Child with acute weakness: don't forget the salts.

Case summaryA 10-year-old boy presented with severe progressive generalised weakness on a background of 3 days of diarrhoea and vomiting. Vital signs were normal. Peripheral neurological examination revealed grade 1-2 power in all limbs, hypotonia and hyporeflexia. Sensation was fully intact. Cranial nerve examination and speech were normal. The ECG (figure 1) and initial venous blood gas (figure 2) are shown.edpract;107/1/21/F1F1F1Figure 1ECG.edpract;107/1/21/F2F2F2Figure 2Venous blood gas. QUESTION 1: What abnormalities are present on the ECG?Peaked T waves, prolonged PR segment and loss of P waves?Shortening of the QT interval and Osborn waves (J waves)?T wave flattening/inversion, prominent U waves and long QU interval?Prolonged QT interval with multiple atrial and ventricular ectopics? QUESTION 2: How would you manage this patient's hypokalaemia? QUESTION 3: What is the likely diagnosis?Conversion disorder.Myasthenia gravis.Periodic paralysis.Guillain-Barré syndrome.Botulism. QUESTION 4: What interventions can be considered for long-term treatment of this condition? Answers can be found on page 2.

A Community-Level Initiative to Prevent Obesity: Results From Kaiser Permanente's Healthy Eating Active Living Zones Initiative in California.

INTRODUCTION: A growing number of health systems are leading health promotion efforts in their wider communities. What impact are these efforts having on health behaviors and ultimately health status? This paper presents evaluation results from the place-based Kaiser Permanente Healthy Eating Active Living Zones obesity prevention initiative, implemented in 2011-2015 in 12 low-income communities in Kaiser Permanente's Northern and Southern California Regions. METHODS: The Healthy Eating Active Living Zones design targeted places and people through policy, environmental, and programmatic strategies. Each Healthy Eating Active Living Zone is a small, low-income community of 10,000 to 20,000 residents with high obesity rates and other health disparities. Community coalitions planned and implemented strategies in each community. A population-dose approach and pre and post surveys were used to assess impact of policy, program, and environmental change strategies; the analysis was conducted in 2016. Population dose is the product of reach (number of people affected by a strategy divided by target population size) and strength (the effect size or relative change in behavior for each person exposed to the strategy). RESULTS: More than 230 community change strategies were implemented over 3 years, encompassing policy, environmental, and programmatic changes as well as efforts to build community capacity to sustain strategies and make changes in the future. Positive population-level results were seen for higher-dose strategies, particularly those targeting youth physical activity. Higher-dose strategies were more likely to be found in communities with the longest duration of investment. CONCLUSIONS: These results demonstrate that strong (high-dose), community-based obesity prevention strategies can lead to improved health behaviors, particularly among youth in school settings. SUPPLEMENT INFORMATION: This article is part of a supplement entitled Building Thriving Communities Through Comprehensive Community Health Initiatives, which is sponsored by Kaiser Permanente, Community Health.

Changes in Nutrition Policies and Dietary Intake in Child Care Homes Participating in Healthy Eating and Active Living Initiative.

INTRODUCTION: From 2012 to 2014, a total of 17 family child care homes participated in a multisector, community-wide initiative to prevent obesity. Strategies included staff workshops, materials, site visits, and technical assistance regarding development and implementation of nutrition policies. The purpose of the evaluation was to examine the impact of the initiative on family child care home nutrition-related policies and practices and child dietary intake. STUDY DESIGN: Pre- and post-intervention without control group. Measures taken at baseline and follow-up included structured observations and questionnaires regarding nutrition policies, practices, and environments; documentation of lunch foods served on 5 days; and lunch plate waste observations on 2 days. Paired t-tests were used to determine the significance of change over time. SETTING/PARTICIPANTS: Seventeen family child care homes in a low-income diverse community in Northern California; children aged 2-5 years who attended the family child care homes. MAIN OUTCOME MEASURES: Change in nutrition-related policies and practices, lunch foods served and consumed. RESULTS: Data was collected at 17 sites for an average of 5.2 children aged 2-5 years per site per day at baseline and 4.6 at follow-up for a total of 333 plate waste observations. There were significant increases in staff training, parental involvement, and several of the targeted nutrition-related practices; prevalence of most other practices either improved or was maintained over time. There were significant increases in the number of sites meeting Child and Adult Care Food Program meal guidelines, variety of fruit and frequency of vegetables offered, and reductions in frequency of juice and high-fat processed meats offered. Adequate portions of all food groups were consumed at both time points with no significant change over time. CONCLUSIONS: A simple, policy-focused intervention by a child care resource and referral agency was successful at reinforcing and improving upon nutrition-related practices at family child care homes. Children consumed adequate, but not excessive, portions of the balanced meals served to them, suggesting there is no reason to offer unhealthy options. SUPPLEMENT INFORMATION: This article is part of a supplement entitled Building Thriving Communities Through Comprehensive Community Health Initiatives, which is sponsored by Kaiser Permanente, Community Health.

Changes in Consumer Purchases in Stores Participating in an Obesity Prevention Initiative.

INTRODUCTION: From 2011 to 2014, small stores in three communities participated in a community-wide obesity prevention initiative. The study aimed to determine how participation in the initiative influenced store environments and consumer purchases. STUDY DESIGN: Pre- and post-intervention without control. Structured observations of the store environments and intercept surveys of adult shoppers at all stores, and of children at two stores, conducted at baseline and follow-up. Manager/owner interviews regarding perceived impacts of the intervention conducted at follow-up. SETTING/PARTICIPANTS: Shoppers at nine small stores in three diverse, low-income communities in Northern California. INTERVENTION: The store interventions were determined locally with combinations of strategies such as product displays, healthier options, marketing and promotion, store layout, and facility improvements that were implemented to varying degrees at each site. MAIN OUTCOME MEASURES: Changes in store environments and purchases of select foods and beverages. RESULTS: Stores experienced consistent, but not always significant, declines in purchases of sweets and chips and increases in purchases of fruits and vegetables at select stores. Decreases in purchases of targeted sugar-sweetened beverages were offset by increases in purchases of other sugar-sweetened beverages. Changes in store environments and promotional activities varied widely from store to store and corresponded to variations in changes in purchasing. The owners/managers perceived benefits to their bottom line and community/customer relations, but challenges were identified that may account for the varied degree of implementation. CONCLUSIONS: Substantive improvements in fruit and vegetable availability and promotion were needed to achieve a measurable impact on purchases but reducing purchases of unhealthy foods, like sweets and chips, required a less consistent intensive effort. These findings suggest it may be challenging to achieve the consistent and targeted implementation of changes and ongoing promotional efforts at a large enough proportion of stores where residents shop that would be required to get measurable impacts at the community level. SUPPLEMENT INFORMATION: This article is part of a supplement entitled Building Thriving Communities Through Comprehensive Community Health Initiatives, which is sponsored by Kaiser Permanente, Community Health.

Improvements in Physical Activity Opportunities: Results From a Community-Based Family Child Care Intervention.

INTRODUCTION: Reaching preschool-aged children to establish healthy lifestyle habits, including physical activity, is an important component of obesity prevention efforts. However, few studies have examined family child care homes where nearly 1 million children receive care. STUDY DESIGN: A pre- and post-intervention evaluation without a control group was conducted to evaluate what changes occurred in family child care homes that participated in the Healthy Eating and Active Living project, a multicomponent obesity prevention initiative, focused on community-driven policy and environmental change in neighborhoods within Kaiser Permanente service areas. SETTING/PARTICIPANTS: From 2012 to 2014, a total of 17 family child care homes in Northern California participated in the intervention. INTERVENTION: A physical activity workshop for child care staff and technical assistance to develop a policy to promote physical activity and other healthy behaviors. MAIN OUTCOME MEASURES: Pre and post observations, questionnaires, and physical activity logs were completed to assess change in physical activity resources available in the family child care homes, the amount of child screen time offered, type and amount of physical activity offered to children, and implementation of physical activity best practices. RESULTS: Between baseline and follow-up, providers significantly increased both the number of structured, adult-led activities (2.6 vs 3.2 activities per day) and the number of structured, adult-led minutes of activity in which children participated (49 vs 83 minutes per day). Providers also improved screen time practices and made improvements to the physical activity environment. CONCLUSIONS: In this study, a community-based organization designed and implemented multicomponent strategies tailored for participating family child care homes. The successful implementation of the intervention likely contributed to implementation of practices that increased opportunities for physical activity for the young children attending these family child care homes. SUPPLEMENT INFORMATION: This article is part of a supplement entitled Building Thriving Communities Through Comprehensive Community Health Initiatives, which is sponsored by Kaiser Permanente, Community Health.

Neurology advanced practice providers: A position paper of the American Academy of Neurology.

There are many factors driving health care reform, including unsustainable costs, poor outcomes, an aging populace, and physician shortages. These issues are particularly relevant to neurology. New reimbursement models are based on value and facilitated by the use of multidisciplinary teams. Integration of advanced practice providers (APPs) into neurology practice offers many advantages with new models of care. Conversely, there are many and varied challenges financially and logistically with these practice models. The American Academy of Neurology has formed a Work Group to address the needs of both neurologists and neurologic APPs and monitor the effect of APPs on quality and cost of neurologic care.

Examining nutrition among a sample of 3- to 5-year-old children living in rural Jamaica.

BACKGROUND: The period of early childhood, defined as three to five years of age, is an important and distinct stage in childhood development. Changes in dietary patterns and composition of diets are exposing children in developing countries to over-nutrition as well as under-nutrition. OBJECTIVE: To describe the nutritional status, dietary patterns, and socio-economic conditions of three to five-year-old children living in rural Jamaica. SAMPLE: A convenience sample of 142 children was recruited over a three-year period. MEASUREMENTS: Height and weight measurements were collected. Household dietary patterns and socio-economic indicators were available from a small group (n = 6) of parents. RESULTS: Children experiencing both under-nutrition and over-nutrition were identified. Nine percent (n = 13) could be classified as moderately to severely under-nourished, and 6.9% (n = 10) classified as overweight. Frying was a common cooking method, and fruits and vegetables were eaten often. CONCLUSIONS: Economic and political changes may place children in developing countries at risk for over-nutrition as well as under-nutrition. The school setting may be an important place to address nutritional issues. This analysis describes the nutritional status of a sample of three to five-year-old children living in rural Jamaica and provides suggestions for future research.

PAT-1 (Slc26a6) is the predominant apical membrane Cl-/HCO3- exchanger in the upper villous epithelium of the murine duodenum.

Basal HCO(3)(-) secretion across the duodenum has been shown in several species to principally involve the activity of apical membrane Cl(-)/HCO(3)(-) exchanger(s). To investigate the identity of relevant anion exchanger(s), experiments were performed using wild-type (WT) mice and mice with gene-targeted deletion of the following Cl(-)/HCO(3)(-) exchangers localized to the apical membrane of murine duodenal villi: Slc26a3 [down-regulated in adenoma (DRA)], Slc26a6 [putative anion transporter 1 (PAT-1)], and Slc4a9 [anion exchanger 4 (AE4)]. RT-PCR of the isolated villous epithelium demonstrated PAT-1, DRA, and AE4 mRNA expression. Using the pH-sensitive dye BCECF, anion exchange rates were measured across the apical membrane of epithelial cells in the upper villus of the intact duodenal mucosa. Under basal conditions, Cl(-)/HCO(3)(-) exchange activity was reduced by 65-80% in the PAT-1(-) duodenum, 30-40% in the DRA(-) duodenum, and <5% in the AE4(-) duodenum compared with the WT duodenum. SO(4)(2-)/HCO(3)(-) exchange was eliminated in the PAT-1(-) duodenum but was not affected in the DRA(-) and AE4(-) duodenum relative to the WT duodenum. Intracellular pH (pH(i)) was reduced in the PAT-1(-) villous epithelium but increased to WT levels in the absence of CO(2)/HCO(3)(-) or during methazolamide treatment. Further experiments under physiological conditions indicated active pH(i) compensation in the PAT-1(-) villous epithelium by combined activities of Na(+)/H(+) exchanger 1 and Cl(-)-dependent transport processes at the basolateral membrane. We conclude that 1) PAT-1 is the major contributor to basal Cl(-)/HCO(3)(-) and SO(4)(2-)/HCO(3)(-) exchange across the apical membrane and 2) PAT-1 plays a role in pH(i) regulation in the upper villous epithelium of the murine duodenum.

Talniflumate increases survival in a cystic fibrosis mouse model of distal intestinal obstructive syndrome.

Intestinal disease in cystic fibrosis (CF) mice closely mirrors aspects of obstructive syndromes in CF patients. The pathogenesis involves accumulation of mucoid debris in the crypts that fuse with intestinal content to form obstructing mucofeculant impactions. Treatment involves modalities that increase the fluidity of the luminal content, such as osmotic laxatives and liquid diets. We investigated the effects of talniflumate (Lomucin, Genaera Corporation, Plymouth Meeting, PA), a compound that may be beneficial to treatment of CF intestinal disease based on three mechanisms of action: mucus synthesis inhibition by blockade of the murine calcium-activated chloride channel 3 (mCLCA3), nonsteroidal anti-inflammatory effects, and inhibition of Cl(-)/HCO (-)(3) exchanger(s) involved in intestinal NaCl absorption. Cohorts of CF mice were fed control diet or diets containing either talniflumate (0.4 mg/g chow) or ibuprofen (0.4 mg/g chow) for 21 days to assess survival. Talniflumate significantly increased CF mouse survival from 26 to 77%, whereas ibuprofen had no effect (22% survival). Oral talniflumate did not alter crypt goblet cell numbers or change intestinal expression of mCLCA3 but tended to decrease crypt mucoid impaction. Ussing chamber studies indicated that talniflumate slightly increased the basal short-circuit current of CF intestine, but the change was not sensitive to secretagogue stimulation or bumetanide inhibition. In contrast, intracellular pH measurements of intact intestinal villous epithelium indicated that talniflumate significantly inhibited apical membrane Cl(-)/HCO (-)(3) exchange by >50%. We conclude that oral talniflumate increases the survival of CF mice, possibly by the beneficial effects of decreasing small intestinal NaCl absorption through the inhibition of apical membrane Cl(-)/HCO (-)(3) exchanger(s).

Chloride conductance of CFTR facilitates basal Cl-/HCO3- exchange in the villous epithelium of intact murine duodenum.

Villi of the proximal duodenum are situated for direct exposure to gastric acid chyme. However, little is known about active bicarbonate secretion across villi that maintains the protective alkaline mucus barrier, a process that may be compromised in cystic fibrosis (CF), i.e., in the absence of a functional CF transmembrane conductance regulator (CFTR) anion channel. We investigated Cl(-)/HCO(3)(-) exchange activity across the apical membrane of epithelial cells located at the midregion of villi in intact duodenal mucosa from wild-type (WT) and CF mice using the pH-sensitive dye BCECF. Under basal conditions, the Cl(-)/HCO(3)(-) exchange rate was reduced by approximately 35% in CF compared with WT villous epithelium. Cl(-)/HCO(3)(-) exchange in WT and CF villi responded similarly to inhibitors of anion exchange, and membrane depolarization enhanced rates of Cl(-)(out)/HCO(3)(-)(in) exchange in both epithelia. In anion substitution studies, anion(in)/HCO(3)(-)(out) exchange rates were greater in WT epithelium using Cl(-) or NO(3)(-), but decreased to the level of the CF epithelium using the CFTR-impermeant anion, SO(4)(2-). Similarly, treatment of WT epithelium with the CFTR-selective blocker glybenclamide decreased the Cl(-)/HCO(3)(-) exchange rate to the level of CF epithelium. The mRNA expression of Slc26a3 (downregulated in adenoma) and Slc26a6 (putative anion exchanger-1) was similar between WT and CF duodena. From these studies of murine duodenum, we conclude 1) characteristics of Cl(-)/HCO(3)(-) exchange in the villous epithelium are most consistent with Slc26a6 activity, and 2) Cl(-) channel activity of CFTR facilitates apical membrane Cl(-)(in)/HCO(3)(-)(out) exchange by providing a Cl(-) "leak" under basal conditions.

Lateral intercellular space volume as a determinant of CFTR-mediated anion secretion across small intestinal mucosa.

Studies of full-thickness, small intestinal preparations have shown that maximal anion secretion [indexed by short-circuit current (I(sc))] during intracellular cAMP (cAMP(i)) stimulation is transient and followed by a decline toward baseline. Declining I(sc) is preceded by decreases in transepithelial conductance (G(t)), which in the small intestine reflects the lateral intercellular space (LIS) volume of the paracellular pathway. We hypothesized that decreases in LIS volume limit the magnitude and duration of cAMP(i)-stimulated anion secretion. Experimental manipulations to increase the patency of the LIS (assessed by G(t) and electron microscopy) were investigated for an effect on the magnitude of cAMP(i)-stimulated anion secretion (assessed by the I(sc) and isotopic fluxes) across murine small intestine. In control studies, changes of G(t) after cAMP(i) stimulation were associated with a morphological "collapse" of the LIS, which did not occur in intestine of CFTR-null mice. Removal of the outer intestinal musculature, exposure to a serosal hypertonic solution, or increased serosal hydrostatic pressure minimized reductions in G(t) and increased the cAMP(i)-stimulated I(sc) response. Increased I(sc) primarily resulted from increased Cl(-) secretion that was largely bumetanide sensitive. However, bumetanide-insensitive I(sc) was also increased, and similar increases occurred in the Na(+)-K(+)-2Cl(-) cotransporter (NKCC1)-null intestine, indicating that activities of non-NKCC1 anion uptake proteins are also affected by LIS volume. Thus LIS patency is an important determinant of the magnitude and duration of CFTR-mediated anion secretion in murine small intestine. Decreases in LIS volume may limit the pool of available anions to basolateral transporters involved in transepithelial secretion.

Abnormal Paneth cell granule dissolution and compromised resistance to bacterial colonization in the intestine of CF mice.

Paneth cells of intestinal crypts contribute to host defense by producing antimicrobial peptides that are packaged as granules for secretion into the crypt lumen. Here, we provide evidence using light and electron microscopy that postsecretory Paneth cell granules undergo limited dissolution and accumulate within the intestinal crypts of cystic fibrosis (CF) mice. On the basis of this finding, we evaluated bacterial colonization and expression of two major constituents of Paneth cells, i.e., alpha-defensins (cryptdins) and lysozyme, in CF murine intestine. Paneth cell granules accumulated in intestinal crypt lumens in both untreated CF mice with impending intestinal obstruction and in CF mice treated with an osmotic laxative that prevented overt clinical symptoms and mucus accretion. Ultrastructure studies indicated little change in granule morphology within mucus casts, whereas granules in laxative-treated mice appear to undergo limited dissolution. Protein extracts from CF intestine had increased levels of processed cryptdins compared with those from wild-type (WT) littermates. Nonetheless, colonization with aerobic bacteria species was not diminished in the CF intestine and oral challenge with a cryptdin-sensitive enteric pathogen, Salmonella typhimurium, resulted in greater colonization of CF compared with WT intestine. Modest downregulation of cryptdin and lysozyme mRNA in CF intestine was shown by microarray analysis, real-time quantitative PCR, and Northern blot analysis. Based on these findings, we conclude that antimicrobial peptide activity in CF mouse intestine is compromised by inadequate dissolution of Paneth cell granules within the crypt lumens.