Explore the vast range of titles available.

Background Debilitating Symptom Complexes Attributed to Ticks (DSCATT) is a chronic, debilitating illness associated with tick bites in Australia. DSCATT is of unknown aetiology, can impact emotional well‐being and has no recognised treatments. Objective The development and piloting of a novel psychotherapeutic adjunctive intervention for DSCATT that aimed to increase daily functioning, improve quality of life and reduce the impact of symptoms in people with DSCATT. Methods This is a single‐site, intervention development and acceptability study. The intervention was developed iteratively according to a Human‐Centred Design (HCD) approach and manualised across four phases, with input from end users at each phase: qualitative interviews, development of the intervention, piloting, and revising and refining the intervention. Acceptability of the prototype intervention was evaluated through thematic template analysis of exit interviews. Self‐report measures were completed before and after intervention delivery. Results Following qualitative interviews with 13 participants (11 females and 2 males; aged 35–70 years), the intervention was informed by an Acceptance and Commitment Therapy (ACT) model interwoven with cognitive and behavioural strategies that targeted DSCATT‐specific difficulties. The manualised intervention consisted of 12 1‐h weekly individual sessions, delivered by psychologists via Telehealth (video call or telephone). Modules addressed the six core psychological processes of ACT, alongside DSCATT‐specific modules addressing cognitive function, sleep and social relationships. Pilot testing and follow‐up interviews were conducted in a separate sample of six individuals with DSCATT (all females; aged 46–71 years). All participants reported that the approach benefited their emotional well‐being and overall health and would recommend it to others with DSCATT. Conclusions This is a novel and theoretically driven psychotherapeutic intervention for DSCATT, co‐produced with patient involvement across four phases. Pilot testing suggested the manualised intervention was feasible and acceptable, supporting future evaluation of feasibility and treatment outcomes with randomised controlled trials. Patient or Public Contribution This study involved the engagement and participation of individuals with DSCATT across four stages of the project, according to an HCD approach—the choice of the intervention; the development of the intervention; the piloting of the intervention, and the assessment of the intervention. Trial Registration The pilot study component of this project was prospectively registered on the Australian and New Zealand Clinical Trial Registry (ANZCTR); trial ID: ACTRN12621001032842.

Background Most patients with Posttraumatic Stress Disorder (PTSD) suffer residual symptoms following first-line treatment. Oxidative stress has been implicated in the pathophysiology of PTSD. N-acetylcysteine (NAC) is a precursor of the brain’s primary antioxidant, glutathione, and may diminish oxidative cellular damage. An 8-week pilot study of NAC in veterans with PTSD found that symptoms were significantly reduced in the NAC group compared to placebo. This study aims to confirm these findings with a larger sample in a double-blind, placebo-controlled trial to further explore the efficacy of NAC as an adjunctive therapy in treatment-resistant PTSD. Methods A multicentre, randomised, double-blind, placebo-controlled trial for adult patients who still meet criteria for PTSD following first-line treatment. The intervention comprises either NAC as a fixed dose regime of 2.7 g/day (900 mg three times daily) administered orally for 12 weeks, or placebo. Standard care for PTSD will continue in addition, including other pharmacotherapies. Detailed clinical data will be collected at randomisation and weeks 4, 8, 12, 16, and 64 post-randomisation, with self-report measures completed weekly from baseline to 16 weeks and at 64 weeks post-randomisation. Blood-based biomarkers will be collected at baseline and 12 weeks to assess the mechanism of effect. The primary outcome measure will be change in Clinician-Administered PTSD Scale for DSM-5 at 12 weeks compared with baseline. Secondary outcomes will be change in quality of life, depression, anxiety, substance use and craving, and somatic symptoms. With 126 completed participants (63 per arm), the study is powered at 80% to detect a true difference in the primary outcome measure using a two-tailed analysis with alpha = 0.05, beta = 0.2. Discussion This is the first multicentre, double blind, randomised, placebo-controlled trial of adjunctive NAC for treatment-resistant PTSD. NAC has an established safety profile, is readily available and easy to administer, and has a favourable tolerability profile, therefore making it an attractive adjunctive therapy. Inclusion of blood analyses to assess potential target engagement biomarkers of oxidative stress and neuroinflammation may help gauge the biological mechanisms of effect of NAC. Trial registration ACTRN12618001784202, retrospectively registered 31/10/2018, URL: http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376004 .

ObjectivesIdiopathic Generalised Epilepsy is not a benign condition with increasing evidence of enduring cognitive deficits beyond seizures. We aimed to describe the temporal distribution, duration, and relationship to sleep of interictal discharges (IEDs) using outpatient ambulatory 24-hour EEG recordings (aEEG) in juvenile absence epilepsy (JAE).MethodsWe retrospectively identified 15 patients with JAE undergoing treatment adjustment with at least three aEEGs between 2012–2020. JAE was classified with onset of first or predominant absence seizures after age 9 years. We used a published automated detection algorithm to assist aEEG review and recorded the timing and length of IEDs. Following training, PH/AD independently marked IEDs with any uncertain or discordant IEDs resolved by WD. For each individual recording, the timing and length of the discharges was plotted against 24-hour clock.Results15 patients (onset age 9 to 16 years), had a total of 14701 IEDs (median 104; IQR 11 – 403). 9917 (67.5%) IEDs occurred between 22:00 and 07:00 (individual aEEG median 63%; IQR 49.8% – 92.3%). IEDs show an overall pattern of clustered discharges during sleep compared to a more sporadic frequency in wakefulness. In addition, during sleep IEDs oscillate between high frequency peaks and quiescent periods throughout the night.ConclusionJAE demonstrates a cyclical pattern in the distribution of IEDs with two-thirds occurring during sleep. The oscillating pattern of IEDs during sleep has not been previously reported in humans and suggests coupling to a sleep phase generator, a critical time for memory encoding.

A number of guidelines are available for the management of congenital heart diseases (CHD) from infancy to adult life. However, these guidelines are for patients living in high-income countries. Separate guidelines, applicable to Indian children, are required when recommending an intervention for CHD, as often these patients present late in the course of the disease and may have coexisting morbidities and malnutrition. Guidelines emerged following expert deliberations at the National Consensus Meeting on Management of Congenital Heart Diseases in India, held on August 10 and 11, 2018, at the All India Institute of Medical Sciences. The meeting was supported by Children's HeartLink, a nongovernmental organization based in Minnesota, USA. The aim of the study was to frame evidence-based guidelines for (i) indications and optimal timing of intervention in common CHD; (ii) follow-up protocols for patients who have undergone cardiac surgery/catheter interventions for CHD; and (iii) indications for use of pacemakers in children. Evidence-based recommendations are provided for indications and timing of intervention in common CHD, including left-to-right shunts (atrial septal defect, ventricular septal defect, atrioventricular septal defect, patent ductus arteriosus, and others), obstructive lesions (pulmonary stenosis, aortic stenosis, and coarctation of aorta), and cyanotic CHD (tetralogy of Fallot, transposition of great arteries, univentricular hearts, total anomalous pulmonary venous connection, Ebstein's anomaly, and others). In addition, protocols for follow-up of postsurgical patients are also described, disease wise. Guidelines are also given on indications for implantation of permanent pacemakers in children.

Breakthrough infections with SARS-CoV-2 Delta variant have been reported in doubly-vaccinated recipients and as re-infections. Studies of viral spread within hospital settings have highlighted the potential for transmission between doubly-vaccinated patients and health care workers and have highlighted the benefits of high-grade respiratory protection for health care workers. However the extent to which vaccination is preventative of viral spread in health care settings is less well studied. Here, we analysed data from 118 vaccinated health care workers (HCW) across two hospitals in India, constructing two probable transmission networks involving six HCWs in Hospital A and eight HCWs in Hospital B from epidemiological and virus genome sequence data, using a suite of computational approaches. A maximum likelihood reconstruction of transmission involving known cases of infection suggests a high probability that doubly vaccinated HCWs transmitted SARS-CoV-2 between each other and highlights potential cases of virus transmission between individuals who had received two doses of vaccine. Our findings show firstly that vaccination may reduce rates of transmission, supporting the need for ongoing infection control measures even in highly vaccinated populations, and secondly we have described a novel approach to identifying transmissions that is scalable and rapid, without the need for an infection control infrastructure.

JustificationA number of guidelines are available for management of congenital heart diseases from infancy to adult life. However, these guidelines are for patients living in high income countries. Separate guidelines, applicable to Indian children, are required when recommending an intervention for congenital heart diseases, as often these patients present late in the course of the disease and may have co-existing morbidities and malnutrition.ProcessGuidelines emerged following expert deliberations at the National Consensus Meeting on Management of Congenital Heart Diseases in India, held on 10th and 11th of August 2018 at the All India Institute of Medical Sciences, New Delhi. The meeting was supported by Children’s HeartLink, a non-governmental organization based in Minnesota, USA.ObjectivesTo frame evidence based guidelines for (i) indications and optimal timing of intervention in common congenital heart diseases; (ii) follow-up protocols for patients who have undergone cardiac surgery/catheter interventions for congenital heart diseases.RecommendationsEvidence based recommendations are provided for indications and timing of intervention in common congenital heart diseases, including left-to-right shunts (atrial septal defect, ventricular septal defect, atrioventricular septal defect, patent ductus arteriosus and others), obstructive lesions (pulmonary stenosis, aortic stenosis and coarctation of aorta) and cyanotic congenital heart diseases (tetralogy of Fallot, transposition of great arteries, univentricular hearts, total anomalous pulmonary venous connection, Ebstein anomaly and others). In addition, protocols for follow-up of post surgical patients are also described, disease wise.