Updates in our understanding of local anaesthetic systemic toxicity: a narrative review.

Despite advances in clinical practice, local anaesthetic systemic toxicity continues to occur with the therapeutic use of local anaesthesia. Patterns of presentation have evolved over recent years due in part to the increasing use of ultrasound which has been demonstrated to reduce risk. Onset of toxicity is increasingly delayed, a greater proportion of clinical reports are secondary to fascial plane blocks, and cases are increasing where non-anaesthetist providers are involved. The evolving clinical context presents a challenge for diagnosis and requires education of all physicians, nurses and allied health professionals about these changing patterns and risks. This review discusses: mechanisms; prevention; diagnosis; and treatment of local anaesthetic systemic toxicity. The local anaesthetic and dose used, site of injection and block conduct and technique are all important determinants of local anaesthetic systemic toxicity, as are various patient factors. Risk mitigation is discussed including the care of at-risk groups, such as: those at the extremes of age; patients with cardiac, hepatic and specific metabolic diseases; and those who are pregnant. Advances in the changing clinical landscape with novel applications and settings for the use of local anaesthesia are also described. Finally, we signpost future directions to potentially improve the management of local anaesthetic systemic toxicity. The utility of local anaesthetics remains unquestionable in clinical practice, and thus maximising the safe and appropriate use of these drugs should translate to improvements in patient care.

Developing a framework for arts in health programs targeting individuals with chronic pain: a mixed-methods study of practitioners.

OBJECTIVES: Chronic pain is a leading cause of morbidity and disability across the world. Cultural engagement may be a valuable tool in addressing the social disconnection that often accompanies chronic pain. This study sought to develop a framework for arts in health programs targeting individuals with chronic pain. STUDY DESIGN: Sequential explanatory mixed-methods study. METHODS: Web-based, cross-sectional survey sent to arts and cultural professionals to assess their experience with arts in health programming. Semi-structured interviews conducted with a sample of survey respondents to explore their perspectives on targeted arts in health programming for individuals with chronic pain. RESULTS: Between October 2019 and January 2020, 208 surveys were completed by arts and cultural professionals. One hundred and twenty (58%) of the respondents indicated that they currently run an arts in health or museums in health program. Among these 120 respondents, 52 (43%) targeted older adults, 50 (42%) targeted individuals with mental health concerns, and 18 (15%) targeted individuals living with pain. Improving well-being (101 [84%]) and reducing social isolation (90 [75%]) were the most common intended program outcomes, while improving pain was the least common outcome (26 [22%]). Fifteen survey respondents were interviewed. Interviewees identified four interdependent themes regarding best practices for arts in health programs pertaining to (1) program content and structure, (2) program facilitation, (3) partnerships, and (4) programs for individuals with chronic pain. CONCLUSIONS: The cultural sector can support chronic pain prevention and treatment efforts through the development of specialized programs. This study provides a framework for developing arts in health programs that support individuals living with chronic pain.

No longer a historical ailment: two cases of childhood scurvy with recommendations for bone health providers.

PURPOSE: Scurvy, due to vitamin C deficiency, is commonly referenced as a "forgotten" or "historical" disease. A growing number of case reports challenge this notion. Bone health providers are often consulted early in the presentation of scurvy to evaluate musculoskeletal complaints resulting from impaired collagen production and disrupted endochondral bone formation. In this report, we describe two cases of childhood scurvy. Our objective is to summarize the key features of scurvy for bone health providers, with the goal of raising awareness and facilitating diagnosis in future cases. CASE DESCRIPTIONS: Case one occurred in a 12-year-old non-verbal, non-ambulatory female on a ketogenic diet for refractory epilepsy. Clinical findings included hemarthrosis, transfusion dependent anemia, elevated inflammatory markers, and epiphysiolysis. Magnetic resonance imaging (MRI) revealed multi-focal bone marrow signal abnormalities and physeal irregularities. Case two occurred in a typically developing 5-year-old male presenting with limp and knee pain. Symptoms progressed despite casting and immobilization. Mild anemia, elevated inflammatory markers, and multi-focal marrow and physeal MRI abnormalities were identified. Subsequent dietary history revealed total absence of fruit or vegetable consumption. The diagnosis of scurvy was confirmed in both cases by undetectable plasma vitamin C concentrations. Treatment with vitamin C led to rapid clinical improvement. CONCLUSION: Scurvy can no longer be considered a historical diagnosis and should not be forgotten when evaluating children with musculoskeletal ailments. Early recognition of the signs, symptoms, and imaging findings of scurvy can reduce the clinical burden of this disease with the timely initiation of vitamin C therapy.

Challenges to the census: international trends and a need to consider public health benefits.

The Canadian government decision to cancel the mandatory long-form census in 2010 (subsequently restored in 2015), along with similar discussions in the United Kingdom (UK) and the United States of America (USA), have brought the purpose and use of census data into focus for epidemiologists and public health professionals. Policy decision-makers should be well-versed in the public health importance of accurate and reliable census data for emergency preparedness planning, controlling disease outbreaks, and for addressing health concerns among vulnerable populations including the elderly, low-income, racial/ethnic minorities, and special residential groups (e.g., nursing homes). Valid census information is critical to ensure that policy makers and public health practitioners have the evidence needed to: (1) establish incidence rates, mortality rates, and prevalence for the full characterization of emerging health issues; (2) address disparities in health care, prevention strategies and health outcomes among vulnerable populations; and (3) plan and effectively respond in times of disaster and emergency. At a time when budget and sample size cuts have been implemented in the UK, a voluntary census is being debated in the US. In Canada, elimination of the mandatory long-form census in 2011 resulted in unreliable population enumeration, as well as a substantial waste of money and resources for taxpayers, businesses and communities. The purpose of this article is to provide a brief overview of recent international trends and to review the foundational role of the census in public health management and planning using historical and current examples of environmental contamination, cancer clusters and emerging infections. Citing a general absence of public health applications of the census in cost-benefit analyses, we call on policy makers to consider its application to emergency preparedness, outbreak response, and chronic disease prevention efforts. At the same time, we call on public health professionals to improve published estimates of monetary benefit (via either cost-benefit or cost-effectiveness analysis) to a given public health intervention.

The electronic structure of iridium oxide electrodes active in water splitting.

Iridium oxide based electrodes are among the most promising candidates for electrocatalyzing the oxygen evolution reaction, making it imperative to understand their chemical/electronic structure. However, the complexity of iridium oxide's electronic structure makes it particularly difficult to experimentally determine the chemical state of the active surface species. To achieve an accurate understanding of the electronic structure of iridium oxide surfaces, we have combined synchrotron-based X-ray photoemission and absorption spectroscopies with ab initio calculations. Our investigation reveals a pre-edge feature in the O K-edge of highly catalytically active X-ray amorphous iridium oxides that we have identified as O 2p hole states forming in conjunction with Ir(III). These electronic defects in the near-surface region of the anionic and cationic framework are likely critical for the enhanced activity of amorphous iridium oxides relative to their crystalline counterparts.

Kullback-Leibler divergence and the Pareto-Exponential approximation.

Recent radar research interests in the Pareto distribution as a model for X-band maritime surveillance radar clutter returns have resulted in analysis of the asymptotic behaviour of this clutter model. In particular, it is of interest to understand when the Pareto distribution is well approximated by an Exponential distribution. The justification for this is that under the latter clutter model assumption, simpler radar detection schemes can be applied. An information theory approach is introduced to investigate the Pareto-Exponential approximation. By analysing the Kullback-Leibler divergence between the two distributions it is possible to not only assess when the approximation is valid, but to determine, for a given Pareto model, the optimal Exponential approximation.

Receptor-independent actions of PPAR thiazolidinedione agonists: is mitochondrial function the key?

Agonists of the peroxisome proliferator activated receptor gamma (PPAR(gamma)) are currently used for treatment of type 2 diabetes due to their insulin sensitizing and glucose metabolism stabilizing effects. More recently some of these same agonists were shown to exert anti-inflammatory and anti-proliferative effects as well. Although PPAR(gamma) agonists can operate via receptor-mediated events occurring at the genomic level, thereby causing long lasting changes in gene expression patterns, recent studies demonstrate non-genomic as well as genomic actions, and receptor-dependent as well as receptor-independent effects of the thiazolidinedione (TZD) class of PPAR(gamma) agonists. In this review we will summarize data describing some of these novel, receptor independent actions of TZDs, review evidence that TZDs directly influence mitochondrial function, and attempt to reconcile how changes in mitochondrial function could contribute to other receptor-independent actions of these drugs.

The relationship of Papanicolaou testing and contacts with the medical care system to stage at diagnosis of cervical cancer.

The relationship of Papanicolaou (Pap) testing and physician visits to stage at diagnosis of cervical cancer was assessed by interviews with 149 women with invasive cervical cancer and 214 women with in situ cervical cancer. A significantly smaller percent of study subjects with invasive disease than in situ disease had at least one Pap test in the 3 years prior to diagnosis (age- and race-adjusted odds ratio: 3.38). The two groups did not differ in visits to a physician for other reasons during this period. Pap testing decreased with increasing age for both groups, but not physician visits. While 65% percent of the subjects with invasive disease aged between 65 and 79 years had never had a Pap test until diagnosis, 88% had seen a physician in the preceding 3 years. Women with regional or distant invasive disease were least likely to have had Pap tests, and, within this group, those aged between 35 and 64 years were also least likely to have seen a physician. Strategies for early detection must reflect missed opportunities and the need to bring those not receiving care into the system.

Molecular characterization of KEX1, a kexin-like protease in mouse Pneumocystis carinii.

Expression screening of a Pneumocystis carinii-infected mouse lung cDNA library with specific monoclonal antibodies (mAbs) led to the identification of a P. carinii cDNA with extensive homology to subtilisin-like proteases, particularly fungal kexins and mammalian prohormone convertases. The 3.1 kb cDNA contains a single open reading frame encoding 1011 amino acids. Structural similarities to fungal kexins in the deduced primary amino acid sequence include a putative proenzyme domain delineated by a consensus autocatalytic cleavage site (Arg-Glu-Lys-Arg), conserved Asp, His, Asn and Ser residues in the putative catalytic domain, a hydrophobic transmembrane spanning domain, and a carboxy-terminal cytoplasmic domain with a conserved tyrosine motif thought to be important for localization of the protease in the endoplasmic reticulum and/or Golgi apparatus. Based on these structural similarities and the classification of P. carinii as a fungus, the protease was named KEX1. Southern blotting of mouse P. carinii chromosomes localized kex1 to a single chromosome of approximately 610 kb. Southern blotting of restriction enzyme digests of genomic DNA from P. carinii-infected mouse lung demonstrated that kex1 is a single copy gene. The function of kexins in other fungi suggests that KEX1 may be involved in the post-translational processing and maturation of other P. carinii proteins.

A comparison of familial and sporadic Alzheimer's disease.

Using a liberal criterion, a conservative probability-based criterion, and a criterion for autosomal dominant inheritance, we classified 36%, 13.5%, and 6.4% of 311 patients, respectively, as having familial Alzheimer's disease (FAD). The mean age of onset was over 70 years for all three categories of FAD. FAD and sporadic Alzheimer's disease (SAD) cases did not differ in clinical features, incidence of risk factors for dementia, or MRI or PET features. We observed earlier age of onset of AD to be related positively to longer duration of disease. Except for the autosomal dominant AD group, there was an earlier age of onset in FAD probands. The inheritance of AD from mothers was from 1.7 to 3.6 times more frequent than from fathers. Among SAD patients only, we found a preponderance of women, who were more frequently affected than would be expected from the male/female ratio in the general population of the same average age. Language performance tended to be less affected in FAD than in SAD patients, contrary to some previous reports.

Unusual manifestations of histoplasmosis in childhood.

Nine previously healthy children were seen with unique, and in several instances, unreported manifestations of acute histoplasmosis. Presenting manifestations included: obstructive airway disease; subacute parotitis; unilateral cervical lymphadenopathy; anterior mediastinal mass-simulating neoplasm; immune hemolytic anemia; a cutaneous lesion with regional lymphadenopathy; mediastinal mass and pericardial effusion; pulmonary infarction; and a symptom complex of cervical lymphadenopathy, CSF pleocytosis, arthritis, and interstitial nephritis. In eight children histoplasmosis was not initially considered, and the correct diagnosis was made only after complex, and sometimes invasive, diagnostic evaluation and considerable delay. All patients recovered fully without antifungal therapy. Reports of uncontrolled trials of new antifungal agents for treatment of histoplasmosis in immunocompetent hosts should be cautiously evaluated.

Laboratory diagnosis of ehrlichiosis and babesiosis.

Over the past 15-20 years, four notable tick-borne infections have emerged in the US, Lyme disease, human monocytic ehrlichiosis (HME), human granulocytic ehrlichiosis (HGE) and babesiosis (Table). In contrast to the laboratory diagnostic procedures established for Lyme disease, RMSF and tularemia, the laboratory diagnostic procedures for the diagnosis of HME, HGE and babesiosis are not yet standardized and continue to be revised.

Short course directly observed therapy to monitor compliance with antiretroviral therapy in human immunodeficiency virus-infected children.

We report our experience with short course directly observed therapy (DOT) in six human immunodeficiency virus-infected children who had a poor response to their prescribed therapy. Four to 8 days of DOT resulted in a significant drop in the viral load of all six children, demonstrating that short course DOT is an effective way to document poor compliance with antiretroviral therapy.

Lack of relation of granulocyte antibodies (antineutrophil antibodies) to neutropenia in children with human immunodeficiency virus infection.

BACKGROUND: Neutropenia in children and adults with HIV infection is frequently observed, perhaps as a result of impaired myelopoiesis, drug myelotoxicity, immune destruction or opportunistic infection. The presence of antineutrophil antibodies (granulocyte antibodies) has been associated with severe neutropenia in some reports but not in others, and such antibody assays can be confounded by the presence of immune complexes and HLA antibodies. METHODS: To determine both the prevalence of granulocyte antibodies in children with HIV infection and whether such antibodies were related to neutropenia, we screened the sera of 30 HIV-infected children by performing granulocyte immunofluorescence, granulocyte agglutination and lymphocytotoxic anti-HLA antibody assays. Reactivity was graded by a standard numeric score calculated per number of reactive cells. RESULTS: Of 26 evaluable sera, 16 (62%) had granulocyte antibodies, 6 (23%) had HLA antibodies and 4 (15%) had neither. There was no correlation between presence of granulocyte antibodies and degree of neutropenia. CONCLUSIONS: We conclude that granulocyte antibodies are highly prevalent in children with HIV infection but do not correlate with the degree of neutropenia. Antineutrophil antibody determination as currently performed does not appear to be useful in the evaluation of the HIV-infected neutropenic child.

Safety, vaccine virus shedding and immunogenicity of trivalent, cold-adapted, live attenuated influenza vaccine administered to human immunodeficiency virus-infected and noninfected children.

OBJECTIVE: To assess the safety of live, attenuated influenza vaccine (LAIV) administered to relatively asymptomatic or mildly symptomatic HIV-infected children and non-HIV-infected children. METHODS: Twenty-five non-HIV and 24 HIV-infected children (CDC Class N or A1,2) were enrolled into this double blind, placebo-controlled study. Children were randomized within each HIV status group to one of two dosing regimens: Regimen 1, Dose 1 = LAIV, Dose 2 = placebo, Dose 3 = LAIV; or Regimen 2, Dose 1 = placebo, Dose 2 = LAIV, Dose 3 = LAIV. Study doses were separated by 28 to 35 days. Reactogenicity events within 10 days and adverse events within 28 to 35 days after each study dose were recorded. Blood HIV RNA concentrations, CD4 counts and CD4% were measured throughout the study on HIV-infected children. Quantitative influenza cultures were performed on nasal aspirates collected periodically from all children up to 28 to 35 days after each study dose. Influenza isolates were assessed for retention of the temperature-sensitive phenotype. Serum influenza HAI antibodies were measured before and after each LAIV vaccination. RESULTS: No significant differences were found in rates of reactogenicity events and vaccine-related adverse events after placebo or the first dose of LAIV within each HIV status group, nor were differences found between HIV-infected and HIV-uninfected children after each dose of LAIV. Overall none of the HIV-infected children experienced a significant LAIV-related serious adverse event or influenza-like illness, making the one sided 95% CI of such a serious event occurring after LAIV 0 to 12%. No significant changes in geometric mean HIV RNA concentrations, CD4 counts or CD4% or prolonged or increased quantity of LAIV virus shedding occurred in HIV-infected children after receiving either dose of LAIV. All recovered influenza isolates retained the temperature-sensitive phenotype. After two doses of LAIV, 83% of the non-HIV-infected and 77% of the HIV-infected children had a > or = 4-fold rise in influenza antibody to at least one of the three LAIV strains. CONCLUSION: If relatively healthy HIV-infected children become exposed to LAIV inadvertently, then serious adverse outcomes would not be expected to occur frequently.

Observation of atomic steps on single crystal surfaces by a commercial scanning electron microscope.

Atomic steps on (111) and (100) crystal surfaces of Pt were observed using a commercial scanning electron microscope (SEM) in secondary electron mode. By comparing the SEM images and those by reflection electron microscopy (REM), the observed contrast was confirmed to be that from atomic steps on crystal surfaces. The contrast mechanism is briefly discussed. One application of this imaging technique is also shown.

Multiphasic diagnostic evaluation of arteriogenic, venogenic, and sinusoidogenic impotency. Value of noninvasive tests compared with penile duplex ultrasonography.

Fifty patients with a mean age of fifty-five years (range 25 to 75 years) in whom vasculogenic impotency was suspected clinically were evaluated to determine the type of vascular lesion involved: arterial insufficiency, venous leak, or sinusoidal dysfunction. All patients underwent first, noninvasive diagnostic tests including penile brachial index, penile brachial subtraction index, and penile plethysmogram, followed by penile duplex ultrasonography with papaverine and phentolamine injection. Patients with abnormal ultrasonography were divided into two groups: One group with suspected sinusoidal dysfunction and those with either arteriogenic or venogenic insufficiency but not considered candidates for surgery; they were not subjected to further studies. Another group with suspected proximal arteriogenic lesions and those with suspected venous leakage considered candidates for surgical correction were subjected to angiography and cavernosometry-cavernosography, respectively. The findings of the noninvasive tests were compared with those provided by the invasive tests. The results indicated that noninvasive tests can predict whether or not impotency is arteriogenic in approximately 90 percent of cases. The noninvasive tests, however, were less accurate in predicting venogenic and sinusoidogenic impotency, for which penile duplex ultrasonography seems to be the choice.