A Comparison of the Psychosocial Functioning of Children with Drug‐Versus Alcohol‐Dependent Fathers

The present study compared the psychosocial functioning of children whose fathers primarily abused illicit drugs other than alcohol (n = 51) to children from a demographically matched sample of families whose fathers abused alcohol (n = 51). Children with drug‐abusing (DA) fathers exhibited significantly more negative child behaviors on a standardized child‐rating scale than did children from homes with alcohol‐abusing fathers. In addition, a significantly greater proportion of children with DA fathers met clinical cutoffs indicative of psychosocial impairment (n = 23; 45%) than did children whose fathers abused alcohol (n = 5; 10%). Mediation analyses indicated that severity of drug, legal, medical, employment, and family problems partially mediated the relationship between type of family (i.e., families with fathers who had an alcohol problem versus families with fathers who had a drug problem) and children's psychosocial adjustment.     

Effect of D,L‐threo‐1‐phenyl‐2‐decanoylamino‐3‐morpholino‐1‐propanol and tetrandrine on the reversion of multidrug resistance in K562/A02 cells

Abstract

We studied the clinical impact of CD38 expression in 226 chronic lymphocytic leukemia patients (CLL) at disease presentation and during follow up to determine its prognostic significance, progression free survival (PFS) and overall survival (OS), and to verify whether this parameter changed over time. Various patients' characteristics were studied including gender, Rai and Binet stages, immunoglobulin light chain expression, lymphocyte doubling time and CD38 expression. After a median follow up of 53 months (range 6–282), 62% CD38 positive(+) patients required therapy. PFS and OS at 84 months were significantly lower for CD38(+) patients: 20 and 71% respectively, compared to CD38 negative(?): 70 and 96%. At multivariate analysis CD38(+) showed to be the best factor for predicting progression: HR 3·3, 95%CI 2·10–5·14, p = 0·000. Its expression did not change in 98% re-evaluated patients. We confirm that CD38(+) is a stable parameter for the identification of CLL patients with a more aggressive disease course.     

A Cost‐Effectiveness Analysis of a Peak Flow‐Based Asthma Education and Self‐Management Plan in a High‐Cost Population

Background. Asthma education and action plans (AP) have been recognized as important components in the optimal management of asthma. Studies have differed on the importance of a peak flow‐based self‐management plans in reducing health care costs and use due to asthma exacerbation. Objective. To analyze the cost‐effectiveness of peak flow‐based action plans in reducing costs associated with ER visits and hospitalizations due to acute asthma exacerbation in a population of high‐risk and high‐cost patients, defined as patients with moderate to severe asthma with a history of recent urgent treatment in the ER or hospitalization due to asthma. Methods. A literature review of randomized clinical trials comparing peak flow‐based (PFB) action plans, symptom‐based (SB) action plans, and usual care/no action plan (NAP) was performed. Probability values regarding the effectiveness of each alternative (as measured by increase/decrease in ER visits and hospitalizations over a 6‐month period) were derived. Incremental cost‐effectiveness and cost‐benefit ratios were calculated for each alternative. Sensitivity analyses were performed. Results. For high‐risk and high‐cost asthma patients, our analysis revealed that the most cost‐effective alternative for reducing ER visits was a peak flow‐based self‐management plan. The peak flow‐based self‐management program had an incremental cost‐effectiveness (C/E) ratio of $ 60.57 per ER visit averted compared to usual care/NAP and a C/E ratio of $31.46 compared to the SB‐AP. The PFB‐AP was also the most cost‐effective in reducing asthma hospitalization costs with an incremental C/E ratio of $300 per hospitalization prevented, compared with usual care and a C/E ratio of $311, compared to a SB‐AP. Analysis yielded a cost‐benefit ratio of 13.79 for the PFB‐AP compared to NAP; the SB‐AP had a cost‐benefit ratio of 11.53 compared to NAP. Conclusion. Cost‐effectiveness and cost‐benefit analyses reveal that for high‐cost patients, a peak flow‐based asthma education and self‐management plan program is the most cost‐effective alternative in reducing costs associated with ER visits and hospitalizations due to asthma exacerbation. Further refinements to this cost‐effectiveness analysis including measuring changes in drug use and costs and patients' productivity losses need to be pursued and may demonstrate additional cost‐savings due to peak flow‐based asthma education plans.     

The Short‐Term Effects and Unintended Long‐Term Consequences of Binge Drinking in College: A 10‐Year Follow‐Up Study

This study addresses binge drinking in college as a risk factor for heavy drinking and alcohol dependence after college. A national probability sample of 1972 college students from the National Longitudinal Surveys of Youth (NLSY79) was interviewed in 1984 and reinterviewed again as adults in 1994. The short‐term effects of binge drinking in college were assessed as well as the extent to which experiences of negative effects in college predicted patterns of alcohol use across the transition from college into postcollege years. As expected, college binge drinkers were comparatively more likely than nonbinge drinkers to experience one or more alcohol‐related problems while in college. In addition, weighted estimates of DSM‐IV‐defined diagnostic criteria in logistic regression models indicated that the binge drinking patterns exhibited during the college years, for some former college students of both genders, posed significant risk factors for alcohol dependence and abuse 10 years after the initial interview, in conjunction with evidence of academic attrition, early departure from college and less favorable labor market outcomes.     

Establishment of T‐Helper‐2 immune response based gerbil model of enteric infection

Background: The reciprocal antagonism of T‐helper‐1 (Th‐1) and Th‐2 type immune responses suggests that helminth parasitic infection may ameliorate disease where a Th‐1 type response dominates. The Mongolian gerbil has been useful in the investigation of the pathogenesis of gastric cancer, since long‐term infection of gerbils with Helicobacter pylori induces adenocarcinoma. In this study the kinetics of worm expulsion and associated immune responses in gerbils infected with Trichinella spiralis were investigated in an attempt to establish an animal model of parasitic infection that could be helpful when investigating the effect of a Th‐2 type response on Th‐1‐based intestinal disorders. Methods: Gerbils were infected with various doses of infective T. spiralis larvae and were euthanized on different days after infection to investigate the intestinal worm recovery, goblet cell population, eosinophil response and serum IgG1 responses. Results: The number of worms recovered from the intestine was dependent on the number of larvae used for the infection. Almost all worms were expelled spontaneously by day 26 post‐infection, when the gerbils had been infected with 375 or 750 larvae. The number of intestinal goblet cells, eosinophils and the serum IgG1 level significantly increased following infection compared with the control. Conclusion: This is the first comprehensive report on the time‐course of T. spiralis infection in gerbils. The data indicate that the T. spiralis‐infected gerbil could be used as a model of the Th‐2‐based response to investigate the effect of a parasite‐induced Th‐2 response on various Th‐1‐mediated intestinal disorders such as H. pylori‐induced gastritis and gastric carcinoma.     

A prospective study of the impact of fluorodeoxyglucose positron emission tomography with concurrent non‐contrast CT scanning on the management of operable pancreatic and peri‐ampullary cancers

BackgroundThe role of fluorodeoxyglucose (FDG) positron emission tomography (PET/CT) scanning in operable pancreas cancer is unclear. We, therefore, wanted to investigate the impact of PET/CT on management, by incorporating it into routine work‐up.MethodsThis was a single‐institution prospective study. Patients with suspected and potentially operable pancreas, distal bile duct or ampullary carcinomas underwent PET/CT in addition to routine work‐up. The frequency that PET/CT changed the treatment plan or prompted other investigations was determined. The distribution of standard uptake values (SUV) among primary tumours, and adjacent to biliary stents was characterised.ResultsFifty‐six patients were recruited. The surgical plan was abandoned in 9 (16%; 95% CI: 6–26) patients as a result of PET/CT identified metastases. In four patients, metastases were missed and seven were inoperable at surgery, not predicted by PET/CT. Unexpected FDG uptake resulted in seven additional investigations, of which two were useful. Among primary pancreatic cancers, a median SUV was 4.9 (range 2–12.1). SUV was highest around the biliary stent in 17 out of 28 cases. PET/CT detected metastases in five patients whose primary pancreatic tumours demonstrated mild to moderate avidity (SUV < 5).ConclusionsPET/CT in potentially operable pancreas cancer has limitations. However, as a result of its ability to detect metastases, PET/CT scanning is a useful tool in the selection of such patients for surgery.     

A study of Chitosan and c‐di‐GMP as mucosal adjuvants for intranasal influenza H5N1 vaccine

Please cite this paper as: Svindland et al. (2012) A study of Chitosan and c‐di‐GMP as mucosal adjuvants for intranasal influenza H5N1 vaccine. Influenza and Other Respiratory Viruses 10.1111/irv.12056000(000), 000–000. Background  Highly pathogenic avian influenza A/H5N1 virus remains a potential pandemic threat, and it is essential to continue vaccine development against this subtype. A local mucosal immune response in the upper respiratory tract may stop influenza transmission. It is therefore important to develop effective intranasal pandemic influenza vaccines that induce mucosal immunity at the site of viral entry. Objectives  We evaluated the humoral and cellular immune responses of two promising mucosal adjuvants (Chitosan and c‐di‐GMP) for intranasal influenza H5N1 vaccine in a murine model. Furthermore, we evaluated the concept of co‐adjuvanting an experimental adjuvant (c‐di‐GMP) with chitosan. Methods  BALB/c mice were intranasally immunised with two doses of subunit NIBRG‐14 (H5N1) vaccine (7·5, 1·5 or 0·3 μg haemagglutinin (HA) adjuvanted with chitosan (CSN), c‐di‐GMP or both adjuvants. Results  All adjuvant formulations improved the serum and local antibody responses, with the highest responses observed in the 7·5 μg HA CSN and c‐di‐GMP‐adjuvanted groups. The c‐di‐GMP provided dose sparing with protective single radial haemolysis (SRH), and haemagglutination inhibition (HI) antibody responses found in the 0·3 μg HA group. CSN elicited a Th2 response, whereas c‐di‐GMP induced higher frequencies of virus‐specific CD4⁺ T cells producing one or more Th1 cytokines (IFN‐γ⁺, IL‐2⁺, TNF‐α⁺). A combination of the two adjuvants demonstrated effectiveness at 7·5 μg HA and triggered a more balanced Th cytokine profile. Conclusion  These data show that combining adjuvants can modulate the Th response and in combination with ongoing studies of adjuvanted intranasal vaccines will dictate the way forward for optimal mucosal influenza vaccines.     

Efficacy and Safety of Fluticasone Propionate/Salmeterol HFA 134A MDI in Patients with Mild‐to‐Moderate Persistent Asthma

The objective of this study was to compare the efficacy and safety of fluticasone propionate (FP) (44 µg)/salmeterol (21 µg) delivered as two inhalations twice daily via a single hydrofluoroalkane (HFA 134a) metered dose inhaler (MDI) (FSC) with that of placebo HFA 134a (PLA), fluticasone propionate 44 µg chlorofluorocarbon (CFC) alone and salmeterol 21 µg CFC alone (S) in patients (n = 360) with persistent asthma previously treated with β₂‐agonists (short‐ or long‐acting) or inhaled corticosteroids (ICS). After 12 weeks of treatment, patients treated with FSC had a significantly greater increase (p ≤ 0.006) in mean FEV₁ AUC(bl) compared with PLA, FP, or S. At end point, mean change from baseline in morning predose FEV₁ for FSC (0.58 L) was significantly (p ≤ 0.004) greater than PLA (0.14 L), FP (0.36 L), and S (0.25 L). Patients treated with FSC also had a significantly higher probability of remaining in the study without being withdrawn due to worsening asthma (2%) compared with those in the PLA (29%) and S (25%) groups (p < 0.001). Finally, treatment with FSC resulted in significantly (p ≤ 0.007) greater improvements in morning and evening peak expiratory flow, need for rescue albuterol, and asthma symptom scores compared with FP, S, and PLA. The safety profile of FSC was also similar to FP or S alone. Initial maintenance treatment of the two main components of asthma, inflammation, and smooth muscle dysfunction (e.g., bronchoconstriction), with FSC results in greater overall improvements in asthma control compared with treatment of either individual component alone.     

A European multi‐center trial investigating the anti‐restenotic effect of intravascular sonotherapy after stenting of de novo lesions (EUROSPAH: EUROpean Sonotherapy Prevention of Arterial Hyperplasia)

BACKGROUND: Intravascular sonotherapy (IST) reduces neointimal hyperplasia post‐stenting in animal studies. Euro‐SPAH is a multi‐center, double blind, randomized trial investigating the efficacy of IST to reduce in‐stent late loss.

METHODS: Patients with angina or silent ischaemia with stented de novo lesions were randomised to sham or IST. The sample size had a 90% power to detect a late loss difference of 0.21?mm at 6 months. The secondary endpoints were MACE at 1, 6, 12 months and neo‐intimal hyperplasia on IVUS at 6 months.

RESULTS: At 23 sites in Europe, 403 patients were randomized, with successful treatment with sham or IST in 95.6%. There were no significant differences between the groups in terms of baseline demographics or lesion characteristics. Angiographic follow‐up was obtained in 89%. In‐stent late loss was not significantly different. The restenosis rate at 6 months was 23% in the IST group versus 25% in the sham group. The IVUS measurements confirm the absence of effect of IST on neointimal hyperplasia. At one year, the event‐free survival did not significantly differ between the two groups.

CONCLUSION: The use of sonotherapy following stent implantation in de novo lesions does not reduce intra‐stent neointimal hyperplasia, or effect the angiographic restenosis rate compared to sham treatment. (Int J Cardiovasc Intervent 2004; 2:?53–60)     

Children's Self‐Reports of Characteristics of Their Asthma Episodes

Our purpose was to examine school‐age children's self‐reports of characteristics of their asthma episodes including the precipitating events, symptoms experienced during the episodes, and interventions used to resolve the episodes. Children's self‐reports of their asthma episodes were assessed over a 6‐week period for 42 children with persistent asthma who participated in a randomized, controlled clinical trial to evaluate the efficacy of an asthma self‐management program on adherence to recommended daily peak expiratory flow rate monitoring. Children were instructed to answer the following questions on the Asthma Report Form each time they experienced an asthma episode: 1) What were you doing; 2) How did you feel; and 3) What did you do to help your breathing? Of the children, 71% experienced at least one asthma episode during the 6 weeks. There were a total of 206 episodes. Physical activity (51%) was the most cited trigger, cough alone or combined with other symptoms (84%) was the predominant symptom, and rescue asthma medication (59%) was identified most often as the intervention used by the children to resolve the asthma episode. Children's self‐reports provided valuable information about their asthma episodes. The finding that most of the children experienced at least one asthma episode during the 6‐week period underscores the importance of family education on how to handle asthma episodes effectively at home. Because physical activity was cited most often as a trigger for asthma episodes, families should receive education on preventive steps for averting an asthma episode prior to the child engaging in physical activity.     

A 21‐year analysis of stage I gallbladder carcinoma: is cholecystectomy alone adequate?

Objectives

Gallbladder carcinoma (GBC) is a rare disease that is often diagnosed incidentally in its early stages. Simple cholecystectomy is considered the standard treatment for stage I GBC. This study was conducted in a large cohort of patients with stage I GBC to test the hypothesis that the extent of surgery affects survival.

Methods

The National Cancer Institute''s Surveillance, Epidemiology and End Results (SEER) database was queried to identify patients in whom microscopically confirmed, localized (stage I) GBC was diagnosed between 1988 and 2008. Surgical treatment was categorized as cholecystectomy alone, cholecystectomy with lymph node dissection (C + LN) or radical cholecystectomy (RC). Age, gender, race, ethnicity, T1 sub-stage [T1a, T1b, T1NOS (T1 not otherwise specified)], radiation treatment, extent of surgery, cause of death and survival were assessed by log-rank and Cox''s regression analyses.

Results

Of 2788 patients with localized GBC, 1115 (40.0%) had pathologically confirmed T1a, T1b or T1NOS cancer. At a median follow-up of 22 months, 288 (25.8%) had died of GBC. Five-year survival rates associated with cholecystectomy, C + LN and RC were 50%, 70% and 79%, respectively (P < 0.001). Multivariate analysis showed that surgical treatment and younger age were predictive of improved disease-specific survival (P < 0.001), whereas radiation therapy portended worse survival (P = 0.013).

Conclusions

In the largest series of patients with stage I GBC to be reported, survival was significantly impacted by the extent of surgery (LN dissection and RC). Cholecystectomy alone is inadequate in stage I GBC and its use as standard treatment should be reconsidered.     

A meta‐analysis of extended versus standard lymphadenectomy in patients undergoing pancreatoduodenectomy for pancreatic adenocarcinoma

BackgroundLymph node involvement in pancreatic adenocarcinoma is a key prognostic factor. Therefore, extending the number of lymph node stations excised in pancreatoduodenectomy may be beneficial to patients with pancreatic adenocarcinoma. This systematic review and meta‐analysis examines the outcomes of extended versus standard lymphadenectomy in the published literature.MethodsA meta‐analysis of randomized controlled trials (RCTs) comparing extended with standard lymphadenectomy in patients undergoing pancreatoduodenectomy for pancreatic adenocarcinoma was performed. Perioperative outcomes were assessed as pooled odds ratios (ORs) and weighted mean differences. Overall survival was analysed for patients with positive and negative lymph nodes. Results were reported according to the PRISMA statement.ResultsFive RCTs were included, accounting for 724 patients. Extended lymphadenectomy was associated with greater operative time [mean difference: 63 min, 95% confidence interval (CI) 29–96; P < 0.001], increased need for blood transfusions (mean difference: 0.20, 95% CI 0.01–0.30; P = 0.030) and greater postoperative morbidity (OR 1.5, 95% CI 1.25–2.00; P = 0.030), as well as with prolonged diarrhoea after circumferential autonomic nerve dissection around major vessels (OR 12.2, 95% CI 5.3–28.5; P < 0.001). Median survival was similar across the groups in the whole cohort, as well as in subgroups of patients with, respectively, positive and negative lymph nodes.ConclusionsExtended lymphadenectomy has a harmful impact on patients undergoing oncological pancreatoduodenectomy compared with standard lymphadenectomy.     

Does extremity‐MRI improve erosion detection in severely damaged joints? A study of long‐standing rheumatoid arthritis using three imaging modalities

BACKGROUND: Long-standing rheumatoid arthritis produces unique challenges when assessing damage due to joint deformity. The use of extremity magnetic resonance imaging (eMRI) offers the possibility of improved disease assessment because of greater patient tolerability. OBJECTIVES: The aim of this cross-sectional study was to compare the identification of wrist erosions in a severe rheumatoid arthritis cohort by eMRI with a restricted field of view (eMRI-RV) to radiography and high field MRI, using the latter as the reference. METHODS: Fifteen patients (87% female, median age 56 years) with active rheumatoid arthritis (median DAS28 7.01 and disease duration 11 years) on leflunomide were enrolled. Radiography of hands, eMRI-RV (0.2 T MagneVu MV 1000) and high field MRI of unilateral wrist joints were performed. RESULTS: Of 86 comparable wrist joint areas, high field MRI identified 70 erosions, eMRI-RV 32 and radiography 4. With high field MRI considered the reference, the sensitivity, specificity and accuracy of eMRI-RV for erosions were 46%, 94% and 55%, and the corresponding values for x ray were 6%, 100% and 23%, respectively. CONCLUSIONS: In severely damaged rheumatoid arthritis joints, sensitivity of erosion detection was markedly higher for eMRI-RV than radiography, using high field MRI as the reference. eMRI-RV was, however, less sensitive than high field MRI.     

Incidence,etiology and bone marrow characteristics of non‐chemotherapy‐induced agranulocytosis

Abstract

Objective: Agranulocytosis is a rare but fatal condition. The majority of cases are associated with drugs. However, in‐patient incidences and the relationship between clinical outcomes and bone marrow characteristics have not been established.

Methods: We conducted a retrospective study in a university hospital. A total of 38 in‐patients diagnosed with agranulocytosis were analyzed.

Results: The average incidence of agranulocytosis in Songklanagarind Hospital between 1993 and 2007 was 0·98 cases per 10?000 admissions per year. Antimicrobial agents were the most common etiology (63% of patients) and antithyroid agents were the second most common (13·6%). Two patterns of bone marrow were noted: type I was characterized by a left‐shifted granulopoiesis and type II was recognized as having hypocellular bone marrow with markedly reduced granulocyte precursors. A significantly higher mortality was associated with type II.

Conclusion: Antimicrobial agents are the most common cause and the rare granulocyte precursors in bone marrow are associated with higher mortality rates.     

A population‐based audit for diagnosing colorectal cancer

Background: Knowledge of the diagnostic work‐up of colorectal cancer is a prerequisite to improve its quality. Family history is one of few known risk factors of the disease and it is therefore important to investigate to what extent this factor is used in routine management. Methods: Copies of records from all health‐care suppliers visited during diagnostic work‐up were requested for 227/235 (97%) patients with recently diagnosed colorectal cancer in the county of Västmanland during 1998–99. A first consultation was identified and records and all diagnostic measures related to the initial consultation were scrutinized. A family history of colorectal cancer was known for 179 patients. Results: Most of the patients, 107 (66%) colon and 57 (86%) rectal cancer patients, had consulted with a general practitioner. The median diagnostic work‐up time was 42 days (IQ 12–110) for colon and 23 days (IQ 0–49) for rectal cancer. A double‐contrast barium enema was the most commonly used diagnostic method for colon cancer. Family history was documented at the first consultation in 2/179 (1%) cases. In patients with right‐sided cancer, median diagnostic work‐up time was 53 days in patients with a positive result of faecal occult blood test (FOBT) as compared with 448 in patients with a negative result (P?Conclusion: Primary care is the key actor in diagnosing rectal cancer. The restricted capacity for X‐ray is one of the main obstacles in detection of colon cancer. Family history is rarely documented during diagnostic work‐up of colorectal cancer. The benefit of using FOBT in symptomatic patients is questioned.