Do Socioeconomic Factors Influence Knowledge, Attitudes, and Representations of End-of-Life Practices? A Cross-Sectional Study.

OBJECTIVE: Access to palliative and end-of-life (EOL) care might be influenced by knowledge, attitudes, and representations of these practices. Socioeconomic factors might then affect what people know about EOL care practices, and how they perceive them. This study aims to compare knowledge, attitudes, and representations regarding EOL practices including assisted suicide, medical assistance in dying, and continuous palliative sedation of adults, according to socioeconomic variables. METHODS: A cross-sectional community-based questionnaire study featuring two evolving vignettes and five end-of-life practices was conducted in Quebec, Canada. Three sample subgroups were created according to the participants' perceived financial situation and three according to educational attainment. Descriptive analysis was used to compare levels of knowledge, attitudes, and representations between the subgroups. RESULTS: Nine hundred sixty-six (966) people completed the questionnaire. Two hundred and seventy participants (28.7%) had a high school diploma or less, and 42 participants (4.4%) were facing financial hardship. The majority of respondents supported all end-of-life options and the loosening of eligibility requirements for medical assistance in dying. Differences between subgroups were minor. While respondents in socioeconomically disadvantaged subgroups had less knowledge about EOL practices, those with lower educational attainment were more likely to be in favor of medical assistance in dying, and less likely to favor continuous palliative sedation. CONCLUSIONS: People living with situational social and economic vulnerabilities face multiple barriers in accessing health care. While they may have poorer knowledge about EOL practices, they have a positive attitude towards medical assistance in dying and assisted suicide, and a negative attitude towards continuous palliative sedation. This highlights the need for future research and interventions aimed at empowering this population and enhancing their access to EOL care.

Improving End-of-Life Care and Advance Care Planning for Frail Older Adults in Canad.

We present five Key Concepts that describe priorities for improving end-of-life care for frail older adults in Canada, and recommendations based on each Key Concept. Key Concept #1: Our end-of-life care system is focused on cancer, not frailty. Key Concept #2: We need better strategies to systematically identify frail older adults who would benefit from a palliative approach. Key Concept #3: The majority of palliative and end-of-life care will be, and should be, provided by clinicians who are not palliative care specialists. Key Concept #4: Organizational change and innovative funding models could deliver far better end-of-life care to frail individuals for less than we are currently spending. Key Concept #5: Improving the quality and quantity of advance care planning for frail older adults could reduce unwanted intensive care and costs at the end of life, and improve the experience for individuals and family members alike.

Factors influencing communication and decision-making about life-sustaining technology during serious illness: a qualitative study.

OBJECTIVES: We aimed to identify factors influencing communication and decision-making, and to learn how physicians and nurses view their roles in deciding about the use of life-sustaining technology for seriously ill hospitalised patients and their families. DESIGN: The qualitative study used Flanagan's critical incident technique to guide interpretive description of open-ended in-depth individual interviews. SETTING: Participants were recruited from the medical wards at 3 Canadian hospitals. PARTICIPANTS: Interviews were completed with 30 healthcare professionals (9 staff physicians, 9 residents and 12 nurses; aged 25-63 years; 73% female) involved in decisions about the care of seriously ill hospitalised patients and their families. MEASURES: Participants described encounters with patients and families in which communication and decision-making about life-sustaining technology went particularly well and unwell (ie, critical incidents). We further explored their roles, context and challenges. Analysis proceeded using constant comparative methods to form themes independently and with the interprofessional research team. RESULTS: We identified several key factors that influenced communication and decision-making about life-sustaining technology. The overarching factor was how those involved in such communication and decision-making (healthcare providers, patients and families) conceptualised the goals of medical practice. Additional key factors related to how preferences and decision-making were shaped through relationships, particularly how people worked toward 'making sense of the situation', how physicians and nurses approached the inherent and systemic tensions in achieving consensus with families, and how physicians and nurses conducted professional work within teams. Participants described incidents in which these key factors interacted in dynamic and unpredictable ways to influence decision-making for any particular patient and family. CONCLUSIONS: A focus on more meaningful and productive dialogue with patients and families by (and between) each member of the healthcare team may improve decisions about life-sustaining technology. Work is needed to acknowledge and support the non-curative role of healthcare and build capacity for the interprofessional team to engage in effective decision-making discussions.

Neurobiological mechanisms of repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex in depression: a systematic review.

Depression is one of the most prevalent mental illnesses worldwide and a leading cause of disability, especially in the setting of treatment resistance. In recent years, repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising alternative strategy for treatment-resistant depression and its clinical efficacy has been investigated intensively across the world. However, the underlying neurobiological mechanisms of the antidepressant effect of rTMS are still not fully understood. This review aims to systematically synthesize the literature on the neurobiological mechanisms of treatment response to rTMS in patients with depression. Medline (1996-2014), Embase (1980-2014) and PsycINFO (1806-2014) were searched under set terms. Three authors reviewed each article and came to consensus on the inclusion and exclusion criteria. All eligible studies were reviewed, duplicates were removed, and data were extracted individually. Of 1647 articles identified, 66 studies met both inclusion and exclusion criteria. rTMS affects various biological factors that can be measured by current biological techniques. Although a number of studies have explored the neurobiological mechanisms of rTMS, a large variety of rTMS protocols and parameters limits the ability to synthesize these findings into a coherent understanding. However, a convergence of findings suggest that rTMS exerts its therapeutic effects by altering levels of various neurochemicals, electrophysiology as well as blood flow and activity in the brain in a frequency-dependent manner. More research is needed to delineate the neurobiological mechanisms of the antidepressant effect of rTMS. The incorporation of biological assessments into future rTMS clinical trials will help in this regard.

Relative potential for selection of quinolone-resistance-determining-region mutations in Streptococcus pneumoniae by gemifloxacin, gatifloxacin and moxifloxacin.

Serial passage of a clinical isolate of Streptococcus pneumoniae, in the presence of moxifloxacin, gatifloxacin or gemifloxacin, gave rise to resistant isolates. Non-susceptibility as defined by Clinical and Laboratory Standards Institute (CLSI, formerly NCCLS) breakpoints arose on Days 10, 11, and 12 with gatifloxacin, gemifloxacin, and moxifloxacin respectively. Moxifloxacin and gatifloxacin selected for a single step quinolone-resistant-determining-region (QRDR) mutation in DNA gyrase (GyrA) on Day 4 and 7 respectively, whereas gemifloxacin selected simultaneously for multi-step mutations in gyrase and topoisomerase IV (ParC) on Day 17 and activated a non-reserpine inhibited efflux mechanism by Day 4. As found in clinical isolates, mutations included Ser-81-Phe and Glu-85-Lys in GyrA and Ser-79-Phe or Asp-83-Tyr in ParC. At high MICs, moxifloxacin showed a previously unreported 4 amino-acid deletion in GyrB as well as a more unusual substitution Ser-79-Leu/Ile in ParC. Gemifloxacin showed a 2- to 16-fold greater activity than moxifloxacin or gatifloxacin against strains with two or more QRDR mutations, however, its potency did not translate to nonsusceptibility and gemifloxacin MIC values were either at or well above the CLSI nonsusceptible breakpoint concentration.

Outcomes after "unroofing" of a myocardial bridge of the left anterior descending coronary artery in children with hypertrophic cardiomyopathy.

The importance of myocardial bridging of a coronary artery in the setting of hypertrophic cardiomyopathy is controversial, although we have previously reported an association with myocardial ischemia and sudden death in children. We report five symptomatic children in whom symptoms or evidence of myocardial ischemia resolved or improved after supraarterial myotomy alone.

Altered central somatosensory processing in chronic pain patients with "hysterical" anesthesia.

OBJECTIVE: The authors hypothesized that central factors may underlie sensory deficits in patients with nondermatomal somatosensory deficits (NDSD) and that functional brain imaging would reveal altered responses in supraspinal nuclei. BACKGROUND: Patients with chronic pain frequently present with NDSD, ranging from hypoesthesia to complete anesthesia in the absence of substantial pathology and often in association with motor weakness and occasional paralysis. Patients with pain and such pseudoneurologic symptoms can be classified as having both a pain disorder and a conversion disorder (Diagnostic and Statistical Manual of Mental Disorders-IV classification). METHODS: The authors tested their hypothesis with functional MRI (fMRI) of brush and noxious stimulation-evoked brain responses in four patients with chronic pain and NDSD. RESULTS: The fMRI findings revealed altered somatosensory-evoked responses in specific forebrain areas. Unperceived stimuli failed to activate areas that were activated with perceived touch and pain: notably, the thalamus, posterior region of the anterior cingulate cortex (ACC), and Brodmann area 44/45. Furthermore, unperceived stimuli were associated with deactivations in primary and secondary somatosensory cortex (S1, S2), posterior parietal cortex, and prefrontal cortex. Finally, unperceived (but not perceived) stimuli activated the rostral ACC. CONCLUSIONS: Diminished perception of innocuous and noxious stimuli is associated with altered activity in many parts of the somatosensory pathway or other supraspinal areas. The cortical findings indicate a neurobiological component for at least part of the symptoms in patients presenting with nondermatomal somatosensory deficits.

The effect of task relevance on the cortical response to changes in visual and auditory stimuli: an event-related fMRI study.

Attention is, in part, a mechanism for identifying features of the sensory environment of potential relevance to behavior. The network of brain areas sensitive to the behavioral relevance of multimodal sensory events has not been fully characterized. We used event-related fMRI to identify brain regions responsive to changes in both visual and auditory stimuli when those changes were either behaviorally relevant or behaviorally irrelevant. A widespread network of "context-dependent" activations responded to both task-irrelevant and task-relevant events but responded more strongly to task-relevant events. The most extensive activations in this network were located in right and left temporoparietal junction (TPJ), with smaller activations in left precuneus, left anterior insula, left anterior cingulate cortex, and right thalamus. Another network of "context-independent" activations responded similarly to all events, regardless of task relevance. This network featured a large activation encompassing left supplementary and cingulate motor areas (SMA/CMA) as well as right IFG, right/left precuneus, and right anterior insula, with smaller activations in right/left inferior temporal gyrus and left posterior cingulate cortex. Distinct context-dependent and context-independent subregions of activation were also found within the left and right TPJ, left anterior insula, and left SMA/CMA. In the right TPJ, a subregion in the supramarginal gyrus showed sensitivity to the behavioral context (i.e., relevance) of stimulus changes, while two subregions in the superior temporal gyrus did not. The results indicate a role for the TPJ in detecting behaviorally relevant events in the sensory environment. The TPJ may serve to identify salient events in the sensory environment both within and independent of the current behavioral context.

Streptococcal meningitis resulting from contact with an infected horse.

We report a case of group C streptococcal meningitis in a woman with a history of close animal contact as well as head trauma as a result of a kick by a horse. Blood and cerebrospinal fluid cultures grew Streptococcus equi subsp. zooepidemicus, as did a throat culture taken from the colt that had kicked her 2 weeks prior to admission.

Development and validation of a single robust HPLC method for the characterization of a pharmaceutical starting material and impurities from three suppliers using three separate synthetic routes.

Novel approaches to the development of analytical procedures for monitoring incoming starting material in support of chemical/pharmaceutical processes are described. High technology solutions were utilized for timely process development and preparation of high quality clinical supplies. A single robust HPLC method was developed and characterized for the analysis of the key starting material from three suppliers. Each supplier used a different process for the preparation of this material and, therefore, each suppliers' material exhibited a unique impurity profile. The HPLC method utilized standard techniques acceptable for release testing in a QC/manufacturing environment. An automated experimental design protocol was used to characterize the robustness of the HPLC method. The method was evaluated for linearity, limit of quantitation, solution stability, and precision of replicate injections. An LC-MS method that emulated the release HPLC method was developed and the identities of impurities were mapped between the two methods.

A multimodal cortical network for the detection of changes in the sensory environment.

Sensory stimuli undergoing sudden changes draw attention and preferentially enter our awareness. We used event-related functional magnetic-resonance imaging (fMRI) to identify brain regions responsive to changes in visual, auditory and tactile stimuli. Unimodally responsive areas included visual, auditory and somatosensory association cortex. Multimodally responsive areas comprised a right-lateralized network including the temporoparietal junction, inferior frontal gyrus, insula and left cingulate and supplementary motor areas. These results reveal a distributed, multimodal network for involuntary attention to events in the sensory environment. This network contains areas thought to underlie the P300 event-related potential and closely corresponds to the set of cortical regions damaged in patients with hemineglect syndromes.