Craniectomy size for subdural haematomas and the impact on brain shift and outcomes

BACKGROUND: Midline shift in trauma relates to the severity of head injury. Large craniectomies are thought to help resolve brain shift but can be associated with higher rates of morbidity. This study explores the relationship between craniectomy size and subtemporal decompression for acute subdural haematomas with the resolution of brain compression and outcomes. No systematic study correlating these measures has been reported. METHOD: A retrospective study of all adult cases of acute subdural haematomas that presented to a Major Trauma Centre and underwent a primary decompressive craniectomy between June 2008 and August 2013. Data collection included patient demographics and presentation, imaging findings and outcomes. All imaging metrics were measured by two independent trained assessors. Compression was measured as midline shift, brainstem shift and cisternal effacement. RESULTS: Thirty-six patients with mean age of 36.1 ± 12.5 (range 16-62) were included, with a median follow-up of 23.5 months (range 2.2-109.6). The median craniectomy size was 88.7 cm2 and the median subtemporal decompression was 15.0 mm. There was significant post-operative resolution of shift as measured by midline shift, brainstem shift and cisternal effacement score (all p < .00001). There was no mortality, and the majority of patients made a good recovery with 82.8% having a Modified Rankin Score of 2 or less. There was no association between craniectomy size or subtemporal decompression and any markers of brain shift or outcome (all R2 < 0.05). CONCLUSIONS: This study suggests that there is no clear relationship between craniectomy size or extent of subtemporal decompression and resolution of brain shift or outcome. Further studies are needed to assess the relative efficacy of large craniectomies and the role of subtemporal decompression

Opioid-related deaths during hospital admissions or shortly after discharge in the United Kingdom: A thematic framework analysis of coroner reports

BACKGROUND: People who use heroin and other illicit opioids are at high risk of fatal overdose in the days after hospital discharge, but the reasons for this risk have not been studied. METHODS: We used the National Programme on Substance Abuse Deaths, a database of coroner reports for deaths following psychoactive drug use in England, Wales, and Northern Ireland. We selected reports where the death occurred between 2010 and 2021, an opioid was detected in toxicology testing, the death was related to nonmedical opioid use, and death was either during an acute medical or psychiatric hospital admission or within 14 days after discharge. We used thematic framework analysis of factors that may contribute to the risk of death during hospital admission or after discharge. RESULTS: We identified 121 coroners’ reports; 42 where a patient died after using drugs during hospital admission, and 79 where death occurred shortly after discharge. The median age at death was 40 (IQR 34–46); 88 (73%) were male; and sedatives additional to opioids were detected at postmortem in 88 cases (73%), most commonly benzodiazepines. In thematic framework analysis, we categorised potential causes of fatal opioid overdose into three areas: (a) hospital policies and actions. Zero-tolerance policies mean that patients conceal drug use and use drugs in unsafe places such as locked bathrooms. Patients may be discharged to locations such as temporary hostels or the street while recovering. Some patients bring their own medicines or illicit opioids due to expectations of low-quality care, including undertreated withdrawal or pain; (b) high-risk use of sedatives. People may increase sedative use to manage symptoms of acute illness or a mental health crisis, and some may lose tolerance to opioids during a hospital admission; (c) declining health. Physical health and mobility problems posed barriers to post-discharge treatment for substance use, and some patients had sudden deteriorations in health that may have contributed to respiratory depression. CONCLUSION: Hospital admissions are associated with acute health crises that increase the risk of fatal overdose for patients who use illicit opioids. Hospitals need guidance to help them care for this patient group, particularly in relation to withdrawal management, harm reduction interventions such as take-home naloxone, discharge planning including continuation of opioid agonist therapy during recovery, management of poly-sedative use, and access to palliative care

The impact of main belt asteroids on infrared--submillimetre photometry and source counts

> Among the components of the infrared and submillimetre sky background, the closest layer is the thermal emission of dust particles and minor bodies in the Solar System. This contribution is especially important for current and future infrared and submillimetre space instruments --like those of Spitzer, Akari and Herschel -- and must be characterised by a reliable statistical model. > We describe the impact of the thermal emission of main belt asteroids on the 5...1000um photometry and source counts, for the current and future spaceborne and ground-based instruments, in general, as well as for specific dates and sky positions. > We used the statistical asteroid model (SAM) to calculate the positions of main belt asteroids down to a size of 1km, and calculated their infrared and submillimetre brightness using the standard thermal model. Fluctuation powers, confusion noise values and number counts were derived from the fluxes of individual asteroids. > We have constructed a large database of infrared and submillimetre fluxes for SAM asteroids with a temporal resolution of 5 days, covering the time span January 1, 2000 -- December 31, 2012. Asteroid fluctuation powers and number counts derived from this database can be obtained for a specific observation setup via our public web-interface. > Current space instruments working in the mid-infrared regime (Akari and Spitzer Space Telescopes) are affected by asteroid confusion noise in some specific areas of the sky, while the photometry of space infrared and submillimetre instruments in the near future (e.g. Herschel and Planck Space Observatories) will not be affected by asteroids. Faint main belt asteroids might also be responsible for most of the zodiacal emission fluctuations near the ecliptic.Comment: accepted for publication in Astronomy & Astrophysics; Additional material (appendices) and the related web-interface can be found at: "http://kisag.konkoly.hu/solarsystem/irsam.html

Factors associated with alcohol reduction in harmful and hazardous drinkers following alcohol brief intervention in Scotland: a qualitative enquiry

Background: Alcohol Brief Intervention (ABI) uses a motivational counselling approach to support individuals to reduce excessive alcohol consumption. There is growing evidence on ABI’s use within various health care settings, although how they work and which components enhance success is largely unknown. This paper reports on the qualitative part of a mixed methods study. It explores enablers and barriers associated with alcohol reduction following an ABI. It focuses on alcohol’s place within participants’ lives and their personal perspectives on reducing consumption. There are a number of randomised controlled trials in this field though few ABI studies have addressed the experiences of hazardous/harmful drinkers. This study examines factors associated with alcohol reduction in harmful/hazardous drinkers following ABI. Methods: This qualitative study was underpinned by a realist evaluation approach and involved semistructured interviews with ten harmful or hazardous alcohol drinkers. Participants (n = 10) were from the intervention arm of a randomised controlled trial (n = 124). All had received ABI, a 20 min motivational counselling interview, six months previously, and had reduced their alcohol consumption. Interviews were recorded, transcribed verbatim and thematically analysed. Results: Participants described their views on alcohol, its’ place in their lives, their personal perspectives on reducing their consumption and future aspirations. Conclusions: The findings provide an insight into participants’ views on alcohol, ABI, and the barriers and enablers to change. Participants described a cost benefit analysis, with some conscious consideration of the advantages and disadvantages of reducing intake or abstaining from alcohol. Findings suggest that, whilst hospital admission can act as a catalyst, encouraging individuals to reflect on their alcohol consumption through ABI may consolidate this, turning this reflective moment into action. Sustainability may be enhanced by the presence of a ‘significant other’ who encourages and experiences benefit. In addition having a purpose or structure with activities linked to employment and/or social and leisure pursuits offers the potential to enhance and sustain reduced alcohol consumption. Trial registration: Trial registration number TRN NCT00982306 September 22nd 200

Concurrent adaptation to opposing visual displacements during an alternating movement.

It has been suggested that, during tasks in which subjects are exposed to a visual rotation of cursor feedback, alternating bimanual adaptation to opposing rotations is as rapid as unimanual adaptation to a single rotation (Bock et al. in Exp Brain Res 162:513–519, 2005). However, that experiment did not test strict alternation of the limbs but short alternate blocks of trials. We have therefore tested adaptation under alternate left/right hand movement with opposing rotations. It was clear that the left and right hand, within the alternating conditions, learnt to adapt to the opposing displacements at a similar rate suggesting that two adaptive states were formed concurrently. We suggest that the separate limbs are used as contextual cues to switch between the relevant adaptive states. However, we found that during online correction the alternating conditions had a significantly slower rate of adaptation in comparison to the unimanual conditions. Control conditions indicate that the results are not directly due the alternation between limbs or to the constant switching of vision between the two eyes. The negative interference may originate from the requirement to dissociate the visual information of these two alternating displacements to allow online control of the two arms

In an in vitro model of human tuberculosis, monocyte-microglial networks regulate matrix metalloproteinase-1 and -3 gene expression and secretion via a p38 mitogen activated protein kinase-dependent pathway.

BACKGROUND: Tuberculosis (TB) of the central nervous system (CNS) is characterized by extensive tissue inflammation, driven by molecules that cleave extracellular matrix such as matrix metalloproteinase (MMP)-1 and MMP-3. However, relatively little is known about the regulation of these MMPs in the CNS. METHODS: Using a cellular model of CNS TB, we stimulated a human microglial cell line (CHME3) with conditioned medium from Mycobacterium tuberculosis-infected primary human monocytes (CoMTb). MMP-1 and MMP-3 secretion was detected using ELISAs confirmed with casein zymography or western blotting. Key results of a phospho-array profile that detects a wide range of kinase activity were confirmed with phospho-Western blotting. Chemical inhibition (SB203580) of microglial cells allowed investigation of expression and secretion of MMP-1 and MMP-3. Finally we used promoter reporter assays employing full length and MMP-3 promoter deletion constructs. Student's t-test was used for comparison of continuous variables and multiple intervention experiments were compared by one-way ANOVA with Tukey's correction for multiple pairwise comparisons. RESULTS: CoMTb up-regulated microglial MMP-1 and MMP-3 secretion in a dose- and time-dependent manner. The phospho-array profiling showed that the major increase in kinase activity due to CoMTb stimulation was in p38 mitogen activated protein kinase (MAPK), principally the α and γ subunits. p38 phosphorylation was detected at 15 minutes, with a second peak of activity at 120 minutes. High basal extracellular signal-regulated kinase activity was further increased by CoMTb. Secretion and expression of MMP-1 and MMP-3 were both p38 dependent. CoMTb stimulation of full length and MMP-3 promoter deletion constructs demonstrated up-regulation of activity in the wild type but a suppression site between -2183 and -1612 bp. CONCLUSIONS: Monocyte-microglial network-dependent MMP-1 and MMP-3 gene expression and secretion are dependent upon p38 MAPK in tuberculosis. p38 is therefore a potential target for adjuvant therapy in CNS TB

Regulation of the tumour suppressor PDCD4 by miR-499 and miR-21 in oropharyngeal cancers

© 2016 Zhang et al. Background: The rates of oropharyngeal cancers such as tonsil cancers are increasing. The tumour suppressor protein Programmed Cell Death Protein 4 (PDCD4) has been implicated in the development of various human cancers and small RNAs such as microRNAs (miRNAs) can regulate its expression. However the exact regulation of PDCD4 by multiple miRNAs in oropharyngeal squamous cell carcinoma (SCC) is not well understood. Results: Using two independent oropharyngeal SCC cohorts with a focus on the tonsillar region, we identified a miRNA profile differentiating SCC tissue from normal. Both miR-21 and miR-499 were highly expressed in tonsil SCC tissues displaying a loss of PDCD4. Interestingly, expression of the miRNA machinery, Dicer1, Drosha, DDX5 (Dead Box Helicase 5) and DGCR8 (DiGeorge Syndrome Critical Region Gene 8) were all elevated by greater than 2 fold in the tonsil SCC tissue. The 3'UTR of PDCD4 contains three binding-sites for miR-499 and one for miR-21. Using a wild-type and truncated 3'UTR of PDCD4, we demonstrated that the initial suppression of PDCD4 was mediated by miR-21 whilst sustained suppression was mediated by miR-499. Moreover the single miR-21 site was able to elicit the same magnitude of suppression as the three miR-499 sites. Conclusion: This study describes the regulation of PDCD4 specifically in tonsil SCC by miR-499 and miR-21 and has documented the loss of PDCD4 in tonsil SCCs. These findings highlight the complex interplay between miRNAs and tumour suppressor gene regulation and suggest that PDCD4 loss may be an important step in tonsillar carcinogenesis

Encephalomeningocele cases over 10 years in Thailand: a case series

BACKGROUND: Encephalomeningocele, especially in the frontoethmoidal region, is a form of neural tube defect which affects patients in Southeast Asia more commonly than in Western countries. Its underlying cause is not known but teratogenic environmental agents are suspected. However, nutritional deficiency, as in spina bifida, cannot be excluded. METHODS: This study reports 21 cases of meningocele (without brain tissue in the lesion) and encephalomeningocele (with brain tissue) that were admitted to our hospital for surgical corrections in the period of ten years, from 1990 to 1999. Clinicopathological findings, as well as occupations of family members and prenatal exposures to infectious agents or chemicals were reviewed and analyzed. RESULTS: The most commonly involved area was the frontoethmoidal region, found in 20 cases. The combined pattern between nasoethmoidal and nasoorbital defects was found most frequently (11 from 21 cases) and had more associated abnormalities. Encephalomeningocele had more related abnormalities than meningocele with proportions of 0.6 and 0.3, respectively. CONCLUSIONS: Here, we confirmed that genetic defects are not likely to be the single primary cause of this malformation. However, we could not draw any conclusions on etiologic agents. We suggest that case control studies and further investigation on the role of nutritional deficiencies, especially folic acid, in the pathogenesis of encephalomeningocele are necessary to clarify the underlying mechanisms

Validation of the treatment identification strategy of the HEDIS addiction quality measures: concordance with medical record review

<p>Abstract</p> <p>Background</p> <p>Strategies to accurately identify the occurrence of specific health care events in administrative data is central to many quality improvement and research efforts. Many health care quality measures have treatment identification strategies based on diagnosis and procedure codes - an approach that is inexpensive and feasible but usually of unknown validity. In this study, we examined if the diagnosis/procedure code combinations used in the 2006 HEDIS Initiation and Engagement quality measures to identify instances of addiction treatment have high concordance with documentation of addiction treatment in clinical progress notes.</p> <p>Methods</p> <p>Four type of records were randomly sampled from VHA electronic medical data: (a) Outpatient records from a substance use disorder (SUD) specialty clinic with a HEDIS-qualified substance use disorder (SUD) diagnosis/CPT code combination (n = 700), (b) Outpatient records from a non-SUD setting with a HEDIS-qualified SUD diagnosis/CPT code combination (n = 592), (c) Specialty SUD Inpatient/residential records that included a SUD diagnosis (n = 700), and (d) Non-SUD specialty Inpatient/residential records that included a SUD diagnosis (n = 700). Clinical progress notes for the sampled records were extracted and two raters classified each as documenting or not documenting addiction treatment. Rates of concordance between the HEDIS addiction treatment identification strategy and the raters' judgments were calculated for each record type.</p> <p>Results</p> <p>Within SUD outpatient clinics and SUD inpatient specialty units, 92% and 98% of sampled records had chart evidence of addiction treatment. Of outpatient encounters with a qualifying diagnosis/procedure code combination outside of SUD clinics, 63% had chart evidence of addiction treatment. Within non-SUD specialty inpatient units, only 46% of sampled records had chart evidence of addiction treatment.</p> <p>Conclusions</p> <p>For records generated in SUD specialty settings, the HEDIS strategy of identifying SUD treatment with diagnosis and procedure codes has a high concordance with chart review. The concordance rate outside of SUD specialty settings is much lower and highly variable between facilities. Therefore, some patients may be counted as meeting the 2006 HEDIS Initiation and Engagement criteria without having received the specified amount (or any) addiction treatment.</p

Bridging the data gaps in the epidemiology of hepatitis C virus infection in Malaysia using multi-parameter evidence synthesis

BACKGROUND: Collecting adequate information on key epidemiological indicators is a prerequisite to informing a public health response to reduce the impact of hepatitis C virus (HCV) infection in Malaysia. Our goal was to overcome the acute data shortage typical of low/middle income countries using statistical modelling to estimate the national HCV prevalence and the distribution over transmission pathways as of the end of 2009. METHODS: Multi-parameter evidence synthesis methods were applied to combine all available relevant data sources - both direct and indirect - that inform the epidemiological parameters of interest. RESULTS: An estimated 454,000 (95% credible interval [CrI]: 392,000 to 535,000) HCV antibody-positive individuals were living in Malaysia in 2009; this represents 2.5% (95% CrI: 2.2-3.0%) of the population aged 15-64 years. Among males of Malay ethnicity, for 77% (95% CrI: 69-85%) the route of probable transmission was active or a previous history of injecting drugs. The corresponding proportions were smaller for male Chinese and Indian/other ethnic groups (40% and 71%, respectively). The estimated prevalence in females of all ethnicities was 1% (95% CrI: 0.6 to 1.4%); 92% (95% CrI: 88 to 95%) of infections were attributable to non-drug injecting routes of transmission. CONCLUSIONS: The prevalent number of persons living with HCV infection in Malaysia is estimated to be very high. Low/middle income countries often lack a comprehensive evidence base; however, evidence synthesis methods can assist in filling the data gaps required for the development of effective policy to address the future public health and economic burden due to HCV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0564-6) contains supplementary material, which is available to authorized users