Helicobacter pylori in Vammala, Finland: seroepidemiological studies and a population-based ‘screen-and-treat’ programme

Helicobacter pylorin (helikobakteeri) tartunta saadaan yleensä lapsena ja tauti jää tavallisesti pysyväksi ilman täsmähoitoa. Onnistunut hoito parantaa pysyvästi helikobakteerista aiheutuvan mahan haavataudin ja näyttää ehkäisevän mahalaukun pahanlaatuisten muutosten kehittymistä. Aloitimme Vammalassa terveyskeskuksessa toteutetun kansainvälisesti ainutlaatuisen väestöpohjaisen helikobakteeritulehduksen seulonta- ja hoito-ohjelman pilottitutkimuksella 1994. 1996 kaikki 15-40-vuotiaat ja 1997-2000 15- ja 45-vuotiaat vammalalaiset kutsuttiin verinäyteseulontaan. Yhteensä 4626 henkilöä (75% kutsutuista) osallistui seulontaan. Vasta-ainepositiivisille tarjottiin helikobakteeritulehduksen lopettava lääkekuuri. Toiminnan seurauksena helikobakteeritulehduksen esiintyvyyden laskettiin vähentyneen 12%:sta 4%:iin 15-40-vuotiaiden ikäryhmässä. Tutkimme myös helikobakteerivasta-ainepositiivisten ja -negatiivisten eroja sekä helikobakteeritulehduksen riskitekijöitä kyselytutkimuksella. Lapsuudenkodin asumisahtauden, äidin matalan koulutusasteen, tupakoinnin, alkoholinkäytön, huonojen asunto-olojen ja ylävatsavaivoista johtuvien sairauslomien todettiin liittyvän helikobakteeritulehdukseen monimuuttuja-analyysissa. Tutkimme seulontaohjelmassa käyttämiemme IgG- ja IgA-luokan helikobakteeri-vasta-ainetestien luotettavuutta eri ikäryhmissä ottaen huomioon atrofisen gastriitin esiintyvyyden. 561 kliinisin perustein gastroskopoidun potilaan aineistossa IgG-testi osoittautui erittäin herkäksi kaikissa ikäryhmissä (99%). Tarkkuus oli myös vanhemmissa ikäryhmissä hyvä (97-93%), kun atrofista gastriittia sairastavat suljettiin pois. IgA- ja CagA-helikobakteerivasta-aineiden on todettu liittyvän lisääntyneeseen mahahaava- ja mahasyöpäriskiin. Analysoimme 560 henkilön pariseeruminäytteet, jotka oli otettu kahden vuosikymmenen välein, ja totesimme, että IgA-vasta-aineiden esiintyvyyden lisääntyyminen iän myötä johtuu paitsi syntymäajankohdasta ja uusista infektioista myös IgA-vasta-ainetasojen kohoamisesta helikobakteeritulehduksen aikana. Selvitimme myös CagA-vasta-ainetasojen muuttumista analysoimalla seeruminäytteet, jotka oli otettu kahden vuosikymmenen välein. Totesimme, että samanaikaisesti kun helikobakteerin esiintyvyys väestössä on alentunut, erityisesti CagA-positiiviset infektiot ovat vähentyneet. Tutkimuksemme osoittaa, että Suomessa terveyskeskuksen yhteydessä voidaan toteuttaa näin laajamittainen seulonta- ja hoito-ohjelma, johon suomalaiset osallistuvat aktiivisesti. Nähtäväksi jää, kuinka paljon ohjelma kykeni vähentämään helikobakteeritulehdukseen liittyviä myöhäisseuraamuksia.

Impulsivity, health-related behaviour and disease : A prospective study

In clinical settings impulsivity refers to a symptom of psychiatric disorder, but nonclinically oriented research treats impulsivity as a personality and temperament dimension. This prospective study examined whether impulsivity predicts adverse health-related behaviour and increased risk of health problems in a large, nonclinical sample of 5433 subjects working in 12 Finnish hospitals. The data were collected using two questionnaire surveys at a 2-year interval. After controlling for alcohol use at baseline, higher impulsivity predicted increased alcohol consumption at follow-up in both genders (p < .01) and was associated with increased likelihood of becoming a heavy drinker or taking up smoking (p < .05). Impulsivity also predicted an increased number of cigarettes smoked per day in the follow-up among women (p < .001), but not among men, although adjustment for the number of cigarettes smoked at baseline attenuated these associations (p = .08 for women). In men, higher impulsivity was associated with shorter sleep duration and waking up several times per night independent of baseline characteristics (p < .01), whereas in women, higher impulsivity predicted difficulty in falling asleep and waking up feeling tired after the usual amount of sleep (p < .05). In women, these associations became nonsignificant after adjustment for pre-existing somatic and psychiatric diseases. Finally, higher impulsivity was associated with an increased 2-year incidence of physician-diagnosed peptic ulcer disease (adjusted odds ratio (OR) = 2.42, 95% confidence interval (CI) = 1.21 - 4.82) and onset of depression (OR = 1.95, 95% CI = 1.28 - 2.97) after adjustment for a variety of baseline covariates. In conclusion, this study shows that in a nonclinical population, impulsivity appears to be a risk factor for various unhealthy behaviour and health problems.

The role of probiotics in Helicobacter pylori infection

Helicobacter pylori (H. pylori) infection is a major cause of chronic gastritis and peptic ulcer disease, and it is also designated as a class-I carcinogen for stomach cancer. The role of probiotics in the treatment of gastrointestinal infections is increasingly documented as an alternative or complement to antibiotics, with the potential to decrease the use of antibiotics or reduce their adverse effects. These studies were conducted to investigate the role of probiotics in the treatment of H. pylori infection. Various aspects included: an investigation of the effects of a probiotic combination consisting of Lactobacillus rhamnosus GG, L. rhamnosus LC705, Propionibacterium freudenreichii ssp. shermanii JS and Bifidobacterium breve Bb99 or B. lactis Bb12 as a supplementation to H. pylori eradication therapy, with special reference to tolerability, effectiveness, and microbiota alterations following the treatment; discovering the role of probiotics in vivo with H. pylori infected and uninfected patients, as well as with an in vitro model of H. pylori infection. The probiotic combination therapy was able to reduce significantly the total symptom score, which takes into account both the frequency and the severity of the adverse effects, during the eradication treatment. The supplementation did not improve the success of the eradication treatment significantly, though some difference was seen in the eradication percentages (91% vs. 79%). The quantities of predominant bacterial groups were altered significantly following the triple treatment. Probiotics slightly counteracted the effects of anti-H. pylori treatment, monitored as significantly less alterations in the total numbers of aerobes and lactobacilli/enterococci group bacteria. After probiotic intervention, L. rhamnosus GG adhered to a minority of the patients upper gastrointestinal mucosa, but all of the probiotics survived well through the gastrointestinal tract transit with and without antimicrobial treatment. Probiotic intervention decreased gastrin-17 levels in H. pylori infected patients and appeared to decrease the 13C-urea breath test values. In in vitro Caco-2 cell line experiments, probiotics inhibited H. pylori adhesion to intestinal epithelial cells. Both L. rhamnosus strains, P. freudenreichii ssp. shermanii JS and the combination inhibited the H. pylori-induced acute cell leakage. Simultaneously, both L.rhamnosus strains and the combination transiently improved the epithelial barrier function. The pro-inflammatory effects prevailed when the probiotics were used in combination. According to this series of studies, probiotic combination could have some potential in reducing adverse effects induced by H. pylori eradication treatment and beneficial effects on H. pylori infected subjects.

Gastrointestinal complications after kidney transplantation

The aim of the study was to evaluate gastrointestinal (GI) complications after kidney transplantation in the Finnish population. The adult patients included underwent kidney transplantation at Helsinki University Central Hospital in 1990-2000. Data on GI complications were collected from the Finnish Kidney Transplantation Registry, patient records and from questionnaires sent to patients. Helicobacter pylori IgG and IgA antibodies were measured from 500 patients before kidney transplantation and after a median 6.8-year follow up. Oesophagogastroduodenoscopy with biopsies was performed on 46 kidney transplantation patients suffering from gastroduodenal symptoms and 43 dyspeptic controls for studies of gastroduodenal cytomegalovirus (CMV) infection. Gallbladder ultrasound was performed on 304 patients after a median of 7.4 years post transplantation. Data from these 304 patients were also collected on serum lipids, body mass index and the use of statin medication. Severe GI complications occurred in 147 (10%) of 1515 kidney transplantations, 6% of them fatal after a median of 0.93 years. 51% of the complications occurred during the first post transplantation year, with highest incidence in gastroduodenal ulcers and complications of the colon. Patients with GI complications were older and had more delayed graft function and patients with polycystic kidney disease had more GI complications than the other patients. H.pylori seropositivity rate was 31% and this had no influence on graft or patient survival. 29% of the H.pylori seropositive patients seroreverted without eradication therapy. 74% of kidney transplantation patients had CMV specific matrix protein pp65 or delayed early protein p52 positive findings in the gastroduodenal mucosa, and 53% of the pp65 or p52 positive patients had gastroduodenal erosions without H.pylori findings. After the transplantation 165 (11%) patients developed gallstones. A biliary complication including 1 fatal cholecystitis developed in 15% of the patients with gallstones. 13 (0.9%) patients had pancreatitis. Colon perforations, 31% of them fatal, occurred in 16 (1%) patients. 13 (0.9%) developed a GI malignancy during the follow up. 2 H.pylori seropositive patients developed gastroduodenal malignancies during the follow up. In conclusion, severe GI complications usually occur early after kidney transplantation. Colon perforations are especially serious in kidney transplantation patients and colon diverticulosis and gallstones should be screened and treated before transplantation. When found, H.pylori infection should also be treated in these patients.

Helicobacter pylori: resistance and treatment results in Finland

Background: Helicobacter pylori infection is usually acquired in early childhood and is rarely resolved spontaneously. Eradication therapy is currently recommended virtually to all patients. While the first and second therapies are prescribed without knowing the antibiotic resistance of the bacteria, it is important to know the primary resistance in the population. Aim: This study evaluates the primary resistance of H. pylori among patients in primary health care throughout Finland, the efficacy of three eradication regimens, the symptomatic response to successful therapy, and the effect of smoking on gastric histology and humoral response in H. pylori-positive patients. Patients and methods: A total of 23 endoscopy referral centres located throughout Finland recruited 342 adult patients with positive rapid urease test results, who were referred to upper gastrointestinal endoscopy from primary health care. Gastric histology, H. pylori resistance and H. pylori serology were evaluated. The patients were randomized to receive a seven-day regimen, comprising 1) lansoprazole 30 mg b.d., amoxicillin 1 g b.d. and metronidazole 400 mg t.d. (LAM), 2) lansoprazole 30 mg b.d., amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. (LAC) or 3) ranitidine bismuth citrate 400 mg b.d., metronidazole 400 mg t.d. and tetracycline 500 mg q.d. (RMT). The eradication results were assessed, using the 13C-urea breath test 4 weeks after therapy. The patients completed a symptom questionnaire before and a year after the therapy. Results: Primary resistance of H. pylori to metronidazole was 48% among women and 25% among men. In women, metronidazole resistance correlated with previous use of antibiotics for gynaecologic infections and alcohol consumption. Resistance rate to clarithromycin was only 2%. Intention-to-treat cure rates of LAM, LAC, and RMT were 78%, 91% and 81%. While in metronidazole-sensitive cases the cure rates with LAM, LAC and RMT were similar, in metronidazole resistance LAM and RMT were inferior to LAC (53%, 67% and 84%). Previous antibiotic therapies reduced the efficacy of LAC, to the level of RMT. Dyspeptic symptoms in the Gastrointestinal Symptoms Rating Scale (GSRS) were decreased by 30.5%. In logistic regression analysis, duodenal ulcer, gastric antral neutrophilic inflammation and age from 50 to 59 years independently predicted greater decrease in dyspeptic symptoms. In the gastric body, smokers had milder inflammation and less atrophy and in the antrum denser H. pylori load. Smokers also had lower IgG antibody titres against H. pylori and a smaller proportional decrease in antibodies after successful eradication. Smoking tripled the risk of duodenal ulcers. Conclusions: in Finland H. pylori resistance to clarithromycin is low, but metronidazole resistance among women is high making metronidazole-based therapies unfavourable. Thus, LAC is the best choice for first-line eradication therapy. The effect of eradication on dyspeptic symptoms was only modest. Smoking slows the progression of atrophy in the gastric body.

Critical leg ischaemia with tissue loss : a challenge for the vascular surgeon

There is a widespread reporting habit of combining the outcomes for patients with rest pain (Fontaine III) and tissue loss (Fontaine IV) under the single category of critical leg ischaemia (CLI). This study focused on patients with ischaemic tissue loss treated with infrainguinal bypass surgery (IBS). All patients included in the study were treated at Helsinki University Central Hospital in 2000-2007. First, ulcer healing time after IBS and factors influencing healing time were prospectively assessed in 2 studies including 148 and 110 patients, respectively. Second,the results of redo IBS were retrospectively evaluated in 593 patients undergoing primary IBS for CLI with tissue loss . Third,long-term outcome were retrospectively analysed in 636 patients who underwent IBS for CLI with tissue loss . Fourth, the outcome of IBS was retrospectively compared with endovascular treatment (PTA) of the infrapopliteal arteries in 1023 CLI patients. Fifth, the influence multidrug resistant Pseudomans aeruginosa (MDR Pa) bacteria contamination in CLI patients treated with IBS was retropectively assessed. Sixty-four patients with positive MDR Pa -culture were matched with 64 MDR Pa - negative controls. Complete ulcer healing rate, including the ischemic ulcers and incisional wounds, was 40% at 6 months after IBS and 75% at one year. Diabetes was a risk factor for prolonged complete ulcer healing time. Ischaemic tissue lesions located in mid-and hindfoot healed poorly. At one year after IBS 50% of the patients were alive with salvaged leg and completely healed ulcers. The absence of gap between tertiary graft patency and leg salvage rates indicates the importance of a patent infrainguinal graft to save a leg with ischaemic tissue loss. Long-term survival for patients with ischaemic tissue loss was poor, 38% at 5 years. Only 30% of the patients were alive without amputation at 5 years. Several of the patient comorbidities increased independently the mortality risk; coronary artery disease, renal insufficiency, chronic obstructive lung disease and high age. When both PTA and bypass is feasible, infrapopliteal PTA as a first-line strategy is expected to achieve similar long-term results to bypass surgery in CLI when redo surgery is actively utilized. MDR Pa in a patient with CLI should be considered as a serious event with increased risk of early major amputation or death. Conclusion: Despite a successful infrainguinal bypass healing of the ischaemic ulcers and incisional wounds ulcer healing is a slow process especially in diabetics. Bypass surgery and PTA improve the outcome of the ischaemic leg but the mortality rate of the patients is high due to their severe comorbidities.

High-risk patients and high-risk grafts in infrainguinal bypass for critical limb ischaemia

The main purpose of revascularization procedures for critical limb ischaemia (CLI) is to preserve the leg and sustain the patient s ambulatory status. Other goals are ischaemic pain relief and healing of ischaemic ulcers. Patients with CLI are usually old and have several comorbidities affecting the outcome. Revascularization for CLI is meaningless unless both life and limb are preserved. Therefore, the knowledge of both patient- and bypass-related risk factors is of paramount importance in clinical decision-making, patient selection and resource allocation. The aim of this study was to identify patient- and graft-related predictors of impaired outcome after infrainguinal bypass for CLI. The purpose was to assess the outcome of high-risk patients undergoing infrainguinal bypass and to evaluate the usefulness of specific risk scoring methods. The results of bypasses in the absence of optimal vein graft material were also evaluated, and the feasibility of the new method of scaffolding suboptimal vein grafts was assessed. The results of this study showed that renal insufficiency - not only renal failure but also moderate impairment in renal function - seems to be a significant risk factor for both limb loss and death after infrainguinal bypass in patients with CLI. Low estimated GFR (PIENEMPI KUIN 30 ml/min/1.73 m2) is a strong independent marker of poor prognosis. Furthermore, estimated GFR is a more accurate predictor of survival and leg salvage after infrainguinal bypass in CLI patients than serum creatinine level alone. We also found out that the life expectancy of octogenarians with CLI is short. In this patient group endovascular revascularization is associated with a better outcome than bypass in terms of survival, leg salvage and amputation-free survival especially in presence of coronary artery disease. This study was the first one to demonstrate that Finnvasc and modified Prevent III risk scoring methods both predict the long-term outcome of patients undergoing both surgical and endovascular infrainguinal revascularization for CLI. Both risk scoring methods are easy to use and might be helpful in clinical practice as an aid in preoperative patient selection and decision-making. Similarly than in previous studies, we found out that a single-segment great saphenous vein graft is superior to any other autologous vein graft in terms of mid-term patency and leg salvage. However, if optimal vein graft is lacking, arm vein conduits are superior to prosthetic grafts especially in infrapopliteal bypasses for CLI. We studied also the new method of scaffolding suboptimal quality vein grafts and found out that this method may enable the use of vein grafts of compromised quality otherwise unsuitable for bypass grafting. The remarkable finding was that patients with the combination of high operative risk due to severe comorbidities and risk graft have extremely poor survival, suggesting that only relatively fit patients should undergo complex bypasses with risk grafts. The results of this study can be used in clinical practice as an aid in preoperative patient selection and decision-making. In the future, the need of vascular surgery will increase significantly as the elderly and diabetic population increases, which emphasises the importance of focusing on those patients that will gain benefit from infrainguinal bypass. Therefore, the individual risk of the patient, ambulatory status, outcome expectations, the risk of bypass procedure as well as technical factors such as the suitability of outflow anatomy and the available vein material should all be assessed and taken into consideration when deciding on the best revascularization strategy.