Sexually transmitted and blood-borne infection risk reduction with methadone and buprenorphine/naloxone among people with prescription-type opioid use disorder: Findings from a Canadian pragmatic randomized trial.

INTRODUCTION: People who use drugs are disproportionally affected by sexually transmitted and blood-borne infections (STBBIs). While the benefits of methadone in reducing injecting-risk behaviours are well documented, less is known on its impacts on sexual-related risks, as well as its comparative effectiveness to buprenorphine/naloxone, particularly in the context of highly potent opioids. The aim of this study was to estimate the relative effects of buprenorphine/naloxone and methadone on injecting and STBBI risks among people with prescription-type opioid use disorder (POUD). METHODS: Secondary analysis of a pan-Canadian pragmatic 24-week randomized clinical trial comparing methadone and buprenorphine/naloxone models of care among 272 people with POUD (including licit or illicit opioid analgesics, fentanyl). The Risk Behaviour Survey was used to collect injecting and sexual risks at baseline, and weeks 12 and 24. RESULTS: In total, 210 participants initiated treatment (103 buprenorphine/naloxone and 107 methadone). At baseline, 113/205 (55.1%) participants reported recently injecting drugs, 37/209 (17.7%) unsafe injection practices and 67/162 (41.4%) high-risk sex. Both methadone and buprenorphine/naloxone were associated with reductions in the prevalence of injection drug use and high-risk sex at weeks 12 and 24 with no interactions between treatment arm and time. CONCLUSION: Methadone and buprenorphine/naloxone were similarly effective in reducing injecting and sexual risk behaviours among people with POUD. CLINICAL TRIALS REGISTRATION: clinicaltrials.gov NCT03033732.

Unsupervised home spirometry versus supervised clinic spirometry for respiratory disease: a systematic methodology review and meta-analysis.

BACKGROUND: The number of patients completing unsupervised home spirometry has recently increased due to more widely available portable technology and the COVID-19 pandemic, despite a lack of solid evidence to support it. This systematic methodology review and meta-analysis explores quantitative differences in unsupervised spirometry compared with spirometry completed under professional supervision. METHODS: We searched four databases to find studies that directly compared unsupervised home spirometry with supervised clinic spirometry using a quantitative comparison (e.g. Bland-Altman). There were no restrictions on clinical condition. The primary outcome was measurement differences in common lung function parameters (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC)), which were pooled to calculate overall mean differences with associated limits of agreement (LoA) and confidence intervals (CI). We used the I2 statistic to assess heterogeneity, the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool to assess risk of bias and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess evidence certainty for the meta-analyses. The review has been registered with PROSPERO (CRD42021272816). RESULTS: 3607 records were identified and screened, with 155 full texts assessed for eligibility. We included 28 studies that quantitatively compared spirometry measurements, 17 of which reported a Bland-Altman analysis for FEV1 and FVC. Overall, unsupervised spirometry produced lower values than supervised spirometry for both FEV1 with wide variability (mean difference -107 mL; LoA= -509, 296; I2=95.8%; p<0.001; very low certainty) and FVC (mean difference -184 mL, LoA= -1028, 660; I2=96%; p<0.001; very low certainty). CONCLUSIONS: Analysis under the conditions of the included studies indicated that unsupervised spirometry is not interchangeable with supervised spirometry for individual patients owing to variability and underestimation.

Above and Below the Diaphragm: A Previously Undescribed Case of Recurrent Boerhaave Syndrome Diagnosed With Computerized Tomography Esophagram.

Boerhaave syndrome, defined as a spontaneous rupture of the esophagus, is an uncommon clinical entity. Recurrent spontaneous rupture of the esophagus is even rarer and has only been described in a handful of case reports. The rupture most often occurs in the thoracic esophagus. Spontaneous rupture of the intraabdominal esophagus is extremely rare. The extravasation of gastric contents, including bile, acid, and bacteria, into a body cavity precipitates severe sepsis. This results in a high mortality rate without emergent treatment. Such treatment often necessitates surgical repair with primary closure, tissue grafts, or esophagectomy in particularly severe cases. This is a case of a 64-year-old male who suffered Boerhaave syndrome twice separated by two years. The patient was transferred from an outside facility initially presenting with chest and abdominal pain, which developed after eating. CT esophagram with water soluble contrast demonstrated contrast extravasation into the right mediastinum/hemithorax, consistent with a diagnosis of Boerhaave syndrome. Repair was accomplished with an intercostal muscle pedicle patch, and the patient was subsequently discharged. This case report details, to our knowledge, the first case of a left intraabdominal and right thoracic esophageal rupture combination.

Pyruvate dehydrogenase complex deficiency mimicking congenital cytomegalovirus infection on imaging.

Pyruvate dehydrogenase complex deficiency is a rare and underdiagnosed disease. It can present with clinical manifestations as early as in utero. Both genetic and metabolic testing are available to determine the presence of the disease. Key to survival is early detection and diagnosis, with dietary treatment to prevent further neurological and structural damage to the brain. We present a newborn who presented with ultrasound brain abnormalities in utero that mimicked cytomegalovirus but was diagnosed with pyruvate dehydrogenase complex deficiency after genetic testing.

Pneumopericardium Resulting From Blunt Thoracic Trauma.

Pneumopericardium is a rare clinical condition defined by the presence of air in the pericardial sac. While this initially does not pose much danger, the accumulation of a sufficient amount of air can convert the pneumopericardium to a tension pathology. This may present with the classic signs, symptoms, and lethal dangers of cardiac tamponade. As with cardiac tamponade, treatment involves decompression of the pericardial sac through pericardiocentesis. This may be followed by insertion of a pericardial tube for continued drainage. While cardiac tamponade is well recognized by its classic findings, the rarer pneumopericardium may be more easily missed. This is further complicated by the backdrop of concurrent traumatic injuries in which it typically presents, as well as the absence of the defining accumulated pericardial effusion. We present a case of a 38-year old male who developed pneumopericardium and worsening hemodynamic status as a complication to blunt trauma, a rare etiology for this condition. CT of the chest demonstrated air in the pericardium and a coexisting pneumothorax. A bedside chest tube was placed. Upon resolution of the pneumothorax, his hemodynamic status improved. Repeat bedside ultrasound demonstrated complete resolution of his pneumopericardium. This case emphasizes the importance of early recognition and diagnosis of this rare yet easily missed condition.

Airway clearance techniques and use of mucoactive agents for adult critically ill patients with acute respiratory failure: a qualitative study exploring UK physiotherapy practice.

OBJECTIVES: To explore and describe current UK physiotherapy practice relating to airway clearance techniques and mucoactive agents in critically ill adult patients with acute respiratory failure in the intensive care unit. DESIGN: A descriptive, qualitative study using focus group interviews. Focus groups were audio-recorded, independently transcribed, and data analysed thematically. Participants Senior, experienced physiotherapists, clinically active in critical care. RESULTS: Fifteen physiotherapists participated in four interview sessions. Five themes emerged describing airway clearance techniques: 'Repertoire of airway clearance techniques', 'Staffing and skillset', 'Commencing respiratory physiotherapy', 'Technique selection', and 'Determining effectiveness' were themes related to airway clearance techniques. Five themes were also identified in relation to mucoactive agents: 'Use in clinical practice', 'Decision to commence', 'Selection of agent', 'Stopping mucoactive agents', and 'Determining effectiveness'. A summary of key features of standard practice was developed. CONCLUSIONS: Standard UK physiotherapy practice of airway clearance techniques is variable, but patient-centred and targeted to individual need, with adjunctive use of mucoactive agents to enhance and optimise patient management if required. Based on this study, key features of airway clearance techniques have been summarised to help capture standard care, which could be used in future trials involving ACT as part of usual care.

Mucoactive agents for acute respiratory failure in the critically ill: a systematic review and meta-analysis.

PURPOSE: Acute respiratory failure (ARF) is a common cause of admission to intensive care units (ICUs). Mucoactive agents are medications that promote mucus clearance and are frequently administered in patients with ARF, despite a lack of evidence to underpin clinical decision making. The aim of this systematic review was to determine if the use of mucoactive agents in patients with ARF improves clinical outcomes. METHODS: We searched electronic and grey literature (January 2020). Two reviewers independently screened, selected, extracted data and quality assessed studies. We included trials of adults receiving ventilatory support for ARF and involving at least one mucoactive agent compared with placebo or standard care. Outcomes included duration of mechanical ventilation. Meta-analysis was undertaken using random-effects modelling and certainty of the evidence was assessed using Grades of Recommendation, Assessment, Development and Evaluation. RESULTS: Thirteen randomised controlled trials were included (1712 patients), investigating four different mucoactive agents. Mucoactive agents showed no effect on duration of mechanical ventilation (seven trials, mean difference (MD) -1.34, 95% CI -2.97 to 0.29, I2=82%, very low certainty) or mortality, hospital stay and ventilator-free days. There was an effect on reducing ICU length of stay in the mucoactive agent groups (10 trials, MD -3.22, 95% CI -5.49 to -0.96, I2=89%, very low certainty). CONCLUSION: Our findings do not support the use of mucoactive agents in critically ill patients with ARF. The existing evidence is of low quality. High-quality randomised controlled trials are needed to determine the role of specific mucoactive agents in critically ill patients with ARF. PROSPERO REGISTRATION NUMBER: CRD42018095408.

Interventions for oropharyngeal dysphagia in acute and critical care: a systematic review and meta-analysis.

PURPOSE: To determine the effectiveness of dysphagia interventions compared to standard care in improving oral intake and reducing aspiration for adults in acute and critical care. METHODS: We searched electronic literature for randomised and quasi-randomised trials and bibliography lists of included studies to March 2020. Study screening, data extraction, risk of bias and quality assessments were conducted independently by two reviewers. Meta-analysis used fixed effects modelling. The systematic review protocol is registered and published. RESULTS: We identified 22 studies (19 stroke, 2 intensive care stroke and 1 general intensive care) testing 9 interventions and representing 1700 patients. Swallowing treatment showed no evidence of a difference in the time to return to oral intake (n = 33, MD (days) - 4.5, 95% CI - 10.6 to 1.6, 1 study, P = 0.15) (very low certainty) or in aspiration following treatment (n = 113, RR 0.79, 95% CI 0.44 to 1.45, 4 studies, I2 = 0%, P = 0.45) (low certainty). Swallowing treatment showed evidence of a reduced risk of pneumonia (n = 719, RR 0.71, 95% CI 0.56 to 0.89, 8 studies, I2 = 15%, P = 0.004) (low certainty) but no evidence of a difference in swallowing quality of life scores (n = 239, MD - 11.38, 95% CI - 23.83 to 1.08, I 2 = 78%, P = 0.07) (very low certainty). CONCLUSION: There is limited evidence for the effectiveness of swallowing treatments in the acute and critical care setting. Clinical trials consistently measuring patient-centred outcomes are needed.

Mucoactive agent use in adult UK Critical Care Units: a survey of health care professionals' perception, pharmacists' description of practice, and point prevalence of mucoactive use in invasively mechanically ventilated patients.

BACKGROUND: Mechanical ventilation for acute respiratory failure is one of the most common indications for admission to intensive care units (ICUs). Airway mucus clearance is impaired in these patients medication, impaired mucociliary motility, increased mucus production etc. and mucoactive agents have the potential to improve outcomes. However, studies to date have provided inconclusive results. Despite this uncertainty, mucoactives are used in adult ICUs, although the extent of use and perceptions about place in therapy are not known. AIMS AND OBJECTIVES: We aim to describe the use of mucoactive agents in mechanically ventilated patients in UK adult critical care units. Specifically, our objectives are to describe clinicians perceptions about the use of mucoactive agents, understand the indications and anticipated benefits, and describe the prevalence and type of mucoactive agents in use. METHODS: We conducted three surveys. Firstly, a practitioner-level survey aimed at nurses, physiotherapists and doctors to elucidate individual practitioners perceptions about the use of mucoactive agents. Secondly, a critical care unit-level survey aimed at pharmacists to understand how these perceptions translate into practice. Thirdly, a point prevalence survey to describe the extent of prescribing and range of products in use. The practitioner-level survey was disseminated through the UK Intensive Care Society for completion by a multi-professional membership. The unit-level and point prevalence surveys were disseminated cthrough the UK Clinical Pharmacy Association for completion by pharmacists. RESULTS: The individual practitioners survey ranked 'thick secretions' as the main reason for commencing mucoactive agents determined using clinical assessment. The highest ranked perceived benefit for patient centred outcomes was the duration of ventilation. Of these respondents, 79% stated that further research was important and 87% expressed support for a clinical trial. The unit-level survey found that mucoactive agents were used in 83% of units. The most highly ranked indication was again 'thick secretions' and the most highly ranked expected patient centred clinical benefit being improved gas exchange and reduced ventilation time. Only five critical care units provided guidelines to direct the use of mucoactive agents (4%). In the point prevalence survey, 411/993 (41%) of mechanically ventilated patients received at least one mucoactive agent. The most commonly administered mucoactives were inhaled sodium chloride 0.9% (235/993, 24%), systemic carbocisteine (161/993, 16%) and inhaled hypertonic sodium cloride (127/993, 13%). CONCLUSIONS: Mucoactive agents are used extensively in mechanically ventilated adult patients in UK ICUs to manage 'thick secretions', with a key aim to reduce the duration of ventilation. There is widespread support for clinical trials to determine the optimal use of mucoactive agent therapy in this patient population.

Gangrenous appendicitis contained within a Spigelian hernia.

A 66-year-old man with abdominal pain had a 5-year-old mass subsequently identified as a Spigelian hernia. Exploratory laparotomy revealed a strangulated and gangrenous appendix contained within the hernia, necessitating an appendectomy. This case highlights the importance of early identification and exploration of this rare hernia, so that early management can prevent the development of more serious and dangerous symptoms.

Atraumatic spontaneous hemorrhagic cholecystitis.

Hemorrhagic cholecystitis is a rare subtype of acute cholecystitis. It is considered a medical emergency, with a morbidity rate of 32% to 58% and a mortality rate of 15% to 20%. It presents with an acute onset of intense abdominal or back pain that can be mistaken for other conditions such as thoracic aortic dissection. Diagnosis hinges on a high index of suspicion and confirmatory studies, such as computed tomography scan or ultrasound. Specific risk factors identified in the literature include a history of trauma and anticoagulant use. We present an atypical case of spontaneous hemorrhagic cholecystitis with no antecedent risk factors.

A 2 × 2 factorial, randomised, open-label trial to determine the clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care over 52 weeks in adults with bronchiectasis: a protocol for the CLEAR clinical trial.

BACKGROUND: Current guidelines for the management of bronchiectasis (BE) highlight the lack of evidence to recommend mucoactive agents, such as hypertonic saline (HTS) and carbocisteine, to aid sputum removal as part of standard care. We hypothesise that mucoactive agents (HTS or carbocisteine, or a combination) are effective in reducing exacerbations over a 52-week period, compared to usual care. METHODS: This is a 52-week, 2 × 2 factorial, randomized, open-label trial to determine the clinical effectiveness and cost effectiveness of HTS 6% and carbocisteine for airway clearance versus usual care - the Clinical and cost-effectiveness of hypertonic saline (HTS 6%) and carbocisteine for airway clearance versus usual care (CLEAR) trial. Patients will be randomised to (1) standard care and twice-daily nebulised HTS (6%), (2) standard care and carbocisteine (750 mg three times per day until visit 3, reducing to 750 mg twice per day), (3) standard care and combination of twice-daily nebulised HTS and carbocisteine, or (4) standard care. The primary outcome is the mean number of exacerbations over 52 weeks. Key inclusion criteria are as follows: adults with a diagnosis of BE on computed tomography, BE as the primary respiratory diagnosis, and two or more pulmonary exacerbations in the last year requiring antibiotics and production of daily sputum. DISCUSSION: This trial's pragmatic research design avoids the significant costs associated with double-blind trials whilst optimising rigour in other areas of trial delivery. The CLEAR trial will provide evidence as to whether HTS, carbocisteine or both are effective and cost effective for patients with BE. TRIAL REGISTRATION: EudraCT number: 2017-000664-14 (first entered in the database on 20 October 2017). ISRCTN.com, ISRCTN89040295. Registered on 6 July/2018. Funder: National Institute for Health Research, Health Technology Assessment Programme (15/100/01). SPONSOR: Belfast Health and Social Care Trust. Ethics Reference Number: 17/NE/0339. Protocol version: v3.0 Final_14052018.