Right ventricular dysfunction in patients with COVID-19 pneumonitis whose lungs are mechanically ventilated: a multicentre prospective cohort study.

Cardiovascular complications due to COVID-19, such as right ventricular dysfunction, are common. The combination of acute respiratory distress syndrome, invasive mechanical ventilation, thromboembolic disease and direct myocardial injury creates conditions where right ventricular dysfunction is likely to occur. We undertook a prospective, multicentre cohort study in 10 Scottish intensive care units of patients with COVID-19 pneumonitis whose lungs were mechanically ventilated. Right ventricular dysfunction was defined as the presence of severe right ventricular dilation and interventricular septal flattening. To explore the role of myocardial injury, high-sensitivity troponin and N-terminal pro B-type natriuretic peptide plasma levels were measured in all patients. We recruited 121 patients and 118 (98%) underwent imaging. It was possible to determine the primary outcome in 112 (91%). Severe right ventricular dilation was present in 31 (28%), with interventricular septal flattening present in nine (8%). Right ventricular dysfunction (the combination of these two parameters) was present in seven (6%, 95%CI 3-13%). Thirty-day mortality was 86% in those with right ventricular dysfunction as compared with 45% in those without (p = 0.051). Patients with right ventricular dysfunction were more likely to have: pulmonary thromboembolism (p < 0.001); higher plateau airway pressure (p = 0.048); lower dynamic compliance (p = 0.031); higher plasma N-terminal pro B-type natriuretic peptide levels (p = 0.006); and raised plasma troponin levels (p = 0.048). Our results demonstrate a prevalence of right ventricular dysfunction of 6%, which was associated with increased mortality (86%). Associations were also observed between right ventricular dysfunction and aetiological domains of: acute respiratory distress syndrome; ventilation; thromboembolic disease; and direct myocardial injury, implying a complex multifactorial pathophysiology.

The management of menopause in women with a history of endometriosis: a systematic review.

BACKGROUND: Endometriosis is typically regarded as a premenopausal disease, resolving after natural or iatrogenic menopause due to declining oestrogen levels. Nonetheless, case reports over the years have highlighted the incidence of recurrent postmenopausal endometriosis. It is now clear that both recurrence and malignant transformation of endometriotic foci can occur in the postmenopausal period. Postmenopausal women are commonly treated with hormone replacement therapy (HRT) to treat climacteric symptoms and prevent bone loss; however, HRT may reactivate endometriosis and stimulate malignant transformation in women with a history of endometriosis. Given the uncertain risks of initiating HRT, it is difficult to determine the best menopausal management for this group of women. OBJECTIVE AND RATIONAL: The aim of this study was to systematically review the existing literature on management of menopausal symptoms in women with a history of endometriosis. We also aimed to evaluate the published literature on the risks associated with HRT in these women, and details regarding optimal formulations and timing (i.e. initiation and duration) of HRT. SEARCH METHODS: Four electronic databases (MEDLINE via OVID, Embase via OVID, PsycINFO via OVID and CINAHL via EbscoHost) were searched from database inception until June 2016, using a combination of relevant controlled vocabulary terms and free-text terms related to 'menopause' and 'endometriosis'. Inclusion criteria were: menopausal women with a history of endometriosis and menopausal treatment including HRT or other preparations. Case reports/series, observational studies and clinical trials were included. Narrative review articles, organizational guidelines and conference abstracts were excluded, as were studies that did not report on any form of menopausal management. Articles were assessed for risk of bias and quality using GRADE criteria. OUTCOMES: We present a synthesis of the existing case reports of endometriosis recurrence or malignant transformation in women undergoing treatment for menopausal symptoms. We highlight common presenting symptoms, potential risk factors and outcomes amongst the studies. Sparse high-quality evidence was identified, with few observational studies and only two randomized controlled trials. Given this paucity of data, no definitive conclusions can be drawn concerning risk. WIDER IMPLICATIONS: Due to the lack of high-quality studies, it remains unclear how to advise women with a history of endometriosis regarding the management of menopausal symptoms. The absolute risk of disease recurrence and malignant transformation cannot be quantified, and the impact of HRT use on these outcomes is not known. Multicentre randomized trials or large observational studies are urgently needed to inform clinicians and patients alike.

Hypertensive disorders of pregnancy and outcomes of preterm infants of 24 to 28 weeks' gestation.

OBJECTIVE: To examine the relationship between hypertensive disorders of pregnancy (HDPs) and mortality and major morbidities in preterm neonates born at 24 to 28 weeks of gestation. STUDY DESIGN: Using an international cohort, we retrospectively studied 27 846 preterm neonates born at 240 to 286 weeks of gestation during 2007 to 2010 from 6 national neonatal databases. The incidence of HDP was compared across countries, and multivariable logistic regression analyses were conducted to examine the association of HDP and neonatal outcomes including mortality to discharge, bronchopulmonary dysplasia, severe brain injury, necrotizing enterocolitis and treated retinopathy of prematurity. RESULTS: The incidence of HDP in the entire cohort was 13% (range 11 to 16% across countries). HDP was associated with reduced odds of mortality (adjusted odds ratio (aOR) 0.77; 95% confidence interval (CI) 0.67 to 0.88), severe brain injury (aOR 0.74; 95% CI 0.62 to 0.89) and treated retinopathy (aOR 0.82; 95% CI 0.70 to 0.96), but increased odds of bronchopulmonary dysplasia (aOR 1.16; 95% CI 1.05 to 1.27). CONCLUSIONS: In comparison with neonates born to mothers without HDP, neonates of HDP mothers had lower odds of mortality, severe brain injury and treated retinopathy, but higher odds of bronchopulmonary dysplasia. The impact of maternal HDP on newborn outcomes was inconsistent across outcomes and among countries; therefore, further international collaboration to standardize terminology, case definition and data capture is warranted.

Recommendations for standards of monitoring during anaesthesia and recovery 2015: Association of Anaesthetists of Great Britain and Ireland.

This guideline updates and replaces the 4th edition of the AAGBI Standards of Monitoring published in 2007. The aim of this document is to provide guidance on the minimum standards for physiological monitoring of any patient undergoing anaesthesia or sedation under the care of an anaesthetist. The recommendations are primarily aimed at anaesthetists practising in the United Kingdom and Ireland. Minimum standards for monitoring patients during anaesthesia and in the recovery phase are included. There is also guidance on monitoring patients undergoing sedation and also during transfer of anaesthetised or sedated patients. There are new sections discussing the role of monitoring depth of anaesthesia, neuromuscular blockade and cardiac output. The indications for end-tidal carbon dioxide monitoring have been updated.

A randomized controlled trial comparing a standard postoperative diet with low-volume high-calorie oral supplements following colorectal surgery.

AIM: Postoperative oral nutritional supplementation is becoming a part of most patient care pathways. This study examined the effects of low-volume high-calorie prescribed supplemental nutrition on patient outcome following elective colorectal surgery. METHOD: Patients undergoing elective colorectal resections were randomized to a prescribed nutritional supplementation group (SG) [standard diet + 6 × 60 ml/day of Pro-Cal (60 ml = 200 kcal + 4 g protein)] or conventional postoperative diet group (CG) (standard diet alone). Preoperative and daily postoperative hand-grip strengths were measured using a grip dynamometer after randomization. Daily food intake, return of bowel activity, nausea score for the first 3 days and postoperative length of hospital stay (LOS) were prospectively recorded. Micro-diet standardized software was used to analyse food diaries. Nonparametric tests were used to analyse the data. RESULTS: Fifty-five patients were analysed (SG 28, CG 27). There was no difference in median preoperative and postoperative handgrip strengths at discharge within each group (SG 31.7 vs 31.7 kPa, P = 0.932; CG 28 vs 28.1 kPa, P = 0.374). The total median daily calorie intake was higher in SG than CG (SG 818.5 kcal vs CG 528 kcal; P = 0.002). There was no difference in median number of days to first bowel movement (SG 3 days vs CG 4 days, P = 0.096). The median LOS was significantly shorter in SG than CG (6.5 vs 9 days; P = 0.037). CONCLUSION: Prescribed postoperative high-calorie, low-volume oral supplements in addition to the normal dietary intake are associated with significantly better total daily oral calorie intake and may contribute to a reduced postoperative hospital stay.

Checking anaesthetic equipment 2012: association of anaesthetists of Great Britain and Ireland.

A pre-use check to ensure the correct functioning of anaesthetic equipment is essential to patient safety. The anaesthetist has a primary responsibility to understand the function of the anaesthetic equipment and to check it before use. Anaesthetists must not use equipment unless they have been trained to use it and are competent to do so. A self-inflating bag must be immediately available in any location where anaesthesia may be given. A two-bag test should be performed after the breathing system, vaporisers and ventilator have been checked individually. A record should be kept with the anaesthetic machine that these checks have been done. The 'first user' check after servicing is especially important and must be recorded.

Confirming the drugs administered during anaesthesia: a feasibility study in the pilot National Health Service sites, UK.

BACKGROUND: To help prevent drug errors, it is recommended that drugs should be confirmed/checked with a second person before administration. We aimed to assess the feasibility of introducing second-person or electronic bar-code confirmation of drugs, administered during anaesthesia, in the National Health Service (NHS) settings in the UK. METHODS: Seven NHS sites took part in a pilot study over a 3 month period. Five used a second-person and two used bar-code electronic confirmation of drugs given during anaesthesia. A total of 36 consultant anaesthetists and three trainees, 15 operating department practitioners (ODPs), and seven anaesthetic nurses participated. A group of anaesthetists, ODPs, and nurse practitioners (n=11) from different NHS sites independently observed both methodologies. In addition, each site was visited and observed by one of the study investigators. At the end of the study period, four focus groups (two with participants from pilot sites and two with observers) were held. The discussions were taped, transcribed, and qualitatively analysed. Data were triangulated using observer's notes and investigator's reflective diaries, and processed using line-by-line coding. The codes were then synthesized into themes. RESULTS: Both methods were perceived to contribute to the prevention of drug errors. For the two-person confirmation to be carried out correctly, there should be no distraction or time pressure. The main limitation to the feasibility was that the continuous presence of the second person was not always possible. The process also met with resistance from the staff at some pilot sites. Electronic confirmation was always feasible, as it did not require the presence of a second person. It was found to be intuitive to the anaesthetist's current working practice. However, there were some practical issues related to introduction of new technology and an initial learning curve. CONCLUSIONS: The introduction of two-person confirmation to the NHS would have a significant impact on the existing working practices. Issues related to resources and a cultural change will need to be addressed. Electronic confirmation was more feasible, but the technological aspects of its integration into the operating theatre environment, and learning, will require further attention.

Numbers needed to hospitalize-risks and benefits of admission in the new decade.

While hospitals are central to western style health care systems it is unclear which patients benefit from hospitalization and who might be put at risk. The high cost means that reasons for hospitalization will need to be reviewed in the current economic climate. Accepted grounds for hospitalization include life threatening illness, diagnostic uncertainty with the threat of deteriorating health, the need for specialist expertise or experience or the need for nursing care, including the care of the dying. Some of the traditional surveillance functions of the hospital can now be taken over by technology or alternative settings. These changes will lead to a blurring of margins between Outpatient, Inpatient and Critical Care. Beyond the care of the critically ill patient it is unlikely that all patients currently admitted to hospital benefit from this process and would be admitted in future. A generally accepted system for risk assessment of medial inpatients is urgently needed to allow researchers to examine the effectiveness of health care systems involving hospitalization and the circumstances under which hospitalization is cost effective and improves mortality, morbidity and patient reported outcomes.

Phosphorylation of the androgen receptor is associated with reduced survival in hormone-refractory prostate cancer patients.

Cell line studies demonstrate that the PI3K/Akt pathway is upregulated in hormone-refractory prostate cancer (HRPC) and can result in phosphorylation of the androgen receptor (AR). The current study therefore aims to establish if this has relevance to the development of clinical HRPC. Immunohistochemistry was employed to investigate the expression and phosphorylation status of Akt and AR in matched hormone-sensitive and -refractory prostate cancer tumours from 68 patients. In the hormone-refractory tissue, only phosphorylated AR (pAR) was associated with shorter time to death from relapse (P=0.003). However, when an increase in expression in the transition from hormone-sensitive to -refractory prostate cancer was investigated, an increase in expression of PI3K was associated with decreased time to biochemical relapse (P=0.014), and an increase in expression of pAkt(473) and pAR(210) were associated with decreased disease-specific survival (P=0.0019 and 0.0015, respectively). Protein expression of pAkt(473) and pAR(210) also strongly correlated (P<0.001, c.c.=0.711) in the hormone-refractory prostate tumours. These results provide evidence using clinical specimens, that upregulation of the PI3K/Akt pathway is associated with phosphorylation of the AR during development of HRPC, suggesting that this pathway could be a potential therapeutic target.

Validation of physiological scoring systems in the accident and emergency department.

BACKGROUND: Scoring systems that weigh the degree of abnormality of bedside observations might be able to identify patients at risk of catastrophic deterioration. OBJECTIVES: To establish a frequency distribution for typical physiological scoring systems and to establish the potential benefit of adding these to an existing triage system in accident and emergency departments. METHODS: Physiological data were collected from 53 unselected emergency department admissions, from 50 patients admitted from the emergency department to intensive care, and from 50 patients admitted from emergency department to general wards and then to intensive care. Three different physiological scores were calculated from the data. Identification of sick patients by the scores was compared with triage information from the Manchester Triage System (MTS). RESULTS: Most patients admitted to the emergency department would not be identified as critically ill with the aid of physiological scoring systems. This was true even for patients who were admitted to intensive care. Only in 0-8% of unselected patients did the scores indicate increased risk. In 100 patients admitted to the intensive care, adding of medical emergency team call-out criteria, Modified Early Warning Score or Assessment Score for Sick patient Identification and Step-up in Treatment would identify none, seven or one patient in addition to those triaged as orange and red by the MTS. CONCLUSIONS: Introduction of a physiological scoring system would have identified only a small number of additional patients as critically ill and added little to the triage system currently in use.

Does earlier detection of critically ill patients on surgical wards lead to better outcomes?

INTRODUCTION: Patients at risk of catastrophic deterioration are often identified too late. Delayed identification of sick patients and delayed referral to intensive care units might be associated with poor outcomes. The goal of the review is to assess the potential impact of systems that enable early detection of critically ill surgical patients. MATERIALS AND METHODS: A Medline search was performed in September 2004. Other articles were identified using the bibliographies of papers found through Medline. All interventional trials reviewing the effect of Critical Care Outreach and Medical Emergency Teams were reviewed. RESULTS: There is evidence that simple algorithms based on bedside observations can identify a large proportion of sick patients on general wards. Non-randomised studies have shown mixed results on impact of these interventions on mortality, cardiopulmonary arrests and intensive care admissions. The majority of studies do not specifically address surgical patients. A ward-based randomised trial from the UK seems to suggest improved mortality following the introduction of a Critical Care Outreach service with an Early Warning Score. DISCUSSION AND CONCLUSION: The literature about Critical Care Outreach and Medical Emergency teams is characterised by methodological weaknesses. However there is a common suggestion that early detection might improve outcome of critically ill surgical patients.

Effect of introducing the Modified Early Warning score on clinical outcomes, cardio-pulmonary arrests and intensive care utilisation in acute medical admissions.

The effects of introducing Modified Early Warning scores to identify medical patients at risk of catastrophic deterioration have not been examined. We prospectively studied 1695 acute medical admissions. All patients were scored in the admissions unit. Patients with a Modified Early Warning score > 4 were referred for urgent medical and critical care outreach team review. Data was compared with an observational study performed in the same unit during the proceeding year. There was no change in mortality of patients with low, intermediate or high Modified Early Warning scores. Rates of cardio-pulmonary arrest, intensive care unit or high dependency unit admission were similar. Data analysis confirmed respiratory rate as the best discriminator in identifying high-risk patient groups. The therapeutic interventions performed in response to abnormal scores were not assessed. We are convinced that the Modified Early Warning score is a suitable scoring tool to identify patients at risk. However, outcomes in medical emergency admissions are influenced by a multitude of factors and so it may be difficult to demonstrate the score's benefit without further standardizing the response to abnormal values.

Down-regulation of poison ivy/oak-induced contact sensitivity by treatment with a class II MHC binding peptide:hapten conjugate.

Immune regulation of contact sensitivity to the poison ivy/oak catechol was studied at the level of class II MHC-restricted T cell recognition of hapten:peptide conjugates. In this study we have shown that 1) T cells from C3H/HeN (H-2k) mice, immunized with a synthetic I-Ak binding peptide coupled to 3-pentadecyl-catechol (PDC; a representative catechol in urushiol), recognized peptides derived from syngeneic cells linked to the same catechol; 2) T cells from draining lymph nodes of C3H/HeN mice skin-painted with PDC proliferated in response to a peptide carrier:PDC conjugate only when it was linked at the 7th, but not the 4th or the 10th, position on the peptide carrier; and 3) tolerization studies confirmed down-regulation of PDC-induced delayed-type hypersensitivity following treatment with a single I-Ak binding peptide carrying PDC covalently bound to a lysine residue at the middle (7th) TCR contact position. Tolerization with peptide:PDC conjugate resulted in abrogation of hapten-specific T cell proliferative responses that correlated with diminished IL-2 secretion. On the basis of these data we propose that it may be sufficient to couple the hapten at a single, well-chosen position on a carrier peptide to target a relevant population of T cells involved in contact sensitivity.

Pain relief after inguinal hernia repair: a randomized double-blind study.

A randomized double-blind study was undertaken using 0.5 per cent bupivacaine ilioinguinal field block and oral papaveretum-aspirin tablets to assess pain relief after hernia surgery. A consecutive series of 200 men undergoing repair of a unilateral inguinal hernia underwent random allocation into one of the four groups to receive: bupivacaine and papaveretum-aspirin (group 1), bupivacaine and oral placebo (group 2), saline and papaveretum-aspirin (group 3), or saline and oral placebo (group 4). Patients were prescribed postoperative opiates to be given on demand. Pain levels and mobility were assessed at 6 and 24 h after operation. Patients in group 1 reported significantly less pain, required less additional opiates and had better mobility than those in group 4 (pain score P < 0.001 at 6 h and P = 0.002 at 24 h) and group 3 (P = 0.002 for pain and mobility scores at 6 h). Bupivacaine alone provided good immediate postoperative pain relief (P = 0.002 group 2 versus group 4 at 6 h). The combination of bupivacaine and papaveretum-aspirin provided the best results and is suitable for day-case postoperative analgesia.

Early detection of extravasation of radiographic contrast medium. Work in progress.

Microwave radiometry is a passive and noninvasive technique that allows quick detection of subcutaneous temperature changes. The feasibility of this technique for differentiating normal intravenous infusions of radiographic contrast medium from extravasations of contrast medium was tested in anesthetized dogs. Room-temperature and heated ionic and nonionic contrast media were administered at flow rates ranging from 0.2 to 9.9 mL/sec by means of a power injector. On the basis of these experiments, an algorithm to adjust for extravasation detection thresholds as a function of injection flow rates was developed. With this algorithm, results showed a false-positive rate of 0% at all infusion rates and false-negative rates of 2%, 2%, and 4% at pump speeds of 0.2, 1.0, and 9.9 mL/sec, respectively. The times of these extravasation "alarms" corresponded to maximum extravasated volumes, respectively, of 4, 6.5, and 8 mL. Microwave radiometry has clinical potential for early detection of extravasation of contrast medium administered with power injectors.

Spatial resolution measurements for passive microwave radiometry using a tissue-equivalent phantom.

A tissue-equivalent "hot" line source phantom is described for assessing spatial resolution in passive microwave radiometry systems. LSFs were measured for two rectangular waveguide antennas connected to a 4.7-GHz radiometer. The normalized LSFs and corresponding modulation transfer functions were found to be independent of line source temperature, but dependent upon antenna size, orientation, and line source depth.