Exploring genetic counselors' experiences with non-paternity in clinical settings.

Non-paternity (NP) is a challenging dilemma faced by genetics providers and there is little consensus on whether this finding should be disclosed. Discussions in the literature are highly theoretical, with limited research regarding how disclosure decisions are enacted in practice. We explored genetic counselors' (GCs) clinical experiences with NP to understand if, how, and why this finding is communicated. Our semi-structured interviews with genetic counselors in the United States and Canada were analyzed using reflexive thematic analysis to analyze data inductively, describe themes, and present a meaningful interpretation of the data. Eighteen participants who responded to list-serv messages were interviewed. Our framework describes five salient themes: (1) GC-lab relationship: the GCs awareness of laboratory processes such as quality control metrics that can uncover NP findings and the way in which a finding of NP was disclosed by the laboratory had an impact on disclosure decisions. This triggered a decision-making trajectory that involved (2) consultation, (3) ethical reasoning, and (4) practical constraints. GCs frequently consulted other professionals during decision-making. These conversations impacted disclosure decisions with some consultations carrying greater weight than others. GCs weighed moral concepts of patient autonomy, medical relevance, and preventing harm to rationalize decisions. Access to patients and documentation requirements often dictated how disclosure occurred. Finally, once a decision had been made and enacted, GCs used the experience to reconsider their approach to (5) consenting in future cases, with some GCs altering their pre-test counseling to always include a discussion of NP. Although NP scenarios are frequently unique in context, our findings demonstrate several common decision-making factors GCs harness to navigate the identification of NP through clinical genetic testing.

Epidurals for Coarctation Repair in Children Are Associated with Decreased Postoperative Anti-Hypertensive Infusion Requirement as Measured by a Novel Parameter, the Anti-Hypertensive Dosing Index (ADI).

BACKGROUND: Sympathetically-associated hypertension after coarctation repair is a common problem often requiring anti-hypertensive infusions in an intensive care unit. Epidurals suppress sympathetic output and can reduce blood pressure but have not been studied following coarctation repair in children. We sought to determine whether epidurals for coarctation repair in children were associated with decreased requirement for postoperative anti-hypertensive infusions, if they were associated with changes in hospital course, or with complications. METHODS: In this observational retrospective cohort study, we evaluated all patients age 1-18 years undergoing coarctation repair at our institution during a 10-year period and compared the requirement for postoperative anti-hypertensive infusions in patients with and without epidurals using an anti-hypertensive dosing index (ADI) incorporating total dose-hours of all anti-hypertensive infusions (primary outcome). We also assessed intensive care unit (ICU) and hospital length of stay, discharge on oral anti-hypertensive medication, and complications potentially related to epidurals (secondary outcomes). RESULTS: Children undergoing coarctation repair with epidurals had decreased requirements for postoperative anti-hypertensive infusions compared to children without epidurals (cumulative ADI 65.0 [28.5-130.3] v. 157.0 [68.6-214.7], p = 0.021; mean ADI 49.0 [33.3-131.2] v. 163.0 [66.6-209.8], p = 0.01). After multivariable cumulative logit mixed-effects regression analysis, mean ADI was decreased in patients with epidurals throughout the postoperative period (p < 0.001). Patients with epidurals were 1.6 years older and weighed 10.6 kg more than patients without epidurals but were otherwise comparable. Epidural complications included pruritus (three patients), agitation (one patient), somnolence (one patient), and transient orthostatic hypotension (one patient). Duration of intensive care unit admission, duration of hospital stays, and requirement for anti-hypertensive medication at discharge were similar in patients with and without epidurals. CONCLUSIONS: This is the first study of children receiving an epidural for surgical repair of aortic coarctation via open thoracotomy. In this small, single-institution, observational retrospective cohort study, epidurals for coarctation repair in children were associated with decreased postoperative anti-hypertensive infusion requirements. Epidurals were not associated with length of ICU or hospital stay, or with discharge on anti-hypertensive medication. No significant epidural complications were noted. Prospective study of larger populations will be necessary to confirm these associations, address causality, verify safety, and assess other effects.

Enhancing Recovery After Kasai Portoenterostomy With Epidural Analgesia.

BACKGROUND: Biliary atresia (BA) is a rare obstructive cholangiopathy that presents in early infancy. The Kasai portoenterostomy (PE) improves survival with the native liver. Epidural analgesia is an appealing option to control pain in this fragile patient population, yet its safety, efficacy, and potential benefits remain unproven. METHODS: Patients undergoing PE for BA between 2001 and 2016 at a single institution were identified by ICD codes. Preoperative laboratories, procedure details, and recovery outcomes were reviewed retrospectively. Outcomes of interest were need for postoperative mechanical ventilation, pain scores, normalized opioid administration, return of bowel function, and length of hospital stay after PE. RESULTS: Of 47 infants undergoing PE for BA, 25 received epidural analgesia, and 22 did not. Infants with epidurals received less systemic opioids over the first 96 h postoperatively than those without (P < 0.001). Epidurals were associated with lower pain scores between 6 and 30 h postoperatively (P = 0.01 to 0.04), during which the highest median 6-h interval pain score was 0.2 (IQR 0-1.3) for patients with epidurals yet 2.1 (IQR 1.2-3.3) for patients without. Patients with epidurals (88%, n = 22) were more commonly extubated before leaving the operating room than those without (59%, n = 13; P = 0.02). No significant difference was observed in time to first bowel movement (P = 0.48) or first oral feed (P = 0.81). However, infants with epidurals had shorter hospital stays after PE than those without (6 d [IQR 5-7] versus 8 d [IQR 6.3-11], P = 0.01). No major complications were associated with epidural catheters. CONCLUSIONS: Epidural analgesia in patients undergoing PE for BA appears safe and effectively controls pain while minimizing the need for systemic opioids. Reduced need for mechanical ventilation postoperatively and shortened hospital stays serve as further evidence for using epidurals to enhance recovery after PE.

Cyclic bisphosphonate therapy reduces pain and improves physical functioning in children with osteogenesis imperfecta.

BACKGROUND: Children with osteogenesis imperfecta (OI) experience pain and impaired physical functioning. The longitudinal effect of cyclic bisphosphonate treatment on these symptoms has not been described. We serially evaluated pain and functioning in pediatric patients with OI treated with intravenous bisphosphonate therapy. METHODS: Pain and physical functioning were assessed at multiple time-points over two infusion cycles in 22 OI patients (median age 10 years [range 2-21 years]; 8 girls) receiving cyclic intravenous bisphosphonate therapy. Pain was assessed using the FACES® visual analogue scale; physical functioning, including self-care, was assessed using the PedsQL™ Generic Core inventory. RESULTS: Pain scores decreased significantly immediately following infusion and remained reduced at 4 weeks post-infusion, increasing before and decreasing again after subsequent infusion (F = 25.00, p < 0.001). Physical functioning scaled scores improved 4 weeks after infusion and declined before subsequent infusion across patients (F = 10.87, p = 0.007). Exploratory analyses indicated significantly different effects between mild and moderate-severe OI types for pain, but not for physical functioning. No fractures occurred during the study. CONCLUSION: In children with OI, cyclic intravenous bisphosphonate therapy transiently reduces pain and improves functional abilities. Pain relief occurs immediately following infusion with functional improvements observed 4 weeks later. Both pain and physical functioning return to pretreatment levels by the subsequent infusion.

Association Between a Single General Anesthesia Exposure Before Age 36 Months and Neurocognitive Outcomes in Later Childhood.

IMPORTANCE: Exposure of young animals to commonly used anesthetics causes neurotoxicity including impaired neurocognitive function and abnormal behavior. The potential neurocognitive and behavioral effects of anesthesia exposure in young children are thus important to understand. OBJECTIVE: To examine if a single anesthesia exposure in otherwise healthy young children was associated with impaired neurocognitive development and abnormal behavior in later childhood. DESIGN, SETTING, AND PARTICIPANTS: Sibling-matched cohort study conducted between May 2009 and April 2015 at 4 university-based US pediatric tertiary care hospitals. The study cohort included sibling pairs within 36 months in age and currently 8 to 15 years old. The exposed siblings were healthy at surgery/anesthesia. Neurocognitive and behavior outcomes were prospectively assessed with retrospectively documented anesthesia exposure data. EXPOSURES: A single exposure to general anesthesia during inguinal hernia surgery in the exposed sibling and no anesthesia exposure in the unexposed sibling, before age 36 months. MAIN OUTCOMES AND MEASURES: The primary outcome was global cognitive function (IQ). Secondary outcomes included domain-specific neurocognitive functions and behavior. A detailed neuropsychological battery assessed IQ and domain-specific neurocognitive functions. Parents completed validated, standardized reports of behavior. RESULTS: Among the 105 sibling pairs, the exposed siblings (mean age, 17.3 months at surgery/anesthesia; 9.5% female) and the unexposed siblings (44% female) had IQ testing at mean ages of 10.6 and 10.9 years, respectively. All exposed children received inhaled anesthetic agents, and anesthesia duration ranged from 20 to 240 minutes, with a median duration of 80 minutes. Mean IQ scores between exposed siblings (scores: full scale = 111; performance = 108; verbal = 111) and unexposed siblings (scores: full scale = 111; performance = 107; verbal = 111) were not statistically significantly different. Differences in mean IQ scores between sibling pairs were: full scale = -0.2 (95% CI, -2.6 to 2.9); performance = 0.5 (95% CI, -2.7 to 3.7); and verbal = -0.5 (95% CI, -3.2 to 2.2). No statistically significant differences in mean scores were found between sibling pairs in memory/learning, motor/processing speed, visuospatial function, attention, executive function, language, or behavior. CONCLUSIONS AND RELEVANCE: Among healthy children with a single anesthesia exposure before age 36 months, compared with healthy siblings with no anesthesia exposure, there were no statistically significant differences in IQ scores in later childhood. Further study of repeated exposure, prolonged exposure, and vulnerable subgroups is needed.

Pediatric chronic orchialgia: patient population and patterns of care.

OBJECTIVE: A major hurdle in management of any chronic pain syndrome is understanding the population in which it occurs. We describe our pediatric population of patients with peripubertal and postpubertal chronic orchialgia. PATIENTS AND METHODS: Pediatric patients ≥ 10 years of age seen between 2002 and 2012 were identified by ICD code 608.9, Male Genital Disorder NOS. Patients were included if they had orchialgia without identifiable cause lasting >3 months. Patient history, diagnostic evaluations, treatments, and outcomes were assessed. RESULTS: Seventy-nine pediatric patients were identified. The mean age was 13.3 years (range 10-18); mean duration of orchialgia was 16.3 months (range 3-85). Thirty-three of 79 (42%) had concomitant medical conditions and/or psychiatric-behavioral issues. The mean follow-up was 7.1 months (range 0-70.4) with 41/79 (52%) having more than one office visit follow-up. Eleven patients were referred to a pediatric pain clinic; 10 out of 11 (91%) were evaluated there. Overall, 16 out of 41 (39%) had resolution of pain: nine out of 41 (22%) responding to conservative management vs seven of 10 (70%) responding to pain clinic management (3 to anti-neuropathic medications, 4 to nerve block). CONCLUSION: Many pediatric patients with chronic orchialgia have co-morbidities amenable to multidisciplinary collaborative coordination of care. Referral to pediatric pain clinic can be of significant benefit.

Successful management of a thoracic cerebrospinal fluid cutaneous fistula in a two year old child using a thoracic epidural blood patch.

A case of persistent thoracic cerebrospinal fluid cutaneous fistula in a toddler following radiographically confirmed epidural catheter placement is reported. Treatment of the fistula with a thoracic epidural blood patch was successful.

Novel FOXF1 mutations in sporadic and familial cases of alveolar capillary dysplasia with misaligned pulmonary veins imply a role for its DNA binding domain.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare and lethal developmental disorder of the lung defined by a constellation of characteristic histopathological features. Nonpulmonary anomalies involving organs of gastrointestinal, cardiovascular, and genitourinary systems have been identified in approximately 80% of patients with ACD/MPV. We have collected DNA and pathological samples from more than 90 infants with ACD/MPV and their family members. Since the publication of our initial report of four point mutations and 10 deletions, we have identified an additional 38 novel nonsynonymous mutations of FOXF1 (nine nonsense, seven frameshift, one inframe deletion, 20 missense, and one no stop). This report represents an up to date list of all known FOXF1 mutations to the best of our knowledge. Majority of the cases are sporadic. We report four familial cases of which three show maternal inheritance, consistent with paternal imprinting of the gene. Twenty five mutations (60%) are located within the putative DNA-binding domain, indicating its plausible role in FOXF1 function. Five mutations map to the second exon. We identified two additional genic and eight genomic deletions upstream to FOXF1. These results corroborate and extend our previous observations and further establish involvement of FOXF1 in ACD/MPV and lung organogenesis.

Newly postulated neurodevelopmental risks of pediatric anesthesia: theories that could rock our world.

PURPOSE: General anesthetics can induce apoptotic neurodegeneration and subsequent maladaptive behaviors in animals. Retrospective human studies suggest associations between early anesthetic exposure and subsequent adverse neurodevelopmental outcomes. The relevance of animal data to clinical practice is unclear and to our knowledge the causality underlying observed associations in humans is unknown. We reviewed newly postulated neurodevelopmental risks of pediatric anesthesia and discuss implications for the surgical care of children. MATERIALS AND METHODS: We queried the MEDLINE®/PubMed® and EMBASE® databases for citations in English on pediatric anesthetic neurotoxicity with the focus on references from the last decade. RESULTS: Animal studies in rodents and primates demonstrate apoptotic neuropathology and subsequent maladaptive behaviors after exposure to all currently available general anesthetics with the possible exception of α2-adrenergic agonists. Similar adverse pathological and clinical effects occur after untreated pain. Anesthetic neurotoxicity in animals develops only after exposure above threshold doses and durations during a critical neurodevelopmental window of maximal synaptogenesis in the absence of concomitant painful stimuli. Anesthetic exposure outside this window or below threshold doses and durations shows no apparent neurotoxicity, while exposure in the context of concomitant painful stimuli is neuroprotective. Retrospective human studies suggest associations between early anesthetic exposure and subsequent adverse neurodevelopmental outcomes, particularly after multiple exposures. The causality underlying the associations is unknown. Ongoing investigations may clarify the risks associated with current practice. CONCLUSIONS: Surgical care of all patients mandates appropriate anesthesia. Neurotoxic doses and the duration of anesthetic exposure in animals may have little relevance to clinical practice, particularly surgical anesthesia for perioperative pain. The causality underlying the observed associations between early anesthetic exposure and subsequent adverse neurodevelopmental outcomes is unknown. Anesthetic exposure may be a marker of increased risk. Especially in young children, procedures requiring general anesthesia should be performed only as necessary and general anesthesia duration should be minimized. Alternatives to general anesthesia and the deferral of elective procedures beyond the first few years of life should be considered, as appropriate. Participation in ongoing efforts should be encouraged to generate further data.

Newly postulated neurodevelopmental risks of pediatric anesthesia.

Recent animal and human studies have raised concern that exposure to anesthetic agents in children may cause neuronal damage and be associated with adverse neurodevelopmental outcomes. Exposure of young animals to anesthetic agents above threshold doses and durations during a critical neurodevelopmental window in the absence of concomitant painful stimuli causes widespread neuronal apoptosis and subsequent abnormal behaviors. The relevance of such animal data to humans is unknown. Untreated neonatal pain and stress also are associated with enhanced neuronal death and subsequent maladaptive behaviors, which can be prevented by exposure to these same anesthetic agents. Retrospective observational human studies have suggested a dose-dependent association between multiple anesthetic exposures in early childhood and subsequent learning disability, the causality of which is unknown. Ongoing prospective investigations are underway, the results of which may clarify if and what neurodevelopmental risks are associated with pediatric anesthesia. No change in current practice is yet indicated.

Inhaled nitric oxide attenuates reperfusion inflammatory responses in humans.

BACKGROUND: Reduced bioavailability of endothelium-derived nitric oxide associated with reperfusion could potentially exacerbate the inflammatory response during reperfusion. Evidence suggests the pharmacologic effects of inhaled nitric oxide may extend beyond the pulmonary vasculature, and this is attributed to nitric oxide-derived complexes in blood that ultimately orchestrate antiinflammatory effects. In this study, the authors evaluated the potential for inhaled nitric oxide (80 ppm) to attenuate inflammation instigated by ischemia-reperfusion in a human model using patients undergoing knee surgery where a tourniquet was used to produce a bloodless surgical field. METHODS: Inhaled nitric oxide (80 ppm) was administered before tourniquet application and continued throughout reperfusion until the completion of surgery. Venous blood samples were collected before and after reperfusion, for the measurements of nitrate and nitrite, CD11b/CD18, soluble P-selectin, and lipid hydroperoxide. Muscle biopsies were obtained from the quadriceps muscle before skin closure and analyzed for myeloperoxide, conjugated dienes, and nuclear factor-kappaB translocation. RESULTS: Administration of inhaled nitric oxide (80 ppm) significantly attenuated the inflammatory response characterized by reduced expression of CD11b/CD18, P-selectin, and nuclear factor kappaB compared with the control group. This was accompanied by increased plasma levels of nitrate and nitrite and reduced oxidative stress. CONCLUSIONS: Administration of inhaled nitric oxide at 80 ppm significantly reduces inflammation in lower extremity ischemia-reperfusion in humans. This observation supports the concept that during diseases characterized by dysfunction in nitric oxide metabolism, inhaled nitric oxide may be an effective therapy to replenish systemic nitric oxide, thus retarding inflammatory-mediated injury.