Comprehensive Treatment for Pregnant and/or Parenting Women with Substance Use Disorders and Their Children: A Cross-Cultural Comparison.

Background: Substance use during pregnancy and early parenting years is a well-known global public health problem, but the literature comparing treatment programs for this subpopulation across countries is limited. This article both describes three women-centered treatment programs in the United States, Brazil, and Argentina and examines similarities and differences among the programs in terms of patient characteristics. Such an analysis can better inform clinicians in the assessment and treatment of women who use substances and improve the universal understanding about them. Methods: A secondary data analysis of patient characteristics (e.g., pregnant at treatment admission) and patient history (e.g., substance dependence diagnosis, family history of substance use, co-occurring mental health issues) of reproductive age women (N=356) from substance use treatment programs in the United States, Brazil, and Argentina. Results: The Horizons program admitted the highest percentage of pregnant women (60%), Lua Nova (36%), and Casa Santa Clara (17%). Horizons patients (82%) were more likely to have a substance dependence diagnosis than Lua Nova (15%) or Casa Santa Clara patients (13%). Horizons patients (78%) were more likely to have a family history of substance use than Lua Nova (15%) or Casa Santa Clara (57%) patients. Horizons was also more likely than Lua Nova or Casa Santa Clara to have patients who had entered mental health treatment (70% vs. 19% vs. 9%, respectively). Conclusion: Substance use problems that continue during pregnancy and parenting are common within different cultures and societies. These analyses identified similarities and differences in patient characteristics, history, and treatment programs. Cross-cultural comparisons of treatment approaches provide opportunities for clinicians to explore new ways of caring for this population.

Evidence of Small Airways Disease and the Immediate Effects of Lumacaftor/Ivacaftor in Children with Cystic Fibrosis.

Aim The aim of this study was to explore risk factors for acute changes in lung function following initiation of lumacaftor/ivacaftor (LUM/IVA) in children with cystic fibrosis. Methods Retrospective review of all children commenced on LUM/IVA treatment over a one-year period. CT Thorax images were reviewed for evidence of air trapping using the Brody score. Results Data was collected from 15 children. A transient decline in ppFEV1 was observed after initiation of LUM/IVA in 93% (n=14) of patients with an absolute mean decline of -10.8%. There was a statistically significant inverse relationship between ΔFEV1 and baseline ppFEV1. There was no relationship between air trapping score and ΔFEV1 (p=0.41). Conclusion Pre-existing small airways disease is not a risk factor for acute changes in lung function following initiation of LUM/IVA. Our results suggest that a LUM/IVA-related decline in lung function is more significant in CF children with higher baseline FEV1.

Increased multimodality treatment options has improved survival for Hepatocellular carcinoma but poor survival for biliary tract cancers remains unchanged.

BACKGROUND: Primary hepatobiliary cancer incidence in the UK is rising and survival rates are low. Surgery is the main curative option for these cancers, but multimodality therapies are expanding. The aim of our original study was to determine trends in survival, over an 8-year period, of patients treated for primary hepatobiliary cancers at our tertiary referral Centre. METHOD: Patients treated for the most common types of primary hepatobiliary cancers, namely Hepatocellular carcinoma (HCC), Cholangiocarcinoma and Gallbladder cancer between January 2009 and December 2016 were retrospectively analysed from a prospective database linked to UK Hospital Episode Statistics data. RESULTS: A total of 1536 patients with primary hepatobiliary cancers were assessed and treatment plans formulated at our supra-regional specialist Hepatobiliary MDT. The primary hepatobiliary cancers treated were HCC (n = 836), Cholangiocarcinoma (n = 516), and Gallbladder cancer (n = 184). Survival for all the 3 cancers was significantly better with curative treatment. Overall median survival times were 350, 180, and 150 days respectively for HCC, Cholangiocarcinoma and Gallbladder cancer. Excluding best supportive care patients, the respective survival figures were 900, 600, and 400 days. Survival for HCC patients improved over time and was significantly increased in the final 3 years of the study (p ≤ 0.011 for all). Cholangiocarcinoma and Gallbladder cancer survivals were poor and did not change significantly over time. CONCLUSION: HCC outcome has improved in association with expanded multimodal therapies. Survivals for cholangiocarcinoma and gallbladder cancer remain poor in parallel with limited expansion of multimodal therapies highlighting an unmet therapeutic need for biliary tract cancers.

PARAGON II - A single arm multicentre phase II study of neoadjuvant therapy using irinotecan bead in patients with resectable liver metastases from colorectal cancer.

PURPOSE: Perioperative chemotherapy confers a 3-year progression free survival advantage following resection of colorectal liver metastases (CRLM), but is associated with significant toxicity. Chemoembolisation using drug eluting PVA microspheres loaded with irinotecan (DEBIRI) allows sustained delivery of drug directly to tumour, maximising response whilst minimising systemic exposure. This phase II single arm study examined the safety and feasibility of DEBIRI before resection of CRLM. METHODS: Patients with resectable CRLM received lobar DEBIRI 1 month prior to surgery, with a radiological endpoint of near stasis. The trial had a primary end-point of tumour resectability (R0 resection). Secondary end-points included safety, pathologic tumour response and overall survival. RESULTS: 40 patients received DEBIRI, with a median dose of 103 mg irinotecan (range 64-175 mg). Morbidity was low (2.5%, CTCAE grade 2) with no evidence of systemic chemotoxicity. All patients proceeded to surgery, with 38 undergoing resection (95%, R0 resection rate 74%). 30-day post-operative mortality was 5% (n = 2), with neither death TACE related. 66 lesions were resected, with histologic major or complete pathologic response seen in 77.3% of targeted lesions. At median follow up of 40.6 months, 12 patients (34.3%) had died of recurrent disease with a median overall survival of 50.9 months. Nominal 1, 3 and 5-year OS was 93, 78 & 49% respectively. CONCLUSIONS: Resection after neoadjuvant DEBIRI for CRLM is feasible and safe. Single treatment with DEBIRI resulted in tumour pathologic response and median overall survival comparable to that seen after systemic neoadjuvant chemotherapy. Registered at clinicaltrials.gov (NCT00844233).

Animal attack: an unusual case of multiple trauma in childhood.

A 2½ year old girl attended our facility following attack by a tapir at a city zoo. She sustained multiple injuries including a forearm laceration and multiple perforating wounds to her abdominal wall. She had several procedures, including bowel resection, performed under the care of the General Paediatric Surgery and Plastic Surgery teams and was treated with a course of IV antibiotics. She recovered well and to date has suffered no long-term adverse outcome.

Radiological assessment of response to neoadjuvant transcatheter hepatic therapy with irinotecan-eluting beads (DEBIRI(®)) for colorectal liver metastases does not predict tumour destruction or long-term outcome.

INTRODUCTION: Transcatheter hepatic therapy with irinotecan-eluting beads (DEBIRI(®)) allows targeted delivery of irinotecan direct to liver tissue and colorectal liver metastases (CRLM). Accurate assessment of tumour response to therapy is vital to guide optimal treatment. Preliminary work has suggested existing criteria for radiological response may not reflect pathological response after neoadjuvant DEBIRI. This study assessed the relationship between existing and novel radiological response criteria and pathological tumour response as well as long-term outcome. METHODS: Patients with easily resectable CRLM were treated with DEBIRI 4 weeks prior to resection and pathological tumour response graded using a validated system. Radiological response was assessed using RECIST and novel morphological response criteria. RESULTS: Twenty-two patients with 37 lesions were treated with DEBIRI. Median residual tumour was 20% (range 0-80), median necrosis 45% (10-100) and median fibrosis 10% (10-70). Twenty patients (91%) demonstrated stable disease by RECIST, with 11 (50%) demonstrating partial morphological response. Neither radiological response criteria correlated with pathological response. Overall median disease free survival (DFS) was 13.6 months (95% CI 4.7-22.5). Radiological response was not associated with DFS. CONCLUSION: Existing criteria reporting short-term radiological response to DEBIRI do not accurately predict pathological tumour response or long-term outcome. Further work is necessary to define the optimum timing and method of assessing response to DEBIRI.

Hepatic activation of irinotecan predicts tumour response in patients with colorectal liver metastases treated with DEBIRI: exploratory findings from a phase II study.

PURPOSE: The response of colorectal liver metastases to the cytotoxic agent irinotecan varies widely. Attempts to correlate tumour metabolism with response have been mixed. This study investigated the hepatic metabolism of irinotecan as a potential predictor of tumour response to irinotecan-eluting beads (DEBIRI). METHODS: Ten patients with colorectal liver metastases were treated with 200 mg irinotecan (as DEBIRI) as part of the PARAGON II study. Hepatic expression of key metabolising enzymes was measured using mass spectrometry-based proteomics. Serum drug concentrations and hepatic irinotecan metabolism were characterised and correlated with tumour response. RESULTS: Serum concentrations of irinotecan metabolites did not correlate with hepatic metabolism or pathological response. There was a strong correlation between hepatic CES-2 expression and activation of irinotecan (r (2) = 0.96, p < 0.001). Patients with a UGT1A1*28 6/7 SNP showed no difference in drug metabolism or pathological response. Hepatic CES-2 mediated activation of irinotecan clearly correlated with tumour replacement by fibrosis (r (2) = 0.54, p = 0.01). CONCLUSION: This study provides the first evidence that hepatic activation of irinotecan predicts tumour response. Delivery of liver-targeted irinotecan to normal liver tissue rather than tumour may be a more rational approach to maximise response.

The EIF2AK3 gene region and type I diabetes in subjects from South India.

Mutations in the EIF2AK3 gene underlie susceptibility to the Wolcott-Rallison syndrome, which is a monogenic disease associated with insulin-deficient neonatal diabetes. Furthermore, suggestive evidence of linkage between type 1 diabetes (T1DM) and the EIF2KA3 chromosomal region has been reported in Scandinavian families. We have investigated the hypothesis that polymorphic variants in and around the EIF2AK3 gene might partially account for susceptibility to T1DM in South Indian subjects. Excess transmission of the common alleles of two polymorphic markers (D2S1786 and 15INDEL, located within the gene) downstream of EIF2AK3, either singly (D2S1786, P = 0.01) and 15INDEL (P = 0.02) or as a combination (P < 0.001), were found in 234 families with a T1DM proband. There was also a clear paternal effect for the 15INDEL marker (P = 0.005) on disease susceptibility. The presence of the common allele of both markers was found in decreased frequency in the subjects with normal glucose tolerance compared to probands with T1DM (both P

Cryptogenic fibrosing alveolitis with preserved lung volumes.

BACKGROUND: Cryptogenic fibrosing alveolitis (CFA) is an uncommon disorder of unknown aetiology characterised by interstitial fibrosis which typically shows a restrictive pattern on pulmonary function testing. Some patients with CFA and relative preservation of lung volumes have been described and it has been suggested that their volume preservation may be due to concomitant emphysema. In a retrospective study the relative frequency of preserved lung volumes in CFA, its relationship to emphysema determined by CT scanning, its clinical features, and its subsequent natural history were investigated. METHODS: Using predefined characteristics 48 patients with CFA were identified from pulmonary function records over a three year period. Volume preservation was defined as a forced vital capacity (FVC) of > 80% predicted at presentation. Patients with relative volume preservation were compared with those with more typical pulmonary restriction and clinical data at presentation, and details of their subsequent prognosis, treatment and loss of lung function with time were obtained. Where available, computed tomographic (CT) scans for the two groups were compared in a blinded fashion to score the extent of fibrosis and the presence of concomitant emphysema. RESULTS: Twenty one (44%) of the patients with CFA had a FVC of > 80% predicted. They were more likely to be male (76% versus 48%) and to be current smokers (57% versus 22%) with a heavier life time cigarette consumption than the restricted patients (mean (SE) 38 (4.6) versus 25 (4.5) pack years). There were no significant differences in prognosis and subsequent treatment between the groups. Comparable HRCT scans were available in 23 subjects (seven preserved, 16 restricted). They showed no difference in extent of the pulmonary fibrosis but patients with volume preservation were more likely to show concomitant emphysema (86% versus 19%). Patients with emphysema on HRCT scans were heavier smokers (41(10) versus 21(17) pack years) than those without emphysema but there was no difference in the extent of CFA score between the two groups. CONCLUSIONS: In this area of high smoking prevalence a significant number of patients with CFA presented with relative preservation of lung volumes and FEV1/FVC ratio. In many of these subjects this appears to reflect coincidental emphysema. This may make interpretation of gas transfer factor used to monitor progression in CFA difficult. However, there was no evidence that lung volumes at presentation were of prognostic significance.

Baseline data on the delivery of clinical preventive services provided by nurse practitioners.

The National Alliance of Nurse Practitioners (NANP) was one of five primary care provider groups that participated in a national government-sponsored survey on clinical preventive services (CPSs). The survey was based on 17 of the Healthy People 2000 national health objectives related to CPSs. This survey was sent to 2000 randomly selected nurse practitioners (NPs) to obtain information concerning the percentage of their patients who "routinely" receive the specified assessment and intervention services. Data from 892 completed and returned survey instruments indicated that NPs already exceed the Healthy People 2000 objective targets in some important clinical preventive assessment and intervention areas. They are close to the targets in a number of other CPS areas. In some areas, however, NP provision of preventive services was reported to be below the Healthy People 2000 targets. This data has far-reaching implications for NP practice, basic and continuing education, and curriculum reform.

Fatty acids in some common food items in Canada.

Fat content and fatty acid (FA) composition of 100 common items in 17 food categories from the Canadian retail market were determined. Of these, 52 samples were made from partially hydrogenated fat. Their fat (in parentheses) and trans FA levels were as follows: breads (3.7% fat) 15.7%, hamburger buns (5.5% fat) 26.3%, cakes (8.7-36.7% fat) 10.1-25.7%, candies/chocolates (27.1% fat) 11.1%, cereals (1.3-12.9% fat) 9.2-33.7%, cookies (5.0-40.5% fat) 7.6-38.7%, crackers (9.2-33.0% fat) 13.8-35.4%, donuts (16.6-29.6% fat) 27.7-32.7%, french fries (pre-cooked) (4.3-4.5% fat) 32.8-42.8%, muffins (12.5-23.7% fat) 16.5-24.2%, pizza crusts (6.0-7.2% fat) 22.1-28.8%, shortenings (100% fat) 17.4-20.2%, potato chips (33.2-40.0% fat) 29.7-39.7%, and corn chips (25.0-34.2%) 29.9-33.9%. Generally the sum of saturated and trans FA in the food items made with partially hydrogenated fat was higher than that of the corresponding food items made with unhydrogenated oils. The higher levels of saturates plus trans were at the expense of the essential fatty acids (EFA). The high-fat foods, such as cakes, cookies, crackers, donuts and potato chips, made with partially hydrogenated fat, were substantially lower in EFA and contained relatively higher levels of trans polyunsaturated fatty acids (PUFA). In some samples of potato chips and french fries, the level of trans PUFA was almost the same or more than the sum of linoleic and linolenic acids.

Lipid content and composition of coffee brews prepared by different methods.

The lipid content and composition of boiled, filtered, dripped, Turkish and espresso coffees prepared from roasted beans of Coffea arabica and Coffea robusta, and of coffees prepared from different brands of instant coffee were examined. The lipid content varied with the method of preparation. While coffee brews filtered through filter paper contained less than 7 mg lipids, those prepared by boiling without filtering and espresso coffee reached 60-160 mg lipids/150-ml cup. Coffee brew filtered through a metal screener contained 50 mg lipids/150-ml cup. Although the lipid content varied, the method of preparation of the brew and filtration had no important influence on the lipid composition. During paper filtration lipids remained mainly in spent coffee grounds, and the brew and filter paper retained only 0.4 and 9.4%, respectively, of the total lipids recovered. However, the lipids in the brew, filter paper and spent coffee grounds had the same profile, indicating that there was no preferential retention of a particular lipid component in filter paper. Triglycerides and diterpene alcohol esters were the major lipid classes in coffee brewed from ground coffee beans, and ranged from 86.6 to 92.9 and 6.5 to 12.5% of total lipids, respectively. For coffee brews made from instant coffee, the levels of these two lipid classes were 96.4-98.5 and 1.6-3.6%, respectively. The lipid contents of both regular and decaffeinated instant coffees varied slightly from one brand to the other, and ranged from 1.8 to 6.6 mg/150-ml cup.

Role of charge suppression and ionic strength in free zone electrophoresis of proteins.

The free zone electrophoretic mobility of proteins can be predicted from the protein's amino acid content by applying a model based on the Debye-Hückle-Henry theory and Henderson-Hasselbalch equation. Calculated mobilities are always greater than actual mobility but a pH-independent proportionality (described by the constant FZ) is found between the two. Thus, determination of a protein's mobility at one pH allows, with the use of the model and FZ, calculation of its mobility at other pH conditions. This leads directly to optimum conditions for the electrophoretic resolution of proteins in capillary zone electrophoresis. The fundamental nature of FZ is examined and found to be a function of a proteins molecular weight, charge, and solution ionic strength. This work aids in explaining the form of previously proposed empirically based equations for peptide and protein mobility.