Risk analysis of severe myelotoxicity with temozolomide: The effects of clinical and genetic factors

A benefit of temozolomide (TMZ) is that myelotoxicity is uncommon. Recently, several small series have reported significant myelotoxicity resulting in treatment delays or death. The ability to predict risk of myelotoxicity may influence patient care. We retrospectively reviewed 680 malignant glioma patients and developed a clinical risk formula for myelotoxicity for each gender by logistic regression. The variables that remained were assigned a score of 1 and added together for a final risk score. Women experienced more myelotoxicity than did men (p = 0.015). For males, risk factors included body surface area (BSA) ≥ 2 m² (odds ratio [OR] = 2.712, p = 0.04), not on steroids (OR = 2.214, p = 0.06), and on bowel medication (OR = 3.955, p = 0.008). For females, final factors included no prior chemotherapy (OR = 3.727, p = 0.001), creatinine ≥ 1 mg/dl (OR = 6.08, p = 0.002), platelets < 270,000/mm³ (OR = 2.438, p = 0.03), BSA < 2 m² (OR = 4.178, p = 0.04), not on medication for gastroesophageal reflux disease (OR = 2.942, p = 0.01), and on analgesics (OR = 2.169, p = 0.05). Age was included because of observable trends. Risk of developing myelotoxicity ranged from 0% to 33% (male) and from 0% to 100% (females). Polymorphisms in NQO1 (NAD(P)H dehydrogenase, quinone 1), MGMT (O⁶-methylguanine-DNA methyltransferase), and GSTP1 (glutathione S-transferase pi 1) were related to risk of developing myelotoxicity in a subset of patients. Myelotoxicity with TMZ is a significant clinical issue for those at risk. Use of a clinical model to predict risk and evaluation of identified genetic polymorphisms related to myelotoxicity may allow for individualized dosing, optimizing patient management.     

Making sporting clubs healthy and welcoming environments: A strategy to increase participation

Sporting clubs are an ideal setting to promote community-wide participation in physical activity. Using the principles of the Ottawa Charter as a guide, this study explored the factors affecting the development of supportive environments as a mechanism to increase participation in club sport. The Victorian Health Promotion Foundation (VicHealth) funds State Sporting Associations (SSAs) to develop healthy and welcoming environments (HWE) in their associated clubs. The program focus areas are: welcoming and inclusive environments, sports injury prevention, 'smoke-free' environments, responsible serving of alcohol, sun protection and healthy eating. This paper sought to determine whether or not SSA Executive Officers (EOs) believe that the creation of a supportive environment will facilitate sporting club membership and to identify the factors that affect the development of the HWEs. Forty-two (82.4%) of the 51 funded SSAs completed a general survey and 36 (70.6%) of EOs responded to questions that were specifically addressed to them. EOs from six SSAs also participated in semi-structured interviews. SSA EOs (97.2%) believed that the creation of HWE in clubs would facilitate increases in participant membership. However, the data indicate incomplete development of the HWE focus areas at the club level because of limited club capacity and limited SSA support. Reportedly, the SSAs are at the stage of raising program awareness at the club level. It is suggested that SSAs should plan a structured approach to the development of HWEs that acknowledges the diverse capacity of their clubs, and garner the support of key club volunteers in order to establish HWEs.     

Dendritic spine detection using curvilinear structure detector and LDA classifier

Dendritic spines are small, bulbous cellular compartments that carry synapses. Biologists have been studying the biochemical pathways by examining the morphological and statistical changes of the dendritic spines at the intracellular level. In this paper a novel approach is presented for automated detection of dendritic spines in neuron images. The dendritic spines are recognized as small objects of variable shape attached or detached to multiple dendritic backbones in the 2D projection of the image stack along the optical direction. We extend the curvilinear structure detector to extract the boundaries as well as the centerlines for the dendritic backbones and spines. We further build a classifier using Linear Discriminate Analysis (LDA) to classify the attached spines into valid and invalid types to improve the accuracy of the spine detection. We evaluate the proposed approach by comparing with the manual results in terms of backbone length, spine number, spine length, and spine density.     

Nocturnal care interactions with patients in critical care units.

BACKGROUND: Sleep deprivation is common in critically ill patients and may have long-term effects on health outcomes and patients' morbidity. Clustering nocturnal care has been recommended to improve patients' sleep. OBJECTIVES: To (1) examine the frequency, pattern, and types of nocturnal care interactions with patients in 4 critical care units; (2) analyze the relationships among these interactions and patients' variables (age, sex, acuity) and site of admission to the intensive care unit; and (3) analyze the differences in patterns of nocturnal care activities among the 4 units. METHODS: A randomized retrospective review of the medical records of 50 patients was used to record care activities from 7 PM to 7 AM in 4 critical care units. RESULTS: Data consisted of interactions during 147 nights. The mean number of care interactions per night was 42.6 (SD 11.3). Interactions were most frequent at midnight and least frequent at 3 AM. Only 9 uninterrupted periods of 2 to 3 hours were available for sleep (6% of 147 nights studied). Frequency of interactions correlated significantly with patients' acuity scores (r = 0.32, all Ps < .05). A sleep-promoting intervention was documented for only 1 of the 147 nights, and 62% of routine daily baths were provided between 9 PM and 6 AM. CONCLUSIONS: The high frequency of nocturnal care interactions left patients few uninterrupted periods for sleep. Interventions to expand the period around 3 AM when interactions are least common could increase opportunities for sleep.     

Neurology of Sepsis

Sepsis is a systemic inflammatory response syndrome occurring secondary to infection and labeled severe when end organ dysfunction or tissue hypoperfusion transpires. Sepsis-associated mortality remains high among critically ill patients, with chronic disease and immunosuppression being the most common risk factors. Studies demonstrate that early recognition and treatment are vital to decreasing mortality. Some of the least understood effects of sepsis are the associated neurologic complications. The peripheral nervous system (PNS) has gained most consideration and thought, largely due to dependence on mechanical ventilation. Central nervous system (CNS) complications related to sepsis have only more recently gained attention but continue to go unnoticed. Aside from the clinical examination, electroencephalography (EEG) is a sensitive tool for prognostication or uncovering non-convulsive seizures in encephalopathic patients. Further studies are needed to further define the urgency of a prevention and treatment plan for the deleterious effects of sepsis on the PNS and CNS.     

Psychiatric and Behavioural Disorders in Children with Epilepsy (ILAE Task Force Report): Anxiety,depression and childhood epilepsy

Anxiety and depression are relatively common in children with epilepsy: anxiety has been reported in 15–36% and depression in 8–35% of patients. In some cases these conditions may be related specifically to the epilepsy or its treatment. For example, some antiepileptic drugs are known to be associated with depression in adults and are likely to have a similar effect in young people. Emotional reactions to the epilepsy, for example anxieties and social phobia related specifically to the seizures, might be expected and require appropriate management. However, there is a growing recognition of the bidirectional relationship between epilepsy and psychiatric disorders, including depression, largely based on adult data. Cognitive behavioural therapy and serotonin reuptake inhibitors are used for treatment of both anxiety and depression in children with epilepsy. There is a need for greater understanding of the causes of these conditions in young people and there is also a need for better evidence for optimal treatment.     

Psychiatric and Behavioural Disorders in Children with Epilepsy (ILAE Task Force Report): Subtle behavioural and cognitive manifestations of epilepsy

A subtle behavioural or cognitive manifestation of epilepsy can be defined in two ways. First, epileptiform discharges not presenting as obvious seizures may nevertheless affect cognition and/or behaviour. Second, the actual seizures may be obvious but the way they affect cognition or behaviour may not be. There is a growing body of evidence indicating that the epileptiform discharges in benign epilepsy with centrotemporal spikes can affect behaviour and cognition. The focal discharges in other forms of epilepsy can also be associated with behavioural change. The Landau‐Kleffner syndrome, the CSWS syndrome, transitory cognitive impairment and transient epileptic amnesia provide further examples of cognitive and behavioural manifestations resulting from subtle manifestations of the epilepsy. Prompt, effective antiepileptic treatment with medication or surgery can improve behaviour and cognition in at least some cases.     

Psychiatric and Behavioural Disorders in Children with Epilepsy (ILAE Task Force Report): When should pharmacotherapy for psychiatric/behavioural disorders in children with epilepsy be prescribed?

The most important factor in deciding whether psychotropic medication should be prescribed is a meticulous assessment of the possible causes of the behavioural/psychiatric disturbance. This assessment should include a consideration of the possible roles of the epilepsy itself, treatment of the epilepsy, associated brain damage or dysfunction, reactions to the epilepsy and causes that are unrelated to the epilepsy or its treatment. If the epilepsy itself or antiepileptic drug treatment are responsible for the disorder then a review of antiepileptic medication is required. Contrary to popular myth, most psychotropic medications are not contraindicated in children with epilepsy. Treatment with methylphenidate, dexamfetamine, atomoxetine, clonidine or low‐dose risperidone are unlikely to precipitate seizures. The selective serotonin reuptake inhibitors might protect against seizures but some of these are powerful enzyme inhibitors, implying that careful monitoring to avoid antiepileptic drug toxicity is recommended. In many cases, the appropriate approach will be through other interventions such as behavioural management or providing the young person with empowering strategies, implying that psychotropic pharmacotherapy should not be the first‐line treatment. However, if assessment indicates that psychotropic medication is necessary, it can be of great benefit.