Treatment of atopic asthma in primary health care guided by exhaled nitric oxide measurement

Aims: The overall aims of this thesis were to increase knowledge about how patients with asthma rate their health and investigate if we can improve asthma management, with focus on asthma as a chronic inflammatory disease, by use of measurement of the fraction of exhaled nitric oxide (FENO) in monitoring of asthma in primary health care. Methods: Study I included data from a public health questionnaire, which was sent to 8,200 persons (age > 18 years) randomly selected from the population register in Stockholm County. After two reminders, 5,355 persons had responded (67.5 %). Study II was a longitudinal, non-controlled study. Twenty patients with physician-diagnosed atopic asthma and perennial asthma symptoms (age 18 - 50 years) were consecutively recruited from Runby primary health care centre and examined four times during eight weeks (baseline, 2, 4 and 8 weeks). Data for study III and IV were collected in a randomised, controlled study, conducted at 17 primary health care centres in the middle and south of Sweden. A total of 187 non-smoking participants with physician-diagnosed asthma, verified perennial allergy and ongoing inhaled corticosteroid (ICS) treatment (age 18 – 64 years) were randomised to FENO-guided treatment or usual care and were followed up for five visits during one year. Results: Respondents with asthma in study I had approximately three times higher odds of fair/poor self-rated health (SRH) than those in the corresponding sex and age groups who did not have asthma, excepting younger women (18 – 44 years). SRH was associated at least as strong as quality of life to asthma. Study II showed a significant correlation between FENO and IgE-antibody levels against perennial allergens at baseline (r = 0.47, p = 0.04), which disappeared after a step-up in ICS treatment. Nine patients had persistently elevated FENO at last visit (mean 35 ppb vs. 16 ppb). This group was more frequently exposed to relevant allergens or colds (89 % vs. 27 %, p < 0.05) and had higher perennial IgE levels compared with the normalised group (mean 28.9 vs. 10.7 kU/l, p < 0.05). Results from study III showed that total and specific IgE levels decreased 10 – 36 % (p < 0.05 all, except for mugwort) over one year. The changes were not related to any change in allergen exposure, and specific IgG4 levels remained unaltered. The decrease in IgE against perennial allergens related to mean ICS dose (p = 0.030), ii months on leukotriene-receptor antagonist (LTRA) (p = 0.013) and change in FENO (p = 0.003), and interestingly also to change in the Asthma Control Questionnaire (ACQ) score (p = 0.012) and Mini-Asthma Quality of Life Questionnaire (mAQLQ) score (p = 0.009), as well as change in SRH rating (p = 0.041). In study IV, the change in mAQLQ score over one year (primary endpoint) did not differ between the groups (p = 0.197), whereas the mAQLQ symptom domain score (p = 0.041) and the ACQ score (p = 0.045) both improved significantly more in the FENO-guided group. Furthermore, the moderate exacerbation rate was reduced by almost 50 % in the FENO-guided group (p = 0.024). Mean overall ICS use was similar in the two groups (p = 0.95). Conclusions: In Sweden, men > 18 years and women > 45 years with asthma score SRH worse compared with people in corresponding sex and age groups without asthma, which indicates that there is a need to improve asthma management. Exposure to relevant allergens, and type and degree of sensitisa-tion, are important factors to consider when assessing the FENO value. Optimised anti-inflammatory treatment with ICS and LTRA in asthma patients with ongoing treatment at baseline resulted in reduced total and specific IgE levels which were unrelated to the degree of allergen exposure. Using FENO to guide anti-inflammatory treatment within primary care significantly improved asthma symptom control and reduced exacerbation rate in adults with atopic asthma without increasing overall ICS use. FENO-guided anti-inflammatory treatment appears useful to improve the management of patients with atopic asthma

Trends in the socioeconomic patterning of overweight and obesity and predictions of the future prevalence of diabetes in India

The prevalence of overweight and obesity in India has increased substantially in recent decades, and Indians are particularly predisposed to diabetes. Despite this, recent trends in the socioeconomic patterning of overweight and obesity are currently unknown, and reliable future forecasts of overweight, obesity and diabetes to assist policy makers are over-simplistic. The main aims of this thesis were to: (I) examine recent trends in the socioeconomic patterning of overweight and obesity in India, (II) estimate the future prevalence of overweight, obesity and diabetes to 2040, and (III) estimate residual lifetime risk of diabetes. The first objective was addressed using multilevel regression analysis, and the second and third by building dynamic simulation models. Input data were extracted from national surveys, census demographic data and community level cohort studies. The research identified considerably greater increases in overweight and obesity prevalence between 1998 and 2016 in poorer, compared to richer, socioeconomic groups particularly in urban areas, the most economically developed states, and among women. Among 20-69-year-old Indians, overweight and obesity prevalence is forecast to reach 30% and 10% among men, and 27% and 14% among women by 2040. The resultant prevalence of diabetes among urban men and women, respectively, in 2040 is expected to reach 27% and 25%. The lifetime probability of developing diabetes at 20 years among urban men and women is 69% and 75%, respectively, however is considerably higher among the obese population. This thesis marks the most recent attempt to identify the trends in the socioeconomic patterning of excess weight in India, the most thorough attempt to forecast future overweight, obesity and diabetes, and the first to examine the lifetime risk of diabetes. These findings are intended to guide future policy and monitor progress goals related to both excess weight and diabetes

Peroral endoscopic myotomy (POEM) for treating esophageal motility disorders

Review Article on Endoscopic Therapy© Annals of Translational Medicine. All rights reserved. Pneumatic dilatation and Heller myotomy have been thoroughly studied as the most viable treatment options for achalasia. The pendulum, however, is shifting to the minimally invasive approach. Since Inoue et al. published the experience of the first 17 cases of peroral endoscopic myotomy (POEM) in 2010, there have been at least 5,000 cases performed worldwide and the number is increasing exponentially. Experts across the globe have been extending the indications to various esophageal motility disorders, to patients of extremes of age, sigmoidal esophagus and re-operated patients. There are a few variations in technique across different centers in defining the gastroesophageal junction (GEJ) and adequacy of myotomy, the optimal length, site of myotomy and whether the full thickness of the muscle wall should be cut. Large case series demonstrated its promising efficacy & reasonable complication profile. Randomized controlled trial in comparison with the gold standard, Heller myotomy, is ongoing. The future application of submucosal tunnelling technique is thrilling with its extension in tumour resection, antropyloromyotomy and other natural orifice transluminal endoscopic surgery (NOTES).published_or_final_versio

HMG-CoA reductase regulates CCL17-induced colon cancer cell migration via geranylgeranylation and RhoA activation.

Simvastatin is widely used to lower cholesterol levels in patients with cardiovascular diseases, although accumulating evidence suggests that statins, such as simvastatin, also exert numerous anti-tumoral effects

Intraperitoneal chemotherapy for gastric cancer with peritoneal carcinomatosis: is HIPEC the only answer?

Gastric cancer with peritoneal carcinomatosis is notorious for its dismal prognosis. While the pathophysiology of peritoneal dissemination is still controversial, the rapid downhill course is universal. Patients usually suffer abdominal distension, intestinal obstruction and various complications before they succumb after a median of 3 - 6 months. Although not adopted in most international treatment guidelines, intraperitoneal chemotherapy has growing evidence compared with conventional systemic chemotherapy for the treatment of peritoneal carcinomatosis. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is well-established for clinical benefit but is technically demanding with substantial treatment-related morbidities and mortality. On the other hand, normothermic intraperitoneal chemotherapy in the form of bidirectional neoadjuvant treatment is promising with various newer chemotherapeutic agents. Regardless of the treatment technique applied, the essential element of success is meticulous patient selection and availability of expertise. Future direction is along the line of personalized treatment with the application of translational science.published_or_final_versio

Standardized uptake value (SUV) in PET/CT for esophageal cancer correlates with pathological stage and predicts R-category of resection

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Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma: magnifying endoscopy findings

Gastric mucosaâ associated lymphoid tissue lymphoma is uncommon and most patients have an indolent clinical course. The clinical presentation and endoscopic findings can be subtle and diagnosis can be missed on white light endoscopy. Magnifying endoscopy may help identify the abnormal microstructural and microvascular patterns, and target biopsies can be performed. We describe herein the case of a 64-year-old woman with Helicobacter pyloriâ negative gastric mucosaâ associated lymphoid tissue lymphoma diagnosed by screening magnification endoscopy. Helicobacter pyloriâ eradication therapy was given and she received biological therapy. She is in clinical remission after treatment. The use of magnification endoscopy in gastric mucosaâ associated lymphoid tissue lymphoma and its management are reviewed.published_or_final_versio

Use of flow cytometry in the analysis of stage III squamous cell carcinoma of the oesophagus and its association with MIB-1

Aims - To examine the prognostic and pathobiological importance of DNA content in oesophageal squamous cell carcinomas in Hong Kong Chinese subjects; to evaluate its association with the immunohistochemical proliferative marker MIB-1. Methods - Paraffin wax embedded tumour tissue and adjacent normal tissue (control tissue) samples from 45 resected stage III oesophageal squamous cell carcinomas were studied using flow cytometric analysis. The DNA content and the clinicopathological data of these patients were analysed together with the MIB-1 labelling index. Results - DNA aneuploidy was present in 14 (31%) of the 45 cases. However, the DNA content did not correlate significantly with the age, sex, or survival of the patients, nor the length, location, differentiation and MIB-1 labelling index of the oesophageal carcinomas. The synthetic (S) phase fraction of diploid tumours bore no relation to the patients' survival or MIB-1 score. Conclusions - Flow cytometry was not as useful as the MIB-1 labelling index in predicting the biological characteristics of the tumours and the prognosis of patients with oesophageal squamous cell carcinomas. This study does not support the routine use of DNA flow cytometric analysis in oesophageal cancers.published_or_final_versio

Predictive factors in the evaluation of treatment response to neoadjuvant chemoradiotherapy in patients with advanced esophageal squamous cell cancer (Review Article)

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Fältskiktsväxter i gran- och tallbestånd i södra Småland

Det svenska landskapet och dess markanvändning har förändrats kraftigt de senaste århundrandena, tät skogsmark har ersatt tidigare öppen mark och i södra Sverige har granen kommit att bli allt vanligare. Detta gör det intressant att undersöka vilka förutsättningar dagens skogslandskap skapar för växters livsmiljöer och om en signifikant skillnad mellan gran- och talldominerade skogar finns. Studien utgick från ett datamaterial över fältskiktsväxter som påträffats under en inventering av 30 granbestånd och 30 tallbestånd i södra Småland. Viktade indikatorvärden beräknades baserat på tabellvärden för ljus, markreaktion, fuktighet, temperatur och kväve. En lista sammanställdes över hävdgynnade växter och utifrån den så beräknades medeltäckningen av växterna beståndsvis. Tallbestånden hyste totalt sett mer fältvegetation än granbestånden. Ingen statistiskt signifikant skillnad konstaterades mellan gran- och tallbestånden för indikatorvärdena ljus, temperatur och markreaktion. Granbestånden fick ett signifikant högre medelvärde för fuktighet. För kväve var granbeståndens medelvärde högre än tallbestånden. Ingen signifikant skillnad i täckningsgrad av hävdgynnade växter kunde styrkas mellan gran- och tallbestånden. Tallbestånden fick ett lägre ljusvärde än väntat, vilket förmodligen beror på det stora inslaget av skuggtåliga risväxter. Skillnaden i fuktighetsvärde förklarades av granskogars mäktigare humusskikt och lägre solinstrålning. Skillnad i kvävevärde kan bero på den högre kvävedepositionen i granskogar. Många växtarter tycks vara generalister avseende temperatur och markreaktion vilket gav ett litet underlag att basera statistiken på, något som kan ha påverkat dessa värdens utfall. Trädslagsval föreföll ha en begränsad påverkan på täckningsgraden av hävdgynnade växter, skötsel och andra ståndortsfaktorer kan förmodligen vara av större betydelse.The Swedish landscape has changed in recent centuries; meadows and pastoral lands have become increasingly forested and in southern Sweden, Norway spruce has become more common. Thus, it is interesting to study which conditions contemporary forest landscapes are subjecting plants to, how it affects their habitats and if a significant difference between Norway spruce and Scots pine dominated forest stands exists. This study is based on data from a survey in southern Småland of the field vegetation in 60 stands, 30 dominated by Norway spruce and 30 by Scots pine. Ellenberg’s weighted indicator values were calculated based on table values for light, soil reaction, humidity, temperature and nitrogen. A list of plant species typically related to managed lands i.e. meadows and semi natural grasslands was compiled, and average plant coverage was calculated. Field vegetation abundance was generally higher in Scots pine stands. The indicator values of light, temperature and soil reaction showed no statistically significant difference between the two stand types. The Norway spruce stands showed significantly higher values for moisture and nitrogen. No significant difference between the two stand types was detected for the coverage of plants related to managed lands. The pine stands had a lower light value than expected, probably due to the large proportion of dwarf shrubs, such as Vaccinium myrtillus and V. vitis-idaea. Differences in moisture value may be due to the generally thicker humus layer and lower solar radiation characteristic for Norway spruce forests. Higher nitrogen values might be explained by the higher nitrogen deposition in Norway spruce forests. Many plants are seemingly generalists regarding temperature and soil reaction, which might have affected the results. Focal tree species does not seem to impact the coverage of plants related to managed lands, forest management and other stand factors may be of greater importance