Inflammatory Myofibroblastic Tumor Presenting as a Partial Bowel Obstruction: A Case Report.

Intussusception, or telescoping of the bowel, is a rare condition in the adult population that can lead to serious complications, such as obstruction or ischemia. Most cases of intussusception are idiopathic and present with a pathognomonic "target sign" on imaging. Rarely, in adults, intussusceptions can be found with lead points, some of which may be neoplastic. Treatments for intussusception include air enemas or surgical intervention if enemas are unsuccessful in resolving the telescoped bowel. This case report discusses an atypical presentation of intussusception in an adult female with a "whirlpool sign" on imaging rather than the typical "target sign." She was found to have incorporation of mesenteric fat into telescoping bowel causing edema and partial bowel obstruction. The affected bowel was removed laparoscopically, and an end-to-end anastomosis was formed. Pathology of the resected bowel revealed a non-immunoreactive inflammatory myofibroblastic neoplasm as the lead point. Most inflammatory myofibroblastic tumors stain positive for desmin, smooth muscle actin, and anaplastic lymphoma kinase (ALK), whereas this patient was non-immunoreactive. The patient tolerated surgery well and is now pain-free with normal gastrointestinal function. This case report hopes to heighten awareness of atypical presentations of intussusceptions, the use of imaging to help aid in uncertain diagnoses, and the appropriate surgical treatment for symptomatic patients.

Building a Capacity of Sexual Assault Nurse Examiners in an Underserved U.S.-Mexico Border Region.

ABSTRACT: Sexual assault nurse examiners (SANEs) conduct medical forensic examinations for persons who have been sexually assaulted. Positive psychological effects, high prosecution rates, and increased victim self-efficacy to seek resources for recovery were reported among sexual assault victims who received forensic care from SANEs. However, such endeavors may be very challenging to achieve because of the severe shortage of certified SANEs. This article will describe how one institution located in a medically underserved U.S.-Mexico border town built a SANE program to increase the capacity of SANEs in the region through 3-year grant funding. The lessons learned, challenges faced during implementation, and sustainability plans including integrating SANEs into the local medicolegal system to seek justice for sexual assault victims are critically addressed in this article.

Efficacy of Fosphenytoin as First-Line Antiseizure Medication for Neonatal Seizures Compared to Phenobarbital.

Currently used treatment protocols for neonatal seizures vary among centers with limited evidence to support the choice of a given antiseizure medication. Because of concerns about the potential negative impact of phenobarbital on long-term neurodevelopment outcomes, our unit transitioned to fosphenytoin as the first-line antiseizure medication. A retrospective observational cohort study was conducted to compare the acute and long-term outcomes of fosphenytoin and phenobarbital as first-line antiseizure medication for neonatal seizure treatment. The 2 study groups had similar baseline characteristics for neonatal variables as well as maternal antenatal complications. We did not find any differences in the acute outcomes between the 2 groups. However, significantly fewer infants in the fosphenytoin group had moderate-to-severe neurodevelopmental delay at the 18- and 24-month assessments. In conclusion, although both medications were equally efficacious for acute neonatal seizure control, fosphenytoin had the potential for significantly better neurodevelopmental outcomes at 18-24 months of age.

Evaluation of an Assertive Management and Integrated Care Service for Frequent Emergency Department Attenders with Substance Use Disorders: The Impact Project: Evaluating an assertive management service for frequent ED attenders with substance use disorders.

INTRODUCTION: Frequent attenders to Emergency Departments (ED) often have contributing substance use disorders (SUD), but there are few evaluations of relevant interventions. We examine one such pilot assertive management service set in Sydney, Australia (IMPACT), aimed at reducing hospital presentations and costs, and improving client outcomes. METHODS: IMPACT eligibility criteria included moderate-to-severe SUD and ED attendance on ≥5 occasions in the previous year. A pre-post intervention design examined clients' presentations and outcomes 6 months before and after participation to a comparison group of eligible clients who did not engage. RESULTS: Between 2014 and 2015, 34 clients engaged in IMPACT, with 12 in the comparison group. Clients demonstrated significant reductions in preventable (p < 0.05) and non-preventable (p < 0.01) ED presentations and costs, and in hospital admissions and costs (p < 0.01). IMPACT clients also reported a significant reduction in use days for primary substance (p < 0.01). The comparison group had a significant reduction (p < 0.05) in non-preventable visits only. CONCLUSIONS: Assertive management services can be effective in preventing hospital presentations and costs for frequent ED attenders with SUDs and improving client outcomes, representing an effective integrated health approach. The IMPACT service has since been refined and integrated into routine care across a number of hospitals in Sydney, Australia.

Nephrolithiasis and Nephrocalcinosis From Topiramate Therapy in Children With Epilepsy.

INTRODUCTION: Adults treated with topiramate may develop nephrolithiasis, but its frequency in children on topiramate is unknown. Topiramate inhibits renal carbonic anhydrase, which can lead to renal tubular acidosis and hypercalciuria. We studied 40 consecutive children who initiated topiramate therapy for seizures between January 1997 and February 2003, followed for a mean of 36 months. METHODS: Serum electrolytes, urinary calcium/creatinine ratios, and renal ultrasonography were performed before topiramate and every 6 months thereafter. RESULTS: Four children developed nephrolithiasis and/or nephrocalcinosis, which resolved on discontinuation of topiramate. In 40 patients, the mean urinary calcium/creatinine ratio increased over time (P < 0.001). The mean serum bicarbonate in 40 patients decreased over time (P < 0.01). Twenty-three children had urinary calcium/creatinine ratios before topiramate. Nine children with baseline hypercalciuria (defined as urinary calcium/creatinine >0.21) were compared with the 14 children with baseline normal urinary calcium excretion. A greater increase in urinary calcium/creatinine ratios occurred in hypercalciuric children (P < 0.001) and a greater decrease in serum bicarbonate levels occurred in the hypercalciuric children (P < 0.05) compared with children with baseline normal calcium excretion. Greater urinary calcium excretion was associated with increasing doses of topiramate (P = 0.039). CONCLUSION: Our study shows that long-term therapy with topiramate in children is associated with persistent hypercalciuria and metabolic acidosis, which can lead to nephrocalcinosis and/or nephrolithiasis. All children initiating topiramate therapy should have baseline and follow-up urinary calcium/creatinine studies, serum electrolytes, and periodic renal ultrasonography, if the urinary calcium/creatinine ratio increases to a level above normal for age.

Evaluation of the Combined Application of Neuromuscular Electrical Stimulation and Volitional Contractions on Thigh Muscle Strength, Knee Pain, and Physical Performance in Women at Risk for Knee Osteoarthritis: A Randomized Controlled Trial.

BACKGROUND: Knee osteoarthritis (OA) is a leading cause of disability that is associated with quadriceps weakness. However, strengthening in people with or with risk factors for knee OA can be poorly tolerated. OBJECTIVE: To assess the efficacy of a 12-week low-load exercise program, using a hybrid training system (HTS) that uses the combination of neuromuscular electrical stimulation and volitional contractions, for improving thigh muscle strength, knee pain relief, and physical performance in women with or with risk factors for knee OA. DESIGN: Randomized, single-blinded, controlled trial. SETTING: Exercise training laboratory. PARTICIPANTS: Forty-two women 44-85 years old with risk factors for knee OA. INTERVENTIONS: Participants randomized to 12 weeks of biweekly low-load resistance training with the HTS or on an isokinetic dynamometer (control). OUTCOMES: Maximum isokinetic knee extensor torque. Secondary measures included maximum isokinetic knee flexor torque, knee pain (Knee Injury and Osteoarthritis Outcome Score), and timed 20-m walk and chair stand tests. RESULTS: The HTS and control treatments resulted in muscle strengthening, decreased knee pain, and improved physical performance. HTS group quadriceps and hamstring strength increased by 0.06 ± 0.04 Nm/kg (P > .05) and 0.05 ± 0.02 Nm/kg (P = .02), respectively. Control group quadriceps and hamstring strength increased by 0.03 ± 0.04 Nm/kg (P > .05) and 0.06 ± 0.02 Nm/kg (P = .009), respectively. Knee pain decreased by 11.9 ± 11.5 points (P < .001) for the HTS group and 14.1 ± 15.4 points (P = .001) for the control group. The 20-m walk time decreased by 1.60 ± 2.04 seconds (P = .005) and 0.95 ± 1.2 seconds (P = .004), and chair stand time decreased by 4.8 ± 10.0 seconds (P > .05) and 1.9 ± 4.7 seconds (P > .05) in the HTS and control groups, respectively. These results did not differ statistically between the HTS and control groups. CONCLUSIONS: These results suggest the HTS is effective for alleviating pain and improving physical performance in women with risk factors for knee OA. However, the HTS does not appear to be superior to low-load resistance training for improving muscle strength, pain relief, or physical function. CLINICAL TRIAL REGISTRATION NUMBER: NCT02802878. LEVEL OF EVIDENCE: I.

Findings and lessons learnt from implementing Australia's first health service based take-home naloxone program.

INTRODUCTION AND AIMS: Opioid overdose prevention programs providing take-home naloxone have been expanding internationally. This paper summarises findings and lessons learnt from the Overdose Prevention and Emergency Naloxone Project which is the first take-home naloxone program in Australia implemented in a health care setting. METHODS: The Project intervention provided education and take-home naloxone to opioid-using clients at Kirketon Road Centre and The Langton Centre in Sydney. The evaluation study examined uptake and acceptability of the intervention; participants' knowledge and attitudes regarding overdose and participants' experience in opioid overdose situations six months after the intervention. Participants completed baseline, post-training and follow-up questionnaires regarding overdose prevention and management which were analysed using repeated measures analysis of variance. RESULTS: Eighty-three people participated in the intervention, with 35 (42%) completing follow-up interviews-51% reporting using naloxone with 30 overdoses successfully reversed. There were significant improvements in knowledge and attitudes immediately following training with much retained at follow-up, particularly regarding feeling informed enough (97%) and confident to inject naloxone (100%). DISCUSSION: Take-home naloxone programs can be successfully implemented in Australian health settings. Barriers to uptake, such as lengthy processes and misperceptions around interest in overdose prevention, should be addressed in future program implementation.

Patients want to know about the 'cardiac blues'.

BACKGROUND: Much attention has been given to identifying and supporting the minority of patients who develop severe clinical depression after a cardiac event. However, relatively little has been given to supporting the many patients who experience transient but significant emotional disturbance that we term the 'cardiac blues'. OBJECTIVE: The aim of this study was to investigate patients' preferences regarding information provision about cardiac blues. METHODS: One hundred and sixty consecutive cardiac patients admitted to two Victorian hospitals in Australia were interviewed three times over six months. They were asked about emotional issues, including information provision preferences. RESULTS: Four out of five (81%) patients would like to have received information about the cardiac blues, but only a minority received this information. CONCLUSION: Most patients want to know about cardiac blues. The development and evaluation of resources for health professionals and patients to support recovery through cardiac blues appears warranted.

A novel mechanism controlling resetting speed of the circadian clock to environmental stimuli.

Many aspects of mammalian physiology are driven through the coordinated action of internal circadian clocks. Clock speed (period) and phase (temporal alignment) are fundamental to an organism's ability to synchronize with its environment. In humans, lifestyles that disturb these clocks, such as shift work, increase the incidence of diseases such as cancer and diabetes. Casein kinases 1δ and ε are closely related clock components implicated in period determination. However, CK1δ is so dominant in this regard that it remains unclear what function CK1ε normally serves. Here, we reveal that CK1ε dictates how rapidly the clock is reset by environmental stimuli. Genetic disruption of CK1ε in mice enhances phase resetting of behavioral rhythms to acute light pulses and shifts in light cycle. This impact of CK1ε targeting is recapitulated in isolated brain suprachiasmatic nucleus and peripheral (lung) clocks during NMDA- or temperature-induced phase shift in association with altered PERIOD (PER) protein dynamics. Importantly, accelerated re-entrainment of the circadian system in vivo and in vitro can be achieved in wild-type animals through pharmacological inhibition of CK1ε. These studies therefore reveal a role for CK1ε in stabilizing the circadian clock against phase shift and highlight it as a novel target for minimizing physiological disturbance in shift workers.

Low-dose serotherapy improves early immune reconstitution after cord blood transplantation for primary immunodeficiencies.

Cord blood transplantation (CBT) is curative for many primary immunodeficiencies (PIDs) but is associated with risks of viral infection and graft-versus-host disease (GvHD). Serotherapy reduces GvHD but potentially increases the risk of viral infection by delaying immune reconstitution. Because many PID patients have pre-existing viral infections, the optimal dose of serotherapy is unclear. We performed a retrospective analysis in 34 consecutive PID patients undergoing CBT and compared immune reconstitution, viral infection, GvHD, mortality, and long-term immune function between high-dose (n = 11) and low-dose (n = 9) serotherapy. Serotherapy dose had no effect on neutrophil engraftment. Median CD3(+) engraftment occurred at 92.5 and 97 days for high- and low-dose serotherapy, respectively. The low-dose serotherapy group had higher CD3(+), CD4(+), and early thymic emigrant counts at 4 months compared with the high-dose group. GvHD severity and number of viral infections did not differ between serotherapy doses. Survival from the transplantation process was 90.9% for high-dose and 100% for low-dose groups. In conclusion, low-dose serotherapy enhanced T cell reconstitution and thymopoiesis during the first year after CBT with no increase in GvHD.

Red flags for persistent or worsening anxiety and depression after an acute cardiac event: a 6-month longitudinal study in regional and rural Australia.

BACKGROUND: While early symptoms of anxiety and depression resolve for many patients soon after an acute cardiac event, the persistence or worsening of symptoms indicates increased mortality risk. It is therefore important to identify the predictors, or red flags, of persistent or worsening anxiety and depression symptoms. Most previous research has focussed on metropolitan patients, hence the need for studies of regional and rural dwellers. METHOD: In this study, 160 cardiac patients consecutively admitted to two hospitals in regional Victoria, Australia, were interviewed in hospital and 2 and 6 months after discharge. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. Growth mixture modelling was used to identify the trajectories of anxiety and depression over the 6 months after the acute event, and post-hoc tests identified predictors of persistent or worsening symptoms. RESULTS: For both anxiety and depression, three common symptom trajectories were identified. Inhospital anxiety symptoms tended to persist over time, whereas inhospital depression symptoms resolved for some patients and worsened for others. A mental health history, younger age, smoking, financial stress, poor self-rated health, and social isolation were red flags for persistent anxiety and worsening depression. Additionally, diabetes, and other comorbidities were red flags for persistent anxiety. CONCLUSIONS: The results highlight several potential red flags for increased risk of persistent anxiety or worsening depressive symptoms after a cardiac event, including demographic, psychosocial, and behavioural indicators. These red flags could assist with identification of at-risk patients on admission to or discharge from hospital, thereby enabling targeting of interventions.

Effects of nitazoxanide on pharmacokinetics and pharmacodynamics of a single dose of warfarin.

PURPOSE: The effects of nitazoxanide on warfarin pharmacokinetics and pharmacodynamics are examined. METHODS: This was a Phase I, single-center, open-label, randomized, two-way, crossover study. Secondary endpoints included an evaluation of the effect of nitazoxanide on coagulation parameters observed after a single dose of warfarin and an assessment of the overall tolerability of study treatments. Fourteen healthy men were selected for the study. The study consisted of two treatment periods (Treatment A and Treatment B), each lasting 6 days, with a washout period of at least 21 days between both warfarin intakes. All subjects were scheduled to receive both Treatment A and Treatment B, according to the randomization list. Treatment A consisted of a single oral dose of 25 mg warfarin sodium (five 5-mg tablets). Treatment B consisted of a single oral intake of 25 mg warfarin sodium (five 5-mg tablets) and one 500-mg tablet of nitazoxanide (with nitazoxanide 500 mg continued twice daily for up to 6 days). RESULTS: All 14 subjects received Treatment B, and 13 of the 14 subjects received Treatment A. Pharmacokinetic results were similar in both treatments, and pharmacodynamic parameters were similar in both treatments. Fourteen adverse events occurred in eight subjects after administration of at least one dose of the study drug. Eleven adverse events occurred in six subjects after treatment with warfarin and nitazoxanide, and three adverse events occurred in two subjects after treatment with warfarin alone. At discharge, a high hemoglobin level and a low total bilirubin level were reported in both groups. CONCLUSION: Coadministration of nitazoxanide twice daily for six days did not affect the pharmacokinetic or pharmacodynamic properties of a single 25-mg dose of warfarin sodium. Administration of a single dose of warfarin or combined administration of a single dose of warfarin and multiple doses of nitazoxanide appeared safe and well tolerated.

Methods and motivations for buprenorphine diversion from public opioid substitution treatment clinics.

This study aimed to develop a better understanding of the motives for suspected buprenorphine diversion during supervised dosing. Structured interviews were conducted with clients after 71 episodes of diversion at 3 opioid substitution treatment clinics in Sydney, Australia. Interviews were conducted by the clinic manager. An equivalent number of suspected episodes involved diversion via removal of buprenorphine from the mouth (n = 35), and secretion of buprenorphine in the mouth (n = 32). Denial of diversion occurred in 45% of suspected episodes and was significantly associated with secretion of buprenorphine in the mouth (P < .0001), suggesting a possible misunderstanding between clinicians and clients to what constitutes diversion. Motivations for diversion included "stockpiling" for later sublingual use (n = 15), discarding buprenorphine (n = 11), and giving it to another person (n = 5). A consistent definition of diversion of supervised dosed of buprenorphine is required. Diversion of supervised doses may represent a single episode of nonadherence to dosing instructions or more significant ambivalence over treatment. Responses to suspected diversion should aim to minimise harm and maximise treatment outcomes.

Structural analysis of synthetic polymer mixtures using ion mobility and tandem mass spectrometry.

Ion mobility (IM) combined with tandem mass spectrometry (MS/MS) has been employed to separate and differentiate between polyether oligomers with the same nominal molecular weights. Poly(ethylene glycol)s with the same nominal mass-to-charge ratio (m/z), but with differing structures, were separated using ion mobility. IM-MS/MS data were able to aid identification of the backbone and end groups of the four individual polyethers in the two sets of isobaric mixtures. The MS/MS data from the resolved oligomers enabled a detailed structural characterization of the polyether mixtures to be completed in one experiment.

End-group characterisation of poly(propylene glycol)s by means of electrospray ionisation-tandem mass spectrometry (ESI-MS/MS).

The end-group functionalisation of a series of poly(propylene glycol)s has been characterised by means of electrospray ionisation-tandem mass spectrometry (ESI-MS/MS). A series of peaks with mass-to-charge ratios that are close to that of the precursor ion were used to generate information on the end-group functionalities of the poly(propylene glycol)s. Fragment ions resulting from losses of both of the end groups were noted from some of the samples. An example is presented of how software can be used to significantly reduce the length of time involved in data interpretation (which is typically the most time-consuming part of the analysis).

Novel software for the assignment of peaks from tandem mass spectrometry spectra of synthetic polymers.

Novel software has been developed to aid the interpretation of tandem mass spectrometry (MS/MS) data from synthetic polymers. The software is particularly focused toward aiding the end-group determination of these materials by significantly speeding up the interpretation process. This allows information on the initiator and/or chain transfer agents, used to generate the polymer, and the mechanism of termination to be inferred from the data much more rapidly. The software allows the validity of hypothesized structures to be rapidly tested by automatically annotating the data file using previously proposed fragmentation rules for synthetic polymers. Low-energy collision-induced dissociation (CID) data from methacrylate, styrene, and polyether oligomers are used as example data for the software. Exact-mass CID information was used to aid the understanding of the dissociation mechanism of the polymers. The software can use exact-mass data to provide more confidence in the results. The MS/MS results indicate that the fragmentation pathways are those previously proposed for these polymers.

The rapid characterisation of poly(ethylene glycol) oligomers using desorption electrospray ionisation tandem mass spectrometry combined with novel product ion peak assignment software.

A rapid method for the characterisation of polyglycol esters and ethers is described which uses accurate mass desorption electrospray ionisation (DESI) quadrupole time-of-flight mass spectrometry (Q-ToFMS). The results are combined with newly developed software which aids the interpretation of product ions produced using collision-induced dissociation (CID) of selected precursor ions. The poly(ethylene glycol) (PEG) samples analysed were PEG dibenzoate, PEG monooleate, PEG butyl ether, PEG bis(2-ethyl hexanoate) and PEG diacrylate. Lithium metal was used for cationisation of the PEG oligomers since it yielded the most useful structural information compared with other group I metals. The full scan mass spectra and product ion mass spectra were all obtained in <5 s. Interpretation of the MS/MS product ion spectra, using the product ion interpretation software which incorporates previously developed fragmentation rules, was carried out in <1 s.

Generation of end-group information from polyethers by matrix-assisted laser desorption/ionisation collision-induced dissociation mass spectrometry.

A series of polyethers, namely poly(ethylene glycol) (PEG), poly(propylene glycol) (PPG), poly(butylene glycol) (PBG) and poly(tetramethylene glycol) (PTMeG), has been characterised by means of matrix-assisted laser desorption/ionisation collision-induced dissociation (MALDI-CID) using a hybrid sector orthogonal-time-of-flight (TOF) instrument. The data indicate that this technique can be used to generate information about the end-group functionality of these polymers, including in some cases information about branching of the alkyl chains of the initiating groups. Proposals are made for the fragmentation pathways for these polymers.