Cánulas nasales de alto flujo para la asistencia respiratoria en pacientes adultos de cuidados intensivos / High-flow nasal cannulae for respiratory support in adult intensive care patient

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From proband to provider: is there an obligation to inform genetic relatives of actionable risks discovered through direct-to-consumer genetic testing?

Direct-to-consumer genetic testing is a growing phenomenon, fuelled by the notion that knowledge equals control. One ethical question that arises concerns the proband's duty to share information indicating genetic risks in their relatives. However, such duties are unenforceable and may result in the realisation of anticipated harm to relatives. We argue for a shift in responsibility from proband to provider, placing a duty on test providers in the event of identified actionable risks to relatives. Starting from Parker and Lucassen's (2004) 'joint account model', we adapt Kilbride's (2018) application of the rule of rescue and balance it against the relative's right not to know, placing responsibility on the providers of direct-to-consumer genetic testing. Where the risk of disease to a relative is actionable, we argue providers ought to share results even in the face of the proband's objections. Confidentiality issues are navigated by a pre-emptive consent model, whereby consumers agree to the sharing of certain information with their relatives ahead of testing and as a condition of testing. When a relative is informed, the proband's privacy is protected by maximal deidentification, and the rights of the relative are met by a stepwise approach to informing that allows them to decide how much information they receive.

High-flow nasal cannulae for respiratory support in adult intensive care patients.

BACKGROUND: High-flow nasal cannulae (HFNC) deliver high flows of blended humidified air and oxygen via wide-bore nasal cannulae and may be useful in providing respiratory support for adults experiencing acute respiratory failure, or at risk of acute respiratory failure, in the intensive care unit (ICU). This is an update of an earlier version of the review. OBJECTIVES: To assess the effectiveness of HFNC compared to standard oxygen therapy, or non-invasive ventilation (NIV) or non-invasive positive pressure ventilation (NIPPV), for respiratory support in adults in the ICU. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, Web of Science, and the Cochrane COVID-19 Register (17 April 2020), clinical trial registers (6 April 2020) and conducted forward and backward citation searches. SELECTION CRITERIA: We included randomized controlled studies (RCTs) with a parallel-group or cross-over design comparing HFNC use versus other types of non-invasive respiratory support (standard oxygen therapy via nasal cannulae or mask; or NIV or NIPPV which included continuous positive airway pressure and bilevel positive airway pressure) in adults admitted to the ICU. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by Cochrane. MAIN RESULTS: We included 31 studies (22 parallel-group and nine cross-over designs) with 5136 participants; this update included 20 new studies. Twenty-one studies compared HFNC with standard oxygen therapy, and 13 compared HFNC with NIV or NIPPV; three studies included both comparisons. We found 51 ongoing studies (estimated 12,807 participants), and 19 studies awaiting classification for which we could not ascertain study eligibility information. In 18 studies, treatment was initiated after extubation. In the remaining studies, participants were not previously mechanically ventilated. HFNC versus standard oxygen therapy HFNC may lead to less treatment failure as indicated by escalation to alternative types of oxygen therapy (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.45 to 0.86; 15 studies, 3044 participants; low-certainty evidence). HFNC probably makes little or no difference in mortality when compared with standard oxygen therapy (RR 0.96, 95% CI 0.82 to 1.11; 11 studies, 2673 participants; moderate-certainty evidence). HFNC probably results in little or no difference to cases of pneumonia (RR 0.72, 95% CI 0.48 to 1.09; 4 studies, 1057 participants; moderate-certainty evidence), and we were uncertain of its effect on nasal mucosa or skin trauma (RR 3.66, 95% CI 0.43 to 31.48; 2 studies, 617 participants; very low-certainty evidence). We found low-certainty evidence that HFNC may make little or no difference to the length of ICU stay according to the type of respiratory support used (MD 0.12 days, 95% CI -0.03 to 0.27; 7 studies, 1014 participants). We are uncertain whether HFNC made any difference to the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) within 24 hours of treatment (MD 10.34 mmHg, 95% CI -17.31 to 38; 5 studies, 600 participants; very low-certainty evidence). We are uncertain whether HFNC made any difference to short-term comfort (MD 0.31, 95% CI -0.60 to 1.22; 4 studies, 662 participants, very low-certainty evidence), or to long-term comfort (MD 0.59, 95% CI -2.29 to 3.47; 2 studies, 445 participants, very low-certainty evidence). HFNC versus NIV or NIPPV We found no evidence of a difference between groups in treatment failure when HFNC were used post-extubation or without prior use of mechanical ventilation (RR 0.98, 95% CI 0.78 to 1.22; 5 studies, 1758 participants; low-certainty evidence), or in-hospital mortality (RR 0.92, 95% CI 0.64 to 1.31; 5 studies, 1758 participants; low-certainty evidence). We are very uncertain about the effect of using HFNC on incidence of pneumonia (RR 0.51, 95% CI 0.17 to 1.52; 3 studies, 1750 participants; very low-certainty evidence), and HFNC may result in little or no difference to barotrauma (RR 1.15, 95% CI 0.42 to 3.14; 1 study, 830 participants; low-certainty evidence). HFNC may make little or no difference to the length of ICU stay (MD -0.72 days, 95% CI -2.85 to 1.42; 2 studies, 246 participants; low-certainty evidence). The ratio of PaO2/FiO2 may be lower up to 24 hours with HFNC use (MD -58.10 mmHg, 95% CI -71.68 to -44.51; 3 studies, 1086 participants; low-certainty evidence). We are uncertain whether HFNC improved short-term comfort when measured using comfort scores (MD 1.33, 95% CI 0.74 to 1.92; 2 studies, 258 participants) and responses to questionnaires (RR 1.30, 95% CI 1.10 to 1.53; 1 study, 168 participants); evidence for short-term comfort was very low certainty. No studies reported on nasal mucosa or skin trauma. AUTHORS' CONCLUSIONS: HFNC may lead to less treatment failure when compared to standard oxygen therapy, but probably makes little or no difference to treatment failure when compared to NIV or NIPPV. For most other review outcomes, we found no evidence of a difference in effect. However, the evidence was often of low or very low certainty. We found a large number of ongoing studies; including these in future updates could increase the certainty or may alter the direction of these effects.

ANTECEDENTES: Las cánulas nasales de alto flujo (HFNC) administran flujos elevados de una mezcla humedecida de aire y oxígeno a través de cánulas nasales de gran calibre y pueden ser útiles para proporcionar asistencia respiratoria a los adultos que presentan insuficiencia respiratoria aguda, o que tienen riesgo de presentarla, en la unidad de cuidados intensivos (UCI). Esta es una actualización de una versión anterior de la revisión. OBJETIVOS: Evaluar la eficacia de las HFNC en comparación con la oxigenoterapia estándar, o la ventilación no invasiva (VNI) o la ventilación con presión positiva no invasiva (VPPNI), para la asistencia respiratoria de adultos en la UCI. MÉTODOS DE BÚSQUEDA: Se realizaron búsquedas en CENTRAL, MEDLINE, Embase, CINAHL, Web of Science y en el Registro Cochrane de covid­19 (17 de abril de 2020), registros de ensayos clínicos (6 de abril de 2020) y se realizaron búsquedas de citas prospectivas y retrospectivas. CRITERIOS DE SELECCIÓN: Se incluyeron los estudios controlados aleatorizados (ECA) con un diseño de grupos paralelos o cruzados que compararon el uso de HFNC versus otro tipo de asistencia respiratoria no invasiva (oxigenoterapia estándar a través de cánulas nasales o mascarilla; o VNI o VPPNI que incluía la presión positiva continua en las vías respiratorias y la presión positiva de dos niveles en las vías respiratorias) en adultos ingresados en la UCI. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Se utilizaron los procedimientos metodológicos estándar previstos por la Colaboración Cochrane. RESULTADOS PRINCIPALES: Se incluyeron 31 estudios (22 de grupos paralelos y nueve de diseño cruzado) con 5136 participantes; esta actualización incluyó 20 estudios nuevos. Veintiún estudios compararon la HFNC con la oxigenoterapia estándar, y 13 compararon la HFNC con la VNI o la VPPNI; tres estudios incluyeron ambas comparaciones. Se encontraron 51 estudios en curso (con una estimación de 12 807 participantes) y 19 estudios en espera de clasificación en los que no fue posible determinar la información de elegibilidad del estudio. En 18 estudios el tratamiento se inició después de la extubación. En el resto de los estudios, los participantes no habían recibido de forma previa ventilación mecánica. HFNC versus oxigenoterapia estándar La HFNC podría conducir a un menor fracaso del tratamiento, según lo indicado por el escalamiento a tipos alternativos de oxigenoterapia (razón de riesgos [RR] 0,62; intervalo de confianza [IC] del 95%: 0,45 a 0,86; 15 estudios, 3044 participantes; evidencia de certeza baja). La HFNC probablemente da lugar a poca o ninguna diferencia en la mortalidad cuando se compara con la oxigenoterapia estándar (RR 0,96; IC del 95%: 0,82 a 1,11; 11 estudios, 2673 participantes; evidencia de certeza moderada). La HFNC probablemente da lugar a poca o ninguna diferencia con respecto a los casos de neumonía (RR 0,72; IC del 95%: 0,48 a 1,09; cuatro estudios, 1057 participantes; evidencia de certeza moderada), y no se sabe con certeza su efecto sobre la mucosa nasal ni el traumatismo cutáneo (RR 3,66; IC del 95%: 0,43 a 31,48; dos estudios, 617 participantes; evidencia de certeza muy baja). Se encontró evidencia de certeza baja de que la HFNC podría dar lugar a poca o ninguna diferencia en la duración de la estancia en la UCI según el tipo de asistencia respiratoria utilizada (DM 0,12 días; IC del 95%: ­0,03 a 0,27; siete estudios, 1014 participantes). No se sabe con certeza si la HFNC dio lugar a alguna diferencia en el cociente entre la presión parcial de oxígeno arterial y la fracción de oxígeno inspirado (PaO2/FiO2) en las primeras 24 horas del tratamiento (DM 10,34 mmHg; IC del 95%: ­17,31 a 38; cinco estudios, 600 participantes; evidencia de certeza muy baja). No se sabe con certeza si la HFNC dio lugar a alguna diferencia en la comodidad a corto plazo (DM 0,31; IC del 95%: ­0,60 a 1,22; cuatro estudios, 662 participantes, evidencia de certeza muy baja), o en la comodidad a largo plazo (DM 0,59; IC del 95%: ­2,29 a 3,47; dos estudios, 445 participantes, evidencia de certeza muy baja). HFNC versus VNI o VPPNI No se encontró evidencia de una diferencia entre los grupos en el fracaso del tratamiento cuando se utilizó la HFNC después de la extubación o sin el uso previo de ventilación mecánica (RR 0,98; IC del 95%: 0,78 a 1,22; cinco estudios, 1758 participantes; evidencia de certeza baja), ni en la mortalidad hospitalaria (RR 0,92; IC del 95%: 0,64 a 1,31; cinco estudios, 1758 participantes; evidencia de certeza baja). No hay certeza sobre el efecto del uso de la HFNC en la incidencia de la neumonía (RR 0,51; IC del 95%: 0,17 a 1,52; tres estudios, 1750 participantes; evidencia de certeza muy baja), y la HFNC podría dar lugar a poca o ninguna diferencia en el barotraumatismo (RR 1,15; IC del 95%: 0,42 a 3,14; un estudio, 830 participantes; evidencia de certeza baja). La HFNC podría suponer una diferencia escasa o nula en la duración de la estancia en la UCI (DM ­0,72 días; IC del 95%: ­2,85 a 1,42; dos estudios, 246 participantes; evidencia de certeza baja). El cociente PaO2/FiO2 podría ser menor hasta 24 horas con el uso de la HFNC (DM ­58,10 mmHg; IC del 95%: ­71,68 a ­44,51; tres estudios, 1086 participantes; evidencia de certeza baja). No se sabe si la HFNC mejoró la comodidad a corto plazo cuando se midió mediante puntuaciones de comodidad (DM 1,33; IC del 95%: 0,74 a 1,92; dos estudios, 258 participantes) y respuestas a cuestionarios (RR 1,30; IC del 95%: 1,10 a 1,53; un estudio, 168 participantes); la evidencia para la comodidad a corto plazo fue de certeza muy baja. Ningún estudio informó sobre la mucosa nasal ni el traumatismo cutáneo. CONCLUSIONES DE LOS AUTORES: La HFNC podría dar lugar a un menor fracaso del tratamiento en comparación con la oxigenoterapia estándar, pero probablemente suponga una escasa o nula diferencia en el fracaso del tratamiento en comparación con la VNI o la VPPNI. Para la mayoría de los demás desenlaces de la revisión, no se encontró evidencia de una diferencia en el efecto. Sin embargo, la certeza de la evidencia se consideró baja o muy baja. Se encontró un gran número de estudios en curso; incluirlos en futuras actualizaciones podría aumentar la certeza o podría alterar la dirección de estos efectos.

Interventions to reduce body temperature to 35 °C to 37 °C in adults and children with traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability, with an estimated 5.5 million people experiencing severe TBI worldwide every year. Observational clinical studies of people with TBI suggest an association between raised body temperature and unfavourable outcome, although this relationship is inconsistent. Additionally, preclinical models suggest that reducing temperature to 35 °C to 37.5 °C improves biochemical and histopathological outcomes compared to reducing temperature to a lower threshold of 33 °C to 35 °C. It is unknown whether reducing body temperature to 35 °C to 37.5 °C in people admitted to hospital with TBI is beneficial, has no effect, or causes harm. This is an update of a review last published in 2014. OBJECTIVES: To assess the effects of pharmacological interventions or physical interventions given with the intention of reducing body temperature to 35 °C to 37.5 °C in adults and children admitted to hospital after TBI. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Web of Science, and PubMed on 28 November 2019. We searched clinical trials registers, grey literature and references lists of reviews, and we carried out forward citation searches of included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with participants of any age admitted to hospital following TBI. We included interventions that aimed to reduce body temperature to 35 °C to 37.5 °C: these included pharmacological interventions (such as paracetamol, or non-steroidal anti-inflammatory drugs), or physical interventions (such as surface cooling devices, bedside fans, or cooled intravenous fluids). Eligible comparators were placebo or usual care. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, and assessed risks of bias. We assessed the certainty of the evidence with GRADE. MAIN RESULTS: We included one RCT with 41 participants. This study recruited adult participants admitted to two intensive care units in Australia, and evaluated a pharmacological intervention. Researchers gave participants 1 g paracetamol or a placebo intravenously at four-hourly intervals for 72 hours. We could not be certain whether intravenous paracetamol influenced mortality at 28 days (risk ratio 2.86, 95% confidence interval 0.32 to 25.24). We judged the evidence for this outcome to be very low certainty, meaning we have very little confidence in this effect estimate, and the true result may be substantially different to this effect. We downgraded the certainty for imprecision (because the evidence was from a single study with very few participants), and study limitations (because we noted a high risk of selective reporting bias). This study was otherwise at low risk of bias. The included study did not report the primary outcome for this review, which was the number of people with a poor outcome at the end of follow-up (defined as death or dependency, as measured on a scale such as the Glasgow Outcome Score), or any of our secondary outcomes, which included the number of people with further intracranial haemorrhage, extracranial haemorrhage, abnormal intracranial pressure, or pneumonia or other serious infections. The only other completed trial that we found was of a physical intervention that compared advanced fever control (using a surface cooling device) versus conventional fever control in 12 participants. The trial was published as an abstract only, with insufficient details to allow inclusion, so we have added this to the 'studies awaiting classification' section, pending further information from the study authors or publication of the full study report. We identified four ongoing studies that will contribute evidence to future updates of the review if they measure relevant outcomes and, in studies with a mixed population, report data separately for participants with TBI. AUTHORS' CONCLUSIONS: One small study contributed very low-certainty evidence for mortality to this review. The uncertainty is largely driven by limited research into reduction of body temperature to 35 °C to 37.5 °C in people with TBI. Further research that evaluates pharmacological or physical interventions, or both, may increase certainty in this field. We propose that future updates of the review, and ongoing and future research in this field, incorporate outcomes that are important to the people receiving the interventions, including side effects of any pharmacological agent (e.g. nausea or vomiting), and discomfort caused by physical therapies.

Long-term GnRH agonist therapy before in vitro fertilisation (IVF) for improving fertility outcomes in women with endometriosis.

BACKGROUND: Endometriosis is known to have an impact on fertility and it is common for women affected by endometriosis to require fertility treatments, including in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI), to improve the chance of pregnancy. It has been postulated that long-term gonadotrophin-releasing hormone (GnRH) agonist therapy prior to IVF or ICSI can improve pregnancy outcomes. This systematic review supersedes the previous Cochrane Review on this topic (Sallam 2006). OBJECTIVES: To determine the effectiveness and safety of long-term gonadotrophin-releasing hormone (GnRH) agonist therapy (minimum 3 months) versus no pretreatment or other pretreatment modalities, such as long-term continuous combined oral contraception (COC) or surgical therapy of endometrioma, before standard in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) in women with endometriosis. SEARCH METHODS: We searched the following electronic databases from their inception to 8 January 2019: Cochrane Gynaecology and Fertility Specialised Register of Controlled Trials, CENTRAL via the Cochrane CENTRAL Register of Studies ONLINE (CRSO), MEDLINE, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL). We searched trial registries to identify unpublished and ongoing trials. We also searched DARE (Database of Abstracts of Reviews of Effects), Web of Knowledge, OpenGrey, Latin American and Caribbean Health Science Information Database (LILACS), PubMed, Google and reference lists from relevant papers for any other relevant trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) involving women with surgically diagnosed endometriosis that compared use of any type of GnRH agonist for at least three months before an IVF/ICSI protocol to no pretreatment or other pretreatment modalities, specifically use of long-term continuous COC (minimum of 6 weeks) or surgical excision of endometrioma within six months prior to standard IVF/ICSI. The primary outcomes were live birth rate and complication rate per woman randomised. DATA COLLECTION AND ANALYSIS: Two independent review authors assessed studies against the inclusion criteria, extracted data and assessed risk of bias. A third review author was consulted, if required. We contacted the study authors, as required. We analysed dichotomous outcomes using Mantel-Haenszel risk ratios (RRs), 95% confidence intervals (CIs) and a fixed-effect model. For small numbers of events, we used a Peto odds ratio (OR) with 95% CI instead. We analysed continuous outcomes using the mean difference (MD) between groups and presented with 95% CIs. We studied heterogeneity of the studies via the I2 statistic. We assessed the quality of evidence using GRADE criteria. MAIN RESULTS: We included eight parallel-design RCTs, involving a total of 640 participants. We did not assess any of the studies as being at low risk of bias across all domains, with the main limitation being lack of blinding. Using GRADE methodology, the quality of the evidence ranged from very low to low quality. Long-term GnRH agonist therapy versus no pretreatment We are uncertain whether long-term GnRH agonist therapy affects the live birth rate (RR 0.48, 95% CI 0.26 to 0.87; 1 RCT, n = 147; I2 not calculable; very low-quality evidence) or the overall complication rate (Peto OR 1.23, 95% CI 0.37; to 4.14; 3 RCTs, n = 318; I2 = 73%; very low-quality evidence) compared to standard IVF/ICSI. Further, we are uncertain whether this intervention affects the clinical pregnancy rate (RR 1.13, 95% CI 0.91 to 1.41; 6 RCTs, n = 552, I2 = 66%; very low-quality evidence), multiple pregnancy rate (Peto OR 0.14, 95% CI 0.03 to 0.56; 2 RCTs, n = 208, I2 = 0%; very low-quality evidence), miscarriage rate (Peto OR 0.45, 95% CI 0.10 to 2.00; 2 RCTs, n = 208; I2 = 0%; very low-quality evidence), mean number of oocytes (MD 0.72, 95% CI 0.06 to 1.38; 4 RCTs, n = 385; I2 = 81%; very low-quality evidence) or mean number of embryos (MD -0.76, 95% CI -1.33 to -0.19; 2 RCTs, n = 267; I2 = 0%; very low-quality evidence). Long-term GnRH agonist therapy versus long-term continuous COC No studies reported on this comparison. Long-term GnRH agonist therapy versus surgical therapy of endometrioma No studies reported on this comparison. AUTHORS' CONCLUSIONS: This review raises important questions regarding the merit of long-term GnRH agonist therapy compared to no pretreatment prior to standard IVF/ICSI in women with endometriosis. Contrary to previous findings, we are uncertain as to whether long-term GnRH agonist therapy impacts on the live birth rate or indeed the complication rate compared to standard IVF/ICSI. Further, we are uncertain whether this intervention impacts on the clinical pregnancy rate, multiple pregnancy rate, miscarriage rate, mean number of oocytes and mean number of embryos. In light of the paucity and very low quality of existing data, particularly for the primary outcomes examined, further high-quality trials are required to definitively determine the impact of long-term GnRH agonist therapy on IVF/ICSI outcomes, not only compared to no pretreatment, but also compared to other proposed alternatives to endometriosis management.