KRT17High/CXCL8+ tumor cells display both classical and basal features and regulate myeloid infiltration in the pancreatic cancer microenvironment.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is generally divided in two subtypes, classical and basal. Recently, single cell RNA sequencing has uncovered the co-existence of basal and classical cancer cells, as well as intermediary cancer cells, in individual tumors. The latter remains poorly understood; here, we sought to characterize them using a multimodal approach. EXPERIMENTAL DESIGN: We performed subtyping on a single cell RNA sequencing dataset containing 18 human PDAC samples to identify multiple intermediary subtypes. We generated patient-derived PDAC organoids for functional studies. We compared single cell profiling of matched blood and tumor samples to measure changes in the local and systemic immune microenvironment. We then leveraged longitudinally patient-matched blood to follow individual patients over the course of chemotherapy. RESULTS: We identified a cluster of KRT17-high intermediary cancer cells that uniquely express high levels of CXCL8 and other cytokines. The proportion of KRT17High/CXCL8+ cells in patient tumors correlated with intra-tumoral myeloid abundance, and, interestingly, high pro-tumor peripheral blood granulocytes, implicating local and systemic roles. Patient-derived organoids maintained KRT17High/CXCL8+cells and induced myeloid cell migration in an CXCL8-dependent manner. In our longitudinal studies, plasma CXCL8 decreased following chemotherapy in responsive patients, while CXCL8 persistence portended worse prognosis. CONCLUSIONS: Through single cell analysis of PDAC samples we identified KRT17High/CXCL8+ cancer cells as an intermediary subtype, marked by a unique cytokine profile and capable of influencing myeloid cells in the tumor microenvironment and systemically. The abundance of this cell population should be considered for patient stratification in precision immunotherapy.

Enrichment of adeno-associated virus serotype 5 full capsids by anion exchange chromatography with dual salt elution gradients.

Adeno-associated virus-based gene therapies have demonstrated substantial therapeutic benefit for the treatment of genetic disorders. In manufacturing processes, viral capsids are produced with and without the encapsidated gene of interest. Capsids devoid of the gene of interest, or "empty" capsids, represent a product-related impurity. As a result, a robust and scalable method to enrich full capsids is crucial to provide patients with as much potentially active product as possible. Anion exchange chromatography has emerged as a highly utilized method for full capsid enrichment across many serotypes due to its ease of use, robustness, and scalability. However, achieving sufficient resolution between the full and empty capsids is not trivial. In this work, anion exchange chromatography was used to achieve empty and full capsid resolution for adeno-associated virus serotype 5. A salt gradient screen of multiple salts with varied valency and Hofmeister series properties was performed to determine optimal peak resolution and aggregate reduction. Dual salt effects were evaluated on the same product and process attributes to identify any synergies with the use of mixed ion gradients. The modified process provided as high as ≥75% AAV5 full capsids (≥3-fold enrichment based on the percent full in the feed stream) with near baseline separation of empty capsids and achieved an overall vector genome step yield of >65%.

Factors Associated With Clinician Self-Reported Resource Use in Acute Care and Ambulatory Pediatrics.

The objective of this study is to determine predictors of resource use among pediatric providers for common respiratory illnesses. We surveyed pediatric primary care, emergency department (ED)/urgent care (UC), and hospital medicine providers at a free-standing children's hospital system. Five clinical vignettes assessed factors affecting resource use for upper respiratory infections, bronchiolitis, and pneumonia, including provider-type, practice location, tolerance to uncertainty, and medical decision-making behaviors. The response rate was 75.3% (168/223). The ED/UC and primary care providers had higher vignette scores, indicating higher resource use, compared with inpatient providers; advanced practice providers (APPs) had higher vignette scores compared with physicians. In multivariate analysis, being an ED/UC provider, an APP, and greater concern for bad outcomes were associated with higher vignette scores. Overall, provider type and location of practice may predict resource use for children with respiratory illnesses. Interventions targeted at test-maximizing providers may improve quality of care and reduce resource burden.

Minimizing the "Kitchen Sink" Approach: De-implementation of Unnecessary Care for Patients with Anaphylaxis in a Pediatric Emergency Department.

Epinephrine is the only medication that prevents morbidity and mortality in anaphylaxis. Systemic corticosteroids and H2 receptor antagonists (H2RA) may benefit select cases but are not universally indicated. This study aims to de-implement the universal use of steroids and H2RAs and emphasize epinephrine-focused care for children with anaphylaxis during acute care visits. The study aims to reduce steroid and H2RA use from 81% and 60%, respectively, to 30% by December 2019. Methods: The primary outcome measures were the percent of patients receiving steroids and H2RAs in the emergency department (ED) or urgent care (UC). Process measure was the frequency of intravenous (IV) line placement. Balancing measures were ED/UC length of stay, admission rate, and ED/UC return visit rate. In addition, a multidisciplinary team designed the following interventions: (1) anaphylaxis clinical pathway to emphasize epinephrine-focused care, outline criteria for second-line therapies and a provider guideline for ED/UC observation; (2) standardize unit-based anaphylaxis medication kits; (3) optimize electronic medical record tools, including order sets and discharge instructions to be concordant with guideline recommendations. Results: The study included 870 patients. There was special cause variation in the use of steroids (81%-33%) and H2RAs (60%-11%), ED/UC Length of stay decreased (6.2-5.0 hours). There was no special cause variation in admission rates or ED/UC return visit rates. Conclusion: Universal use of systemic steroids and H2RAs can be safely de-implemented in pediatric patients with anaphylaxis using quality improvement methods.

Omphalitis and Concurrent Serious Bacterial Infection.

OBJECTIVE: Describe the clinical presentation, prevalence of concurrent serious bacterial infection (SBI), and outcomes among infants with omphalitis. METHODS: Within the Pediatric Emergency Medicine Collaborative Research Committee, 28 sites reviewed records of infants ≤90 days of age with omphalitis seen in the emergency department from January 1, 2008, to December 31, 2017. Demographic, clinical, laboratory, treatment, and outcome data were summarized. RESULTS: Among 566 infants (median age 16 days), 537 (95%) were well-appearing, 64 (11%) had fever at home or in the emergency department, and 143 (25%) had reported fussiness or poor feeding. Blood, urine, and cerebrospinal fluid cultures were collected in 472 (83%), 326 (58%), and 222 (39%) infants, respectively. Pathogens grew in 1.1% (95% confidence interval [CI], 0.3%-2.5%) of blood, 0.9% (95% CI, 0.2%-2.7%) of urine, and 0.9% (95% CI, 0.1%-3.2%) of cerebrospinal fluid cultures. Cultures from the site of infection were obtained in 320 (57%) infants, with 85% (95% CI, 80%-88%) growing a pathogen, most commonly methicillin-sensitive Staphylococcus aureus (62%), followed by methicillin-resistant Staphylococcus aureus (11%) and Escherichia coli (10%). Four hundred ninety-eight (88%) were hospitalized, 81 (16%) to an ICU. Twelve (2.1% [95% CI, 1.1%-3.7%]) had sepsis or shock, and 2 (0.4% [95% CI, 0.0%-1.3%]) had severe cellulitis or necrotizing soft tissue infection. There was 1 death. Serious complications occurred only in infants aged <28 days. CONCLUSIONS: In this multicenter cohort, mild, localized disease was typical of omphalitis. SBI and adverse outcomes were uncommon. Depending on age, routine testing for SBI is likely unnecessary in most afebrile, well-appearing infants with omphalitis.

Do the Guidelines Apply?-A Multisite, Combined Stakeholder Qualitative Case Study to Understand Care Decisions in Bronchiolitis.

BACKGROUND: Clinical practice guidelines for bronchiolitis recommend against tests and treatments that do not improve outcomes, yet most children admitted with bronchiolitis continue to receive them. An improved understanding of factors that influence care decisions across multiple stakeholders and diverse settings is needed to develop effective strategies to de-implement (or reduce) unnecessary testing and treatment. METHODS: We explored health care provider, care team, and parent perspectives on testing and treatment in bronchiolitis to develop a combined stakeholder account of care decisions. We conducted a qualitative case study across 2 geographically distinct university affiliated children's hospitals representing a generally low and high test/treatment utilizing hospital respectively from March 2019 to May 2020. We conducted 46 semistructured interviews and 3 focus groups with a total of 74 participants. Data were analyzed using applied thematic analysis and findings were triangulated across participant group and data collection method. RESULTS: Three themes emerged around care decisions: 1) awareness and perceptions of the guidelines or evidence; 2) perceptions of expected tests or treatments, and 3) organizational culture and existing care processes. Provider and care team participants commonly described parent expectations as drivers of utilization. Conversely, parents generally reported a lack of expectations for tests/treatments and that tests/treatments did not improve their experience of care. CONCLUSIONS: This study illuminated factors associated with the differential adoption of evidence and targets for future de-implementation strategies. Importantly, incongruent with provider and care team perceptions, parents reported that they desire an evidence-based, less-is-more approach to bronchiolitis care.

Neonatal Mastitis and Concurrent Serious Bacterial Infection.

OBJECTIVES: Describe the clinical presentation, prevalence, and outcomes of concurrent serious bacterial infection (SBI) among infants with mastitis. METHODS: Within the Pediatric Emergency Medicine Collaborative Research Committee, 28 sites reviewed records of infants aged ≤90 days with mastitis who were seen in the emergency department between January 1, 2008, and December 31, 2017. Demographic, clinical, laboratory, treatment, and outcome data were summarized. RESULTS: Among 657 infants (median age 21 days), 641 (98%) were well appearing, 138 (21%) had history of fever at home or in the emergency department, and 63 (10%) had reported fussiness or poor feeding. Blood, urine, and cerebrospinal fluid cultures were collected in 581 (88%), 274 (42%), and 216 (33%) infants, respectively. Pathogens grew in 0.3% (95% confidence interval [CI] 0.04-1.2) of blood, 1.1% (95% CI 0.2-3.2) of urine, and 0.4% (95% CI 0.01-2.5) of cerebrospinal fluid cultures. Cultures from the site of infection were obtained in 335 (51%) infants, with 77% (95% CI 72-81) growing a pathogen, most commonly methicillin-resistant Staphylococcus aureus (54%), followed by methicillin-susceptible S aureus (29%), and unspecified S aureus (8%). A total of 591 (90%) infants were admitted to the hospital, with 22 (3.7%) admitted to an ICU. Overall, 10 (1.5% [95% CI 0.7-2.8]) had sepsis or shock, and 2 (0.3% [95% CI 0.04-1.1]) had severe cellulitis or necrotizing soft tissue infection. None received vasopressors or endotracheal intubation. There were no deaths. CONCLUSIONS: In this multicenter cohort, mild localized disease was typical of neonatal mastitis. SBI and adverse outcomes were rare. Evaluation for SBI is likely unnecessary in most afebrile, well-appearing infants with mastitis.

Evaluation of green light exposure on headache frequency and quality of life in migraine patients: A preliminary one-way cross-over clinical trial.

BACKGROUND: Pharmacological management of migraine can be ineffective for some patients. We previously demonstrated that exposure to green light resulted in antinociception and reversal of thermal and mechanical hypersensitivity in rodent pain models. Given the safety of green light emitting diodes, we evaluated green light as a potential therapy in patients with episodic or chronic migraine. MATERIAL AND METHODS: We recruited (29 total) patients, of whom seven had episodic migraine and 22 had chronic migraine. We used a one-way cross-over design consisting of exposure for 1-2 hours daily to white light emitting diodes for 10 weeks, followed by a 2-week washout period followed by exposure for 1-2 hours daily to green light emitting diodes for 10 weeks. Patients were allowed to continue current therapies and to initiate new treatments as directed by their physicians. Outcomes consisted of patient-reported surveys. The primary outcome measure was the number of headache days per month. Secondary outcome measures included patient-reported changes in the intensity and frequency of the headaches over a two-week period and other quality of life measures including ability to fall and stay asleep, and ability to perform work. Changes in pain medications were obtained to assess potential reduction. RESULTS: When seven episodic migraine and 22 chronic migraine patients were analyzed as separate cohorts, white light emitting diodes produced no significant change in headache days in either episodic migraine or chronic migraine patients. Combining data from the episodic migraine and chronic migraine groups showed that white light emitting diodes produced a small, but statistically significant reduction in headache days from (days ± SEM) 18.2 ± 1.8 to 16.5 ± 2.01 days. Green light emitting diodes resulted in a significant decrease in headache days from 7.9 ± 1.6 to 2.4 ± 1.1 and from 22.3 ± 1.2 to 9.4 ± 1.6 in episodic migraine and chronic migraine patients, respectively. While some improvement in secondary outcomes was observed with white light emitting diodes, more secondary outcomes with significantly greater magnitude including assessments of quality of life, Short-Form McGill Pain Questionnaire, Headache Impact Test-6, and Five-level version of the EuroQol five-dimensional survey without reported side effects were observed with green light emitting diodes. Conclusions regarding pain medications reduction with green light emitting diode exposure were not possible. No side effects of light therapy were reported. None of the patients in the study reported initiation of new therapies. DISCUSSION: Green light emitting diodes significantly reduced the number of headache days in people with episodic migraine or chronic migraine. Additionally, green light emitting diodes significantly improved multiple secondary outcome measures including quality of life and intensity and duration of the headache attacks. As no adverse events were reported, green light emitting diodes may provide a treatment option for those patients who prefer non-pharmacological therapies or may be considered in complementing other treatment strategies. Limitations of this study are the small number of patients evaluated. The positive data obtained support implementation of larger clinical trials to determine possible effects of green light emitting diode therapy.This study is registered with clinicaltrials.gov under NCT03677206.

Decline in prevalence of congenital sensorineural deafness in Dalmatian dogs in the United Kingdom.

BACKGROUND: Congenital sensorineural deafness (CSD) is the most common type of deafness in Dalmatian dogs. OBJECTIVES: To use results of CSD screening in Dalmatian dogs in the United Kingdom in genetic analysis and to determine any changes in the prevalence of CSD in this breed over time. ANIMALS: A total of 8955 Dalmatian puppies undergoing hearing function screening using brainstem auditory evoked response (BAER) between July 1992 and February 2019. METHODS: Results of BAER testing and pigmentation phenotypic data were linked to the UK Kennel Club Dalmatian pedigree database. Mixed model analysis was used to estimate variance parameters. RESULTS: The overall prevalence of CSD was 17.8% (13.4%, unilateral; 4.4%, bilateral). Heritability of CSD was approximately 0.3 (across models) and significantly >0. Genetic correlations between CSD and blue irises (+0.6) and pigmented head patch (-0.86) were large in magnitude and significantly different form 0. Significant improving phenotypic and genetic trends were identified, likely as the result of selection against deafness, equivalent to avoiding breeding with the 4% to 5% of animals with the highest genetic risk of CSD. CONCLUSIONS AND CLINICAL IMPORTANCE: A decrease in the prevalence and genetic risk of CSD implies breeders have been selecting for hearing dogs. Selective breeding based on estimated breeding values (EBVs) can help further decrease the prevalence of CSD in Dalmatians in the future.

A genome-wide association study of deafness in three canine breeds.

Congenital deafness in the domestic dog is usually related to the presence of white pigmentation, which is controlled primarily by the piebald locus on chromosome 20 and also by merle on chromosome 10. Pigment-associated deafness is also seen in other species, including cats, mice, sheep, alpacas, horses, cows, pigs, and humans, but the genetic factors determining why some piebald or merle dogs develop deafness while others do not have yet to be determined. Here we perform a genome-wide association study (GWAS) to identify regions of the canine genome significantly associated with deafness in three dog breeds carrying piebald: Dalmatian, Australian cattle dog, and English setter. We include bilaterally deaf, unilaterally deaf, and matched control dogs from the same litter, phenotyped using the brainstem auditory evoked response (BAER) hearing test. Principal component analysis showed that we have different distributions of cases and controls in genetically distinct Dalmatian populations, therefore GWAS was performed separately for North American and UK samples. We identified one genome-wide significant association and 14 suggestive (chromosome-wide) associations using the GWAS design of bilaterally deaf vs. control Australian cattle dogs. However, these associations were not located on the same chromosome as the piebald locus, indicating the complexity of the genetics underlying this disease in the domestic dog. Because of this apparent complex genetic architecture, larger sample sizes may be needed to detect the genetic loci modulating risk in piebald dogs.

Congenital sensorineural deafness in English setters in the United Kingdom: prevalence and association with phenotype and sex.

BACKGROUND: The English setter (ES) is predisposed to congenital sensorineural deafness (CSD). CSD prevalence and association with phenotype in the UK ES population are previously unreported. METHODS: The database of the authors' institution was searched for ES puppies undergoing brainstem auditory evoked response (BAER) testing for CSD screening (2000-2018). Inclusion criteria were BAER performed at 5-10 weeks of age, testing of complete litters and available phenotypic data. The age, sex, presence of patches at birth, coat colour, iris colour, hearing status and BAER-determined parental hearing status of each puppy were recorded. Multivariable binary logistic regression was performed to determine the significance of these variables as predictors for the likelihood of puppies being unilaterally or bilaterally deaf. RESULTS: Inclusion criteria were met for 447 puppies. Hearing was bilaterally normal in 427 (95.5 per cent) puppies. The prevalence of unilateral and bilateral CSD was 3.6 per cent and 0.9 per cent, respectively. Females were 3.3 times more likely to be deaf than males, and puppies with both parents of unknown hearing status were 4.6 times more likely to be deaf than those with at least one normal parent. CONCLUSION: The prevalence of CSD was 4.5 per cent, with female puppies and those with two parents of unknown hearing status at greatest risk.

Prevalence of congenital sensorineural deafness in a population of client-owned purebred kittens in the United Kingdom.

BACKGROUND: Data about congenital sensorineural deafness (CSD) in white blue-eyed cats derive mainly from research colonies, and information about client-owned cats is limited. OBJECTIVES: To describe the prevalence of CSD in a client-owned population of white purebred kittens and colored littermates in the United Kingdom. ANIMALS: One hundred thirty-two solid white client-owned purebred kittens and 61 colored littermates, 6 to 21 weeks of age. METHODS: Retrospective (56 cases) and prospective (137 cases) study. Hearing was assessed by brainstem auditory evoked response testing, and the entire litter was tested. RESULTS: Congenital sensorineural deafness was diagnosed only in solid white kittens, with a prevalence of 30.3% (15.9% bilateral, 14.4% unilateral). The prevalence of CSD was significantly higher in white kittens with 1 (44.4%) or 2 (50%) blue irises than in those without blue irises (22.2%). Kittens with at least 1 blue iris were 3.2 times more likely to have CSD than kittens without blue irises. In solid white kittens, CSD was diagnosed in 7 of 15 (46.7%) Turkish Vankedisi, 8 of 18 (44.0%) Maine Coon, 18 of 41 (43.9%) Norwegian Forest, 3 of 11 (27.3%) British Shorthair, 2 of 12 (16.7%) Devon Rex, 2 of 12 (8.3%) Persian, 1 of 21 (4.8%) Russian, and 0 of 2 Sphinx. The prevalence of CSD was significantly different in Norwegian Forest, Maine Coon, and Turkish Vankedisi kittens compared with Persian or Russian kittens. CONCLUSION AND CLINICAL IMPORTANCE: We identified a high prevalence of CSD in a population of client-owned purebred white kittens in the United Kingdom and suggest differences in breed-specific prevalence of CSD.

Interventions to Reduce Over-Utilized Tests and Treatments in Bronchiolitis.

OBJECTIVES: The American Academy of Pediatrics published bronchiolitis clinical practice guidelines in 2014 recommending against the routine use of bronchodilators, chest radiographs, or respiratory viral testing in children with a clinical diagnosis of bronchiolitis. Our aim in this project was to align care with the American Academy of Pediatrics clinical practice guidelines by decreasing the overuse of these interventions. METHODS: This study included patients who were admitted to a non-ICU setting with a primary or secondary diagnosis of bronchiolitis. The team used a multidisciplinary kickoff event to understand the problem and develop interventions, including sharing provider-specific data and asking providers to sign a pledge to reduce use. We used a novel, real-time data dashboard to collect and analyze data. RESULTS: Special cause variation on control charts indicated improvement for all outcomes for inpatients during the intervention season. Pre- and postanalyses in which we compared baseline to intervention values for all admitted patients and patients who were discharged from the emergency department or urgent care revealed a significant reduction in the ordering of chest radiographs (from 22.7% to 13.6%; P ≤ .001), respiratory viral testing (from 12.5% to 9.8%; P = .001), and bronchodilators (from 17.5% to 10.3%; P = .001) without changes in balancing measures (eg, hospital readmission within 7 days [1.7% (preanalysis) and 1.0% (postanalysis); P = .21]) for bronchiolitis. CONCLUSIONS: This multidisciplinary improvement initiative resulted in a significant reduction in use for bronchiolitis care at our institution. Our approach, which included a novel, real-time data dashboard and interventions such as individual providers pledging to reduce use, may have the potential to reduce overuse in other settings and diseases.

Emergency Department-initiated Home Oxygen for Bronchiolitis: A Prospective Study of Community Follow-up, Caregiver Satisfaction, and Outcomes.

OBJECTIVE: Retrospective studies have shown home oxygen to be a safe alternative to hospitalization for some patients with bronchiolitis living at high altitudes. We aimed to prospectively describe adverse events, follow-up, duration of home oxygen, factors associated with failure, and caregiver preferences. METHODS: This was a prospective observational study of hypoxemic bronchiolitis patients ages 3 to 18 months who were discharged from a tertiary care pediatric emergency department on home oxygen over three winters (2011-2014). Caregivers were contacted on postdischarge days ~3, 7, 14, and 28 while on oxygen. Caregivers not reached by phone were sent a survey and their primary care physicians were contacted. Records of admitted subjects were reviewed. Outcome measures included hospital readmission, positive pressure ventilation (noninvasive or intubation), outpatient follow-up, duration of home oxygen therapy, and caregiver satisfaction. RESULTS: A total of 274 patients were enrolled. Forty-eight (17.5%) were admitted and 225 (82.1%) were discharged on oxygen. The median age was 8 months. Eighteen subjects were lost to follow-up. A total of 196 (87.1%) were successfully treated with outpatient oxygen, and 11 (4.9%) failed outpatient therapy and were hospitalized. Only one hospitalized patient required invasive ventilation. The median duration of home oxygen was 7 days. Child noncompliance was the most common problem (reported by 14%). The median caregiver comfort level with home oxygen was 9 of 10. Eighty-eight percent of caregivers would again choose home oxygen over admission. CONCLUSIONS: This study confirms that outpatient oxygen therapy can reduce hospitalizations due to bronchiolitis in a relatively high-altitude setting, with low failure and complication rates. Caregivers are comfortable with home oxygen and prefer it to hospitalization.

Evaluation of quality of life of carers of Italian spinoni with idiopathic epilepsy.

The carers of all UK Kennel Club registered Italian spinoni (IS) born between January 1, 2000 and December 31, 2011 were invited to participate in the study. The carers of 47 of 63 IS diagnosed with idiopathic epilepsy (IE) returned the questionnaire, which included numerous questions on various aspects of IE including the effect of IE on the dog's carer's quality of life. Median epileptic seizure number in the three months before study end or death was five epileptic seizures, 72 per cent of dogs had cluster seizures, 94 per cent of dogs were administered one or more antiepileptic medications and 36 per cent of dogs were euthanased due to poorly controlled IE. Seventy-one per cent and 65 per cent of the participants were moderately to extremely worried about the frequency and severity of their dog's epileptic seizures, respectively. Caring for an IS with IE caused conflict with the carer's work, education or daily activity often or very often in 50 per cent of the participants. Overall the limitations on the carer's life due to caring for an IS with IE were considered as very to extremely bothersome in 29 per cent of the participants, a little to moderately bothersome in 40 per cent of the participants and not at all bothersome in 31 per cent of the participants.

Prevalence, heritability and genetic correlations of congenital sensorineural deafness and coat pigmentation phenotype in the English bull terrier.

BACKGROUND: Congenital sensorineural deafness (CSD) is the most common type of deafness in dogs and it occurs in numerous canine breeds including the English bull terrier. This study estimates prevalence, heritability and genetic correlations of CSD and coat pigmentation phenotypes in the English bull terrier in England. RESULTS: Hearing status was assessed by brainstem auditory evoked response in 1060 English bull terrier puppies tested at 30-78 (mean 43.60) days of age as complete litters. Gender, coat and iris colour and parental hearing status were recorded. The prevalence of CSD in all 1060 puppies was 10.19 % with 8.21 % unilaterally deaf and 1.98 % bilaterally deaf. The coat was predominately coloured in 49.15 % puppies and white with or without a patch in 50.85 % puppies. The majority (96.29 %) of deaf puppies had a white coat (with or without a patch); 19.29 % of the puppies with a white coat (with or without a patch) were deaf. Heritability and genetic correlations were estimated using residual maximum likelihood. Heritability of hearing status as a trichotomous trait (bilaterally normal/unilaterally deaf/bilaterally deaf) was estimated at 0.15 to 0.16 and was significantly different to zero (P < 0.01). Heritability of coat pigmentation phenotype (all white/white with patches/coloured) was 0.49 (standard error 0.077). Genetic correlation of CSD with coat pigmentation phenotype was estimated at -0.36 to -0.37 (CSD associated with all white coat), but was not significantly larger than zero (P > 0.05). Analysis of CSD in all white and white patched puppies only estimated the heritability of CSD as 0.25 and was significantly greater than zero (P < 0.01), and the heritability of coat colour (all white/white with patches) as 0.20 (standard error 0.096). The genetic correlation was estimated at -0.53 to -0.54 (CSD associated with all white coat) but was just above the statistical threshold determining significant difference to zero (P = 0.06). CONCLUSIONS: These results indicate that CSD occurs predominantly in white English bull terriers and there is genetic variation in CSD beyond that associated with coat colour.

Paroxysmal Dyskinesia in Norwich Terrier Dogs.

BACKGROUND: Episodic muscular hypertonicity in Norwich terrier dogs was first reported in a brief communication in 1984. Since then, the condition has remained poorly characterized. OBJECTIVES: The aims of this study were to characterize the phenomenology, clinical course, and family history of paroxysmal dyskinesia in the Norwich terrier and to estimate its prevalence in the United Kingdom. METHODS: The owners of Norwich terrier dogs born since January 1, 2000 were invited to complete a specifically designed questionnaire aimed at identifying affected and unaffected dogs and investigating the clinical characteristics of this paroxysmal dyskinesia. Pedigrees were collected and reviewed. RESULTS: The questionnaire was returned for 198 Norwich terrier dogs. Of these, 26 (13%) were classified as affected by paroxysmal dyskinesia after revision of the questionnaires and after obtaining videos of the episodes, veterinary medical records, and telephone interviews with the owners. All dogs were neurologically normal between episodes. No significant abnormalities were detected on diagnostic investigations. Mean age at the first episode was 3 years. The episodes were characterized by sustained muscular hypertonicity in the pelvic limbs, lumbar region, and thoracic limbs, impairing posture and locomotion without loss of consciousness. Episode frequency varied both between and within individuals. Stress, anxiety, excitement, and variation in daily routine were recognized as episode triggers in 13 dogs. Episode duration generally was from 2 to 5 minutes (range, from < 2 to 30 minutes). The majority of affected dogs were related. CONCLUSIONS: Paroxysmal dyskinesia segregates in an extended pedigree of Norwich terrier dogs and thus is potentially an inherited disorder in this breed.

Use of capnographs to assess quality of pediatric ventilation with 3 different airway modalities.

OBJECTIVES: Prehospital pediatric airway management is difficult and controversial. Options include bag-mask ventilation (BMV), endotracheal tube (ETT), and laryngeal mask airway (LMA). Emergency Medical Services personnel report difficulty assessing adequacy of BMV during transport. Capnography, and capnograph tracings in particular, provide a measure of real-time ventilation currently used in prehospital medicine but have not been well studied in pediatric patients or with BMV. Our objective was to compare pediatric capnographs created with 3 airway modalities. METHODS: This was a prospective study of pediatric patients requiring ETT or LMA ventilation during elective surgical procedures. Data were collected during BMV using 2 bag types (flow-inflating and self-inflating). The ETT or LMA was placed and ventilation with each bag type repeated. Ten- to 14-second capnographs were reviewed by 2 blinded anesthesiologists who were asked to assess ventilation and identify the airway and bag type used. Descriptive statistics, κ, and risk ratios were calculated. RESULTS: Twenty-nine patients were enrolled. Median age was 4.4 years (2 months to 16.8 years). One hundred sixteen capnographs were reviewed. Reviewers were unable to differentiate between airway modalities and agreed on adequacy of ventilation 77% of the time (κ = 0.6, P < .001). Bag-mask ventilation was rated inadequate more frequently than ETT or LMA ventilation. There were no difference between ETT and LMA ventilation and no difference between the 2 bag types. CONCLUSION: Capnographs are generated during BMV and are virtually identical to those produced with ETT or LMA ventilation. Attention to capnographs could improve outcomes during emergency treatment and transport of critically ill pediatric patients requiring ventilation with any of these airway modalities.