https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52902 Wed 28 Feb 2024 16:13:54 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34983 Wed 28 Feb 2024 15:19:47 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49111 Wed 27 Sep 2023 13:31:53 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54994 Wed 27 Mar 2024 16:38:54 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45267 150 U/L; and > double admission baseline ALT (for presentations within 24 h post-overdose). Secondary outcomes included adverse reactions to acetylcysteine (cutaneous and systemic). Finding: Out of 6419 paracetamol overdoses, 2763 received acetylcysteine. For the primary analysis, 1003 received the 2-bag and 783 the 3-bag acetylcysteine regimen. When presentation bloods were performed 4 to 8-h post-overdose, 21 (3.1%) developed ALI with the 2-bag regimen vs 16 (2.9%) with the 3-bag regimen (Difference: 0.2%, 95%CI:-1.6 to 2.2). The incidence of hepatotoxicity was: 1.2% (n = 8) with the two-bag regimen and 1.6% (n = 9) with the three-bag regimen (Difference -0.4%, 95%CI -1.75, 0.91). When presentation bloods were performed 8 to 24-h post-overdose, 70 (21%) developed ALI with the 2-bag regimen vs 46 (23%) with the 3-bag regimen (Difference: -2%, 95%CI -9.12 to 5.36). There were significantly less cutaneous and systemic non-allergic anaphylactic reactions recorded after treatment with the two-bag than the three-bag regimen (1.3% [n = 17] and 7.1% [n = 65], Difference: -5.8%, 95%CI -7.6 to -4.0, p < 0.0001), respectively. Interpretation: A two-bag intravenous acetylcysteine regimen was found to be non-inferior to the three-bag regimen with regards to efficacy in preventing acute liver injury for early presentations of paracetamol overdose. No important differences were seen for any other presentations. The two-bag regimen also decreased the incidence of both non-allergic anaphylactic reactions and gastrointestinal adverse events from acetylcysteine treatment.]]> Wed 26 Oct 2022 16:38:34 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45250 Wed 26 Oct 2022 15:22:02 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36361 Wed 24 May 2023 12:19:20 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48158 Wed 24 Apr 2024 11:38:58 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53350 75% decline), the ratio of incident cases to number of people living with HIV (incidence-to-prevalence ratio threshold <0·03), and the ratio of incident cases to deaths (incidence-to-mortality ratio threshold <1·0). Findings: In 2019, there were 36·8 million (95% uncertainty interval [UI] 35·1–38·9) people living with HIV worldwide. There were 0·84 males (95% UI 0·78–0·91) per female living with HIV in 2019, 0·99 male infections (0·91–1·10) for every female infection, and 1·02 male deaths (0·95–1·10) per female death. Global progress in incident cases and deaths between 2010 and 2019 was driven by sub-Saharan Africa (with a 28·52% decrease in incident cases, 95% UI 19·58–35·43, and a 39·66% decrease in deaths, 36·49–42·36). Elsewhere, the incidence remained stable or increased, whereas deaths generally decreased. In 2019, the global incidence-to-prevalence ratio was 0·05 (95% UI 0·05–0·06) and the global incidence-to-mortality ratio was 1·94 (1·76–2·12). No regions met suggested thresholds for progress. Interpretation: Sub-Saharan Africa had both the highest HIV burden and the greatest progress between 1990 and 2019. The number of incident cases and deaths in males and females approached parity in 2019, although there remained more females with HIV than males with HIV. Globally, the HIV epidemic is far from the UNAIDS benchmarks on progress metrics. Funding: The Bill & Melinda Gates Foundation, the National Institute of Mental Health of the US National Institutes of Health (NIH), and the National Institute on Aging of the NIH.]]> Wed 22 Nov 2023 10:32:54 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41947 Wed 22 Mar 2023 14:31:19 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41428 Wed 22 Mar 2023 10:36:57 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49110 Wed 13 Mar 2024 07:53:13 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14375 Wed 11 Apr 2018 14:02:24 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:18827 Wed 11 Apr 2018 13:01:16 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19496 Wed 11 Apr 2018 09:40:34 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41666 Wed 10 Aug 2022 12:13:25 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49869 Wed 07 Jun 2023 15:54:43 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41411 Wed 07 Feb 2024 17:04:33 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38551 Wed 03 Nov 2021 14:23:53 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49074 40 years), sex (male or female), and number of comorbidities (≤1 and ≥2). Randomisation was done using random sequence generation in block randomisation in a 1:1 ratio. Budesonide dry powder was delivered using a turbohaler at a dose of 400 μg per actuation. Participants were asked to take two inhalations twice a day until symptom resolution. The primary endpoint was COVID-19-related urgent care visit, including emergency department assessment or hospitalisation, analysed for both the per-protocol and intention-to-treat (ITT) populations. The secondary outcomes were self-reported clinical recovery (symptom resolution), viral symptoms measured using the Common Cold Questionnare (CCQ) and the InFLUenza Patient Reported Outcome Questionnaire (FLUPro), body temperature, blood oxygen saturations, and SARS-CoV-2 viral load. The trial was stopped early after independent statistical review concluded that study outcome would not change with further participant enrolment. This trial is registered with ClinicalTrials.gov, NCT04416399. Findings: From July 16 to Dec 9, 2020, 167 participants were recruited and assessed for eligibility. 21 did not meet eligibility criteria and were excluded. 146 participants were randomly assigned—73 to usual care and 73 to budesonide. For the per-protocol population (n=139), the primary outcome occurred in ten (14%) of 70 participants in the usual care group and one (1%) of 69 participants in the budesonide group (difference in proportions 0·131, 95% CI 0·043 to 0·218; p=0·004). For the ITT population, the primary outcome occurred in 11 (15%) participants in the usual care group and two (3%) participants in the budesonide group (difference in proportions 0·123, 95% CI 0·033 to 0·213; p=0·009). The number needed to treat with inhaled budesonide to reduce COVID-19 deterioration was eight. Clinical recovery was 1 day shorter in the budesonide group compared with the usual care group (median 7 days [95% CI 6 to 9] in the budesonide group vs 8 days [7 to 11] in the usual care group; log-rank test p=0·007). The mean proportion of days with a fever in the first 14 days was lower in the budesonide group (2%, SD 6) than the usual care group (8%, SD 18; Wilcoxon test p=0·051) and the proportion of participants with at least 1 day of fever was lower in the budesonide group when compared with the usual care group. As-needed antipyretic medication was required for fewer proportion of days in the budesonide group compared with the usual care group (27% [IQR 0–50] vs 50% [15–71]; p=0·025) Fewer participants randomly assigned to budesonide had persistent symptoms at days 14 and 28 compared with participants receiving usual care (difference in proportions 0·204, 95% CI 0·075 to 0·334; p=0·003). The mean total score change in the CCQ and FLUPro over 14 days was significantly better in the budesonide group compared with the usual care group (CCQ mean difference −0·12, 95% CI −0·21 to −0·02 [p=0·016]; FLUPro mean difference −0·10, 95% CI −0·21 to −0·00 [p=0·044]). Blood oxygen saturations and SARS-CoV-2 load, measured by cycle threshold, were not different between the groups. Budesonide was safe, with only five (7%) participants reporting self-limiting adverse events. Interpretation: Early administration of inhaled budesonide reduced the likelihood of needing urgent medical care and reduced time to recovery after early COVID-19. Funding: National Institute for Health Research Biomedical Research Centre and AstraZeneca.]]> Wed 03 May 2023 16:14:55 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49052 Wed 03 May 2023 15:47:20 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41422 Wed 03 Aug 2022 12:06:41 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41420 Wed 03 Aug 2022 11:59:24 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52918 Wed 01 Nov 2023 09:31:20 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19871 Tue 24 Aug 2021 15:15:16 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:42433 Tue 23 Aug 2022 09:58:38 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53282 Tue 21 Nov 2023 10:16:25 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48576 Tue 21 Mar 2023 17:22:54 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47980 Tue 21 Mar 2023 16:56:35 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44603 Tue 18 Oct 2022 08:37:37 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41919 Tue 16 Aug 2022 11:00:51 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47983 60 years (12·7, 11·6 months). Interpretation: Population-level improvements in OS for dnMBC have not been consistently observed in rMBC cohorts nor older women. These findings have implications for counselling patients about prognosis, planning cancer services and trial stratification. Funding: SL was funded in part by a National Health and Medical Research Council (NHMRC) Project Grant ID: 1125433. NH was funded by the NBCF Chair in Breast Cancer Prevention grant (EC-21–001) and a NHMRC Investigator (Leader) grant (194410). BD and SAP were funded in part by the NHMRC Centre of Research Excellence in Medicines Intelligence (1196900).]]> Tue 14 Feb 2023 14:22:54 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:43838 Tue 04 Oct 2022 11:46:36 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41753 Thu 30 Mar 2023 16:09:25 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:42105 PIK3CA-mutant cancer cells. The LORELEI trial tested whether taselisib in combination with letrozole would result in an increased proportion of objective responses and pathological complete responses. Methods: In this multicentre, randomised, double-blind, parallel-cohort, placebo-controlled phase 2, study, we enrolled postmenopausal women (aged ≥18 years) with histologically confirmed, oestrogen receptor (ER)-positive, HER2-negative, stage I–III, operable breast cancer, from 85 hospitals in 22 countries worldwide. To be eligible, patients had have an Eastern Cooperative Oncology Group (ECOG) performance status 0–1, adequate organ function, and had to have evaluable tumour tissue for PIK3CA genotyping. Patients were randomly assigned (1:1) by means of a permuted block algorithm (block size of four) via an interactive voice or web-based response system, to receive letrozole (2·5 mg/day orally, continuously) with either 4 mg of oral taselisib or placebo (on a 5 days-on, 2 days-off schedule) for 16 weeks, followed by surgery. Randomisation was stratified by tumour size and nodal status. Site staff, patients, and the sponsor were masked to treatment assignment. Coprimary endpoints were the proportion of patients who achieved an objective response by centrally assessed breast MRI and a locally assessed pathological complete response in the breast and axilla (ypT0/Tis, ypN0) at surgery in all randomly assigned patients and in patients with PIK3CA-mutant tumours. Analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02273973, and is closed to accrual. Findings: Between Nov 12, 2014, and Aug 12, 2016, 334 participants were enrolled and randomly assigned to receive letrozole and placebo (n=168) or letrozole and taselisib (n=166). Median follow-up was 4·9 months (IQR 4·7–5·1). The study met one of its primary endpoints: the addition of taselisib to letrozole was associated with a higher proportion of patients achieving an objective response in all randomly assigned patients (66 [39%] of 168 patients in the placebo group vs 83 [50%] of 166 in the taselisib group; odds ratio [OR] 1·55, 95% CI 1·00–2·38; p=0·049) and in the PIK3CA-mutant subset (30 [38%] of 79 vs 41 [56%] of 73; OR 2·03, 95% CI 1·06–3·88; p=0·033). No significant differences were observed in pathological complete response between the two groups, either in the overall population (three [2%] of 166 in the taselisib group vs one [1%] of 168 in the placebo group; OR 3·07 [95% CI 0·32–29·85], p=0·37) or in the PIK3CA-mutant cohort (one patient [1%) vs none [0%]; OR not estimable, p=0·48). The most common grade 3–4 adverse events in the taselisib group were gastrointestinal (13 [8%] of 167 patients), infections (eight [5%]), and skin–subcutaneous tissue disorders (eight [5%]). In the placebo group, four (2%) of 167 patients had grade 3 or worse vascular disorders, two (1%) had gastrointestinal disorders, and two (1%) patients had grade 3 or worse infections and infestations. There was no grade 4 hyperglycaemia and grade 3 cases were asymptomatic. Serious adverse events were more common in the taselisib group (eight [5%] patients with infections and seven [4%] with gastrointestinal effects) than in the placebo group (one [1%] patient each with grade 3 postoperative wound and haematoma infection, grade 4 hypertensive encephalopathy, grade 3 acute cardiac failure, and grade 3 breast pain). One death occurred in the taselisib group, which was not considered to be treatment-related. Interpretation: The increase in the proportion of patients who achieved an objective response from the addition of taselisib to endocrine therapy in a neoadjuvant setting is consistent with the clinical benefit observed in hormone receptor-positive, HER2-negative, metastatic breast cancer.]]> Thu 25 Aug 2022 10:26:11 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48574 Thu 24 Aug 2023 15:19:53 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53399 Thu 23 Nov 2023 13:44:14 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:53381 Thu 23 Nov 2023 12:19:50 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48040 Thu 23 Mar 2023 10:12:39 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:29827 Thu 14 Apr 2022 10:59:21 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:40611 Thu 11 Aug 2022 13:48:34 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51477 Thu 07 Sep 2023 10:46:14 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14325 Sat 24 Mar 2018 08:26:22 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:15698 Sat 24 Mar 2018 08:22:27 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:10736 Sat 24 Mar 2018 08:14:29 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:11196 Sat 24 Mar 2018 08:13:35 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:11140 Sat 24 Mar 2018 08:10:29 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17172 Sat 24 Mar 2018 08:06:31 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:18283 Sat 24 Mar 2018 08:04:33 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:18127 Sat 24 Mar 2018 08:04:29 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17298 Sat 24 Mar 2018 08:01:46 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20771 vs as-needed 1·05, 0·92–1·20). We recorded no difference between treatment groups for time to recovery (adjusted p=0·79). Adherence to regular tablets (median tablets consumed per participant per day of maximum 6; 4·0 [IQR 1·6–5·7] in the regular group, 3·9 [1·5–5·6] in the as-needed group, and 4·0 [1·5–5·7] in the placebo group), and number of participants reporting adverse events (99 [18·5%] in the regular group, 99 [18·7%] in the as-needed group, and 98 [18·5%] in the placebo group) were similar between groups. Interpretation: Our findings suggest that regular or as-needed dosing with paracetamol does not affect recovery time compared with placebo in low-back pain, and question the universal endorsement of paracetamol in this patient group.]]> Sat 24 Mar 2018 08:00:22 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17782 Sat 24 Mar 2018 07:57:23 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17973 ENO) to guide management are equivocal. We tested the hypothesis that a management algorithm for asthma in pregnancy based on F_ENO and symptoms would reduce asthma exacerbations. Methods: We undertook a double-blind, parallel-group, controlled trial in two antenatal clinics in Australia. 220 pregnant, non-smoking women with asthma were randomly assigned, by a computer-generated random number list, before 22 weeks’ gestation to treatment adjustment at monthly visits by an algorithm using clinical symptoms (control group) or F_ENO concentrations (active intervention group) used to uptitrate (F_ENO >29 ppb) or downtitrate (F_ENO <16 ppb) inhaled corticosteroid dose. Participants, caregivers, and outcome assessors were masked to group assignment. Longacting β2 agonist and minimum dose inhaled corticosteroid were used to treat symptoms when F_ENO was not increased. The primary outcome was total asthma exacerbations (moderate and severe). Analysis was by intention to treat. This study is registered with the Australian and New Zealand Clinical Trials Registry, number 12607000561482. Findings: 111 women were randomly assigned to the F_ENO group (100 completed) and 109 to the control group (103 completed). The exacerbation rate was lower in the F_ENO group than in the control group (0·288 vs 0·615 exacerbations per pregnancy; incidence rate ratio 0·496, 95% CI 0·325–0·755; p=0·001). The number needed to treat was 6. In the F_ENO group, quality of life was improved (score on short form 12 mental summary was 56·9 [95% CI 50·2–59·3] in F_ENO group vs 54·2 [46·1–57·6] in control group; p=0·037) and neonatal hospitalisations were reduced (eight [8%] vs 18 [17%]; p=0·046). Interpretation: Asthma exacerbations during pregnancy can be significantly reduced with a validated F_ENO-based treatment algorithm.]]> Sat 24 Mar 2018 07:56:43 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:4663 Sat 24 Mar 2018 07:19:34 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:4662 Sat 24 Mar 2018 07:19:34 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:4851 Sat 24 Mar 2018 07:18:46 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22197 8 weeks' duration) without active respiratory disease or infection were randomly assigned to receive gabapentin (maximum tolerable daily dose of 1800 mg) or matching placebo for 10 weeks. Block randomisation was done with randomisation generator software, stratified by sex. Patients and investigators were masked to assigned treatment. The primary endpoint was change in cough-specific quality of life (Leicester cough questionnaire [LCQ] score) from baseline to 8 weeks of treatment, analysed by intention to treat. 62 patients were randomly assigned to gabepentin (n=32) or placebo (n=30) and ten patients withdrew before the study end. Gabapentin significantly improved cough-specific quality of life compared with placebo (between-group difference in LCQ score during treatment period 1·80, 95% CI 0·56-3·04; p=0·004; number needed to treat of 3·58). Side-effects occurred in ten patients (31%) given gabapentin (the most common being nausea and fatigue) and three (10%) given placebo. The treatment of refractory chronic cough with gabapentin is both effective and well tolerated. These positive effects suggest that central reflex sensitisation is a relevant mechanism in refractory chronic cough.]]> Sat 24 Mar 2018 07:16:25 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48183 Sat 11 Mar 2023 12:23:26 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:54031 25 years to <60 years) to be referred for outpatient psychiatric care following self-harm. More recent studies were associated with a small increase in the proportion of presentations (events) that were referred to, and received, psychiatric outpatient treatment. No macro-level factor explained between-study heterogeneity. Interpretation: There is considerable scope for improvement in the allocation and provision of both in- and out-patient psychiatric care following hospital-presenting self-harm, particularly considering that the period after discharge from general hospitals represents the peak risk period for repeat self-harm and suicide. Given the marked between-study heterogeneity, the basis for allocation of aftercare treatment is therefore not yet known and should be further studied. Funding: There was no specific funding for this review.]]> Mon 29 Jan 2024 13:33:54 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:44500 7, intracerebral haemorrhage volume <70 mL, no identified or suspected secondary cause of intracerebral haemorrhage, no thrombotic events within the previous 12 months, no planned surgery in the next 24 h, and no use of anticoagulation), had contrast extravasation on CT angiography (the so-called spot sign), and were treatable within 4·5 h of symptom onset and within 1 h of CT angiography. Patients were randomly assigned (1:1) to receive either 1 g of intravenous tranexamic acid over 10 min followed by 1 g over 8 h or matching placebo, started within 4·5 h of symptom onset. Randomisation was done using a centralised web-based procedure with randomly permuted blocks of varying size. All patients, investigators, and staff involved in patient management were masked to treatment. The primary outcome was intracerebral haemorrhage growth (>33% relative or >6 mL absolute) at 24 h. The primary and safety analyses were done in the intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT01702636). Findings: Between March 1, 2013, and Aug 13, 2019, we enrolled and randomly assigned 100 participants to the tranexamic acid group (n=50) or the placebo group (n=50). Median age was 71 years (IQR 57-79) and median intracerebral haemorrhage volume was 14·6 mL (7·9-32·7) at baseline. The primary outcome was not different between the two groups: 26 (52%) patients in the placebo group and 22 (44%) in the tranexamic acid group had intracerebral haemorrhage growth (odds ratio [OR] 0·72 [95% CI 0·32-1·59], p=0·41). There was no evidence of a difference in the proportions of patients who died or had thromboembolic complications between the groups: eight (16%) in the placebo group vs 13 (26%) in the tranexamic acid group died and two (4%) vs one (2%) had thromboembolic complications. None of the deaths was considered related to study medication. Interpretation: Our study does not provide evidence that tranexamic acid prevents intracerebral haemorrhage growth, although the treatment was safe with no increase in thromboembolic complications. Larger trials of tranexamic acid, with simpler recruitment methods and an earlier treatment window, are justified. Funding: National Health and Medical Research Council, Royal Melbourne Hospital Foundation.]]> Mon 13 Nov 2023 13:34:03 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47964 70 mm Hg associated with worse outcomes]), right atrial volume index (pinteraction=0·012 [≥29·7 mL/m2, worse outcomes]), and sex (pinteraction=0·02 [men, worse outcomes]). There were no differences in the composite safety endpoint between the two groups (n=116 [38%] for shunt device vs n=97 [31%] for sham procedure; p=0·11). Interpretation: Placement of an atrial shunt device did not reduce the total rate of heart failure events or improve health status in the overall population of patients with heart failure and ejection fraction of greater than or equal to 40%. Funding: Corvia Medical.]]> Mon 13 Feb 2023 15:45:01 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51418 Mon 04 Sep 2023 14:57:16 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45262 p=<0.0001) by up to a 24 fold (96% reduction) and in nasal wash (p=0.0107) up to a 15 fold (93% reduction) in comparison to untreated animals. Interpretation: The results of our study support clinical development of a therapy based on prophylactic TLR2/6 innate immune activation in the URT, to reduce SARS-CoV-2 transmission and provide protection against COVID-19.]]> Fri 28 Oct 2022 11:45:44 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:52791 Fri 27 Oct 2023 14:07:59 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49724 Fri 23 Jun 2023 10:08:54 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:51957 Fri 22 Sep 2023 17:07:03 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49499 Fri 19 May 2023 12:01:55 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:42271 Fri 19 Aug 2022 14:44:24 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:48462 Fri 17 Mar 2023 12:14:40 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:39715 SLC16A2 gene encoding monocarboxylate transporter 8 (MCT8), is characterised by intellectual and motor disability resulting from cerebral hypothyroidism and chronic peripheral thyrotoxicosis. We sought to systematically assess the phenotypic characteristics and natural history of patients with MCT8 deficiency. Methods: We did an international, multicentre, cohort study, analysing retrospective data from Jan 1, 2003, to Dec 31, 2019, from patients with MCT8 deficiency followed up in 47 hospitals in 22 countries globally. The key inclusion criterion was genetically confirmed MCT8 deficiency. There were no exclusion criteria. Our primary objective was to analyse the overall survival of patients with MCT8 deficiency and document causes of death. We also compared survival between patients who did or did not attain full head control by age 1·5 years and between patients who were or were not underweight by age 1–3 years (defined as a bodyweight-for-age Z score <–2 SDs or <5th percentile according to WHO definition). Other objectives were to assess neurocognitive function and outcomes, and clinical parameters including anthropometric characteristics, biochemical markers, and neuroimaging findings. Findings: Between Oct 14, 2014, and Jan 17, 2020, we enrolled 151 patients with 73 different MCT8 (SLC16A2) mutations. Median age at diagnosis was 24·0 months (IQR 12·0-60·0, range 0·0-744·0). 32 (21%) of 151 patients died; the main causes of mortality in these patients were pulmonary infection (six [19%]) and sudden death (six [19%]). Median overall survival was 35·0 years (95% CI 8·3–61·7). Individuals who did not attain head control by age 1·5 years had an increased risk of death compared with patients who did attain head control (hazard ratio [HR] 3·46, 95% CI 1·76–8·34; log-rank test p=0·0041). Patients who were underweight during age 1–3 years had an increased risk for death compared with patients who were of normal bodyweight at this age (HR 4·71, 95% CI 1·26–17·58, p=0·021). The few motor and cognitive abilities of patients did not improve with age, as evidenced by the absence of significant correlations between biological age and scores on the Gross Motor Function Measure-88 and Bayley Scales of Infant Development III. Tri-iodothyronine concentrations were above the age-specific upper limit in 96 (95%) of 101 patients and free thyroxine concentrations were below the age-specific lower limit in 94 (89%) of 106 patients. 59 (71%) of 83 patients were underweight. 25 (53%) of 47 patients had elevated systolic blood pressure above the 90th percentile, 34 (76%) of 45 patients had premature atrial contractions, and 20 (31%) of 64 had resting tachycardia. The most consistent MRI finding was a global delay in myelination, which occurred in 13 (100%) of 13 patients. Interpretation: Our description of characteristics of MCT8 deficiency in a large patient cohort reveals poor survival with a high prevalence of treatable underlying risk factors, and provides knowledge that might inform clinical management and future evaluation of therapies. Funding: Netherlands Organisation for Health Research and Development, and the Sherman Foundation.]]> Fri 17 Jun 2022 17:24:04 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:47327 Fri 13 Jan 2023 11:06:42 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:38069 Fri 12 Nov 2021 12:17:35 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41775 80%) in 2017. More than 253 000 people did not have access to sewer or septic sanitation facilities in the city of Harare, Zimbabwe, despite 88·6% (95% UI 87·2–89·7) access overall. Many units were able to transition from the least safe facilities in 2000 to safe facilities by 2017; for units in which populations primarily practised open defecation in 2000, 686 (95% UI 664–711) of the 1830 (1797–1863) units transitioned to the use of improved sanitation. Geographical disparities in access to improved water across units decreased in 76·1% (95% UI 71·6–80·7) of countries from 2000 to 2017, and in 53·9% (50·6–59·6) of countries for access to improved sanitation, but remained evident subnationally in most countries in 2017. Interpretation: Our estimates, combined with geospatial trends in diarrhoeal burden, identify where efforts to increase access to safe drinking water and sanitation facilities are most needed. By highlighting areas with successful approaches or in need of targeted interventions, our estimates can enable precision public health to effectively progress towards universal access to safe water and sanitation.]]> Fri 12 Aug 2022 11:56:50 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41776 Fri 12 Aug 2022 11:56:34 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:37048 Fri 07 Aug 2020 15:02:13 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:49118 Fri 05 May 2023 11:46:16 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41586 Fri 05 Aug 2022 14:51:46 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:41508 Fri 05 Aug 2022 11:14:33 AEST ]]>