Pancreatic Enzyme Use Reduces Pancreatitis Frequency in Children With Acute Recurrent or Chronic Pancreatitis: A Report From INSPPIRE.

INTRODUCTION: Among children who suffer from acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP), acute pancreatitis (AP) episodes are painful, often require hospitalization, and contribute to disease complications and progression. Despite this recognition, there are currently no interventions to prevent AP episodes. In this retrospective cohort study, we assessed the impact of pancreatic enzyme therapy (PERT) use on clinical outcomes among children with pancreatic-sufficient ARP or CP. METHODS: Children with pancreatic-sufficient ARP or CP in the INSPPIRE-2 cohort were included. Clinical outcomes were compared for those receiving vs not receiving PERT, as well as frequency of AP before and after PERT. Logistic regression was used to study the association between development of AP episodes after starting PERT and response predictors. RESULTS: Among 356 pancreatic-sufficient participants, 270 (76%) had ARP, and 60 (17%) received PERT. Among those on PERT, 42% did not have a subsequent AP episode, during a mean 2.1 years of follow-up. Children with a SPINK1 mutation ( P = 0.005) and those with ARP (compared with CP, P = 0.008) were less likely to have an AP episode after starting PERT. After initiation of PERT, the mean AP annual incidence rate decreased from 3.14 down to 0.71 ( P < 0.001). DISCUSSION: In a retrospective analysis, use of PERT was associated with a reduction in the incidence rate of AP among children with pancreatic-sufficient ARP or CP. These results support the need for a clinical trial to evaluate the efficacy of PERT to improve clinical outcomes among children with ARP or CP.

Acute pancreatitis in children: risk factors, management, and outcomes.

PURPOSE OF REVIEW: Pediatric acute pancreatitis is an infrequent but potentially serious condition in children. Most have mild cases with spontaneous resolution, but up to one-third of patients can have moderate or severe disease or progress to recurrent or chronic pancreatitis. RECENT FINDINGS: Significant advances have been made in the field of pediatric pancreatology with a recognition that pediatric acute pancreatitis can vary significantly from adult disease with different risk factors and outcomes. There is better understanding of appropriate management for pediatric pancreatitis as well as growing literature in complications of pancreatitis. SUMMARY: The most common risk factors for pediatric acute pancreatitis include biliary disease, drug/toxin and idiopathic. Management involves adequate fluid resuscitation, early enteral nutrition and appropriate pain control. Systemic and local complications, including SIRS, necrosis and fluid collections, can occur in up to one-third of patients and care is largely supportive with a careful step-up approach to fluid collections and necrosis.

Pediatric Drug-Associated Pancreatitis Reveals Concomitant Risk Factors and Poor Reliability of Causality Scoring: Report From INSPPIRE.

OBJECTIVES: Drug-associated acute pancreatitis (DAP) studies typically focus on single acute pancreatitis (AP) cases. We aimed to analyze the (1) characteristics, (2) co-risk factors, and (3) reliability of the Naranjo scoring system for DAP using INSPPIRE-2 (the INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2) cohort study of acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) in children. METHODS: Data were obtained from ARP group with ≥1 episode of DAP and CP group with medication exposure ± DAP. Physicians could report multiple risk factors. Pancreatitis associated with Medication (Med) (ARP+CP) was compared to Non-Medication cases, and ARP-Med vs CP-Med groups. Naranjo score was calculated for each DAP episode. RESULTS: Of 726 children, 392 had ARP and 334 had CP; 51 children (39 ARP and 12 CP) had ≥1 AP associated with a medication; 61% had ≥1 AP without concurrent medication exposure. The Med group had other risk factors present (where tested): 10 of 35 (28.6%) genetic, 1 of 48 (2.1%) autoimmune pancreatitis, 13 of 51 (25.5%) immune-mediated conditions, 11 of 50 (22.0%) obstructive/anatomic, and 28 of 51 (54.9%) systemic risk factors. In Med group, 24 of 51 (47%) had involvement of >1 medication, simultaneously or over different AP episodes. There were 20 ARP and 4 CP cases in "probable" category and 19 ARP and 7 CP in "possible" category by Naranjo scores. CONCLUSIONS: Medications were involved in 51 of 726 (7%) of ARP or CP patients in INSPPIRE-2 cohort; other pancreatitis risk factors were present in most, suggesting a potential additive role of different risks. The Naranjo scoring system failed to identify any cases as "definitive," raising questions about its reliability for DAP.

10†kHz Shifted-Excitation Raman Difference Spectroscopy with Charge-Shifting Charge-Coupled Device Read-Out for Effective Mitigation of Dynamic Interfering Backgrounds.

In this work we demonstrate an advanced concept of a charge-shifting charge-coupled device (CCD) read-out combined with shifted excitation Raman difference spectroscopy (SERDS) capable of operating at up to 10 kHz acquisition rates for the effective mitigation of fast-evolving interfering backgrounds in Raman spectroscopy. This rate is 10-fold faster than that achievable with an instrument we described previously and is overall 1000-fold faster than possible with conventional spectroscopic CCDs capable of operating at up to ∼10 Hz rates. The speed enhancement was realized by incorporating a periodic mask at the internal slit of an imaging spectrometer permitting a smaller shift of the charge on the CCD (8 pixels) to be required during the cyclic shifting process compared with the earlier design which employed an 80-pixel shift. The higher acquisition speed enables the more accurate sampling of the two SERDS spectral channels, enabling it to effectively tackle highly challenging situations with rapidly evolving interfering fluorescence backgrounds. The performance of the instrument is evaluated for heterogeneous fluorescent samples which are moved rapidly in front of the detection system aiming at the differentiation of chemical species and their quantification. The performance of the system is compared with that of the earlier 1 kHz design and a conventional CCD operated at its maximum rate of 5.4 Hz as previously. In all situations tested, the newly developed 10 kHz system outperformed the earlier variants. The 10 kHz instrument can benefit a number of prospective applications including: disease diagnosis where high sensitivity mapping of complex biological matrices in the presence of natural fluorescence bleaching restricts achievable limits of detection; accurate data acquisition from moving heterogeneous samples (or moving a handheld instrument in front of the sample during data acquisition) or data acquisition under varying ambient light conditions (e.g., due to casting shadows, sample or instrument movement). Other beneficial scenarios include monitoring rapidly evolving Raman signals in the presence of largely static background signals such as in situations where a heterogeneous sample is moving rapidly in front of a detection system (e.g., a conveyor belt) in the presence of static ambient light.

The use of DXA for early detection of pediatric cystic fibrosis-related bone disease.

BACKGROUND: Cystic fibrosis (CF)-related bone disease (CFBD) is seen in adults and can be associated with respiratory illness and malnutrition. There is limited and conflicting data regarding CFBD in pediatric CF. With longer life expectancy and promotion of disease prevention, pediatric CFBD demands further investigation. METHODS: Our center initiated a quality improvement (QI) project from April 2016 to December 2018 to improve CFBD screening in patients 8 years or older, per current CF Foundation (CFF) guidelines. Our team formulated a dual-energy X-ray absorptiometry (DXA) scan algorithm based upon degree of bone mineral density (BMD); shared CFBD guideline recommendations in our quarterly newsletter; and ordered scans for eligible patients at weekly review meetings. We reviewed DXA results from 141 patients after institutional review board approval and gathered data including comorbidities, genetics, anthropometric measures, medication exposure, and relevant serum studies. RESULTS: Fifty-three percent of our patients had normal BMD (n = 75). Seventeen patients (12%) had a Z score ≤ -2. Patients with lower BMD also had lower mean forced expiratory volume (FEV1 ) percent predicted (FEV1 %) (p < 0.001) as well as lower body mass index % (p = 0.001). Patients with lower BMD were overall older at time of DXA (p = 0.016). During study duration, 13 patients who had abnormal DXA results underwent repeat DXAs after physical therapy; 11 of the 13 showed improvement in DXA results. CONCLUSIONS: A DXA scan is a useful screening tool and can be used to identify pediatric patients who could benefit from further therapy and interventions to preserve adequate bone health and avoid further loss. QI initiatives can lead to improved screening and diagnosis and earlier intervention such as physical therapy. Further studies are needed to better understand the utility of physical therapy in children with CF.

Analysis of INSPPIRE-2 Cohort: Risk Factors and Disease Burden in Children With Acute Recurrent or Chronic Pancreatitis.

OBJECTIVES: The objective of this study is to investigate risk factors and disease burden in pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). METHODS: Data were obtained from INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2), the largest multi-center prospective cohort study in pediatric patients with ARP or CP. RESULTS: Of 689 children, 365 had ARP (53%), 324 had CP (47%). CP was more commonly associated with female sex, younger age at first acute pancreatitis (AP) attack, Asian race, family history of CP, lower BMI%, genetic and obstructive factors, PRSS1 mutations and pancreas divisum. CFTR mutations, toxic-metabolic factors, medication use, hypertriglyceridemia, Crohn disease were more common in children with ARP. Constant or frequent abdominal pain, emergency room (ER) visits, hospitalizations, medical, endoscopic or surgical therapies were significantly more common in CP, episodic pain in ARP. A total of 33.1% of children with CP had exocrine pancreatic insufficiency (EPI), 8.7% had diabetes mellitus. Compared to boys, girls were more likely to report pain impacting socialization and school, medical therapies, cholecystectomy, but no increased opioid use. There was no difference in race, ethnicity, age at first AP episode, age at CP diagnosis, duration of disease, risk factors, prevalence of EPI or diabetes between boys and girls. Multivariate analysis revealed that family history of CP, constant pain, obstructive risk factors were predictors of CP. CONCLUSIONS: Children with family history of CP, constant pain, or obstructive risk factors should raise suspicion for CP.

Outpatient Pain Management in Children With Chronic Pancreatitis: A Scoping Systematic Review.

OBJECTIVES: Although pain management is central to pediatric chronic pancreatitis (CP) care, no evidence-based guidelines exist. In this scoping systematic review, we sought promising strategies for CP pain treatment in children. METHODS: We systematically reviewed literature on pain management in children and adults with CP, and 2 conditions with similar pain courses: juvenile idiopathic arthritis and sickle cell disease. RESULTS: Of 8997 studies identified, 287 met inclusion criteria. There are no published studies of analgesic medications, antioxidants, dietary modification, integrative medicine, or regional nerve blocks in children with CP. In adults with CP, studies of nonopioid analgesics, pancreatic enzymes, and dietary interventions have mixed results. Retrospective studies suggest that endoscopic retrograde cholangiopancreatography and surgical procedures, most durably total pancreatectomy with islet autotransplant, improve pain for children with CP. Follow-up was short relative to a child's life. Large studies in adults also suggest benefit from endoscopic therapy and surgery, but lack conclusive evidence about optimal procedure or timing. Studies on other painful pediatric chronic illnesses revealed little generalizable to children with CP. CONCLUSIONS: No therapy had sufficient high-quality studies to warrant untempered, evidence-based support for use in children with CP. Multicenter studies are needed to identify pain management "best practices."

Validity and reliability of Raman spectroscopy for carotenoid assessment in cattle skin.

Carotenoids are powerful antioxidants capable of helping to protect the skin from the damaging effects of exposure to sun by reducing the free radicals in skin produced by exposure to ultraviolet radiation, and they may also have a physical protective effect in human skin. Since carotenoids are lipophilic molecules which can be ingested with the diet, they can accumulate in significant quantities in the skin. Several studies on humans have been conducted to evaluate the protective function of carotenoids against various diseases, but there is very limited published information available to understand the mechanism of carotenoid bioavailability in animals. The current study was conducted to investigate the skin carotenoid level (SCL) in two cattle skin sets - weaners with an unknown feeding regime and New Generation Beef (NGB) cattle with monitored feed at three different ages. Rapid analytical and sensitive Raman spectroscopy has been shown to be of interest as a powerful technique for the detection of carotenoids in cattle skin due to the strong resonance enhancement with 532 nm laser excitation. The spectral difference of both types of skin were measured and quantified using univariate and linear discriminant analysis. SCL was higher in NGB cattle than weaners and there is a perfect classification accuracy between weaners and NGB cattle skin using carotenoid markers as a basis. Further work carried out on carotenoid rich NGB cattle skin of 8, 12 and 24 months of age identified an increasing trend in SCL with age. The present work validated the ability of Raman spectroscopy to determine the skin carotenoid level in cattle by comparing it with established HPLC methods. There is an excellent correlation of R2 = 0.96 between the two methods that could serve as a model for future application for larger population studies.

Anion-regulated binding selectivity of Cr(III) in collagen.

We present a mechanism for the selectivity of covalent/electrostatic binding of the Cr(III) ion to collagen, mediated by the kosmotropicity of the anions. Although a change in the long-range ordered structure of collagen is observed after covalent binding (Cr(III)-OOC) in the presence of SO4 2- at pH 4.5, the νsym (COO- ) band remains intense, suggesting a relatively lower propensity for the Cr(III) to bind covalently instead of electrostatically through Cr(H2 O)6 3+ . Replacing SO4 2- with Cl- reduces the kosmotropic effect which further favors the electrostatic binding of Cr(III) to collagen. Our findings allow a greater understanding of mechanism-specific metal binding in the collagen molecule. We also report for the first time, surface-enhanced Raman spectroscopy to analyze binding mechanisms in collagen, suggesting a novel way to study chemical modifications in collagen-based biomaterials.

Ultrasensitive surface-enhanced Raman scattering detection of biological pollutants by controlled evaporation on omniphobic substrates.

A simple and highly sensitive method, combining slippery liquid-infused porous substrates and surface-enhanced Raman spectroscopy (SLIPSERS) was used to detect biological pollutants at very low concentrations. Two commonly used rodenticides (brodifacoum and sodium monofluoroacetate) with long biological half-lives were selected as analytes. The SLIPSERS platform gives reproducible SERS enhancement and this allows "label-free" SERS detection of these environmental pollutants. Analyte ions were detected down to a concentration of 10-14 M for brodifacoum and 10-9 M for sodium monofluoroacetate. The limit of detection, limit of quantification and limit of linearity for brodifacoum are 10-12 M, 10-10 M and 10-6 M respectively. The SLIPSERS method uses a physical process to significantly increase analyte concentration, and SERS enhancement and therefore can be generally applied to a range of environmental pollutants. The method can be successfully used for ultra-sensitive detection of several chemical and biological contaminants and meet the emerging needs of environmental monitoring and food safety analysis.

Raman spectroscopic detection of carotenoids in cattle skin.

Carotenoids, powerful anti-oxidants, play a significant role in protecting the skin from oxidation and help in balancing the redox status of skin. This study was aimed at investigating cattle skin to identify carotenoids in the lower epidermis (grain) and dermis (corium) layers for classification using Raman spectroscopy which is a powerful technique for the detection of carotenoids in cattle skin due to the strong resonance enhancement with 532 nm laser excitation. The spectral differences identified between these two layers were quantified by the univariate analysis of Raman peak heights and partial least squares (PLS) analysis. We compared the performance of the Raman spectroscopy method with the standard method, high performance liquid chromatography. The univariate analysis results demonstrated that the lower epidermis of the skin has a higher concentration of carotenoid than dermis using the carotenoid Raman peaks at 1151 cm-1 and 1518 cm-1. The carotenoid Raman intensity was linearly correlated with the total carotenoid concentration determined by standard HPLC methods. Partial Least Squares Regression analysis gives excellent results with R 2 = 0.99. Our results indicate that Raman spectroscopy is a potential tool to determine carotenoids in cattle skin with high precision.

Effect of Taping of Thoracic and Abdominal Muscles on Pelvic Alignment and Forward Reach Distance Among Stroke Subjects: A Randomized Controlled Trial.

INTRODUCTION: The objective of this study was to find the immediate as well as short-term effect on pelvic alignment and forward arm reach distance in sitting among stroke patients following thoracic spine and abdominal muscles taping along with conventional therapy. METHODS: Thirty subjects with stroke attending the physiotherapy programme at Department of Physiotherapy at a tertiary care hospital underwent this randomized controlled experimental study. Subjects in the experimental group received taping, along with conventional physiotherapy treatment, for restricting thoracic kyphosis and facilitating abdominal muscles. Subjects in the control group received only conventional physiotherapy treatment. To assess the change in pelvic alignment and forward arm reach distance while sitting, Palpation MeterTM (PALMTM) and sit and reach test were used, respectively. RESULTS: In the experimental group, pelvic obliquity was corrected (4.1 ± 0.94) and anterior pelvic tilt revealed improvement (4.9 ± 2.1, p value < 0.001). In the control group, no improvement in pelvic alignment was recorded. Improvement in forward arm reach distance was similar in both groups (p value = 0.804). CONCLUSION: Taping as an adjunctive treatment method to physiotherapy can cause immediate as well as short-term improvement of pelvic alignment in sitting, following stroke. It also, immediately improves the sit and reach distance in the same population.

Development of a quantitative method for the analysis of cocaine analogue impregnated into textiles by Raman spectroscopy.

Cocaine trafficking in the form of textile impregnation is routinely encountered as a concealment method. Raman spectroscopy has been a popular and successful testing method used for in situ screening of cocaine in textiles and other matrices. Quantitative analysis of cocaine in these matrices using Raman spectroscopy has not been reported to date. This study aimed to develop a simple Raman method for quantifying cocaine using atropine as the model analogue in various types of textiles. Textiles were impregnated with solutions of atropine in methanol. The impregnated atropine was extracted using less hazardous acidified water with the addition of potassium thiocyanate (KSCN) as an internal standard for Raman analysis. Despite the presence of background matrix signals arising from the textiles, the cocaine analogue could easily be identified by its characteristic Raman bands. The successful use of KSCN normalised the analyte signal response due to different textile matrix background interferences and thus removed the need for a matrix-matched calibration. The method was linear over a concentration range of 6.25-37.5 mg/cm2 with a coefficient of determination (R2 ) at 0.975 and acceptable precision and accuracy. A simple and accurate Raman spectroscopy method for the analysis and quantification of a cocaine analogue impregnated in textiles has been developed and validated for the first time. This proof-of-concept study has demonstrated that atropine can act as an ideal model compound to study the problem of cocaine impregnation in textile. The method has the potential to be further developed and implemented in real world forensic cases.

Parental perspectives regarding primary-care weight-management strategies for school-age children.

To identify parental perspectives regarding weight-management strategies for school-age children, focus groups were conducted of parents of overweight and obese (body mass index ≥ 85th percentile) 6-12-year-old children recruited from primary-care clinics. Questions focused on the role of the primary-care provider, effective components of weight-management strategies and feasibility of specific dietary strategies. Focus groups were recorded, transcribed and analysed using margin coding and grounded theory. Six focus groups were held. The mean age (in years) for parents was 32, and for children, eight; 44% of participants were Latino, 33%, African-American and 23%, white. Parents' recommendations on the primary-care provider's role in weight management included monitoring weight, providing guidance regarding health risks and lifestyle changes, consistent follow-up and using discretion during weight discussions. Weight-management components identified as key included emphasising healthy lifestyles and enjoyment, small changes to routines and parental role modelling. Parents prefer guidance regarding healthy dietary practices rather than specific weight-loss diets, but identified principles that could enhance the acceptability of these diets. For dietary guidance to be feasible, parents recommended easy-to-follow instructions and emphasising servings over counting calories. Effective weight-management strategies identified by parents include primary-care provider engagement in weight management, simple instructions regarding healthy lifestyle changes, parental involvement and deemphasising specific weight-loss diets. These findings may prove useful in developing primary-care weight-management strategies for children that maximise parental acceptance.

A Lean Six Sigma quality improvement project to increase discharge paperwork completeness for admission to a comprehensive integrated inpatient rehabilitation program.

Lean Six Sigma (LSS) process analysis can be used to increase completeness of discharge summary reports used as a critical communication tool when a patient transitions between levels of care. The authors used the LSS methodology as an intervention to improve systems process. Over the course of the project, 8 required elements were analyzed in the discharge paperwork. The authors analyzed the discharge paperwork of patients (42 patients preintervention and 143 patients postintervention) of a comprehensive integrated inpatient rehabilitation program (CIIRP). Prior to this LSS project, 61.8% of required discharge elements were present. The intervention improved the completeness to 94.2% of the required elements. The percentage of charts that were 100% complete increased from 11.9% to 67.8%. LSS is a well-established process improvement methodology that can be used to make significant improvements in complex health care workflow issues. Specifically, the completeness of discharge documentation required for transition of care to CIIRP can be improved.