Rhinovirus 2A is the key protease responsible for instigating the early block to gene expression in infected cells.

Human rhinoviruses (HRVs) express 2 cysteine proteases, 2A and 3C, that are responsible for viral polyprotein processing. Both proteases also suppress host gene expression by inhibiting mRNA transcription, nuclear export and cap-dependent translation. However, the relative contribution that each makes in achieving this goal remains unclear. In this study, we have compared both the combined and individual ability of the two proteases to shut down cellular gene expression using a novel dynamic reporter system. Our findings show that 2A inhibits host gene expression much more rapidly than 3C. By comparing the activities of a representative set of proteases from the three different HRV species, we also find variation in the speed at which host gene expression is suppressed. Our work highlights the key role that 2A plays in early suppression of the infected host cell response and shows that this can be influenced by natural variation in the activity of this enzyme.

Efficacy of a Fractionated 1540-nm Erbium Glass Laser in the Treatment of Dermatofibromas.

BACKGROUND: Treatment of dermatofibromas, beyond surgical excision, has remained inadequate and elusive. Nonsurgical treatment options are desired by both patients and physicians. Erbium glass lasers are known for targeting and remodeling the dermis but have not yet been studied for the treatment of dermatofibromas. OBJECTIVE: To evaluate the efficacy and safety of the fractional 1540-nm erbium glass laser for treatment of dermatofibromas. METHODS: Thirty-five patients representing 44 dermatofibromas completed 2 consecutive monthly treatments with a non-ablative, fractional 1540-nm erbium glass laser and were evaluated at 4, 8, and 12 weeks after the initial treatment. Dermatofibromas were evaluated using patient surveys given before and after the treatments. RESULTS: By week 4, patients reported improvement in color and texture of the dermatofibromas. These improvements were durable through week 12. No complications were reported. CONCLUSIONS: This study demonstrates that the fractional 1540-nm erbium glass laser may be used to improve the color and texture of dermatofibromas and achieve positive patient reported outcomes after only 2 treatments. J Drugs Dermatol. 2022;21(11):1201-1205. doi:10.36849/JDD.6287.

Clinical and economic outcomes of remotely delivered cognitive behaviour therapy versus treatment as usual for repeat unscheduled care users with severe health anxiety: a multicentre randomised controlled trial.

BACKGROUND: It is challenging to engage repeat users of unscheduled healthcare with severe health anxiety in psychological help and high service costs are incurred. We investigated whether clinical and economic outcomes were improved by offering remote cognitive behaviour therapy (RCBT) using videoconferencing or telephone compared to treatment as usual (TAU). METHODS: A single-blind, parallel group, multicentre randomised controlled trial was undertaken in primary and general hospital care. Participants were aged ≥18 years with ≥2 unscheduled healthcare contacts within 12 months and scored >18 on the Health Anxiety Inventory. Randomisation to RCBT or TAU was stratified by site, with allocation conveyed to a trial administrator, research assessors masked to outcome. Data were collected at baseline, 3, 6, 9 and 12 months. The primary outcome was change in HAI score from baseline to six months on an intention-to-treat basis. Secondary outcomes were generalised anxiety, depression, physical symptoms, function and overall health. Health economics analysis was conducted from a health service and societal perspective. RESULTS: Of the 524 patients who were referred and assessed for trial eligibility, 470 were eligible and 156 (33%) were recruited; 78 were randomised to TAU and 78 to RCBT. Compared to TAU, RCBT significantly reduced health anxiety at six months, maintained to 9 and 12 months (mean change difference HAI -2.81; 95% CI -5.11 to -0.50; P = 0.017). Generalised anxiety, depression and overall health was significantly improved at 12 months, but there was no significant change in physical symptoms or function. RCBT was strictly dominant with a net monetary benefit of £3,164 per participant at a willingness to pay threshold of £30,000. No treatment-related adverse events were reported in either group. CONCLUSIONS: RCBT may reduce health anxiety, general anxiety and depression and improve overall health, with considerable reductions in health and informal care costs in repeat users of unscheduled care with severe health anxiety who have previously been difficult to engage in psychological treatment. RCBT may be an easy-to-implement intervention to improve clinical outcome and save costs in one group of repeat users of unscheduled care. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov on 19 Nov 2014 with reference number NCT02298036.

Safety of non-ablative fractional laser for acne scars within 1 month after treatment with oral isotretinoin: A randomized split-face controlled trial.

BACKGROUND AND OBJECTIVE: Based on reports of poor wound healing and scarring, it is currently recommended that patients wait 6 months after completion of oral isotretinoin therapy before the safe initiation of laser treatment. Our aim was to evaluate the safety of non-ablative fractional laser (NAFL) treatment for acne scars within 1 month after isotretinoin therapy. STUDY DESIGN/METHODS: This was a randomized split-face controlled trial involving 10 patients with acne scars who had completed isotretinoin treatment. All patients received three treatments each spaced 4 weeks apart with an erbium-doped 1550 nm NAFL on one side of the face within 1 month after isotretinoin therapy. The untreated side acted as a control. Wound healing and adverse effects as well as acne scar improvement were evaluated by two blinded dermatologists. RESULTS: All patients demonstrated normal wound healing post NAFL treatments, and neither hypertrophic scars nor keloids were observed. Acne scar improvement was satisfactory. CONCLUSION: NAFL treatment for acne scarring appears to be well tolerated within 1 month of completing isotretinoin treatment. Dermatologists should reevaluate the current recommendation to wait 6 months after isotretinoin treatment for acne scar revision with lasers. Other larger studies are necessary to further challenge this dogma. Lasers Surg. Med. 49:886-890, 2017. © 2017 Wiley Periodicals, Inc.

Limited linkages of aboveground and belowground phenology: A study in grape.

PREMISE OF THE STUDY: Plant phenology influences resource utilization, carbon fluxes, and interspecific interactions. Although controls on aboveground phenology have been studied to some degree, controls on root phenology are exceptionally poorly understood. METHODS: We used minirhizotrons to examine the timing of grape root production over 5 yr in Fredonia, New York, USA, in a humid continental climate; and over 3 yr in Oakville, California, USA, in a Mediterranean climate. We used data from previous experiments to examine the relationship of root phenology with aboveground phenology. We compared interannual variability in root and shoot growth and determined the influence of abiotic factors on the timing of root initiation, peak root standing crop, peak root growth rate, and cessation of root growth. KEY RESULTS: Root phenology was not tightly coupled with aboveground phenological periods. Both sites typically had one yearly root flush and high interannual variability in root growth. Root phenology was more variable in California than in New York. In this and other published studies, interannual variation in root phenology was greater than variation in aboveground phenology. The three phenological phases of root growth-root initiation, peak root growth, and root cessation-were related to different suites of abiotic factors. CONCLUSIONS: Root phenology is highly variable among years. Analysis of potential controlling factors over several years suggest that belowground phenological phases should be analyzed separately from each other. If aboveground grape phenology responds differently than belowground phenology to changes in air temperature, global warming may further uncouple the timing of aboveground and belowground growth.

A perforating pilomatricomal horn on the arm of an 11-year-old girl.

Cutaneous horns are uncommon in adults and rare in the pediatric population. Although verruca vulgaris, solar keratosis, and squamous cell carcinoma are more common entities that can present as cutaneous horns in the general population, conditions such as molluscum contagiosum, juvenile xanthgranuloma, and pyogenic granuloma have been reported causes in the pediatric population. We present a case of a perforating pilomatricoma presenting as a cutaneous horn in an 11 year old girl.

Integrating psychological screening into reviews of patients with COPD.

BACKGROUND: People with chronic obstructive pulmonary disease (COPD) have a high prevalence of anxiety and depression, which can have an impact on their symptoms and the way they manage their condition. Intervention that takes psychological distress into account may lead to better outcomes than simple advice-giving. AIM: To explore the feasibility of integrating psychological screening and intervention into nurse-led reviews of patients with COPD. METHOD: Nurses were given training on a pathway developed for patients with COPD. This included screening for depression and anxiety and assessing their severity; providing self-management education by means of a motivational approach; and offering pulmonary rehabilitation. RESULTS: The nurses' level of confidence increased following training. Patients were accepting of the screening process and felt more able and motivated to manage their condition after the intervention. Eleven of the 35 patients that took part in the study period had evidence of anxiety and/or depression. Out of a total of 16 patients eligible for pulmonary rehabilitation, 12 agreed to referral. Of these, three patients were seen by their GP, one was started on antidepressants, and one was referred to the psychology service. CONCLUSION: Training practice nurses to screen for depression and anxiety, and to offer self-management education using a motivational interviewing approach, increased the reported capability and motivation of patients with COPD to manage their condition. It may also improve the uptake of pulmonary rehabilitation. Use of this pathway does not place a burden on other care providers or greatly increase prescribing costs.

Multi-endpoint in vitro toxicological assessment of snus and tobacco-free nicotine pouch extracts.

'Modern' oral tobacco-free nicotine pouches (NPs) are a nicotine containing product similar in appearance and concept to Swedish snus. A three-step approach was taken to analyse the biological effects of NPs and snus extracts in vitro. ToxTracker was used to screen for biomarkers for oxidative stress, cell stress, protein damage and DNA damage. Cytotoxicity, mutagenicity, and genotoxicity were assessed in the following respective assays: Neutral Red Uptake (NRU), Ames and Mouse Lymphoma Assay (MLA). Targeted analysis of phosphorylation signalling and inflammatory markers under non-toxic conditions was used to investigate any potential signalling pathways or inflammatory response. A reference snus (CRP1.1) and four NPs with various flavours and nicotine strengths were assessed. Test article extracts was generated by incubating one pouch in 20 mL of media (specific to each assay) with the inclusion of the pouch material. NP extracts did not induce any cytotoxicity or mutagenic response, genotoxic response was minimal and limited signalling or inflammatory markers were induced. In contrast, CRP1.1 induced a positive response in four toxicological endpoints in the absence of S9: Srxn1 (oxidative stress), Btg2 (cell stress), Ddit3 (protein damage) and Rtkn (DNA damage), and three endpoints in presence of S9: Srxn1, Ddit3 and Rtkn. CRP1.1 was genotoxic when assessed in MLA and activated signalling pathways involved in proliferation and cellular stress and specifically induced phosphorylation of c-JUN, CREB1, p53, p38 MAPK and to a lesser extent AKT1S1, GSK3α/ß, ERK1/2 and RSK1 in a dose-dependent manner. CRP 1.1 extracts resulted in the release of several inflammatory mediators including cytokines IL-1α, IL5, IL6, IL8, IL-1RA, MIF and TNF-ß, receptor IL-2RA, and growth factors FGF-basic, VEGF and M-CSF. In conclusion these assays contribute to the weight of evidence assessment of the potential comparative health risks of NPs and snus.

Procedural pain in neonates in Australian hospitals: a survey update of practices.

AIM: The study aims to determine whether there has been improved uptake of the evidence for the management of procedural pain in neonates throughout Australia. METHODS: An Australian-wide survey was undertaken to determine the use of breastfeeding and sucrose and whether a clinical practice guideline (CPG) or pain assessment tool was used. RESULTS: Data were available from 196 (91%) of the 215 eligible hospitals. A CPG informed the management of neonatal pain in 76 (39%) of the hospitals. There was wide variation in their use between the states, and a significantly higher use of a CPG in higher-level care units. A pain assessment tool was only used in 21 (11%) of the units with greater use in the higher level care neonatal intensive care units (50%) and surgical neonatal intensive care units (80%). Awareness of breastfeeding for procedural pain was reported by 90% of the 196 respondents while 78% reported that it was actually used. Awareness of sucrose for procedural pain was lower than breastfeeding at 79%, with 53% reporting that they used sucrose in their unit. Overall, 89% of the respondents reported that either breastfeeding or sucrose was used for the management of procedural pain in their units. CONCLUSION: There has been an increase in awareness and use of sucrose and breastfeeding for procedural pain in Australia since previous surveys were undertaken in 2004. Continued resources, local pain champions and a national interest group to promote the use of pain management for procedural pain in neonates are needed for continued uptake of the evidence.

Technical validation of the EMMA capnometer under hyperbaric conditions.

INTRODUCTION: End-tidal carbon dioxide (ETCO2) monitoring is essential for monitoring intubated critical care patients, yet its use in hyperbaric environments can be problematic. We postulated that the EMMA mainstream capnometer may function accurately under hyperbaric conditions. METHODS: Stage 1. The EMMA mainstream capnometer was tested at 101 kPa against a reference side-stream capnometer, Philips IntelliVue M3015B microstream, using 10 customised reference gases of various carbon dioxide (CO2) concentrations (2.47%-8.09%, or 18.5-60.7 mmHg at 101 kPa) in either air or oxygen. Stage 2. The functionality and accuracy of the EMMA capnometer was tested under hyperbaric conditions, 121-281 kPa, using the same test gases. RESULTS: At 101 kPa, the EMMA capnometer measured CO2 at levels lower than expected (mean of differences = -2.5 mmHg (95% CI -2.1 to -2.9, P < 0.001)). The Philips capnometer measured CO2 more closely to expected CO2 (mean of differences = -1.1 mmHg (95% CI -0.69 to -1.4, P < 0.001). Both devices demonstrated a significant linear relationship with expected CO2. The EMMA capnometer functioned up to the maximum test pressure (281 kPa). The device over-read CO2 measurements at pressures > 141 kPa. Although variance increased at pressures in the therapeutic range for hyperbaric treatments, a significant linear relationship between expected and EMMA measured CO2 was demonstrated. The EMMA capnometer tolerated pressures to 281 kPa, but its display was limited to CO2 < 99 mmHg. CONCLUSIONS: This study validated EMMA capnometer function to 281 kPa in the hyperbaric environment. The device over-read CO2 measurements at pressures >141 kPa, however there was a linear relationship between expected and measured CO2. The EMMA capnometer may be clinically useful for monitoring expired CO2 in patients undergoing hyperbaric oxygen treatment.

Determining best practice for technical assessment of hookah surface supply diving equipment during diving fatality investigation.

INTRODUCTION: This study aimed to develop a standard process and checklist for technical investigation of hookah diving equipment and apply it to Tasmanian hookah fatality investigations from the last 25 years. METHODS: A literature search was undertaken to identify technical reports and equipment investigations associated with diving accidents. The information was assimilated to create a process and checklist for specifically assessing the hookah apparatus. The checklist was then applied in a gap analysis of Tasmanian hookah diving fatality technical reports from 1995 to 2019. RESULTS: As no papers specifically describing technical evaluation of hookah equipment were identified, references evaluating scuba equipment were used to create a hookah technical assessment process incorporating unique features of the hookah. Features included: owner responsibility for air quality; maintenance, function; exhaust proximity to air intake; reservoir volume; output non-return valves; line pressure; sufficiency of supply; entanglement; hose severance risk; gas supply failure and hosing attachment to the diver. Seven hookah diving deaths occurred in Tasmania (1995-2019) of which three had documented technical assessment. Gap analysis identified inconsistent structure between reports with variability in the case descriptors. Missing technical data included: overview of the hookah systems; accessories; weights; how the apparatus was worn by the diver; compressor suitability; assessment of hookah function; breathing gas output and exhaust position relative to air intake. CONCLUSIONS: The study demonstrated a need to standardise technical reporting of hookah equipment after diving accidents. The checklist generated may serve as a resource for future hookah assessments and inform strategies for preventing future hookah accidents.

Safety and performance of intravenous pumps and syringe drivers in hyperbaric environments.

INTRODUCTION: Critically ill patients require continuation of their care when receiving hyperbaric oxygen treatment. This care may be facilitated via portable electrically powered devices such as intravenous (IV) infusion pumps and syringe drivers, which may create risks in the absence of a comprehensive safety evaluation. We reviewed published safety data for IV infusion pumps and powered syringe drivers in hyperbaric environments and compared the evaluation processes to key requirements documented in safety standards and guidelines. METHODS: A systematic literature review was undertaken to identify English language papers published in the last 15 years, describing the safety evaluations of IV pumps and/or syringe drivers for use in hyperbaric environments. Papers were critically assessed in relation to the requirements of international standards and safety recommendations. RESULTS: Eight studies of IV infusion devices were identified. There were deficiencies in the published safety evaluations of IV pumps for hyperbaric use. Despite a simple, published process for evaluating new devices, and available guidelines for fire safety, only two devices had comprehensive safety assessments. Most studies focused only on whether the device functioned normally under pressure and did not consider implosion/explosion risk, fire safety, toxicity, oxygen compatibility or risk of pressure damage. CONCLUSIONS: Intravenous infusion (and other electrically powered) devices require comprehensive assessment before use under hyperbaric conditions. This would be enhanced by a publicly accessible database hosting the risk assessments. Facilities should conduct their own assessments specific to their environment and practices.

Clinical effectiveness of active Alpha-Stim AID versus sham Alpha-Stim AID in major depression in primary care in England (Alpha-Stim-D): a multicentre, parallel group, double-blind, randomised controlled trial.

BACKGROUND: Randomised sham-controlled trials of cranial electrostimulation with the Alpha-Stim Anxiety Insomnia and Depression (AID) device have reported improved anxiety and depression symptoms; however, no adequately powered sham-controlled trials in major depression are available. We investigated whether active Alpha-Stim AID is superior to sham Alpha-Stim AID in terms of clinical effectiveness for depression symptoms in major depression. METHODS: The Alpha-Stim-D trial was a multicentre, parallel group, double-blind, randomised controlled trial, recruiting participants from 25 primary care centres in two regions in England, UK. Eligible participants were aged 16 years or older with a current diagnosis of primary major depression, a score of 10-19 on the nine-item Patient Health Questionnaire, and had been offered or prescribed and reported taking antidepressant medication for at least 6 weeks in the previous 3 months. Main exclusion criteria were contraindications to Alpha-Stim AID device use, having persistent suicidal ideation or self-harm, neurological conditions, a substance use disorder or dependence, an eating disorder, bipolar disorder, or non-affective psychosis, or receiving psychological treatment in the past 3 months. Eligible participants were randomly assigned (1:1, minimised by region, anxiety disorder, and antidepressant use) to 1 h daily use of active (100 µA) or sham Alpha-Stim AID treatment for 8 weeks. Randomisation was via an independent web-based system, with participants, outcome assessors, and data analyst masked to treatment assignment. The primary outcome was change from baseline in score on the 17-item Hamilton Depression Rating Scale (HDRS-17, GRID version) at 16 weeks after randomisation, with participants analysed by intention to treat (ITT; all randomly assigned participants). Safety was assessed in all randomly assigned participants. The trial is registered with the ISRCTN registry (ISRCTN11853110); status completed. FINDINGS: Between Sept 8, 2020, and Jan 14, 2022, 236 eligible participants were randomly assigned to active or sham Alpha-Stim AID (n=118 each). 156 (66%) participants were women, 77 (33%) were men, and three (1%) self-reported as other gender; 200 (85%) were White British or Irish; and the mean age was 38·0 years (SD 15·3; range 16-83). 102 (86%) participants in the active Alpha-Stim AID group and 98 (83%) in the sham group were followed up 16 weeks after randomisation. In the ITT population, mean change in GRID-HDRS-17 at 16 weeks was -5·9 (95% CI -7·1 to -4·8) in the active Alpha-Stim AID group and -6·5 (-7·7 to -5·4) in the sham group (mean change difference -0·6 [95% CI -1·0 to 2·2], p=0·46). Among the 236 participants, 17 adverse events were reported in 17 (7%) participants (nine [8%] participants in the active Alpha-Stim AID group; and eight [7%] participants in the sham group). One serious adverse event of suicidal ideation leading to hospitalisation was reported in the sham group, which was judged to be unrelated to the device. INTERPRETATION: Active Alpha-Stim AID was safe and acceptable, but no more clinically effective than sham Alpha-Stim AID in major depression. FUNDING: National Institute for Health Research Applied Research Collaboration East Midlands and Electromedical Products International.

Is fixation failure after plate fixation of the symphysis pubis clinically important?

BACKGROUND: Plate fixation is a recognized treatment for pelvic ring injuries involving disruption of the pubic symphysis. Although fixation failure is well known, it is unclear whether early or late fixation failure is clinically important. QUESTIONS/PURPOSES: We therefore determined (1) the incidence and mode of failure of anterior plate fixation for traumatic pubic symphysis disruption; (2) whether failure of fixation was associated with the types of pelvic ring injury or pelvic fixation used; (3) the complications, including the requirement for reoperation or hardware removal; and (4) whether radiographic followup of greater than 1 year alters subsequent management. METHODS: We retrospectively reviewed 148 of 178 (83%) patients with traumatic symphysis pubis diastasis treated by plate fixation between 1994 and 2008. Routine radiographic review, pelvic fracture classification, method of fixation, incidence of fixation failure, timing and mode of failure, and the complications were recorded after a minimum followup of 12 months (mean, 45 months; range, 1-14 years). RESULTS: Hardware breakage occurred in 63 patients (43%), of which 61 were asymptomatic. Breakage was not related to type of plate, fracture classification, or posterior pelvic fixation. Five patients (3%) required revision surgery for failure of fixation or symptomatic instability of the symphysis pubis, and seven patients (5%) had removal of hardware for other reasons, including late deep infection in three (2%). Routine radiographic screening as part of annual followup after 1 year did not alter management. CONCLUSIONS: Our observations suggest the high rate of late fixation failure after plate fixation of the symphysis pubis is not clinically important.

Application of ToxTracker for the toxicological assessment of tobacco and nicotine delivery products.

Consumer demands and innovation have led to an increasingly diverse range of nicotine delivery systems, driven by a desire to reduce risk associated with traditional combustible cigarettes. This speed of change provides a mandate for rapid new product assessment. We have used the validated technology ToxTracker®, to assess biomarkers of DNA damage, protein misfolding, oxidative and cellular stress, across the categories of cigarette (1R6F), tobacco heating product (THP 1.4) and electronic cigarette (ePen 3). In addition, we compared the commonly used test matrices for tobacco and nicotine products; whole aerosol aqueous extracts (AqE) and gas vapour phase (GVP), determining their suitability across the product categories. We demonstrated a significant reduction in oxidative stress and cytotoxicity for THP 1.4 over cigarette, further reduced for ePen 3, when assessed by both dilution and nicotine dosimetry. We also identified that while the extraction matrices AqE and GVP from combustible products were equivalent in the induced responses, this was not true of the other category examples, moreover THP 1.4 GVP demonstrates a >50 % reduction in both toxicity and cytotoxicity endpoints over AqE. This indicates that unlike cigarette, the active components or toxicants for THP and electronic cigarette are associated with the aerosol fraction of these categories.

A randomised controlled trial investigating the clinical and cost-effectiveness of Alpha-Stim AID cranial electrotherapy stimulation (CES) in patients seeking treatment for moderate severity depression in primary care (Alpha-Stim-D Trial).

BACKGROUND: Major depression is the second leading cause of years lost to disability worldwide and is a leading contributor to suicide. However, first-line antidepressants are only fully effective for 33%, and only 40% of those offered psychological treatment attend for two sessions or more. Views gained from patients and primary care professionals are that greater treatment uptake might be achieved if people with depression could be offered alternative and more accessible treatment options. Although there is evidence that the Alpha-Stim Anxiety Insomnia and Depression (AID) device is safe and effective for anxiety and depression symptoms in people with anxiety disorders, there is much less evidence of efficacy in major depression without anxiety. This study investigates the effectiveness of the Alpha-Stim AID device, a cranial electrotherapy stimulation (CES) treatment that people can safely use independently at home. The device provides CES which has been shown to increase alpha oscillatory brain activity, associated with relaxation. METHODS: The aim of this study is to investigate the clinical and cost-effectiveness of Alpha-Stim AID in treatment-seeking patients (aged 16 years upwards) with moderate to moderately severe depressive symptoms in primary care. The study is a multi-centre parallel-group, double-blind, non-commercial, randomised controlled superiority trial. The primary objective of the study is to examine the clinical efficacy of active daily use of 8 weeks of Alpha-Stim AID versus sham Alpha-Stim AID on depression symptoms at 16 weeks (8 weeks after the end of treatment) in people with moderate severity depression. The primary outcome is the 17-item Hamilton Depression Rating Scale at 16 weeks. All trial and treatment procedures are carried out remotely using videoconferencing, telephone and postal delivery considering the COVID-19 pandemic restrictions. DISCUSSION: This study is investigating whether participants using the Alpha-Stim AID device display a reduction in depressive symptoms that can be maintained over 8 weeks post-treatment. The findings will help to determine whether Alpha-Stim AID should be recommended, including being made available in the NHS for patients with depressive symptoms. TRIAL REGISTRATION: ISRTCN ISRCTN11853110 . Registered on 14 August 2020.

Hyperbaric Oxygen for Lower Limb Trauma (HOLLT): an international multi-centre randomised clinical trial.

INTRODUCTION: Hyperbaric oxygen treatment (HBOT) is sometimes used in the management of open fractures and severe soft tissue crush injury, aiming to reduce complications and improve outcomes. METHODS: Patients with open tibial fractures were randomly assigned within 48 hours of injury to receive standard trauma care or standard care plus 12 sessions of HBOT. The primary outcome was the incidence of necrosis or infection or both occurring within 14 days of injury. RESULTS: One-hundred and twenty patients were enrolled. Intention to treat primary outcome occurred in 25/58 HBOT assigned patients and 34/59 controls (43% vs 58%, odds ratio (OR) 0.55, 95% confidence interval (CI) 0.25 to 1.18, P = 0.12). Tissue necrosis occurred in 29% of HBOT patients and 53% of controls (OR 0.35, 95% CI 0.16 to 0.78, P = 0.01). There were fewer late complications in patients receiving HBOT (6/53 vs 18/52, OR 0.22, 95% CI 0.08 to 0.64, P = 0.007) including delayed fracture union (5/53 vs 13/52, OR 0.31, 95% CI 0.10 to 0.95, P = 0.04). Quality of life measures at one and two years were superior in HBOT patients. The mean score difference in short form 36 was 2.90, 95% CI 1.03 to 4.77, P = 0.002, in the short musculoskeletal function assessment (SMFA) was 2.54, 95% CI 0.62 to 4.46, P = 0.01; and in SMFA daily activities was 19.51, 95% CI 0.06 to 21.08, P = 0.05. CONCLUSIONS: In severe lower limb trauma, early HBOT reduces tissue necrosis and the likelihood of long-term complications, and improves functional outcomes. Future research should focus on optimal dosage and whether HBOT has benefits for other injury types.

Elective high-frequency oscillatory versus conventional ventilation in preterm infants: a systematic review and meta-analysis of individual patients' data.

BACKGROUND: Population and study design heterogeneity has confounded previous meta-analyses, leading to uncertainty about effectiveness and safety of elective high-frequency oscillatory ventilation (HFOV) in preterm infants. We assessed effectiveness of elective HFOV versus conventional ventilation in this group. METHODS: We did a systematic review and meta-analysis of individual patients' data from 3229 participants in ten randomised controlled trials, with the primary outcomes of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age, death or severe adverse neurological event, or any of these outcomes. FINDINGS: For infants ventilated with HFOV, the relative risk of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age was 0.95 (95% CI 0.88-1.03), of death or severe adverse neurological event 1.00 (0.88-1.13), or any of these outcomes 0.98 (0.91-1.05). No subgroup of infants (eg, gestational age, birthweight for gestation, initial lung disease severity, or exposure to antenatal corticosteroids) benefited more or less from HFOV. Ventilator type or ventilation strategy did not change the overall treatment effect. INTERPRETATION: HFOV seems equally effective to conventional ventilation in preterm infants. Our results do not support selection of preterm infants for HFOV on the basis of gestational age, birthweight for gestation, initial lung disease severity, or exposure to antenatal corticosteroids. FUNDING: Nestlé Belgium, Belgian Red Cross, and Dräger International.