, Peto OR 2.21 (95% CI 1.15 to 4.25); hypertension, Peto OR 2.81 (95% CI 1.38 to 5.75); and nasopharyngitis, Peto OR 2.71 (95% CI 1.30 to 5.66). AUTHORS' CONCLUSIONS: With an overall high grade of evidence this review revealed an improvement of clinical results (ACR50, 28 joint disease activity score (DAS-28) remission and HAQ scores) with certolizumab pegol. Adverse events were more frequent with certolizumab; there was a statistically significant increase in the number of serious adverse events, infections and hypertension.

Clubes de lectura en el siglo xxi / Journal club sat XXIth century

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