Shared mental models of cancer survivorship care.

Quality cancer survivorship care relies on care continuity within the healthcare team. The purpose of this study was to explore the perspectives of healthcare team members regarding cancer survivorship care using the framework of shared mental models. Semi-structured interviews of cancer survivors, primary support individuals, oncology providers, primary care providers and registered nurses were completed. Data were extrapolated to seven primary themes with associated secondary themes. Primary themes included survivor definition and identity, care setting, team member roles, care gaps, survivor needs, barriers to care and facilitators of care. Through these themes, participants emphasised the individuality of the survivorship experience, acknowledged care gaps and described ongoing needs of cancer survivors. Information provision and communication were noted as care facilitators. Through clarification of team member roles, healthcare providers will be equipped to promote cancer survivor transition by focusing on care continuity, communication and collaboration.

Parental beliefs about portion size, not children's own beliefs, predict child BMI.

BACKGROUND: Increases in portion size are thought by many to promote obesity in children. However, this relationship remains unclear. Here, we explore the extent to which a child's BMI is predicted both by parental beliefs about their child's ideal and maximum portion size and/or by the child's own beliefs. METHODS: Parent-child (5-11 years) dyads (N = 217) were recruited from a randomized controlled trial (n = 69) and an interactive science centre (n = 148). For a range of main meals, parents estimated their child's 'ideal' and 'maximum tolerated' portions. Children completed the same tasks. RESULTS: An association was found between parents' beliefs about their child's ideal (ß = .34, p < .001) and maximum tolerated (ß = .30, p < .001) portions, and their child's BMI. By contrast, children's self-reported ideal (ß = .02, p = .718) and maximum tolerated (ß = -.09, p = .214) portions did not predict their BMI. With increasing child BMI, parents' estimations aligned more closely with their child's own selected portions. CONCLUSIONS: Our findings suggest that when a parent selects a smaller portion for their child than their child self-selects, then the child is less likely to be obese. Therefore, public health measures to prevent obesity might include instructions to parents on appropriate portions for young children.

Comparison of Standard Culture-Based Method to Culture-Independent Method for Evaluation of Hygiene Effects on the Hand Microbiome.

Hands play a critical role in the transmission of microbiota on one's own body, between individuals, and on environmental surfaces. Effectively measuring the composition of the hand microbiome is important to hand hygiene science, which has implications for human health. Hand hygiene products are evaluated using standard culture-based methods, but standard test methods for culture-independent microbiome characterization are lacking. We sampled the hands of 50 participants using swab-based and glove-based methods prior to and following four hand hygiene treatments (using a nonantimicrobial hand wash, alcohol-based hand sanitizer [ABHS], a 70% ethanol solution, or tap water). We compared results among culture plate counts, 16S rRNA gene sequencing of DNA extracted directly from hands, and sequencing of DNA extracted from culture plates. Glove-based sampling yielded higher numbers of unique operational taxonomic units (OTUs) but had less diversity in bacterial community composition than swab-based sampling. We detected treatment-induced changes in diversity only by using swab-based samples (P < 0.001); we were unable to detect changes with glove-based samples. Bacterial cell counts significantly decreased with use of the ABHS (P < 0.05) and ethanol control (P < 0.05). Skin hydration at baseline correlated with bacterial abundances, bacterial community composition, pH, and redness across subjects. The importance of the method choice was substantial. These findings are important to ensure improvement of hand hygiene industry methods and for future hand microbiome studies. On the basis of our results and previously published studies, we propose recommendations for best practices in hand microbiome research.IMPORTANCE The hand microbiome is a critical area of research for diverse fields, such as public health and forensics. The suitability of culture-independent methods for assessing effects of hygiene products on microbiota has not been demonstrated. This is the first controlled laboratory clinical hand study to have compared traditional hand hygiene test methods with newer culture-independent characterization methods typically used by skin microbiologists. This study resulted in recommendations for hand hygiene product testing, development of methods, and future hand skin microbiome research. It also demonstrated the importance of inclusion of skin physiological metadata in skin microbiome research, which is atypical for skin microbiome studies.

Mid-term follow-up of whiplash with Bournemouth Questionnaire: the significance of the initial depression to pain ratio.

INTRODUCTION: The Bournemouth Questionnaire (BQ) was used to report the short to mid-term outcome of a prospective cohort of patients who had sustained Whiplash Associated Disorder (WAD), and establish whether outcome could be predicted on initial assessment. METHODS: One hundred patients with WAD grades I-III on the Quebec Task Force Classification were referred for physiotherapy (neck posture advice, initially practised under the direct supervision of a therapist). BQ scores were recorded on the first visit, at six weeks, then at final follow-up. RESULTS: Seventy-six percent of patients were available at final follow-up, 58% women. The mean age was 43.2 years old and follow-up time 38 months (28-48). Symptoms plateaued after six weeks in the majority and improved gradually thereafter. When the individual BQ components on initial presentation were reassessed, patients who score disproportionately highly in BQ Question 5 (Depression) had a worse outcome. To quantify this, the ratio of BQ Questions 5 (Depression)/1 (Pain) was calculated. BQ5/1 ratio greater than 1 on initial presentation had an odds ratio of 2 for poor outcome (p= 0.02). CONCLUSION: The BQ can therefore be used to identify patients with a disproportionately high depression score (BQ5) who are highly likely to clinically deteriorate in the medium term.

PPARγ activation blocks development and reduces established neuropathic pain in rats.

Peroxisome proliferator-activated receptor gamma (PPARγ) is emerging as a new pharmacotherapeutic target for chronic pain. When oral (3-30 mg/kg/day in chow for 7 wk) or twice-daily intraperitoneal (1-10 mg/kg/day for 2 wk) administration began before spared nerve injury (SNI), pioglitazone, a PPARγ agonist, dose-dependently prevented multiple behavioral signs of somatosensory hypersensitivity. The highest dose of intraperitoneal pioglitazone did not produce ataxia or reductions in transient mechanical and heat nociception, indicating that inhibitory effects on hypersensitivity were not secondary to adverse drug-induced behaviors or antinociception. Inhibitory effects on hypersensitivity persisted at least one week beyond cessation of pioglitazone administration, suggestive of long-lasting effects on gene expression. Blockade of PPARγ with GW9662, an irreversible and selective PPARγ antagonist, dose-dependently reduced the inhibitory effect of pioglitazone on hypersensitivity, indicating a PPARγ-dependent action. Remarkably, a single preemptive injection of pioglitazone 15 min before SNI attenuated hypersensitivity for at least 2 weeks; this was enhanced with a second injection delivered 12 h after SNI. Pioglitazone injections beginning after SNI also reduced hypersensitivity, albeit to a lesser degree than preemptive treatment. Intraperitoneal pioglitazone significantly reduced the nerve injury-induced up-regulation of cd11b, GFAP, and p-p38 in the dorsal horn, indicating a mechanism of action involving spinal microglia and/or astrocyte activation. Oral pioglitazone significantly reduced touch stimulus-evoked phospho-extracellular signal-related kinase (p-ERK) in lamina I-II, indicating a mechanism of action involving inhibition of central sensitization. We conclude that pioglitazone reduces spinal glial and stimulus-evoked p-ERK activation and that PPARγ activation blocks the development of and reduces established neuropathic pain.

American Academy of Neurology policy on pharmaceutical and device industry support.

OBJECTIVE: To examine the American Academy of Neurology (AAN)'s prevention and limitation of conflicts of interest (COI) related to relationships with pharmaceutical and medical device manufacturers and other medically related commercial product and service companies (industry). METHODS: We reviewed the AAN's polices governing its interactions with industry, mechanisms for enforcement, and the recent findings of the board-appointed COI task force, in the context of the 2009 David Rothman and colleagues' article in JAMA, the Council of Medical Specialty Societies (CMSS) Code for Interactions with Companies (Code), efforts of the American Medical Association in this area, and increased public and Congressional scrutiny of physician/physician organizations' relationships with industry. RESULTS: The AAN's Policy on Conflicts of Interest provides 4 mechanisms for addressing COI: avoidance, separation, disclosure, and regulation. The AAN's Principles Governing Academy Relationships with External Sources of Support, including recent amendments proposed by the COI task force, regulate industry interaction with AAN programming, products, and leadership. With the Policy, Principles, and other methods of COI prevention, the AAN meets or exceeds all recommendations of the CMSS Code. CONCLUSIONS: With its adherence to the Principles since 2004, the AAN has been a leader among professional medical associations in appropriately managing COI related to interactions with industry. Recent amendments to the Principles maintain the AAN's position as a leader in a time of increased public scrutiny of physicians' and professional medical associations' relationships with industry. The AAN is responsive to the recommendations of the COI task force, and has adopted the CMSS Code.

Acetazolamide efficacy in hypokalemic periodic paralysis and the predictive role of genotype.

OBJECTIVES: Acetazolamide has been the most commonly used treatment for hypokalemic periodic paralysis since 1968. However, its mechanism of efficacy is not fully understood, and it is not known whether therapy response relates to genotype. We undertook a clinical and genetic study to evaluate the response rate of patients treated with acetazolamide and to investigate possible correlations between response and genotype. METHODS: We identified a total of 74 genotyped patients for this study. These included patients who were referred over a 15-year period to the only U.K. referral center or to a Chinese center and who underwent extensive clinical evaluation. For all genotyped patients, the response to acetazolamide therapy in terms of attack frequency and severity was documented. Direct DNA sequencing of CACNA1S and SCN4A was performed. RESULTS: Only 46% of the total patient cohort (34 of 74) reported benefit from acetazolamide. There was a greater chance of benefit in patients with mutations in CACNA1S (31 responded of 55 total) than in those with mutations in SCN4A (3 responded of 19 total). Patients with mutations that resulted in amino acids being substituted by glycine in either gene were the least likely to report benefit. CONCLUSIONS: This retrospective study indicates that only approximately 50% of genotyped patients with hypokalemic periodic paralysis respond to acetazolamide. We found evidence supporting a relationship between genotype and treatment response. Prospective randomized controlled trials are required to further evaluate this relationship. Development of alternative therapies is required.

The non-dystrophic myotonias: molecular pathogenesis, diagnosis and treatment.

The non-dystrophic myotonias are an important group of skeletal muscle channelopathies electrophysiologically characterized by altered membrane excitability. Many distinct clinical phenotypes are now recognized and range in severity from severe neonatal myotonia with respiratory compromise through to milder late-onset myotonic muscle stiffness. Specific genetic mutations in the major skeletal muscle voltage gated chloride channel gene and in the voltage gated sodium channel gene are causative in most patients. Recent work has allowed more precise correlations between the genotype and the electrophysiological and clinical phenotype. The majority of patients with myotonia have either a primary or secondary loss of membrane chloride conductance predicted to result in reduction of the resting membrane potential. Causative mutations in the sodium channel gene result in an abnormal gain of sodium channel function that may show marked temperature dependence. Despite significant advances in the clinical, genetic and molecular pathophysiological understanding of these disorders, which we review here, there are important unresolved issues we address: (i) recent work suggests that specialized clinical neurophysiology can identify channel specific patterns and aid genetic diagnosis in many cases however, it is not yet clear if such techniques can be refined to predict the causative gene in all cases or even predict the precise genotype; (ii) although clinical experience indicates these patients can have significant progressive morbidity, the detailed natural history and determinants of morbidity have not been specifically studied in a prospective fashion; (iii) some patients develop myopathy, but its frequency, severity and possible response to treatment remains undetermined, furthermore, the pathophysiogical link between ion channel dysfunction and muscle degeneration is unknown; (iv) there is currently insufficient clinical trial evidence to recommend a standard treatment. Limited data suggest that sodium channel blocking agents have some efficacy. However, establishing the effectiveness of a therapy requires completion of multi-centre randomized controlled trials employing accurate outcome measures including reliable quantitation of myotonia. More specific pharmacological approaches are required and could include those which might preferentially reduce persistent muscle sodium currents or enhance the conductance of mutant chloride channels. Alternative strategies may be directed at preventing premature mutant channel degradation or correcting the mis-targeting of the mutant channels.

Primary episodic ataxias: diagnosis, pathogenesis and treatment.

Primary episodic ataxias are autosomal dominant channelopathies that manifest as attacks of imbalance and incoordination. Mutations in two genes, KCNA1 and CACNA1A, cause the best characterized and account for the majority of identified cases of episodic ataxia. We summarize current knowledge of clinical and genetic diagnosis, genotype-phenotype correlations, pathophysiology and treatment of episodic ataxia syndromes. We focus on unresolved issues including phenotypic and genetic heterogeneity, lessons from animal models and technological advancement, rationale and feasibility of various treatment strategies, and shared mechanisms underlying episodic ataxia and other far more prevalent paroxysmal conditions such as epilepsy and migraine.

Zaspopathy in a large classic late-onset distal myopathy family.

Distal myopathies have been associated with mutations in titin, dysferlin, GNE, desmin and myosin. Of these, only titin mutations were previously known to cause dominant late-onset distal myopathy. Recent findings, however, have indicated that patients affected with myofibrillar myopathy have a more distal than proximal muscle phenotype and a proportion of these may have mutations in myotilin, ZASP or filamin C, besides previously known desmin and alphaB-crystallin. Here we report that the disorder in one of the well-characterized autosomal dominant distal myopathy families, the Markesbery et al. family, first reported in 1974, is caused by ZASP mutation A165V. Previous linkage to the titin locus 2q31 proved incorrect. ZASP expression by immunoblotting shows normal presence of the main 32 and 78 kDa bands and immunohistochemistry in patients reveals normal Z-disc localization except for moderate accumulations together with myotilin, desmin alphaB-crystallin and alpha-actinin. Muscle imaging reveals involvement in both the posterior and anterior compartments of the lower leg and considerable affection of proximal leg muscles at later stages. Haplotype studies in this family and in five other unrelated families with European ancestry carrying the identical A165V mutation share common markers at the locus suggesting the existence of a founder mutation.

Should finger rings be removed prior to scrubbing for theatre?

Finger rings increase surface bacterial counts. Although scrubbing reduces these (P=0.05), there are more bacteria under rings than on adjacent skin or the opposite hand. If rings are removed before scrubbing, bacterial counts are reduced but remain higher than on adjacent skin or the opposite hand. Ideally, finger rings should not be worn by theatre staff. However, if they are, they should be removed prior to scrubbing for surgical operations.

The primary periodic paralyses: diagnosis, pathogenesis and treatment.

Periodic paralyses (PPs) are rare inherited channelopathies that manifest as abnormal, often potassium (K)-sensitive, muscle membrane excitability leading to episodic flaccid paralysis. Hypokalaemic (HypoPP) and hyperkalaemic PP and Andersen-Tawil syndrome are genetically heterogeneous. Over the past decade mutations in genes encoding three ion channels, CACN1AS, SCN4A and KCNJ2, have been identified and account for at least 70% of the identified cases of PP and several allelic disorders. No prospective clinical studies have followed sufficiently large cohorts with characterized molecular lesions to draw precise conclusions. We summarize current knowledge of the clinical diagnosis, molecular genetics, genotype-phenotype correlations, pathophysiology and treatment in the PPs. We focus on unresolved issues including (i) Are there additional ion channel defects in cases without defined mutations? (ii) What is the mechanism for depolarization-induced weakness in Hypo PP? and finally (iii) Will detailed electrophysiological studies be able to correctly identify specific channel mutations? Understanding the pathophysiology of the potassium-sensitive PPs ought to reduce genetic complexity, allow subjects to be stratified during future clinical trials and increase the likelihood of observing true clinical effects. Ideally, therapy for the PPs will prevent attacks, avoid permanent weakness and improve quality of life. Moreover, understanding the skeletal muscle channelopathies will hopefully lead to insights into the more common central nervous system channel diseases such as migraine and epilepsy.

Correlating phenotype and genotype in the periodic paralyses.

BACKGROUND: Periodic paralyses and paramyotonia congenita are rare disorders causing disabling weakness and myotonia. Mutations in sodium, calcium, and potassium channels have been recognized as causing disease. OBJECTIVE: To analyze the clinical phenotype of patients with and without discernible genotype and to identify other mutations in ion channel genes associated with disease. METHODS: The authors have reviewed clinical data in patients with a diagnosis of hypokalemic periodic paralysis (56 kindreds, 71 patients), hyperkalemic periodic paralysis (47 kindreds, 99 patients), and paramyotonia congenita (24 kindreds, 56 patients). For those patients without one of the classically known mutations, the authors analyzed the entire coding region of the SCN4A, KCNE3, and KCNJ2 genes and portions of the coding region of the CACNA1S gene in order to identify new mutations. RESULTS: Mutations were identified in approximately two thirds of kindreds with periodic paralysis or paramyotonia congenita. The authors found differences between the disorders and between those with and without identified mutations in terms of age at onset, frequency of attacks, duration of attacks, fixed proximal weakness, precipitants of attacks, myotonia, electrophysiologic studies, serum potassium levels, muscle biopsy, response to potassium administration, and response to treatment with acetazolamide. CONCLUSIONS: Hypokalemic periodic paralysis, hyperkalemic periodic paralysis, and paramyotonia congenita may be distinguished based on clinical data. This series of 226 patients (127 kindreds) confirms some clinical features of this disorder with notable exceptions: In this series, patients without mutations had a less typical clinical presentation including an older age at onset, no changes in diet as a precipitant, and absence of vacuolar myopathy on muscle biopsy.

Reporting clinical trials: full access to all the data.

Authors' right to access to all data obtained in their study