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.

Best practice guidelines in managing the craniofacial aspects of skeletal dysplasia.

BACKGROUND: Recognition and appropriate management of the craniofacial manifestations of patients with skeletal dysplasia are challenging, due to the rarity of these conditions, and dearth of literature to support evidence-based clinical decision making. METHODS: Using the Delphi method, an international, multi-disciplinary group of individuals, with significant experience in the care of patients with skeletal dysplasia, convened to develop multi-disciplinary, best practice guidelines in the management of craniofacial aspects of these patients. RESULTS: After a comprehensive literature review, 23 initial statements were generated and critically discussed, with subsequent development of a list of 22 best practice guidelines after a second round voting. CONCLUSIONS: The guidelines are presented and discussed to provide context and assistance for clinicians in their decision making in this important and challenging component of care for patients with skeletal dysplasia, in order standardize care and improve outcomes.

NSQIP versus institutional morbidity and mortality conference: complementary complication reporting in pediatric spine fusion.

PURPOSE: Other fields of medicine have demonstrated underreported surgical complication rates by institutional M&M compared to NSQIP. However, a study comparing surgical complication rates in the pediatric spine population, using an identical set of patients rather than nationally extrapolated, has not been performed. METHODS: A single institution's ASC-NSQIP Pediatric spine fusion cases and its departmental team-reported M&M database for the same were reviewed for January 1, 2012 to December 31, 2018. Differences in surgical complication reporting between the two databases for the identical patient cohort were recorded. RESULTS: NSQIP identified 50 pediatric spine fusion patients with complications out of 386 NSQIP-algorithm-sampled cases (13%). Of these complications, 23 were not reported in the M&M conference database (6% of NSQIP-sampled cases, 2.5% of all M&M cases). The most common under-reported complication categories include pneumonia (100% under-reported), clostridium difficile (100%), urinary tract infection (83%), and superficial wound disruption (67%). During the same 7 years, M&M covered 924 spine fusions and identified 162 complications. Of these 162 patients, 22 were included in the NSQIP sampling and were not reported as complications (6% of NSQIP sampled patients). CONCLUSION: Recognizing complication rates is central to implement strategies for delivering better quality care. NSQIP data may serve as an important quality check for pediatric spine institutional M&M data, but both may not include all complications even within its sampled patients. In general, NSQIP's protocols identified more medical complications, while M&M has a surgical focus, benefits from the limitless follow-up, and involves timely departmental awareness of complications.

Do Physicians Have Collective, Not Just Individual, Obligations to Respond to the Opioid Crisis?

Evidence-based clinical guidelines could mitigate variations in care for some patients. However, patient and clinician distress can arise when guidelines are misapplied or mandated by processes that are not evidence based, fail to integrate physician expertise and patient preference, or fail to motivate informed, shared decision making. Physicians can choose to collectively advocate at national, state, and local levels for policy changes.

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.

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.

Best practice guidelines for management of spinal disorders in skeletal dysplasia.

BACKGROUND: Disorders of the spine present a common and difficult management concern in patients with skeletal dysplasia. Due to the rarity of these conditions however, the literature, largely consisting of small, single institution case series, is sparse in regard to well-designed studies to support clinical decision making in these situations. METHODS: Using the Delphi method, an international, multi-disciplinary group of individuals, with significant experience in the care of patients with skeletal dysplasia, convened to develop multi-disciplinary, "best practice" guidelines in the care of spinal disorders in patients with skeletal dysplasia. RESULTS: Starting with 33 statements, the group a developed a list of 31 "best practice" guidelines. CONCLUSIONS: The guidelines are presented and discussed to provide context for clinicians in their decision making in this often-challenging realm of care.

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.

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.

Suture wear particles cause a significant inflammatory response in a murine synovial airpouch model.

BACKGROUND: Commonly used contemporary orthopaedic sutures have been identified as a potential causative factor in the development of post-arthroscopic glenohumeral chondrolysis. Currently, little is known about the body's immune response to these materials. The aim of this study was to examine the biological response of synovial tissue to three commonly used orthopaedic sutures, using a murine airpouch model. METHODS: Fifty rats were used in this study (ten per group). An airpouch was created in each rat, and test materials were implanted. Test materials consisted of an intact polyethylene terephthalate suture with a polybutilate coating (suture A), an intact polyethylene suture braided around a central polydiaxannone core (suture B), an intact polyethylene/polyester cobraid suture with a silicone coating (suture C), and particles of suture C (particles C). Rats were sacrificed at 1 or 4 weeks following implantation. Histological (multinucleated giant cell count) and immunohistochemical (expression of matrix metalloproteinases MMP-1,-2,-3,-9,-13) markers of inflammation were examined. RESULTS: Multinucleated giant cells were present in all specimens containing suture material but not in the control specimens. No significant differences were found in the number of giant cells between the intact suture groups at either time point. Significantly higher numbers of giant cells were noted in the particles C group compared to the intact suture C group at both time points (p = 0.021 at 1 week, p = 0.003 at 4 weeks). Quantitative analysis of immunohistochemical staining expression at 4 weeks showed that significantly more MMP (-1,-2,-9,-13) was expressed in the particles C group than the intact suture C group (p = 0.024, p = 0.009, p = 0.002, and p = 0.007 for MMP-1, MMP-2, MMP-9, and MMP-13, respectively). No significant difference was seen in the expression of MMP-3 (p = 0.058). CONCLUSIONS: There were no differences observed between the biological reactivity of commonly used intact orthopaedic sutures A, B, and C. However, wear particles of suture C elicited a significantly greater inflammatory response than intact suture alone. This was confirmed by increased numbers of multinucleated giant cells as well as MMP ( -1,-2,-9,-13) expression. Further studies are needed to determine whether this inflammatory response may play a role in the development of post-arthroscopic glenohumeral chondrolysis or interfere with biological healing. These findings have important clinical implications relating to surgical technique and surgical implant design.

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.

Prevention of colonic neoplasia with polyethylene glycol: A short term randomized placebo-controlled double-blinded trial.

Chemoprevention represents an attractive modality against colorectal cancer (CRC) although widespread clinical implementation of promising agents (e.g. aspirin/NSAIDS) have been stymied by both suboptimal efficacy and concerns over toxicity. This highlights the need for better agents. Several groups, including our own, have reported that the over-the-counter laxative polyethylene glycol (PEG) has remarkable efficacy in rodent models of colon carcinogenesis. In this study, we undertook the first randomized human trial to address the role of PEG in prevention of human colonic neoplasia. This was a double-blind, placebo-controlled, three-arm trial where eligible subjects were randomized to 8g PEG-3350 (n = 27) or 17g PEG-3350 (n = 24), or placebo (n = 24; maltodextrin) orally for a duration of six months. Our initial primary endpoint was rectal aberrant crypt foci (ACF) but this was changed during protocol period to rectal mucosal epidermal growth factor receptor (EGFR). Of the 87 patients randomized, 48 completed study primary endpoints and rectal EGFR unchanged PEG treatment. Rectal ACF had a trend suggesting potentially reduction with PEG treatment (pre-post change 1.7 in placebo versus -0.3 in PEG 8+ 17g doses, p = 0.108). Other endpoints (proliferation, apoptosis, expression of SNAIL and E-cadherin), previously noted to be modulated in rodent models, appeared unchanged with PEG treatment in this clinical trial. We conclude that PEG was generally well tolerated with the trial failing to meet primary efficacy endpoints. However, rectal ACFs demonstrated a trend (albeit statistically insignificant) for suppression with PEG. Moreover, all molecular assays including EGFR were unaltered with PEG underscoring issues with lack of translatability of biomarkers from preclinical to clinical trials. This data may provide the impetus for future clinical trials on PEG using more robust biomarkers of chemoprevention. TRIAL REGISTRATION: ClinicalTrials.gov NCT00828984.

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.

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.

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.