Treatment options for progression or recurrence of glioblastoma: a network meta-analysis

For treatment of first recurrence of GBM, among people previously treated with surgery and standard chemoradiotherapy, the combination treatments evaluated did not improve overall survival compared with LOM monotherapy and were often associated with a higher risk of severe adverse events. Limited evidence suggested that re‐operation with or without re‐irradiation and chemotherapy may be suitable for selected candidates. Evidence on second recurrence is sparse. Re‐irradiation with or without bevacizumab may be of value in selected individuals, but more evidence is needed

Family-centred approaches to the prevention of mother to child transmission of HIV

Background: Prevention of mother to child transmission (PMTCT) programmes have traditionally been narrow in scope, targeting biomedical interventions during the perinatal period, rather than considering HIV as a family disease. This limited focus restricts programmes' effectiveness, and the opportunity to broaden prevention measures has largely been overlooked. Although prevention of vertical transmission is crucial, consideration of the family environment can enhance PMTCT. Family-centred approaches to HIV prevention and care present an important direction for preventing paediatric infections while improving overall family health. This paper reviews available literature on PMTCT programmatic models that have taken a broader or family-centred approach. We describe findings and barriers to the delivery of family-centred PMTCT and identify a number of promising new directions that may achieve more holistic services for children and families. Methods: Literature on the effectiveness of family-centred PMTCT interventions available via PubMed, EMBASE and PsycINFO were searched from 1990 to the present. Four hundred and three abstracts were generated. These were narrowed to those describing or evaluating PMTCT models that target broader aspects of the family system before, during and/or after delivery of an infant at risk of acquiring HIV infection (N = 14). Results: The most common aspects of family-centred care incorporated by PMTCT studies and programme models included counselling, testing, and provision of antiretroviral treatment for infected pregnant women and their partners. Antiretroviral therapy was also commonly extended to other infected family members. Efforts to involve fathers in family-based PMTCT counselling, infant feeding counselling, and general decision making were less common, though promising. Also promising, but rare, were PMTCT programmes that use interventions to enrich family capacity and functioning; these include risk assessments for intimate partner violence, attention to mental health issues, and the integration of early childhood development services. Conclusions: Despite barriers, numerous opportunities exist to expand PMTCT services to address the health needs of the entire family. Our review of models utilizing these approaches indicates that family-centred prevention measures can be effectively integrated within programmes. However, additional research is needed in order to more thoroughly evaluate their impact on PMTCT, as well as on broader family health outcomes

Treatment options for recurrent glioblastoma: a network meta-analysis

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:. To evaluate the effectiveness of further treatment/s for first and subsequent recurrence of glioblastoma multiforme (GBM) among people who have received the standard of care for primary treatment of the disease (chemoradiotherapy) or following development of GBM from a lower grade (radiotherapy with subsequent temozolomide at relapse); and to prepare a brief economic commentary on the available evidence

The nature and prevalence of psychological problems in New Zealand primary healthcare: a report on Mental Health and General Practice Investigation ( MaGPIe)

Aims This paper describes the methods used in a study of the prevalence and types of common mental disorders among patients attending New Zealand general practices, and reports some key findings from the first phase of the study. The study also aimed to determine the degree of associated disability and other factors influencing recognition, management, course and outcome of these disorders, and subsequent papers will address these issues. Methods General practitioners (GPs) were selected randomly. In the first phase of the study, all adult attenders at each practice on selected days were administered a short questionnaire, the General Health Questionnaire (GHQ-12), which screens for psychological symptoms. The GP recorded the reasons for each consultation, and was interviewed at the end of each day about selected patients to determine their opinion about the type of psychological problems experienced. Selected patients were then visited in their own homes and an extensive interview conducted, which included the Composite International Diagnostic Interview (CIDI) to determine mental health status, the World Health Organization’s Disability Assessment Schedule (WHODAS) to determine disability, and a detailed exploration of use of health services. In the second phase of the study, patients were contacted by telephone at three, six, nine and 12 months, and both patients and GPs were re-interviewed at 12 months. Results The study achieved a very high response rate among the GPs (90%). Nearly all eligible patients (93%) completed the GHQ screening, and their response rate was 70% for the first-phase interview. GPs thought that 54% of female and 46% of male patients had experienced some level of psychological problems in the past year. GHQ screening also found that more than half of those attending their general practitioner experienced some psychological symptoms at initial screening, and the CIDI interview found that more than one in three had a diagnosable mental disorder during the past 12 months. The most common mental disorders were depressive, anxiety and substance use disorders. These disorders were more common among younger than older general practice attenders, and comorbidity was high. Conclusions Mental health problems are very common among general practice attenders. Contrary to the prevailing view that general practitioners seldom identify psychological problems in their patients, they identified about half their patients as having some type of psychological problems in the past year, although they considered that these were moderate or severe in about only one in ten patients. Further work from this large New Zealand study will focus on the nature of the relationship between disorder and disability, and on the recognition, management and outcome of psychological problems

Afferent specific role of NMDA receptors for the circuit integration of hippocampal neurogliaform cells.

This is the final version of the article. Available from Nature Publishing Group via the DOI in this record.Appropriate integration of GABAergic interneurons into nascent cortical circuits is critical for ensuring normal information processing within the brain. Network and cognitive deficits associated with neurological disorders, such as schizophrenia, that result from NMDA receptor-hypofunction have been mainly attributed to dysfunction of parvalbumin-expressing interneurons that paradoxically express low levels of synaptic NMDA receptors. Here, we reveal that throughout postnatal development, thalamic, and entorhinal cortical inputs onto hippocampal neurogliaform cells are characterized by a large NMDA receptor-mediated component. This NMDA receptor-signaling is prerequisite for developmental programs ultimately responsible for the appropriate long-range AMPAR-mediated recruitment of neurogliaform cells. In contrast, AMPAR-mediated input at local Schaffer-collateral synapses on neurogliaform cells remains normal following NMDA receptor-ablation. These afferent specific deficits potentially impact neurogliaform cell mediated inhibition within the hippocampus and our findings reveal circuit loci implicating this relatively understudied interneuron subtype in the etiology of neurodevelopmental disorders characterized by NMDA receptor-hypofunction.Proper brain function depends on the correct assembly of excitatory and inhibitory neurons into neural circuits. Here the authors show that during early postnatal development in mice, NMDAR signaling via activity of long-range synaptic inputs onto neurogliaform cells is required for their appropriate integration into the hippocampal circuitry.We thank Daniel Abebe for mouse colony maintenance and Kurt Auville for additional assistance with confocal imaging. We thank UNC Vector Core and Ed Boyden, MIT, Cambridge, MA, USA for generously providing AAV9-syn-Chrimson-TdTomato and AAV9-syn-Chronos-GFP. This work was supported by an intramural award to C.J.M. from the Eunice Kennedy–Shriver National Institute of Child Health and Human Development and a Competitive Fellowship Award to J.C.W. from the National Institute of Neurological Disorders and Strok

The DAFNEplus programme for sustained type 1 diabetes self management: Intervention development using the Behaviour Change Wheel

AIMS: Self-management programmes for type 1 diabetes, such as the UK's Dose Adjustment for Normal Eating (DAFNE), improve short-term clinical outcomes but difficulties maintaining behavioural changes attenuate long-term impact. This study used the Behaviour Change Wheel (BCW) framework to revise the DAFNE intervention to support sustained behaviour change. METHODS: A four-step method was based on the BCW intervention development approach: 1) Identifying self-management behaviours and barriers/enablers to maintaining them via stakeholder consultation and evidence synthesis, and mapping barriers/enablers to the Capability, Opportunity, Motivation-Behaviour (COM-B) model. 2) Specifying behaviour change techniques (BCTs) in the existing DAFNE intervention using the Behaviour Change Techniques Taxonomy (BCTTv1). 3) Identifying additional BCTs to target the barriers/enablers using the BCW and BCTTv1. 4) Parallel stakeholder consultation to generate recommendations for intervention revision. Revised materials were co-designed by stakeholders (diabetologists, psychologists, specialist nurses and dietitians). RESULTS: Thirty-four barriers and five enablers to sustaining self-management post-DAFNE, were identified. The existing DAFNE intervention contained 24 BCTs, which partially addressed the enablers. Twenty-seven BCTs were added, including 'Habit formation', 'Credible source' and 'Conserving mental resources'. Fifteen stakeholder-agreed recommendations for content and delivery were incorporated into the final DAFNEplus intervention, comprising three co-designed components: (1) face-to-face group learning course, (2) individual structured follow-up sessions, (3) technological support, including blood glucose data management. CONCLUSIONS: This method provided a systematic approach to specifying and revising a behaviour change intervention incorporating stakeholder input. The revised DAFNEplus intervention aims to support the maintenance of behavioural changes by targeting barriers and enablers to sustaining self-management behaviours

PARADIGM-2: Two parallel phase I studies of olaparib and radiotherapy or olaparib and radiotherapy plus temozolomide in patients with newly diagnosed glioblastoma, with treatment stratified by MGMT status

Glioblastoma has a dismal prognosis and molecular targeted agents have failed to improve outcomes to date. PARADIGM-2 is a phase I dose escalation study evaluating olaparib plus radiotherapy ± temozolomide in newly diagnosed glioblastoma, using MGMT methylation status to stratify patients and inform treatment schedules

Which factors impact on quality of life for adults with blepharospasm and hemifacial spasm?

Purpose: Benign essential blepharospasm (BEB) and hemifacial spasm (HFS) are debilitating conditions causing spasms to the eyes and/or face and can significantly impact on quality of life (QoL). Initial research has highlighted potential factors impacting on QoL in BEB, but there remains a wealth of demographic, clinical, and psychosocial factors that may contribute to QoL but have not received attention. Methods: Cross-sectional baseline data were collected before a single-masked randomised controlled trial from 130 adults with BEB and HFS recruited from botulinum toxin clinics at Moorfields Eye Hospital, London. QoL was measured using the 24-item Craniocervical Dystonia Questionnaire (CDQ24), which provides a total score and five subscale scores relating to Stigma, Emotional state, Pain, Activities of daily living (ADL), and Social/family life. Treating clinicians provided clinical data. Hierarchical multiple regressions were performed on this baseline data to identify significant predictors of QoL. Results: ADL and Stigma were the areas most impacted upon whilst patients experienced better adjustment in relation to Pain, Social/family life, and Emotional state. CDQ24 Total scores were explained by the model (80% variance) and were significantly associated with appearance concerns, emotional representations, perceived negative consequences of the condition, mood, and dose of botulinum toxin. Conclusions: Patients with BEB and HFS report a detrimental impact on ADL and perceived stigma in relation to their condition. Predominantly, individual perceptions and mood are associated with QoL in this population, rather than demographic and clinical factors, signifying areas to target in the design of future healthcare services or interventions