Nonsteroidal anti-inflammatory drug exposure and the risk of microscopic colitis.

BACKGROUND: Medication consumption has been suggested as a risk factor for microscopic colitis (MC), but studies of varying design have yielded inconsistent results. Our aim was to evaluate the association between medications and MC. METHODS: A hybrid cohort of prospectively identified patients undergoing colonoscopy with biopsies for suspicion of MC (N = 144) and patients with MC enrolled within three months of diagnosis into an MC registry (N = 59) were surveyed on medication use. Medication use was compared between patients with and without diagnosis of MC by chi-squared test and binomial logistic regression adjusted for known risk factors of MC: age and gender. RESULTS: In total, 80 patients with MC (21 new, 59 registry) were enrolled. Patients with MC were more likely to be older (p = 0.03) and female (p = 0.01) compared to those without MC. Aspirin and other non-steroidal anti-inflammatory drugs were more commonly used among patients who developed MC (p < 0.01). After controlling for age and gender, these medications remained independent predictors of MC with odds ratio for any non-steroidal anti-inflammatory drug use of 3.04 (95% CI: 1.65-5.69). No association between MC and other previously implicated medications including proton pump inhibitors and selective serotonin reuptake inhibitors was found. CONCLUSIONS: In this cohort of patients with chronic diarrhea, we found use of aspirin and non-steroidal anti-inflammatory drugs, but not other implicated medications to be associated with the development of MC. Whether these drugs trigger colonic inflammation in predisposed hosts or worsen diarrhea in undiagnosed patients is unclear. However, we feel that these findings are sufficient to discuss potential non-steroidal anti-inflammatory drug cessation in patients newly diagnosed with MC.

Compassionate Care: Making It a Priority and the Science Behind It.

BACKGROUND: Compassion is the deep feeling that arises when confronted with another's suffering coupled with a strong desire to alleviate that suffering. Until recently, evidence was lacking as to whether compassion was innate, acquired, or modifiable. Because patients who experience compassionate health care report better clinical outcomes, an understanding of the science behind it may give rise to methods of incorporating compassion into clinical care delivery. METHODS: A high-level summary of the social and neuroscience research was constructed. RESULTS: Functional neuroimaging of empathy and compassion demonstrates neural networks involving the insula, cingulate, and prefrontal cortices suggesting neurological hard wiring for these emotional and cognitive experiences. Neuroscience and social science research evidence supports the presence of cognitive and/or emotional empathy in all individuals studied; that empathy and compassion can be taught; and that both internal and external factors influence their expression. CONCLUSIONS: Burnout may result when clinicians know what their patients need (thereby activating the empathy/pain neural pathways) but are unable to deliver that care (therefore inactivation of the compassion/reward neural pathways). Understanding the neuroscience underlying empathy and compassion informs practical programs that mitigate burnout and creates a more compassionate workplace.

Pediatric Orthopaedists Are Not Immune: Characterizing Self-reported Burnout Rates Among POSNA Members.

BACKGROUND: There are no published data characterizing burnout rates for pediatric orthopaedic surgeons. The primary purpose of this study was to identify the rates of self-reported personal and team burnout among members of the Pediatric Orthopaedic Society of North America (POSNA). A secondary aim was to determine whether specific demographic variables were more likely to be associated with self-reported burnout. METHODS: During its 2018 annual meeting, the POSNA Wellness Taskforce launched a web-based survey in which members were asked to respond to 2 previously validated questions related to personal and team burnout. The survey was distributed by a closed POSNA membership e-mail list and responses were analyzed anonymously. Descriptive statistics were calculated. Pearson χ testing was used to analyze differences in burnout rates as a function of age and sex. RESULTS: A total of 615 POSNA members completed the survey, a 47% response rate. Overall, 38% reported personal burnout and 46% reported team burnout. Women were more likely to report both personal (P<0.001) and team burnouts (P<0.005). Members aged 40 to 59 years were more likely to report personal burnout, irrespective of sex (P<0.001). Members aged 50 to 59 years were more likely than those in other age groups to report team burnout (P<0.001). There was no significant association found between the presence of burnout and either race, ethnicity, LGBTQ status, or educational background. CONCLUSIONS: As a group, pediatric orthopaedists report moderately high rates of both personal and team member burnout. Individual-specific factors such as age and sex may play an important role in determining one's risk for experiencing burnout. Recognizing that burnout affects a significant minority of POSNA members is a crucial first step. LEVEL OF EVIDENCE: Level III.

Best practice guidelines regarding diagnosis and management of patients with type II collagen disorders.

PURPOSE: Skeletal dysplasias comprise a heterogeneous group of inherited disorders of development, growth, and maintenance of the human skeleton. Because of their relative rarity and wide phenotypic variability, patients should be accurately identified, uniformly assessed, and managed by clinicians who are aware of their potential complications and possess the knowledge and resources to treat them effectively. This study presents expert guidelines developed to improve the diagnosis and management of patients with type II collagen skeletal disorders to optimize clinical outcomes. METHODS: A panel of 11 multidisciplinary international experts in the field of skeletal dysplasia participated in a Delphi process, which comprised analysis of a thorough literature review with subsequent generation of 26 diagnosis and care recommendations, followed by two rounds of anonymous voting with an intervening face-to-face meeting. Those recommendations with more than 80% agreement were considered as consensual. RESULTS: After the first voting round, consensus was reached to support 12 of 26 (46%) statements. After the panel discussion, the group reached consensus on 22 of 24 revised statements (92%). CONCLUSIONS: Consensus-based, expert best practice guidelines developed as a standard of care to assist accurate diagnosis, minimize associated health risks, and improve clinical outcomes for patients with type II collagen skeletal dysplasias.

Patient Safety Checklists: Do They Improve Patient Safety for Supracondylar Humerus Fractures?

BACKGROUND: The purpose of the study was to investigate whether a safety checklist could be used consistently in an academic center, and, whether its presence correlates with a decreased rate of complications, and therefore, improved overall patient safety. METHODS: Data from 3 years before and after the implementation of the checklist were compared. Prechecklist data from August 2008 through August of 2011, including all operative supracondylar humerus fractures treated at our institution, were retrospectively reviewed. Postchecklist data, from August 2011 to August 2014 were prospectively collected. Patients' charts and their imaging were all reviewed for: fracture type, nerve injury, placement of a medial pin, infection, loss of alignment, loss of fixation, and return to the operating room (OR). Patients who were within the checklist group were reviewed for checklist compliance and concordance of resident and attending-attested checklists. RESULTS: Nine hundred thirty-one operative supracondylar humerus fractures were reviewed-394 in the prechecklist group and 537 in the postchecklist group. There was no significant difference in fracture type between the prechecklist and postchecklist groups. No significant differences were found between prechecklist and postchecklist patients in regards to loss of fixation, loss of alignment, infection, or nerve injury. In the postchecklist group, the number of medial pins placed was significantly less than in the prechecklist group (P=0.0001), but this was not found to have clinical significance. In the prechecklist group, 11 patients returned to the OR for a second procedure, whereas 4 in the postchecklist group had a return to the OR. This finding was significant (P=0.015), but the returns to the OR were not related to checklist parameters. The checklist compliance of the attending physicians was 85.85% and the residents were compliant 83.11% of the time. There were documented discrepancies between resident and attending checklists in 7.38% of all total checklists. CONCLUSIONS: Our patient safety checklists are not necessarily affecting patient care in a clinically significant manner. It is important that we validate and refine these specialty-specific checklists before becoming reliant on them. LEVEL OF EVIDENCE: Level III.

The Pediatric Orthopaedic Society of North America (POSNA) Adopts a Member Health and Wellness Charter.

The Pediatric Orthopaedic Society of North America took actions to address the well-being of its members. The epidemic of physician burnout interferes with the delivery of high-quality care that our patients and families need and deserve, and at the same time places the care-providers at an increased risk of depression and suicide. The actions taken by Pediatric Orthopaedic Society of North America serve as a model for other professional medical societies to emulate.

Novel phenotype of achondroplasia due to biallelic FGFR3 pathogenic variants.

Pathogenic variants in the fibroblast growth factor receptor 3 (FGFR3) gene are responsible for a broad spectrum of skeletal dysplasias, including achondroplasia (ACH). The classic phenotype of ACH is caused by two highly prevalent mutations, c.1138G > A and c.1138G > C (p.Gly380Arg). In the homozygous state, these variant results in a severe skeletal dysplasia, neurologic deficits, and early demise from respiratory insufficiency. Although homozygous biallelic mutations have been reported in patients with ACH in combination with hypochondroplasia or other dominant skeletal dysplasias, thus far, no cases of heterozygous biallelic pathogenic ACH-related variants in FGFR3 have been reported. We describe a novel phenotype of an infant with two ACH-related mutations in FGFR3, p.Gly380Arg and p.Ser344Cys. Discordant features from classic ACH include atypical radiographic findings, severe obstructive sleep apnea, and focal, migrating seizures. We also report the long-term clinical course of her father, who harbors the p.Ser344Cys mutation that has only been reported once previously in a Japanese patient. The phenotype of heterozygous biallelic mutations in FGFR3 associated with ACH is variable, underscoring the importance of recognition and accurate diagnosis to ensure appropriate management.

Best practice guidelines regarding prenatal evaluation and delivery of patients with skeletal dysplasia.

BACKGROUND: Skeletal dysplasia comprises a heterogeneous and collectively common group of inherited disorders of development, growth, and maintenance of the human skeleton. There is potential for increased perinatal morbidity and mortality in pregnant women who themselves have skeletal dysplasia, and for affected fetuses where skeletal dysplasia is suspected in utero. OBJECTIVE: We sought to establish guidelines for perinatal health care professionals who should be aware of these risks, to optimize maternal and child health pregnancy outcomes through best prenatal and delivery management practices. STUDY DESIGN: A panel of 13 multidisciplinary international experts participated in a Delphi process, which comprised consideration of thorough literature review and a list of 54 possible care recommendations subject to 2 rounds of anonymous voting and a face-to-face meeting. Those recommendations with >80% agreement were considered as consensual. RESULTS: During the first round, consensus was reached to support 30 out of the 54 statements. After the panel discussion, the group reached consensus on 40 statements. These statements include guidelines for the evaluation and treatment of pregnant women with skeletal dysplasia and for the unborn child with or suspected to have skeletal dysplasia. CONCLUSION: Consensus-based best practice guidelines are provided as a minimum of standard care to minimize associated health risks, and improve clinical outcomes for patients with skeletal dysplasia.

Spectral biomarkers for chemoprevention of colonic neoplasia: a placebo-controlled double-blinded trial with aspirin.

OBJECTIVE: A major impediment to translating chemoprevention to clinical practice has been lack of intermediate biomarkers. We previously reported that rectal interrogation with low-coherence enhanced backscattering spectroscopy (LEBS) detected microarchitectural manifestations of field carcinogenesis. We now wanted to ascertain if reversion of two LEBS markers spectral slope (SPEC) and fractal dimension (FRAC) could serve as a marker for chemopreventive efficacy. DESIGN: We conducted a multicentre, prospective, randomised, double-blind placebo-controlled, clinical trial in subjects with a history of colonic neoplasia who manifested altered SPEC/FRAC in histologically normal colonic mucosa. Subjects (n=79) were randomised to 325 mg aspirin or placebo. The primary endpoint changed in FRAC and SPEC spectral markers after 3 months. Mucosal levels of prostaglandin E2 (PGE2) and UDP-glucuronosyltransferase (UGT)1A6 genotypes were planned secondary endpoints. RESULTS: At 3 months, the aspirin group manifested alterations in SPEC (48.9%, p=0.055) and FRAC (55.4%, p=0.200) with the direction towards non-neoplastic status. As a measure of aspirin's pharmacological efficacy, we assessed changes in rectal PGE2 levels and noted that it correlated with SPEC and FRAC alterations (R=-0.55, p=0.01 and R=0.57, p=0.009, respectively) whereas there was no significant correlation in placebo specimens. While UGT1A6 subgroup analysis did not achieve statistical significance, the changes in SPEC and FRAC to a less neoplastic direction occurred only in the variant consonant with epidemiological evidence of chemoprevention. CONCLUSIONS: We provide the first proof of concept, albeit somewhat underpowered, that spectral markers reversion mirrors antineoplastic efficacy providing a potential modality for titration of agent type/dose to optimise chemopreventive strategies in clinical practice. TRIAL NUMBER: NCT00468910.

A comparison of the functional health of children with Costello syndrome in 1999 and in 2015.

Costello Syndrome is a rare congenital condition characterized by failure-to-thrive, cardiac abnormalities, distinctive facial features, predisposition to malignant tumors, and developmental delay. In 1999, we analyzed the functional health in a cohort of 18 patients. Since then, a mutation in the HRAS gene has been found to be causative, medical management has been refined, and the level of awareness has increased. The purpose of this study is to compare the functional health outcomes from the 1999 cohort with data prospectively collected from a comparable cohort in 2015. The Pediatric Outcome Data Collection Instrument (PODCI) was administered to parents of children with Costello syndrome during the 2015 International Costello Syndrome Conference. The same instrument and setting were used in the 1999 study. We compared functional health scores from the two groups. A total of 21 participants were included in the 2015 cohort; 15 females (71%) and 6 males (29%). Average age was 5.8 years (range 2-16). When comparing functional health outcomes, we found that the 2015 cohort scored slightly higher in Upper Extremity and Physical Function (57 vs. 54) and Comfort scales (86 vs. 82). However, there was no significant difference in any of the PODCI scales between the two groups. When compared with normative scores, both groups scored significantly lower in every scale except for happiness (p = 0.2952). Despite recent advancements, functional health outcomes in 2015 were similar to those measured in a different cohort in 1999.

Best practices in peri-operative management of patients with skeletal dysplasias.

Patients with skeletal dysplasia frequently require surgery. This patient population has an increased risk for peri-operative complications related to the anatomy of their upper airway, abnormalities of tracheal-bronchial morphology and function; deformity of their chest wall; abnormal mobility of their upper cervical spine; and associated issues with general health and body habitus. Utilizing evidence analysis and expert opinion, this study aims to describe best practices regarding the peri-operative management of patients with skeletal dysplasia. A panel of 13 multidisciplinary international experts participated in a Delphi process that included a thorough literature review; a list of 22 possible care recommendations; two rounds of anonymous voting; and a face to face meeting. Those recommendations with more than 80% agreement were considered as consensual. Consensus was reached to support 19 recommendations for best pre-operative management of patients with skeletal dysplasia. These recommendations include pre-operative pulmonary, polysomnography; cardiac, and neurological evaluations; imaging of the cervical spine; and anesthetic management of patients with a difficult airway for intubation and extubation. The goals of this consensus based best practice guideline are to provide a minimum of standardized care, reduce perioperative complications, and improve clinical outcomes for patients with skeletal dysplasia.

Best practices in the evaluation and treatment of foramen magnum stenosis in achondroplasia during infancy.

Achondroplasia is the most common inherited disorder of bone growth (skeletal dysplasia). Despite this fact, consistent and evidence-based management approaches to recognized, life-threatening complications, such as foramen magnum stenosis, are lacking. This study aims to outline best practice, based on evidence and expert consensus, regarding the diagnosis, assessment, and management of foramen magnum stenosis in achondroplasia during infancy. A panel of 11 multidisciplinary international experts on skeletal dysplasia was invited to participate in a Delphi process. They were: 1) presented with a list of 26 indications and a thorough literature review, 2) given the opportunity to anonymously rate the indications and discuss in face to face discussion; 3) edit the list and rate it in a second round. Those indications with more than 80% agreement were considered as consensual. After two rounds of rating and a face-to-face meeting, consensus was reached to support 22 recommendations for the evaluation and treatment of foramen magnum stenosis in infants with achondroplasia. These recommendations include indications for surgical decompression, ventriculomegaly, and hydrocephalus, sleep-disordered breathing, physical exams and the use of polysomnography and imaging in this condition. We present a consensus-based best practice guidelines consisting of 22 recommendations. It is hoped that these guidelines will lead to more uniform and structured evaluation, standardizing care pathways, and improving mortality and morbidity outcomes for this cohort.

Detection and Nonoperative Management of Pediatric Developmental Dysplasia of the Hip in Infants up to Six Months of Age.

Detection and Nonoperative Management of Pediatric Developmental Dysplasia of the Hip in Infants up to Six Months of Age: Evidence-Based Clinical Practice Guideline is based on a systematic review of the current scientific and clinical research. This guideline has been endorsed by the Society of Diagnostic Medical Sonography, the Society for Pediatric Radiology, American Academy of Pediatrics, and the Pediatric Orthopaedic Society of North America. The purpose of this clinical practice guideline is to help improve treatment and management based on the current evidence. This guideline contains nine recommendations, including both diagnosis and treatment. In addition, the work group highlighted the need for better research in the early diagnosis and treatment of developmental dysplasia of the hip.

Nanoscale changes in chromatin organization represent the initial steps of tumorigenesis: a transmission electron microscopy study.

BACKGROUND: Nuclear alterations are a well-known manifestation of cancer. However, little is known about the early, microscopically-undetectable stages of malignant transformation. Based on the phenomenon of field cancerization, the tissue in the field of a tumor can be used to identify and study the initiating events of carcinogenesis. Morphological changes in nuclear organization have been implicated in the field of colorectal cancer (CRC), and we hypothesize that characterization of chromatin alterations in the early stages of CRC will provide insight into cancer progression, as well as serve as a biomarker for early detection, risk stratification and prevention. METHODS: For this study we used transmission electron microscopy (TEM) images of nuclei harboring pre-neoplastic CRC alterations in two models: a carcinogen-treated animal model of early CRC, and microscopically normal-appearing tissue in the field of human CRC. We quantify the chromatin arrangement using approaches with two levels of complexity: 1) binary, where chromatin is separated into areas of dense heterochromatin and loose euchromatin, and 2) grey-scale, where the statistics of continuous mass-density distribution within the nucleus is quantified by its spatial correlation function. RESULTS: We established an increase in heterochromatin content and clump size, as well as a loss of its characteristic peripheral positioning in microscopically normal pre-neoplastic cell nuclei. Additionally, the analysis of chromatin density showed that its spatial distribution is altered from a fractal to a stretched exponential. CONCLUSIONS: We characterize quantitatively and qualitatively the nanoscale structural alterations preceding cancer development, which may allow for the establishment of promising new biomarkers for cancer risk stratification and diagnosis. The findings of this study confirm that ultrastructural changes of chromatin in field carcinogenesis represent early neoplastic events leading to the development of well-documented, microscopically detectable hallmarks of cancer.

Digital video technology and production 101: lights, camera, action.

Videos are powerful tools for enhancing the reach and effectiveness of health promotion programs. They can be used for program promotion and recruitment, for training program implementation staff/volunteers, and as elements of an intervention. Although certain brief videos may be produced without technical assistance, others often require collaboration and contracting with professional videographers. To get practitioners started and to facilitate interactions with professional videographers, this Tool includes a guide to the jargon of video production and suggestions for how to integrate videos into health education and promotion work. For each type of video, production principles and issues to consider when working with a professional videographer are provided. The Tool also includes links to examples in each category of video applications to health promotion.

EXT2-positive multiple hereditary osteochondromas with some features suggestive of metachondromatosis.

Metachondromatosis (MC) and hereditary multiple osteochondromas (HMO) are thought to be distinct disorders, each with characteristic x-ray and clinical features. Radiographic differences are the current mainstay of differential diagnosis. Both disorders are autosomal dominant, but the majority of patients with HMO have mutations in EXT-1 or EXT 2 genes. The genetic defect in MC is unknown, although recent studies indicate a possible identifiable mutation. The cancer risk in HMO is thought to be greater than in MC, although the small number of cases make such conjecture imprecise. The purpose of this report is to review existing literature and examine whether radiographic findings in HMO and MC can be reliable as a stand-alone means of differential diagnosis. Three members of a multi-generational family with an autosomal dominant exostosis syndrome were studied by clinical examination and complete skeletal survey. The roentgenographic characteristics of all osteochondromas were analyzed. The father underwent gene sequencing for EXT-1 and EXT-2, which revealed a novel EXT-2 mutation. Typical radiographic and clinical findings of both HMO and MC were seen throughout the family as well as in individuals. These family study findings contradict many of the long-standing clinical and x-ray diagnostic criteria for differentiating MC from HMO. The phenotypic crossover between the two conditions in this family, and results of genetic analysis, suggest that in the absence of a definitive genetic diagnosis, radiographic and clinical diagnosis of past and future cases HMO and MC may not be as reliable as previously assumed.

Current trends to consider with evidence-based medicine's importance: societal, financial, legal, and clinical research.

Evidence-based medicine and its quality work products enter current clinical practice at a time when physicians face a confusing, contradictory, and changing practice environment. Disparate expectations by patients and policy makers; physician conflicts of interest, and an assumption that doctors control the cost of healthcare, contribute to fears that evidence based medicine in general and guidelines and performance measures in particular, will be misused. An integrated framework for developing evidence based tools is presented.