Dissertations / Theses on the topic 'Epidemiological study in Sweden'

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease, which primarily affects middle-aged women. The liver histology is characterized by inflammation and destruction of the intrahepatic bile ducts as well as a high frequency of granuloma. Although the etiology is unknown, the occurrence of associated multiorganic abnormalities such as Sjogren's syndrome, scleroderma, rheumatic disorders and thyroid gland diseases have been cited as evidence favouring an autoimmune background. Addison and Gull in 1851 described the first patient with jaundice and xanthomatosis. PBC was first mentioned in 1876 as an entity by Hanot. PBC was considered to be a rare disease until in 1973 Sherlock and Scheuer described 100 patients. Since then a greater awareness of the disease combined with a wider use of laboratory screening methods has led to the discovery of an increasing number of patients with PBC. In an epidemiological investigation of PBC in the northern part of Sweden a point prevalence of 151 per 106 was found, which is the highest so far reported, and the mean annual incidence amounted to 13.3 per 106. Asymptomatic PBC was present in more than one third of the patients which is consistent with the finding in other epidemiological investigations and is supposed to explain the higher prevalence of PBC and the better prognosis. Nevertheless 25 patients died during the study period, 14 as a direct consequence of the liver disease. Chronic intrahepatic cholestasis has been reported in sarcoidosis and, moreover, a high frequency of liver granuloma is found. The implication of the present study is that a negative Kveim test in combination with positive mitochondrial antibodies is accurate in differentiating PBC from sarcoidosis. Multisystem involvement is frequently observed in PBC and the present study confirms this. In the prospective investigation of 26 PBC patients 50 % had arthropathy considered to be associated with PBC. Rheumatoid arthritis was found in 5 patients, who all had symptoms of liver disease in addition. Lung function impairment was present in 56% (1 asymptomatic PBC). Most commonly a reduced diffusion capacity was found (36%). Bronchial asthma was present in three patients, and severe lung emphysema in one. Features of Sjogren's syndrome was found in 73% (3 asymptomatic PBC). In 6 patients keratoconjunctivitis sicca (KCS) was evident with the rose bengal test demonstrating corneal staining and a Schirmer test of less than 5 mm. Radiological findings of sialectasia were demonstrated in 6 patients, of whom 5 had KCS as well. The ultimate treatment in PBC is liver transplantation and to calculate the need for that, good epidemiological surveys are needed, and also indicators of hepatocellular function. The present investigation indicates that determination of the von Willebrand factor could be used for this purpose.

Härtill 6 uppsatser

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Physical activity is an essential component of a healthy life, e.g. to prevent obesity, cardiovascular disease and premature death, of which sports can be an important part. Unfortunately, sports activities increase the risk of both overuse and acute injuries. Severe acute injuries may also lead to a permanent medical impairment (PMI), which may influence the ability to be physically active throughout life. However, sports injuries may be prevented, but a profound understanding of the injuries and how to prevent them is needed. This doctoral thesis examine acute sports injuries reported by licensed athletes of all ages and level of sports nationwide in Sweden, by using national insurance data. Approximately 80% of all the Sports Federations (SF) had their mandatory accident insurance in the insurance company Folksam, and since there is no national sports injury surveillance system in Sweden, this is a unique database, able to be used in epidemiological studies on acute injuries occurring in organized sports in Sweden. The main aim of this thesis was to identify high-risk sports for acute injuries, the most common and the most severe injuries, especially in large sports with numerous licensed athletes, many injuries and injuries resulting in PMI. Based on the results, there will be recommendations regarding sports and body locations where injury prevention efforts should be focused to gain the greatest prevention effect at a national level in Sweden. Another aim was to evaluate the effectiveness of a neuromuscular knee control training program (KCP) that has been implemented nationwide to reduce knee and cruciate ligament injuries, among football players in Sweden. After evaluating the validity and reliability of the information within the database based on international guidelines, acute injury data were examined and the results presented in four papers. These results showed that there is a need of injury prevention especially in motorcycle sports, team ball sports, and ice hockey. Particularly, knee injuries need to be prevented since they were both the most common injuries and leading to PMI. The severe head- and upper limb injuries also need attention. Sixty-nine percent of the PMI injured athletes, were younger than 25 years. The injury prevention training program, KCP can be considered partially implemented nationwide, since 21 out of 24 district SFs provided KCP educations. The incidence of knee and cruciate ligament injuries has decreased among football players in Sweden. A concerning aspect is that there is no national official policy regarding sports injury and injury prevention in Sweden, nor an official authority that has the explicit responsibility for these issues.

In a case-control study comprising 589 cases of male lung cancer in northern Sweden longitudinal data concerning occupations, employments and smoking habits were collected by questionnaires. Pipe smoking was as common as cigarette smoking and gave very similar relative risk. The pipe smoking cases, however, had significantly higher mean age and mean smoking years at the time of diagnosis than the cigarette smoking cases. In ex- smokers, the relative risk gradually decreased from 5 years after smoking cessation but this decrease was much less pronounced in ex-pipe smokers than in ex-cigarette smokers. High relative risks were obtained for small cell and squamous cell carcinomas. For adenocarcinoma the relative risk was considerably lower but still significantly increased. The population etiologic fraction attributable to smoking was about 80% in this series. Some occupational groups (underground miners, copper smelter workers, electricians and plumbers) exposed to previously known lung carcinogenic agents had considerably increased odds ratios, which persisted after adjustment for smoking. A slightly elevated odds ratio was observed in a group of blue collar workers potentially exposed to lung carcinogenic agents but this elevation generally disappeared after adjustment for smoking. For two specific subgroups, asphalt and concrete workers and pulp workers, the overrisk persisted after adjustment for smoking. Farmers and foresters had strikingly low odds ratios, which could only partly be explained by their more moderate smoking habits. The population etiologic fraction attributable to occupation was in the reported material assessed to 9 per cent. Professional drivers had higher average tobacco consumption than non-drivers, which explained the slightly increased crude odds ratio found for the occupational group as a whole. Smoking drivers in an upper age group (70 and over), however, had a high relative risk of lung cancer, while in a lower age group (under 70) no significant increase was found. The results in the older age group suggested a multiplicative effect between smoking and the occupational exposure. The study clearly verified the increased lung cancer risk in underground miners. An obvious dose-response relation was found with high risk after long time exposure. All analyses concerning underground miners suggested an interaction of a multiplicative type between underground mining and smoking in the causation of lung cancer. The cases of small cell carcinoma among the underground miners had shorter average latency time and in contrast to the other part of the material, shorter average age than the cases with epidermoid cancer.

S. 1-40: sammanfattning, s. 41-136: 6 uppsatser

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The overall aim of this thesis was to study the influence of physical activity on health. Risks and benefits of physical activity is of particular interest since there is a global trend of less physical activity among youths and adults. In order to investigate this aim we used a database from a large cross country ski race, Vasaloppet, with participants with a wide age range, and with both elite athletes and ordinary people who exercise and promote their health. The most serious risk of strenuous exercise is sudden death and it is challenging to identify preventive effects of major endemic diseases. Using epidemiological methodology we studied 200 000 Vasaloppet skiers and compared them with the general population. Based on personal identification numbers we added data from Swedish national personal and health registers, clinical registers as the cancer register, Swedeheart, or Swedish stroke register, and socioeconomic information from Statistics Sweden. In the Vasaloppet database we collected data on age, gender, finish time and number of races during the period 1989 to 2010. We evaluated risk of death during the race in two papers (I,II). During 90 years of annual races, cardiac arrest occurred in 20 skiers, of which five survived. The death rate is in average two per 100 000 skiers. We also studied the association with cancer incidence (paper III). The overall reduction of cancer was modest among skiers compared with the general population, but for cancers related to lifestyle the risks were markedly lower. We investigated the risk for recurrent myocardial infarction and found a 30% reduction among skiers (paper IV). In paper V we showed that skiers with a first stroke have a lower incidence of all-cause death. The skiers had a higher frequency of atrial fibrillation but had less severe stroke and no increased risk of recurrent stroke. Thus our data suggest that a lifestyle with a high level of physical activity may work as a protection after a cardiovascular event. Summary: The short excess mortality in endurance physical activity is by far outweighed by the long term protective effect of exercise in cardiovascular diseases and cancer.

Som tandhygienist är det mycket intressant att studera karies-epidemiologiska undersökningar på både nationell och internationell nivå. Syftet med denna litteraturstudie är att beskriva och jämföra kariesstatus (DMFT) hos 12-åringar i Sverige och Irak, och några av de faktorer som kan påverka DMFT komponenternas roll och inverkan.För att besvara syftet användes information från litteratur och tidskrifter samt WHO:s databas om länderna. Resultatet visar att DMFT för 12-åringar i Irak var 1.7 (2003) och i Sverige 1.0 (2005). DT-komponenten, d.v.s. obehandlad karies, var hög hos irakiska barn medan FT- komponenten var hög för danska barn (inga data tillgängliga för Sverige). DMFT-medelvärde, sockerkonsumtion, ekonomiska resurser för tandvård, antal tandvårdpersonal och fluorprogram var mycket olika i Sverige och Irak, men differensen i DMFT var ändå inte markant.
As a dental hygienist it is relevant to study caries epidemiological studies on both national and international levels. The purpose of this literature study has been to describe and compare dental caries status (DMFT) of 12 years olds in Sweden and Iraq and the factors underlying the DMFT and DMFT components and facilitating role. To achieve the objective information from scientific literature and publications, and data from WHO database on these countries were used. Results showed that the DMFT for 12 year olds in Iraq and Sweden was 1.7(2003), 1.0 (2005) respectively. DT component was high among Iraqi children (untreated caries) while the FT component was high in Denmark, (no data was available for Sweden). DMFT mean, sugar consumption, economic resources for dental care, number of dental health professionals, and fluoride applications were very different in Sweden and Iraq, yet DMFT difference was not marked and serious.

Background: Psoriasis is a heterogeneous disease with several clinical manifestations; the symptoms are characterized by redness, scaliness and thickness of the skin. There are several treatment options available for psoriasis and patients with moderate to severe psoriasis generally need systemic agents. In 2004 biologics were introduced for patients with moderate to severe psoriasis in Sweden. Methods: The Swedish Health Care Registers and the Swedish registry for systemic treatment of psoriasis PsoReg, were used to; estimate the incidence of psoriasis cases in the Swedish specialist care, to examine the treatment allocation and important factors related to the initiation of especially biologic treatment. Results: On average 9000 new psoriasis patients entered specialist care in Sweden each year under study, corresponding to an incidence of 98 patients per 100,000 person-years. In the treatment allocation analysis of the incident psoriasis cases in the Swedish specialist care Patients living in a Metropolitan Area and with a University degree were more likely to initiate a biologic treatment. By analysing biologic-naïve patients enrolled in PsoReg, PASI (the physician’s assessment of the psoriasis severity) and Psoriasis Arthropathy were shown to be two important factors associated with the initiation of biologic treatment while sex was not. Furthermore, it was also shown that the decision to initiate biological treatment was more strongly associated with PASI than with DLQI (the patients’ assessment of the disease impact Quality of Life). Conclusion: These studies indicate that there are inequalities in the assignments of systemic psoriasis treatments (especially in biologic treatment). Since the allocation of treatments should not depend on sex, education or residency in a Metropolitan Area but rather the need of care, it is important that future studies continue analysing possible factors that could influence the initiation of treatment in clinical practice.

The aim of this PhD thesis was to expand the current knowledge of “traditional Sami” diet and lifestyle, and to test aspects of the Sami diet and lifestyle, specifically dietary pattern, macronutrient distribution and coffee consumption, in population-based epidemiological studies of mortality and incident cardiovascular disease and cancer in a general population. In Paper I, semi-structured interviews were conducted with 20 elderly Sami concerning their parent’s lifestyle and diet 50-70 years ago. Questionnaire data from 397 Sami and 1842 matched non-Sami were also analyzed, using non-parametric tests and partial least square methodology.  In Papers II-IV, mortality data and incident cancer data for participants in the Västerbotten Intervention Program (VIP) cohort were used for calculations of hazard ratios by Cox regression. In Paper II, a Sami diet score (0-8 points) was constructed by adding one point for each intake above the median for red meat, fatty fish, total fat, berries and boiled coffee, and one point for each intake below the median for vegetables, bread and fibre. In Paper III, deciles of energy-adjusted carbohydrate (descending) and protein (ascending) intake were added to create a Low-Carbohydrate, High-Protein (LCHP) score (2-20 points). In Paper IV, filtered and boiled coffee consumption was studied in relation to incident cancer. In Paper V, a nested case-control study of filtered and boiled coffee consumption and acute myocardial infarction, risk estimates were calculated by conditional logistic regression. Surprisingly, fatty fish may have been more important than reindeer meat for the Sami of southern Lapland in the 1930’s to 1950’s, and it is still consumed more frequently by reindeer-herding Sami than other Sami and non-Sami. Other dietary characteristics of the Sami 50-70 years ago and present-day reindeer-herding Sami were high intakes of fat, blood, and boiled coffee, and low intakes of bread, fibre and cultivated vegetables (Paper I). Stronger adherence to a “traditional Sami” diet, i.e. a higher Sami diet score, was associated with a weak increase in all-cause mortality, particulary apparent in men (Paper II). A diet relatively low in carbohydrates and high in protein, i.e. a high LCHP score, did not predict all-cause mortality compared with low LCHP score, after accounting for saturated fat intake and established risk factors (Paper III).  Neither filtered nor boiled coffee consumption was associated with cancer for all cancer sites combined, or for prostate or colorectal cancer. For breast cancer, consumption of boiled coffee ≥4 versus <1 occasions/day was associated with a reduced risk. An increased risk of premenopausal and a reduced risk of postmenopausal breast cancer were found for both total and filtered coffee. Boiled coffee was positively associated with the risk of respiratory tract cancer, a finding limited to men (Paper IV). A positive association was found between consumption of filtered coffee and the risk of acute myocardial infarction in men (Paper V). In conclusion, the findings of Paper I, in particular the relative importance of fatty fish compared to reindeer meat in the “traditional Sami” diet of the 1930’s-1950’s, suggest that aspects of cultural importance may not always be of most objective importance. The findings of Papers II-V generally did not support health benefits for the factors studied. The relatively good health status of the Sami population is therefore probably not attributable to the studied aspects of the “traditional Sami” lifestyle, but further investigation of cohorts with more detailed information on dietary and lifestyle items relevant for “traditional Sami” culture is warranted.
Syftet med denna avhandling var att beskriva livsstil och kostvanor hos samer. Det var också att undersöka hur en ”traditionell samisk” livsstil påverkar risken att insjukna av eller dö i cancer och hjärt-/kärlsjukdom i en norrländsk normalbefolkning. En majorietsbefolkning har alltså undersökts ur ett minoritetsperspektiv. Avhandlingen belyser framför allt kostvanor, fördelning av de näringsämnen som innehåller energi (kolhydrat, protein, fett) och konsumtion av kok- och bryggkaffe. Bakgrunden till undersökningarna var att samerna, till skillnad från de flesta andra urfolk i världen, kan förvänta sig ett lika långt liv som majoritetsbefolkningen. När det gäller hjärtkärlsjukdom finns inga stora etniska skillnader, men samiska män, särskilt renskötande, har lägre risk att drabbas av cancer än icke-samer. Det finns ingen entydig förklaring till samernas relativt goda hälsa, men det kan finnas ett samband med kostvanor och livsstil. Delstudie I var en intervjustudie med äldre samer och fungerade som bakgrund för de andra delstudierna. Tjugo äldre samer intervjuades om sina föräldrars livsstil och kostvanor för 50-70 år sedan. Dessutom analyserades kostdata från 81 renskötande och 226 icke-renskötande samer och 1842 matchade icke-samer för att se vilka skillnader som fanns mellan grupperna. Intervjuerna visade överraskande att fet fisk kan ha varit viktigare än renkött för samerna i södra Lappland under 1930-1950-talen. Fet fisk äts fortfarande i högre utsträckning av renskötande samer än av andra samer och icke-samer. Saker som har hög kulturell betydelse (i detta fall renkött) behöver alltså inte alltid ha lika stor betydelse ur ett objektivt, vetenskapligt perspektiv. Andra typiska särdrag hos den samiska kosten var en hög andel av fett, blod och kokkaffe och en låg andel av bröd, fibrer och odlade grönsaker. Det dagliga livet hos samerna på 1930-1950-talen präglades också mycket mer av fysisk aktivitet än vad det gör idag. De samiska männen arbetade oftast långt hemifrån, medan kvinnorna hade ansvaret hemmavid för fiske, jordbruk och trädgårdsskötsel (som introducerades under 1930-1950-talen). Kvinnorna tog även hand om hushållsarbetet och barnen. Delstudierna II-V handlade om olika aspekter av samisk kost i relation till dödlighet och sjuklighet. Till dessa användes huvudsakligen data från Västerbottens hälsoundersökningar, men i delstudie V även från MONICA-projektet, som är en del av ett multinationell forskningsprojekt om hjärt-/kärlsjukdom.  Totalt ingick på så sätt data från mer än 80 000 unika individer från en allmän, till största delen icke-samisk, normalbefolkning. Delstudie II byggde på en modell liknande den som använts för att undersöka hälsoeffekter av så kallad Medelhavsdiet.  En poängskala från 0-8 poäng, en så kallad ”Sami diet score”, skapades för att spegla likheter med ”traditionell samisk” kost. Den hälft av deltagarna som åt mest rött kött, fet fisk, fett, bär respektive kokkaffe, fick 1 poäng var, sammanlagt maximalt 5 poäng. Den hälft av deltagarna som åt minst grönsaker, bröd respektive fibrer fick också 1 poäng var, sammanlagt maximalt 3 poäng. Stora likheter med en ”traditionell samisk” kost, det vill säga höga ”Sami diet score” poäng, var förknippade med en svagt ökad dödlighet, särskilt hos männen. Det verkar därför osannolikt att den samiska kosten i sig förklarar den relativt goda hälsan hos samer. Denna fråga är dock mycket svår att undersöka, eftersom kostvanorna kan ha skiljt sig mellan olika samegrupper och över tid. Dessutom äter dagens västerbottningar mycket mindre av vissa livsmedel, jämfört med vad samerna gjorde förr i tiden. Det gäller till exempel fet fisk och bär.  För sådana livsmedel kan det därför vara extra svårt att påvisa samband med dödlighet. Syftet med kostenkäten i Västerbottens hälsoundersökningar är inte heller att spegla en ”traditionell samisk” kost. Det finns till exempel inga frågor om renkött och vilt, utan sådant kött räknas som en del av övrigt rött kött. Det här är första gången som någon undersökt betydelsen av ett ”traditionellt samiskt” kostmönster för hälsan på detta sätt. Fler liknande undersökningar i material med mer detaljerade frågor, som bättre fångar en samisk kost, är önskvärda. Lågkolhydratdieter, som har vissa likheter med den ”traditionella samiska” kosten, är både populära och kontroversiella. Eventuella långtidseffekter för hälsan är till stor del okända. I delstudie III speglades förhållandet mellan kolhydrater och protein i kosten med hjälp av så kallade LCHP (låg-kolhydrat, hög-protein) poäng. Högsta LCHP poäng fick de deltagare som åt minst kolhydrater och mest protein. Höga LCHP poäng påverkade inte risken att dö, eller att dö i cancer eller hjärt-/kärlsjukdom, efter att statistisk hänsyn tagits till intaget av mättat fett och de vanligaste riskfaktorerna. LCHP score användes i denna studie, istället för exempelvis en LCHF (low carbohydrate, high fat) variant. På så sätt kunde betydelsen av total fettmängd och av mättat fett också vägas in i analyserna. Dessutom innehåller kolhydrater och protein samma mängd energi per gram, vilket gör det lättare att byta ut dem mot varandra i en poängskala. Fett innehåller nästan dubbelt så mycket energi per gram som proteiner och kolhydrater. Inte bara olika sorters fett, utan även olika sorters protein och kolhydrater, kan spela roll för hälsan. Det är därför mycket svårt att skilja ut effekterna av mängd och kvalitet av kolhydrater, protein och fett i kosten. I delstudierna IV och V undersöktes risken att bli sjuk i cancer eller få en akut hjärtinfarkt hos västerbottningar som dricker mer respektive mindre kok- och bryggkaffe. De som drack mycket kaffe hade varken ökad generell cancerrisk, eller ökad risk för prostata- eller tjocktarmscancer. Kvinnor som drack kokkaffe ≥ 4 ggr/dag hade minskad risk för bröstcancer jämfört med kvinnor som drack <1 gång/dag.  Både totalt kaffeintag och intag av bryggkaffe var kopplade till ökad risk för bröstcancer hos yngre kvinnor och minskad risk hos äldre. Män som drack mycket kokkaffe hade ökad risk för cancer i luftvägarna. Dessa resultat visar att de som dricker olika sorters kaffe kan ha olika stor risk att drabbas av olika sorters cancer. I tidigare studier har inga starka samband hittats mellan kaffedrickande och cancer. Denna studie var den första att undersöka hur cancerriskerna ser ut hos människor som dricker olika sorters kaffe. När det gäller hjärtinfarkt, hade män som drack mycket bryggkaffe ökad risk, medan inga entydiga resultat kunde visas bland män som drack mycket kokkaffe. Tidigare studier har visat motstridiga resultat när det gäller kaffe och hjärt-/kärlsjukdom, även om kaffekonsumtion är vedertaget förknippat med en del faktorer som kan öka risken att drabbas av hjärtinfarkt, till exempel ökade halter av blodfetter. Betydelsen av kokkaffe har aldrig undersökts tidigare i en studie där uppgifter om kaffedrickande samlats in i förväg. Delstudierna II-V är alla så kallade observationsstudier. I sådana studier följer deltagarna ingen bestämd forskningsplan, utan lever sina normala liv och jämförs sedan med varandra.  I observationsstudier är det mycket svårt att ta hänsyn till alla möjliga störande faktorer som kan finnas i omgivningen. Därför är det i princip omöjligt att bevisa direkta samband mellan orsak och verkan i en observationsstudie. Delstudierna II-V hade emellertid den starkaste design som en observationsstudie kan ha. De byggde på en representativ normalbefolkning (= en befolkningsbaserad kohort), där data samlats in från ett stort antal personer (> 80 000 unika individer) medan de ännu var friska (= en prospektiv kohort).  Resultaten av enstaka observationsstudier har störst betydelse som underlag för att planera nya liknande, eller andra typer av mer riktade undersökningar. De är med andra ord hypotesgrundande. Om däremot flera observationsstudier visar på liknande resultat brukar man utgå från att resultaten är sanna, eller åtminstone sannolika.
(Nordsamiska) Guorahallama ulbmil lea muitalit sámi biepmu ja eallinvuogi birra ja iskat got árbevirolaš sámi borranvierut, makrobiebmama juogustus ja gáffegolaheapmi  váikkuhit jámolašvuođa  ja riskka oažžut borasdávdda dehe váibmo-/ suotnadávdda dábálaš davvi-ruoŧŧelaš ássiid luhtte. Guoktelogi sámi vuorrasa ledje jearahallon daid vánhemiid eallinvuogi  ja borramuša birra 50-70 jagi áigi (Oassedutkan 1). Dasa lassin  397 sámi ja 1842 ruoŧŧelačča biebmandata guorahallojuvvo eahpe-paramehtarlaš iskamiid ja partialalaš unnimus kvadráhta metoda (PLS) mielde. Dát golbma čuovvovaš oassedutkama, gait kohortdutkamat, isket jápminsiva dehe borasdávdabuohccivuođa oaseváldiid luhtte  Västerbottenis dearvas-vuohŧaiskkademiid hárrái (64 603-77 319 iskama) ja riskkaluoitimat leat rehkenaston Cox regrešuvnna  mielde. Oassedutkamis  2  árbevirolaš sámi biebman  lea speadjalaston čuokkesskála vuostá   0 rájes gitta 8 čuoggá.  Dát bealli oaseváldiin geat leat eanemus rukses bierggu, buoiddes guoli, buoiddi, murjiid ja vuoššangáfe borran, lea ožžon 1 čuoggá juohke áidna biebmanelemeanta ovddas, oktiibuot eanemus 5 čuoggá. Vel 3 čuoggá dát bealli oaseváldiin lea ožžon geat lea unnimus šattuid, láibbi ja fiberiid borran, eanemus oktiibuot 3 čuoggá. Oassedutkamis 3 speadjalastá oktavuođa kolhydráhtaid ja proteiinnaid gaskkas  biebmamis  LCHP (vuolit-kolhydráhta, alit-proteiidna) čuoggáid bokte. Alimus LHCP čuoggát (=20) dát oasseváldit leat ožžon geat leat borran unnimus kolhydráhtaid ja eanemus proteiinnaid  ja vuolimus čuoggát (=2)  dát oasseváldit leat ožžon geat leat borran eanemus kolhydráhtaid ja unnimus proteiinnaid. Oassedutkamis 4 riska borasdávdabuohccivuođa ektui guorahallojuvvo brygg- ja vuoššangáffejuhkkiid  luhtte. Oassedutkan 5 lei goallostuvvon dárkkástus-dutkan, gos riska fáhkkatlaš healladávdda oažžut gáffejuhkkiid luhtte rehkenasto logistihkalaš eaktuduvvon regrešuvnna bokte. Sáhttá leahkit nu ahte buoiddes guolli lea rievtti mielde leamašan deaŧaleabbo sámiide go boazobiergu lulli Lapplánddas  1930-1950-logus ja badjeolbmot ain dávjábut borret dan go iežá sámiid ja ruoŧŧelaččat. Iežá sierra erenomášvuohta sámi biebmamis lei alit oassi buoiddis, mális ja vuoššangáfes ja vuolit oassi láibbis, fiberiin ja šaddaduvvon  šattuin (Oassedutkan 1). Stuora seammaláganvuođat árbevirolaš sámi biebmamiin, rievtti mielde alit Sami diet score čuoggát, ledje čatnon veahá aliduvvon jámolašvuhtii  dievdduid luhtte muhto ii fal nissoniid luhtte (Oassedutkan 2). Biebman mas vuolit oassi kolhydráhtaid ja alit oassi proteiinnat, rievtti mielde alit LHCP čuoggát, ii váikkuhan riskka jápmit, maŋŋel go lea statistihkalaččat jurddašan ahte buoiddi borrat ja mat dát leat dát sajáiduvvon riskafáktorat (Oassedutkan 3). Gáffejuhkan ii lean čatnon eaneduvvon borasdávdariskii, iige eaneduvvon riskii oažžut prostata- gassačoalleborasdávdda. Nissoniin mat juhke vuoššangáfe ≥ 4 geardde/beaivái lei geahpeduvvon riska oažžut čižžeborasdávdda go nissonat mat juhke <1 geardde/beaivái.  Ollesgáffe ja brygg-gáffe ledje čatnon eaneduvvon riskii oažžut čižžeborasdávddá nuorat nissoniid luhtte ja geahpeduvvon riskii vuorrasiin luhtte. Dievdduin mat juhke ollu vuoššangáfe lei eaneduvvon riska oažžut borasdávdda (Oassedutkan 4). Dievdduin mat juhke olu brygg-gáfe lei eaneduvvon riska oažžut healladávdda (Oassedutkan 5). Vuorrasit sámiid muitalusat man olu guoli sin vánhemat leat borran boazobierggu ektui 1930-1950-logus, čujuhit ahte bealit main alit kultuvrralaš mearkkašupmi eai dárbbaš seamma nanu objektivalš mearkkašumi atnit. Oassedutkamiid 2-5 bohtosat čujuhit ahte guorahallon bealit árbevirolaš sámi biebmamis ja eallinvuogis eai váikkut gárrasit dearvvašvuođa ja buohccivuođa dábálaš davviruoŧŧelaš ássiid luhtte.
(Lulesamiska) Dán guoradallama ájggom lij sáme biebmov ja viessomvuogev tsuojgodit, ja åtsådit gåk árbbedábak sáme bårråmdábe, stuoräládusebna juohkem ja káffajuhkam nuorttalándak álmmugin, bájnná jábmemav ja bårredávddabalov ja tsåhke-/ varravárredávddabalov. Guoktalågev sáme gatjádaláduvvin sijá äjgádij viessomvuoge ja biebmo birra 50-70 jage dán åvddåla (Oasseåtsålvis 1). Biebbmodáhtá 397 sámes ja 1842 láttes guoradaláduvvin parametragahtes gähttjalimij ja muhtem miere unnemus kvadráhta vuoge (PLS) viehkijn. Gålmmå tjuovvo oasseåtsådime, gájkka kohorttaåtsådime, vuolggin Västerbottena varresvuohtaåtsådimj oassálasstij jábmemårijs jali bårredávddaskihpudagájs (64 603-77 319). Ballamoarremerustallamav dahkin Cox regressionijn.  Oasseåtsådibme 2 spiedjildij avtaárvojt árbbedábak sáme biebmon tjuokkesmåhtajn nållå rájes gávtse tjuoggáj. Dat lahkke oassálasstijs gudi bårrin ienemus ruoppsis biergov, buojdes guolev, buojdev, muorjijt ja máleskáfav, oattjoj avtav tjuoggáv juohkka avta bårråmoases, aktan 5 tjuoggá ienemusát.  Ájn 3 tjuoggá oattjoj dat lahkke oassálasstijs mij båråj binnemus ruonudisájt, lájbijt ja fiberijt, aktan ienemusát 3 tjuoggá. Oasseåtsådibme 3 spiedjilt vidjurijt kolhydráhtaj ja proteijnaj gaskan biebmon nåv gåhtjodum LCHP (vuolle-kolhydráhta, alla-proteijna) tjuoggáj viehkijn.  Alemus LCHP tjuoggájt (=20) oadtjun oassálasste gudi binnemus kolhydráhtajt ja ienemus proteinajt bårrin ja vuolemus LCHP tjuoggájt (=2) oassálasste gudi ienemus kolhydráhtajt ja binnemus proteijnajt bårrin.  Oasseåtsådimen 4 åtsådaláduváj bårredávddaballo brygga- ja máleskáffajuhkkijn. Oasseåtsådibme 5 lij aktijdum guoradim-åtsådibme, gånnå káffajuhkkij tsåhkedávddaballo merustaláduváj aktijdam vihkemáhtsadime baktu. Vuordedahtek lij buojdes guolle ájnnasabbo gå boatsojbierggo sámijda oarjje Lapplándan 1930-1950-lågojn ja ájn vilá ällosáme guolev ienebut bårri gå ietjá sáme ja látte. Ietjá sierra merka sáme biebmon lij alep oasse buojdes, máles ja máleskáfas ja unnep oasse lájbes, fiberis ja sáddjidum ruonudisájs (Oasseåtsådibme 1). Árbbedábak sáme biebmo muoduk biebbmo, alep Sami diet score tjuoggáj, aktijaneduváj lasse jábmemijn sierraláhkáj ålmmåj hárráj (Oasseåtsådibme 2). Biebbmo vuolep kolhydráhttaåsijn ja alep proteijnnaåsijn, alla LCHP tjuoggáj, ittjij jábmembalov bájne, maŋŋel gå statistijkalattjat gehtjadam buojddebårråmijt ja ieme ballovidjurijt (Oasseåtsådibme 3).  Káffajuhkam lij tjanádum juogu de lasse gájkkásasj bårredávddaballuj, jali lasse prostáhta- bahtatjoallebårredávddaj. Kujnajn gudi máleskáfav juhkin ≥ niellji bäjvváj lij binnep njidtjebårredávddaballo gå buohtastahttá kujnaj gudi < akti bäjvváj juhkin. Ålleskáffa ja bryggakáffa tjanáduváj lasse njidtjebårredávddaballuj nuorap kujnaj hárráj ja binnep vuorrasappoj. Ålmmåjn gudi juhkin edna máleskáfav lij lasse bårredávddaballo vuojŋŋamorgánajn (Oasseåtsådibme 4). Ålmmåjn gudi juhkin edna bryggakáfav lij lasse tsåhkedávddaballo (Oasseåtsådibme 5). Vuorrasap sámij tsuojggoma äjgádij guollebårråmis gå buohtastahttá boatsojbierggobårråmijn 1930-1950-lågo, vuosedi biele alla kultuvrak sisanos e agev dárbaha sämmi nanos objektijvak sisanov adnet. Oasseåtsådimij 2-5 båhtusa vuosedi åtsådum biele árbbedábak sámebiebmos ja viessomvuoges e varresvuodav ja skihpudagáv nuorttalándak álmmuga hárráj heva bájne.
(Sydsamiska) Dan goerehtimmien ulmie lea saemien beapmoem jïh jielemevuekiem buerkiestidh jïh dotkedh guktie aerpievuekien saemien beapmoevuekieh, makrobïepmehtimmiej juekeme jïh prïhtjhjovhkeme jaemedem jïh riskem dijpieh vaajmoe-/ jïh soeneskïemtjelassen muhteste noerhtesvöörjen sïejhmi årroji luvnie. Lea göökteluhkie saemien voeresh goerehtamme daej eejtegi jielemevuekien jïh beapmoen dïehre  50-70 jaepiej juassah (Stuhtjedotkeme 1). Dïsse lissine lea beapmoedaatam goerehtamme 397 saemijste jïh 1842 laedtijste ov-parametrihken gïehtjedimmiej jïh partiellen unnemes kvadraaten vuekien mietie (PLS).  Dah golme båetien stuhtjedotkemh, gaajhkh kohortdotkemh, leah dotkeme man gaavhtan jaameme jallh mïetskeåedtjieskïemtjelassh daej luvnie gïeh meatan Västerbottenen healsoedotkemi muhteste (64 603-77 319 dotkemh) jïh riskeryøknemh  dorjeme Cox  regresjovnen viehkine. Stuhtjedotkemisnie 2 lea mohtedamme guktie aerpievuekien saemien beapmoe vaestede låhkoeraajterasse 0 raejeste 8 raajan. Daate bielie daejstie gïeh meatan gïeh jeenemes rööpses bearkoem, buajtehks gueliem, buejtiem, muerjieh jïh voessjemeprïhtjegem byöpmedamme, leah aktem låhkoem åådtjeme fïere guhte beapmoeelementen åvteste, jeenemes 5 låhkoeh. Dïsse lissine 3 låhkoeh åådtje daate bielie daejstie gïeh meatan gïeh unnemes kruanesaath, laejpiem jïh fiberh byöpmedamme, jeenemes 3 låhkoeh. Stuhtjedotkemisnie 3 daelie mohtede kolhydraath jïh proteinh beapmosne LHCP (vuelehks-kolhydraath, jïlle-proteine) låhkoej viehkine. Jillemes LHCP låhkoem åådtjeme (=20) dah gïeh meatan gïeh vaenemes kolhydraath jïh jeenemes proteinh byöpmedamme jïh vueliehkommes LHCP låhkoem (=2) åådtjeme dah gïeh meatan gïeh jeenemes kolhydraath jïh vaenemes proteinh byöpmedamme. Stuhtjedotkemisnie 4 riskem goerehtamme mietskeåedtjieskïemtjelassem åadtjodh brygg- jïh voessjemeprïhtjegejovhkiji luvnie. Stuhjtedotkeme 5 lïj tjetskeme-dotkeme gusnie riskem ryöknoe logistihken regresjovnen baaktoe jis maahta  faahketji vaajmoedåeriesmoerh åadtjodh prïhtjhjovhkiji luvnie. Buajtehks guelie meehti vihkielåbpoe årrodh båatsoesaemide goh bovtsebearkoe åarjel Lapplaantesne 1930-1950-låhkosne jïh daamhtah båatsoesaemieh daam byöpmedieh jeenebe goh jeatjah saemieh jïh laedtieh. Jeatjah sïejhmi sjïere vuekieh saemien beapmosne lea jïlle stuhtje buejteste,  maeleste jïh voessjemeprïhtjegistie jïh vuelie stuhtje laejpeste, fiberistie jïh kruanesaatijste (Stuhtjedotkeme 1). Jeenh saemien aerpievuekien beapmoe, jïlle Sami diet score låhkoeh, provhki vuesiehtidh vaenie jeananamme jaemede ålmaj gaskemsh bene ij nyjsenæjjaj gaskemsh (Stuhtjedotkeme 2). Beapmoe man vuelehks stuhtje kolhydraath jïh stoerre stuhtje proteijnh, jeenh LCHP låhkoeh, ij leah dïjpeme riskem jaemedh, dan mænggan goh lea ussjedamme statistihken muhteste man jeene buejtiem byöpmedidh jïh sijjiedahteme riskefaktovrh ussjedamme. (Stuhtjedotkeme 3). Prïhtjhjovhkeme ij leah tjoelmesovveme jeananamme mïetskeåedtjieriskese, jallh jeananamme riskese prostaate-voeresbuejtiemïetskeåedtjiem åadtjodh. Nyjsenæjjah gïeh voessjemeprïhtjegem jovhkeme ≥ 4 aejkien/biejjesne unnemes riskem utnin njammamïetskeåedtjiem åadtjodh nyjsenæjjaj muhteste gïeh jovhkeme <1 aejkien/biejjesne. Ellies prïhtjege jïh bryggeprïhtjege lea tjoelmesovveme jeananamme riskese njammamïestkeåedtjiem åadtjodh noere nyjsenæjjah luvnie jïh unniedamme riskem voeresi luvnie. Ålmah gïeh jeenh voessjemeprïhtjegem juvhkieh jeananamme riskem utnieh mïetskeåedtjiem åadtjodh girsesne (Stuhtjedotkeme 4). Ålmah gïeh jeenh bryggeprïhtjegem jovhkeme jeananamme riskem utnieh vaajmoedåeriesmoerem åadjtodh (Stuhtjedotkeme 5). Dah saemien voeresi soptsestimmieh man jeeneh gueliem daej eejtegh leah byöpmedamme bovtsebearkoem muhteste 1930-1950-låhkosne, vuesehte ahte daate bielie man vihkeles kultuvren sisvege ij eejnegen seamma objektiven sisvegem utnieh. Illeldahkh stuhtjedotkemijstie 2-5 vuesiehtieh ahte  dah bielieh mejtie lea goerehtamme saemien aerpienvuekien beapmoen jïh jielemevuekien muhteste eah healsoem jïh skïemtjelassem dïjph jeenebe goh sïejme noerhtesvöörjen årrojh.
(Umesamiska) Dahte guoreteme suptseste saamien beäpmoen jah jielemevuökien  biire jah giehtjedie guktie aarpievuökien saamien beäpmoeh, oajviebeäpmoeh jah kaavoeh mietete jaameke vahkake jah  cancerenne jah vajmoen/ virreveättennea nuorthen  allmetjeih luunie. Guökteluhke saamieih boariesh gihtjedihke lie elltie eihtegeh jielemevuökien jah beäpmoen biire dann baelie 50-70 jaapieh (Oasie 1). Jieneh beäpmoe-dataede dahkedihke lie 397 saamieiheste jah 1842 ruotseiheste dennake viehketihenne ieh parmetriske giehtjedemeh jah  partiellen unnemes kvadraten vuökien miete (PLS). Dah gullme oasieh boatien kohort- luhkemeh, allkemme lie jaamemeste jall canceremeste mieteih Västerbottenen varaasgiehtjemeih luunie (64603-77319 ollu) vahkake-tsiehkesjeme dahkedihke Cox-enne regressione. Oasienne 2 vuöjnedihke leh akte laakatjenne aarpievuökien saamien beäpmoeh vuösstede akte tsiehkesjerairoe 0 – 8. Dahte bielie deistie gieh jienemes ruöpses beärrkoede, buöjteks guöliede, buöjtiede borrein jah vuossjeme kaavoede juukein, akte tsiehkie fierte beäpmoih outeste otjoin, jienemes 5 tsiehkieh.Vielie 3 tsiehkieh dahte bielie otjoin gieh unnemes jaamoede jah urhtsede, laipiede jah fiberede borrein, jienemes 3 tsiehkeh. Oasienne 3 vuöjnedihke aktevuotta gasske kolhydrateh jah proteieneh beäpmoenne LCHP-esne (vuöleke kolhydrateh, jylloeke-proteineh) tsiehkie. Jyllemes LCHP tsiehkieh (=20) dainie mietenne unnemes kolhydrateh jah ollomes proteineh borrein jah unnemes LCHP tsiehkieh (2) dainie mietenne ollomes kolhydrateh jah unnemes proteineh borrein. Oasienne 4 giehtjedihke vahkake cancerede brygg- jah vuossjeme kaavoe juukejenne. Oasie 5 tjohkenne lin kontrolle- giehtjedeme vahkake hiehke vaajmoe-narrenne kaavoe-juukejenne tsiehkiesjdihke logistiske regressionenne. Buöjteke guölieh borretdihke mahtein vieliebe buutsebeärrkoeste saamieihesne oarrjel  saamien eätname 1930-1950 jaapienne jah vieliebe borretdihke buutsesaamieiheste guh jeätja saamieh jah ruotse-allmetjeh. Jeätja siejhme sierreme saamien beäpmoesne lin akte jylloeke oasie buöjtie-, viire-, jah vuossjeme kaavoeste jah akte vuöleke oasie laipie-, fibere-, joamoe jah urhtseste (Oasie 1). Ollu aktelaaka aarpievuökien saamien beäpmoeh, ollu Sami diet score tsiehkieh tjohkan lin vieliebe jaameme ollmaihenne sierrelaaka (oasie 2). Beäpmoihenne unne kolhydrateh jah ollu proteineh, ollu LCHP tsiehkie, ieh vahkake lasste jaamet, dann mingjelen guh statistiske ussjede valltedihke leh borremmiean gallane buöjtieste jah vihties vahkake faktoreiheste (oasie 3). Kaavoejuukeminne lin ieh vielebe aarpievuökien cancer-vahkake tjohkenne, jall vielebe vahkake prostate-kolorektale-cancere. Nyesenejah guh vuossjeme kaavoe juukein ≥4  aikieh/biejvie  unnebe vahkake nitje-cancereb lin muhteste nyesenejanneh gieh  <1 aikie/biejvie juukein. Gaihkekaavoe jah brygg-kaavoe lie tjoahkan vielebe nitje cancereb nyesenejanne jah unnebe vahkake boariesh nyesenejaihenne. Ollma guh ollu vuossjeme kaavoeb juukein cancereste gonkelmesenne vieliebe vahkake otjoin (oasie 4). Ollma guh ollu brygg-kaavoe vajmoe-narreme vieleb vahkake otjoin (oasie 5). Dah boariesh saamieh suptsestemeh man jingje guöliede elltie eihtegeh buutsebeärrkoeh borrein 1930-1950-aikie, vuösiete dahte bielie veäksekes kulture miele ieh gaihke aikie darpesjedennake veäksekes objektive miele leh. Oasie 2-5 vuösiete dah giehtjedemes dahte bielie aarpievuökien saamien beäpmoen jah jielemen vuökien ieh varaas jah skieptjeme mietete ieh nuorthen almetejeh ollu.

The aim of this thesis was to study the frequency of MS in the suggested high-risk area of Värmland county by investigating the current prevalence and analyzing the development over time; secondly to investigate some aetiological factors – the pattern of industry, both in relation to MS in Värmland and in the whole country, and also to examine the possible relation between the distribution of MS and ALS, as it has previously shown a positive correlation in two studies; finally to analyze the women-to-men ratio of MS in Sweden because of international reports of an increasing ratio. Clinical data was collected from hospitals and other health care units in the county of Värmland, to calculate the prevalence ratio. The prevalence was 170.07 per 100,000 population on the prevalence day, 31 December 2002. The incidence rates analysed during ten years was 6.46 per 100,000 personyears (1991-1995) and 6.39 (1996-2000). The ecological study used data from the beginning of the 20th century on industries in Värmland and in all Sweden, which were correlated with the two MS prevalence studies (1925-1934 and 2002), and the mortality study on the time period 1952-1990. There was a statistical significant association between large sawmills and the prevalence 1925-1934 (p = 0.022). For all Sweden, wood-pulp factories and papermills correlated significantly with MS mortality 1952-1990 (p = <0.05). Collected data from Causes of death Register and from the Total Population Register were used when analysing mortality from ALS and MS. The previously shown correlation between ALS and MS mortality distribution in the Swedish counties was not confirmed in this study. However, the mean MS mortality rate was still highest in the county in Värmland. The mean MS mortality rates for whole Sweden was increased from 1.65 per 100,000 person-years (1952-1992) to 2.04 (1990-2010). For analysing sex ratio in MS, data from the Swedish Multiple Sclerosis Register and data from Total Population Register of the Swedish Statistics Office were used. These data was analysed by birth day cohort and by year of onset. The sex ratios in Sweden showed a stable women-to-men ratio. These investigations give indication that Värmland is a high-risk region of multiple sclerosis, and particularly the municipality of Säffle. We conclude that Värmland is a suitable area for continued epidemiological studies with both an environment and genetic focus.

Purpose An age-cohort was studied with long-term follow-up. The population was born in 1915, living in the municipality of Skellefteå in 1981. The purpose was to investigate the prevalence and incidence of pseudoexfoliation (PEX), its influence on intraocular pressure (IOP) and development of open-angle glaucoma (OAG). Another purpose was to estimate the value of screening for glaucoma by comparing the screened group within the cohort with the remaining unscreened group. Methods In 1981, 339 (40%) of the 856 individuals in the cohort underwent an eye examination. This screened group was re-examined at seven-year intervals until 2002. At each visit the presence of PEX was registered, IOP was measured and the presence of glaucoma was assessed. After the 21-year follow-up period, glaucoma cases were also searched for in the medical records of the remaining unscreened individuals in the cohort. Proportions of glaucoma were compared between the two groups. Results The prevalence of PEX was 23% (95% confidence interval (CI): 20-26%) at the age of 66 and increased to 61% (CI: 50-71%) at the age of 87. The annual incidence of PEX was 1.8% (CI: 1.3-2.4%). The prevalence of OAG increased from 2.1% (CI: 0.8-4.3%) at the age of 66 years to 25 % (CI: 16-35%) at 87 years. The overall annual incidence of OAG was 0.9% (CI: 0.6-1.3%) and for OAG with PEX 2.1% (CI: 1.2-3.3%). PEX increased the risk of developing glaucoma at least four-fold. The incidence of diagnosed OAG in women was higher in the screened group than in the unscreened group (incidence rate ratio (IRR)=1.94, p=0.035). A corresponding difference could not be verified for men (p=0.58). The mean, agedependent, increase in IOP during the 21-year observation period was 0.05 mmHg/year. Conclusion The prevalence of PEX in this study population was the highest reported, and it increased with age. The presence of PEX increased the risk of developing OAG four times. In this study a higher proportion of OAG was revealed by screening among women but not among men. The age-related IOP increase was clinically insignificant.

Rickettsiae are obligate intracellular gram-negative bacteria transmitted by arthropod vectors. Rickettsiae sometimes cause disease in humans, typically with high fever, headache and occasionally an eschar. In Sweden, Rickettsia helvetica, belonging to the spotted fever group, is the only tick-transmitted rickettsia found free in nature. The pathogenic roll of R. helvetica has not been fully investigated, but it has been implicated in aneruptive fever and cardiac disease. This thesis describes parts of the transmission pathways of rickettsiae in Sweden. Rickettsia infection rates in ticks collected from birds were analysed, and the birds’ role as disseminators and reservoirs was studied. We found that more than one in ten ticks was infected with rickettsia bacteria, predominantly R. helvetica, and that migrating birds contribute not only to long-distance dispersion of bacteria, but also to an inflow of novel and potentially pathogenic rickettsia species, in this case R. monacensis and R. sp. strain Davousti-like species, into Sweden. Further, wild and domestic animals were found to have seroreactivity against R. helvetica, which shows that they are exposed and susceptible to rickettsia. Their role as reservoirs has not been determined, yet they may indirectly be involved in transmission of rickettsia to humans by infected ticks feeding on them. The seroreactivity in humans was also studied. Patients investigated for suspected Borrelioses and blood donors had detectable antibodies against Rickettsia spp., with the highest prevalence detected in the suspected Borreliosis group. This shows that humans in Sweden are exposed to and develop an immune response against rickettsia. The suspicion that R. helvetica may cause severe symptoms was verified by a patient with subacute meningitis where the bacterium was shown for the first time to cause an invasive infection with CNS involvement and where the bacterium was isolated from the patient’s cerebrospinal fluid. Growth characteristics and morphology of R. helvetica were studied to better understand invasiveness and virulence. The findings indicate that the invasiveness is comparable with other rickettsia, though R. helvetica seems to have a stable but slightly slower growth.  Rickettsia helvetica is endemic in Sweden and therefore needs to be considered when investigating disease after a tick bite.
Rickettsia är en liten, strikt intracellulär, gramnegativ bakterie som sprids med vektorer som fästingar, löss och loppor. Bakterien kan orsaka Rickettsios hos människa, en sjukdom där de vanligaste symtomen är hög feber, huvudvärk, muskelvärk och i vissa fall ett bettmärke (eschar). I Sverige är Rickettsia helvetica, som tillhör spotted fever gruppen (SFG), den enda fästingöverförda rickettsia bakterien som hittats allmänt i naturen. Patogeniciteten för R. helvetica är ofullständigt utredd, men ”aneruptive fever” och hjärtmuskelinflammation har rapporterats. Avhandlingen beskriver delar av smittkedjan för SFG rickettsia i Sverige. Bakteriernas förekomst i fästingar plockade från fåglar har studerats, likaså det ekologiska tryck som flyttfåglars bärarskap av infekterade fästingar bidrar med när de korsar olika världsdelar. Mer än var tionde fästing var infekterad med rickettsia bakterier, i huvudsak R. helvetica. Det visade sig att flyttfåglar bidrar inte bara till långväga spridning av bakterier utan även till införsel av nya potentiellt patogena rickettsiaarter, i detta fall identifierades R. monacensis och en R. sp strain Davousti liknande art. Vidare analyserades seroreaktivitet mot Rickettsia helvetica hos både tamdjur och vilda djur, vilket visade på antikroppsutveckling, som uttryck för smittexposition, i mer än vart femte djur. Djurens roll som reservoar för bakterien är inte klarlagd, men oavsett är djuren indirekt involverade i spridningen av bakterien till människa via infekterade fästingar som suger blod. Seroreaktivitet hos människa har också studerats. Patienter, provtagna på grund av misstanke om borreliainfektion, samt blodgivare hade detekterbara antikroppar mot Rickettsiae, med högst prevalens i gruppen med misstänkt borreliainfektion. Fynden visar att människor i Sverige är exponerade för och utvecklar en immunreaktion mot rickettsia. Att R. helvetica skulle kunna ge allvarlig sjukdom verifieras av ett patientfall med subakut meningit där bakterien för första gången visats ge invasiv infektion med påverkan på nervsystemet (CNS engagemang) och där bakterien isolerats från patientens ryggmärgsvätska.  Morfologi och tillväxtegenskaper för R. helvetica undersöktes för att bättre förstå bakteriens invasivitet och virulens. Fynden indikerar att invasiviteten är jämförbar med andra rickettsiaarter men R. helvetica verkar ha en stabil men något långsammare tillväxt. Rickettsia helvetica är endemisk i Sverige och måste tas i beaktande vid sjukdomsutredning efter ett fästingbett.

The epidemiology of urinary tract infection (UTI) in the population of Vännäs (8 000 inhabitants) was studied during one year. The annual incidence increased from 0.5% in the first decade of life to more than 10% in the age group 90-100 years. Male UTI comprised only 13% of the episodes, increased after middle age and contributed 4 0% by > 80 years of age. At 17 PHC centres (PHCCs) a prevalence study (McPHC) of mainly uncomplicated UTI was performed. Most episodes were acutely symptomatic (lower 75%, upper 5%). Microscopy of wet-stained urinary sediment with a minimum of moderate amount of bacteria and/or 5 leukocytes per high power field (4 00 x) as breakpoint resulted in a desired high sensitivity (97%) and 86% efficacy in acutely symptomatic patients. Diagnosis of bacteriuria using Uricult dipslides yielded acceptable results with an overall efficacy of 88%. Nitrite test and Uriglox showed an unacceptable low mean sensitivity ofR56 and 69%, respectively. A positive nitrite, sediment or Uricult , when used in combination, was optimal in diagnosing UTI with a sensitivity of 98% in acutely symptomatic patients during their office visits. The average risk of drug resistance was 17% in the Vännäs study. Sensicult satisfactorily predicted drug sensitivity (93%) but not bacterial drug resistance (50%). Using Uricult with classification of bacteriuria by Gram-grouping, lactose and catalase reactions for targeting UTI therapy, according to local guidelines, resulted in a similar low risk (6 %) of prescribing drugs to which the organisms were resistagt as when using Sensicult (7%). This development of the Uricult method is simple and can be recommended for office practice in PHC. The spectrum of bacteria causing UTI and their drug resistance was more associated with the selection of patients, sex and age than with symptoms. The pattern of drug resistance was little influenced by UTI history and the mean pretherapy resistance for the seven drugs tested in McPHC was low (7%). Drug resistance was increased in failure (mean 24%) but not in early or repeated recurrence. In McPHC therapy resulted in 8% bacteriological failure and 12% early recurrence, irrespective of whether the bacteria were classified as sensitive or resistant in vitro to the drug given. Thus, in order to be of prognostic value for therapy of uncomplicated UTI, high-level breakpoints focusing more on peak urinary drug concentrations need to be studied. UTI symptoms in McPHC were eradicated in only 2/3 of the bacterio- logically cured episodes and in 1/3 of the failures at control 1-3 days posttherapy showing that symptoms are an unreliable indicator of UTI. From current literature, it seems unlikely that asymptomatic bacteriuria (ABU) plays a major role in the development of uremia due to chronic pyelonephritis. With the exception of ABU in pregnancy, therapy seems to yield no benefit. Omitting posttherapy bacteriuria controls in patients with symptoms eradicated, at least in women with uncomplicated UTI, would lead to considerable savings both for patients and the health care system.

Diss. (sammanfattning) Umeå : Umeå universitet, 1988, härtill 6 uppsatser.

digitalisering@umu

Dogslife is the first large-scale, longitudinal cohort study of canine lifestyle, morphology and health. The project involves recruiting the owners of UK-based, Kennel Club registered Labrador Retrievers and asking them to submit data about their dogs via an online questionnaire repeatedly as the dogs age. In this thesis, I have analysed Dogslife data regarding the lifestyle, morphology and health of Labrador Retrievers up to four years of age. A validation study was initially undertaken in order to understand the quality of the Dogslife data because this would underlie all future investigations. Owners were visited and veterinary records scrutinised. It was determined that Dogslife illness reports were subject to recall decay and that minor changes would improve the usability of the questionnaire. Accelerometers were subsequently sent to a subset of the cohort and aspects of the Dogslife exercise questionnaire were found to be correlated to accelerometer readings indicative of sedentary, light and moderate to vigorous exercise. Overall, Dogslife dogs were exercised for over two hours each day with the time spent being dominated by time off lead and on other activities. Dogs in England spent less time exercising than those in Scotland and Wales and dogs in family households spent less time exercising than those in single adult households or households comprising more than one adult. Despite being pedigree animals, the males in the cohort were 2-3cm taller than the breed standard. On average, the females met the breed standard but there was wide variation for both sexes. Working dogs in the cohort were over 2kg lighter than household pets and chocolate coloured dogs were 1.4kg heavier than their black and yellow counterparts. Dogs in multi-dog households were 0.5kg lighter than those in households with no other dog. Heavier dogs spent less time fetching, chasing and retrieving and on other exercise. Over 6,000 signs of illness were reported to Dogslife in the first three and half years and approximately half of them did not involve a veterinary visit. Reported signs were dominated by vomiting and diarrhoea, both of which peaked when the dogs were between 3-6 months of age. For the first time, rates of diarrhoea were shown to be positively associated with human population density in the UK. Limber tail was found to be associated with swimming in the cohort and working dogs were more likely to develop the condition than pets. Genetic analyses identified regions of interest that might predispose the dogs to limber tail on chromosomes 6 and 30. Data from the Dogslife project provide a unique resource for investigating the epidemiology of Labrador Retrievers. This thesis creates a platform for all such future investigations.

The overall aim of this thesis was to investigate pregnancy and childbirth in women with intellectual disability (ID), in Sweden, the health of their newborns and midwifery care for these women. Two register studies and two descriptive studies are included. Pregnancy and birth outcomes as well as data on the newborns’ health were examined by linking data from the National Patient Register and the Medical Birth Register (I-II). The women’s experience of pregnancy and delivery was investigated with repeated interviews (III). Midwives’ knowledge of, experience of and attitudes towards pregnancy and childbirth in women with ID were evaluated with questionnaires (IV). Mothers with ID were more often teenagers, smoked more during pregnancy and had more Caesarean Sections. Their children had a higher proportion of pre-term births, were small-for-gestational-age, stillborn or died in the perinatal period. The women with ID struggled to attain motherhood and feared to lose custody of the child. The pregnancy was seen as a happy event, even though relatives did not always approve. Parent education was considered important, but not adequately adapted to their needs. The birth process was overwhelming and difficult to understand, but the child was welcomed with warm feelings, and breastfeeding was natural. Midwives stated it was different to care for women with ID and requested additional knowledge. The majority of midwives affirmed that women with ID could not manage the mother role satisfactorily, and one-third expressed that women with ID should refrain from having children. A majority of the midwives considered that the children should grow up with the parents with support from family and society, but one out of five stated that the children should grow up in foster care. Conclusion: Women with ID and their children should be considered as risk groups in pregnancy and childbirth. Professionals in maternity services need to elucidate their knowledge and skills for counselling and supporting this particular group of pregnant women in pre-, intra- and post-partum care.

Introduction: A median of 15% of the burden of chronic obstructive pulmonary disease (COPD) may relate to harmful occupational exposures. Much of this data however relates to populations studied outside the UK. The primary aim of this research was to assess the population attributable risk (PAR%) of developing COPD from workplace exposures using a Sheffield based epidemiological study. Methods: 4,000 Sheffield residents were sent postal questionnaires enquiring about respiratory symptoms and chronic respiratory illnesses, smoking status and occupations along with self-reported exposures in the workplace to a variety of different substances including vapours, gases, dusts and fumes (VGDF). A second group were targeted through a hospital department to enrich the study population with cases of COPD. Certain study subgroups were then approached for a quality of life assessment (EQ-5D) and spirometry. Odds ratios and PAR% were then calculated for a range of definitions of COPD and occupational exposures. Results: 2001 postal questionnaires were returned, with 60 from the hospital sample. The mean age was 69.3 years and 48.5% respondents were male. Using a broad definition of COPD (including chronic bronchitis), the adjusted PAR% for ever exposure to VGDF as a contributing factor to COPD development was 58.7%. This reduced to 30.8% using a job exposure matrix as a marker of occupational exposures. Results from the EQ-5D showed those with COPD had a reduced quality of life as compared to those without, and this reduced further in the group exposed to VGDF. Conclusions: Data from this study supports the findings from other international studies, namely exposure to potentially harmful substances at work is associated with increased risk of developing COPD. There is also evidence of an interaction with smoking to potentiate this risk. As such, priority should be given to reducing all harmful workplace exposures to reduce future COPD burden.

Abstract Age-related hearing impairment is the most common type of hearing impairment among adults. Adult-onset hearing impairment is one of the leading causes of disease burden worldwide and it is associated with social isolation and depression. As the proportion of older people is increasing in Western countries, the socioeconomic importance of adult hearing impairment will increase notably. The aim of the present contribution was to study the epidemiological aspects of hearing and related factors among older adults. The prevalence of hearing impairment, defined either by audiometry or by a self-report, and the differences between these two were analyzed. Tinnitus and hyperacusis were also studied. Furthermore, the prevalence of ear diseases, otological risk factors, and noise exposure and their association with hearing thresholds were analyzed. In addition, audiogram configurations and certain subject-related factors and their relation to hearing were assessed. The subjects were randomly sampled from the population register and they responded to an extensive questionnaire. Otological status was examined and pure tone audiometry was conducted. Data on 850 subjects aged 54–66 years were analyzed. Hearing impairment was found to be a highly common condition with a prevalence of 26.7% when defined by better ear and 42.2% when defined by worse ear. Men had worse hearing than women. High-frequency sloping audiogram configurations were common. Self-reported hearing difficulty and measured hearing impairment seem to be associated at high frequencies. At least one ear disease or otological risk factor for hearing impairment was found among 18.4% of the subjects and noise exposure among 46%, more often by men. Interestingly, noise exposure did not seem to associate with hearing levels among subjects screened for ear disease or otological risk factors. The results of the present study suggest that hearing impairment is a highly common condition among older adults and this should be taken into account when future hearing healthcare is planned. Furthermore, it seems that most of the subjects reporting hearing difficulty had no measured hearing impairment according to the criteria applied for eligibility for hearing aid fitting in Finland. Based on the results of the present study, the criteria for hearing impairment entitling persons for hearing aid fitting should be reconsidered
Tiivistelmä Ikäkuulo on yleisin aikuisten kuulovian aiheuttaja, ja aikuisiän kuulovika on merkittävä terveydellinen haittatekijä. Kehittyneiden maiden ikäjakauman painottuessa vanhempiin ikäluokkiin aikuisten kuulovioista tulee merkittävä sosioekonominen rasite yhteiskunnille. Tutkimuksen tavoitteena oli selvittää aikuisten kuulovikojen epidemiologiaa ja kuulovikoihin liittyviä tekijöitä. Myös kuulovian vallitsevuus määriteltynä kuulokäyrän tai tutkittavan oman ilmoituksen perusteella selvitettiin. Samoin tutkittiin muita kuulemiseen liittyviä ongelmia, kuten tinnitusta ja ääniyliherkkyyttä. Edelleen arvioitiin erilaisten kuuloon vaikuttavien tekijöiden, kuten korvasairauksien, muiden kuulovian riskitekijöiden ja melulle altistumisen, vallitsevuutta väestössä sekä niiden assosiaatiota kuulemiseen. Näiden lisäksi tutkittiin kuulokäyrien muotoja ja niiden yhteyttä tutkittavan ilmoittamaan kuulo-ongelmaan. Tutkittavat valittiin satunnaisesti väestörekisteristä. He täyttivät laajan kyselylomakkeen, heidän korvansa tutkittiin lääkärin vastaanotolla ja lisäksi heille tehtiin kuulotutkimukset. Tutkimukseen osallistui 850 55–66-vuotiasta henkilöä. Tutkimus osoitti, että kuulovika on tässä ikäryhmässä hyvin yleinen löydös ja miehillä yleisempi kuin naisilla. Tutkittavan ilmoittama kuulovika ennusti mitattujen kuulokynnysten heikkenemistä korkeilla taajuuksilla (4–8 kHz). Samoin korkeille taajuuksille laskeva kuulokäyrän muoto oli yleisin. Erilaisia kuulovian riskitekijöitä raportoi 18.4 % tutkittavista. Tämän lisäksi 46 % kertoi merkittävästä altistumisesta melulle, miehet naisia useammin. Yllättäen melualtistumisella ei näyttänyt olevan yhteyttä kuulokynnyksiin siinä ryhmässä tutkittavia, joilla ei ollut korvaperäisiä riskitekijöitä kuulovialle. Tutkimustulokset osoittavat, että kuulovika on hyvin yleinen löydös tämän ikäisillä aikuisilla. Vanhenevat ikäluokat ovat merkittävä haaste kuulonhuollolle, ja tämä olisi otettava huomioon päätettäessä kuulonhuollon rahoituksesta. Useat niistä aikuisista, jotka kokivat kuulo-ongelmia, eivät kuulokäyrälöydöksensä mukaan täyttäneet Suomessa käytössä olevia kriteereitä kuulokojesovitukselle. Tämän tutkimuksen perusteella näyttääkin siltä, että kuntoutustarvetta arvioitaessa kuulovian kriteereitä tulisi kansallisesti tarkistaa ottamalla huomioon myös huonomman korvan kuulokynnykset sekä kuulon alenema korkeilla taajuuksilla

Abstract Background: Autism spectrum disorders (ASDs), defined as pervasive developmental disorders (PDDs) in DSM-IV and ICD-10, become manifest in childhood, ranging from a severe form, autism, to milder forms, Asperger syndrome (AS) and pervasive developmental disorder not otherwise specified (PDD-NOS)/atypical autism. AS is also specified in criteria by Gillberg and by Szatmari et al. Different diagnostic criteria sets, overlaps, inaccuracies and exclusion criteria of many comorbid psychiatric disorders in PDDs have caused confusion. In DSM-5, PDDs were replaced by one diagnosis called ASD. Aims and methods: This is an epidemiological study of 8-year-old children and a clinical study of 9- to 16-year-old high-functioning outpatients with AS/autism (HFA). The epidemiological target population (n = 4,422) was rated via the Autism Spectrum Screening Questionnaire (ASSQ) by parents and/or teachers and a screened sample was examined in order to estimate the prevalence of ASDs, to discover deficits in the diagnostic criteria of ASDs, to evaluate DSM-5 draft criteria for ASD, and to assess cut-off scores for the Finnish ASSQ. Comorbid psychiatric disorders were identified and overall level of functioning rated in 50 subjects with AS/HFA. Results: The prevalence of AS according to DSM-IV was 2.5, to ICD-10 2.9, to Gillberg 2.7, and to Szatmari et al. 1.6 per 1,000. The prevalence of autism was 4.1 and that of ASDs 8.4 per 1,000 (DSM-IV). DSM-5 draft criteria were less sensitive in detecting AS/HFA. For 7- to 12-year-old children (IQ ≥ 50), the optimal cut-off scores were 30 in clinical settings and 28 in total population screening using summed parent-rated and teacher-rated ASSQ scores. Comorbid psychiatric disorders were common (prevalence 74%) and often multiple; behavioral disorders in 44%, anxiety disorders in 42%, and tic disorders in 26%. Oppositional defiant disorder, depressive disorder and anxiety disorders as comorbidities indicated significantly lower levels of functioning. Conclusions: Our results indicate the need to standardize the diagnostic criteria. The ICD-11 criteria should be uniform and harmonize with DSM-5. Determining cut-off scores for ASD screening instruments in different languages and cultures is of utmost importance. Clinicians are reminded to investigate psychiatric comorbidity in ASDs in order to target treatment and rehabilitation precisely
Tiivistelmä Lähtökohdat: Autismikirjon häiriöt, ICD-10:ssä ja DSM-IV:ssä nimellä laaja-alaiset kehityshäiriöt, ilmenevät lapsuudessa. Niihin luetaan autismi, Aspergerin oireyhtymä (AS) ja tarkemmin määrittelemätön laaja-alainen kehityshäiriö/epätyypillinen autismi. Gillberg sekä Szatmari työtovereineen ovat myös määritelleet AS:n kriteerit. Useat diagnostiset kriteerit, päällekkäisyydet, epätarkkuudet ja monien psykiatristen liitännäishäiriöiden poissulkeminen laaja-alaisissa kehityshäiriöissä ovat aiheuttaneet sekaannuksia. DSM-5:ssä laaja-alaiset kehityshäiriöt korvattiin yhdellä diagnoosilla: autismikirjon häiriö. Menelmät ja tavoitteet: Väitöstyö muodostui 8-vuotiaita lapsia koskeneesta epidemiologisesta tutkimuksesta sekä 9–16-vuotiaita AS- ja autistisia (HFA) lapsia ja nuoria koskeneesta kliinisestä tutkimuksesta. Vanhemmat ja/tai opettajat täyttivät epidemiologisen kohderyhmän lapsista (n = 4 422) suomennetun autismikirjon seulontalomakkeen (ASSQ), ja seuloutuneille tehtiin diagnostiset tutkimukset. Tämän jälkeen määritettiin autismikirjon esiintyvyys, kartoitettiin diagnostisten kriteerien puutteita, arvioitiin DSM-5-luonnoskriteerit autismikirjon häiriölle ja määritettiin ASSQ:n seulontarajat. Psykiatrinen komorbiditeetti ja sen merkitys toiminnalliseen tasoon tutkittiin AS-/HFA-lapsilla ja -nuorilla (n = 50). Tulokset: AS:n esiintyvyys oli 2,5/1000 DSM-IV:n, 2,9/1000 ICD-10:n, 2,7/1000 Gillbergin ja 1,6/1000 Szatmarin mukaan. Autismin esiintyvyys oli 4,1/1000 ja koko autismikirjon 8,4/1000 (DSM-IV). DSM-5-luonnoskriteerit olivat epäherkät tunnistamaan AS:ää ja HFA:ta. Parhaiten soveltuviksi ASSQ:n seulontarajoiksi alakouluikäisille (ÄO ≥ 50) osoittautuivat 30 kliinisiä tilanteita ja 28 väestöseulontoja varten laskemalla yhteen vanhempien arvioinnin ja opettajan arvioinnin pisteet. Psykiatrisia liitännäishäiriöitä oli 74 %:lla, ja monilla oli useita. Käytöshäiriöitä oli 44 %:lla, ahdistuneisuushäiriöitä 42 %:lla ja tic-häiriöitä 26 %:lla. Uhmakkuus- ja masennushäiriö sekä ahdistuneisuushäiriöt alensivat merkitsevästi toiminnallista tasoa. Päätelmät: Tulokset osoittivat diagnostisten kriteereiden yhtenäistämistarpeen. ICD-11:een on syytä laatia yhdenmukaiset kriteerit DSM-5:n kanssa. Autismikirjon seulontalomakkeille on tarpeen määrittää eri kieliin ja kulttuureihin soveltuvat pisterajat. Psykiatrisen komorbiditeetin selvittäminen autismikirjon häiriöissä on tärkeää, jotta hoito ja kuntoutus voidaan kohdentaa oikein

Magister Scientiae (Medical Bioscience) - MSc(MBS)
The aim of this study was to determine and evaluate the prevalence of TB infection, active TB cases and the risk factors associated with TB infection in Macassar Camp in Macassar (about 40 km from Cape Town on the False Bay coast, with a population of 369). The study design of this epidemiological study was a cross sectional study with a descriptive and an analytic component A comparison between the Mantoux, TB ELISA and X-ray screening tests was performed first. A description of the origin, discovery, characteristics and pathology associated with Mycobacterium tuberculosis as well as the development of the TB epidemic on a global, national and local level, is given. TB was first described to give a South African perspective of the TB epidemic and both the "Virgin Soil" and "Non-Virgin Soil" theory of TB was reviewed. Secondly, ~he TB infection rate in Macassar Camp and the risk factors as well as the determinants of TB infection with regards to overcrowding, ventilation, primary food subsistence level rating (PFSL), social class and employment status were evaluated The third aspect of the study compares prevalence/incidence rates of TB to clinical diagnosis with regards to the symptomatology, radiographs, sputum microscopy, bacteriology and Mantoux test. Lastly the Mantoux test was compared with the TB ELISA test with regards to diagnosis of infection, in new and past confirmed TB cases. The first part of the survey involved the measurement of openable window area and the floor area of each Camp dwelling (to determine if ventilation was within required limits), during the administration of a household questionnaire which was designed to determine the number of occupants, rooms, income, food expenditure per household in the Camp. A personal questionnaire was administered to all Macassar Camp residents to elicit information on demography, knowledge and attitudes to TB, history of past TB, TB contacts, alcohol intake and smoking habits, occupation and BCG status. The Mantoux test were performed on consenting Camp residents in addition to the collection of 5 ml of blood for the TB ELISA tests. The Camp residents heights and weights were recorded prior to the miniature mass chest radiographs being taken. The 'TB suspects' sputa were collected for the microscopy and bacteriological examination. A review of the clinical records of TB patients in the Macassar/Stellenbosch area was also undertaken. The response rate to the household questionnaire was 60 from 63 (95,2%) dwelling units. Whereas the response rate to the personal questionnaire was 296 (80,2%). As for the Mantoux and TB ELISA tests the response rate was 209 (56,6%). Of the 60 dwelling units, 43 (71,7%) were calculated (according to . Batsons Index) to be crowded and 16 (26,7%) dwelling units had an overall ventilation of less than 5% (below the required regulation). There were significantly (p<0,005) more male than female smokers and only 78 (34,2%) of the residents regarded themselves as non-smokers. A similar trend was noted with regards to the alcohol intake of the residents, where only 86 (37,7%) regarded themselves as teetotallers, with significantly more (p=0,003) male than female alcohol consumers. Females sc6red significantly (p=0,002) better than the males with regards to TB knowledge and awareness. Only 199 (67,2%), residents indicated that they had had BeG vaccination. Of the 296 residents responding to the survey, there were 83 children aged 14 years or less. And only 74 of these children were confirmed to have been vaccinated with BeG, resulting in a 89,2% BeG coverage. Two (4,7%) of the 43 children aged 14 years or less were determined to be malnourished on the basis of Z-scores (below -2SD) taking into account height for age as well as weight for height.

This paper seeks to find whether the spectrum auctions in Sweden have been conducted efficiently and if there is a de facto model that suits all auctions. The efficiency is conditions that emphasise truthful bidding, price discovery and limits collusive behaviour. The paper compares three different auction models used in Sweden, a beauty contest used in the allocation of 3G spectrums, and the auction model selected for the upcoming 5G spectrum auction. The auction models are as follows: first and second-price sealed-bid auction, SMRA and CCA. We found that beauty contests should not be used in any spectrum allocation as it did not meet the criteria of efficiency outlined in this paper. The first-price sealed-bid auction is not a suitable format for spectrum auctions. According to the theory, it generates equivalent revenues on average as the second-price format, which shows a higher degree of efficient allocation. We found that depending on the blocks sold, both SMRA and CCA can result in somewhat efficient results, but they are not suitable for a single object auction. We found that no de facto auction format is suitable for every spectrum auction to be conducted in the future, but instead that the auction format is dependent on the characteristics of the individual auctions.

INTRODUCTION: Epidemiological transition theory, first postulated by Omran in 1971, provides a useful framework for understanding cause-specific mortality changes and may contribute usefully to predictions about cause-specific mortality. However, understandings of mortality transitions and associated epidemiological changes remain poorly defined for public health practitioners due to lack of evidence from low- and middle-income countries. Therefore, understanding of the concept and development of epidemiological transition theory as well as population burden of premature mortality attributable to risk factors is needed. OBJECTIVES: This thesis aims to understand how epidemiological transition theory has been applied in different contexts, using available evidence on mortality transitions from high, middle- and low- income countries, as well as the contribution of risk factors to mortality transitions, particularly for premature mortality. METHODS: A Medline literature search from 1971 to 2013 was conducted to synthesise published evidence on mortality transition (paper I). A descriptive analysis of trends in cause of death using INDEPTH data was conducted, focusing on specific causes of death in 12 INDEPTH sites in Africa and Asia, using the INDEPTH 2013 standard population structure for appropriate comparisons across sites (paper II). A retrospective dynamic cohort database was constructed from Swedish population registers for the age range 30-69 years during 1991-2006, to measure reductions in premature non-communicable disease mortality using a life table method (paper III). Prospective cohort data from Västerbotten Intervention Programme from 1990 to 2006 were used to measure the magnitude of premature non-communicable disease mortality reductions associated with risk factor changes for each period of time (paper IV). FINDINGS: There were changes in emphasis in research on epidemiological transition over the four decades from 1971 to 2013, from cause of death to wide-ranging aspects of the determinants of mortality with increasing research interests in low-and middle-income countries, with some unconsidered aspects of social determinants contributing to deviations from classic theoretical pathways. Mortality rates declined in most sites, with the annual reductions in premature adult mortality varied across INDEPTH sites, Sweden, which now is at late stage of epidemiological transition stage, achieved a 25% reduction in premature mortality during 1991-2006. Overall downward trends in risk factors have helped to reduce premature mortality in the population of Västerbotten County, but some benefits were offset by other increasing risks. The largest mortality changes accrued from reductions in smoking, hypertension and hypercholesterolaemia. CONCLUSIONS: This thesis established patterns of current epidemiological transition in high, middle-and low-income countries (Asia and Africa), where the theory fits the transition patterns in some countries, but with some needs for further adjustments in other settings, as well as deviations from the classical ET theory in the last four decades. It highlights the need to identify the burden of mortality and morbidity, particularly for reducing mortality occurring before the age of 70 years and its attribution to risk factors, which are a major public health challenge. This informs shifting of public health priorities and resources towards prevention and control of chronic non-communicable disease risk factors.

The goal of this dissertation is to characterize the distribution and determinants of coccidioidomycosis in greater Tucson, Arizona, using landscape ecology and complex survey methods to control for environmental factors that affect Coccidioides exposure. Notifiable coccidioidomycosis cases reported to the health department in Arizona have dramatically increased since 1997 and indicate a potential epidemic of unknown causes. Epidemic determination is confounded by concurrent changes in notifiable disease reporting-compliance, misdiagnosis, and changing demographics of susceptible populations. A stratified, two-stage, address-based telephone survey of greater Tucson, Arizona, was conducted in 2002 and 2003. Subjects were recruited from direct marketing data by census block groups and landscape strata as determined using a geographic information system (GIS). Subjects were interviewed about potential risk factors. Address-level state health department notifiable-disease surveillance data were compared with self-reported survey data to estimate the true disease frequency.Comparing state surveillance data with the survey data, no coccidioidomycosis epidemic was detectable from 1992 to 2006 after adjusting surveillance data for reporting compliance. State health department surveillance reported only 20% of the probable reportable cases in 2001.Utilizing survey data and geographic coding, it was observed that spatial and temporal disease frequency was highly variable at the census block-group scale and indicates that localized soil disturbance events are a major group-level risk factor. Poststratification by 2000 census demographic data adjusted for selection bias into the survey and response rate. Being Hispanic showed similar odds ratio of self-reporting coccidioidomycosis diagnosis as of being non-Hispanic White race-ethnicity when controlled by other risk factors. Cigarette smoking in the home and having a home located in the low Hispanic foothills and low Hispanic riparian strata were associated with elevated risk of odds ratios for coccidioidomycosis. Sample stratification by landscape and demographics controlled for differential classification of susceptibility and exposures between strata.Clustered, address-based telephone surveys provide a feasible and valid method to recruit populations from address-based lists by using a GIS to design a survey and population survey statistical methods for the analysis. Notifiable coccidioidomycosis case surveillance can be improved by including reporting compliance in the analysis. Pathogen exposures and host susceptibility are important predictable group-level determinants of coccidioidomycosis that were controlled by stratified sampling using a landscape ecology approach.

Placental function is central for normal pregnancy and in many of the major pregnancy disorders. We used magnetic resonance imaging techniques to investigate placental function in normal pregnancy, in early and late preeclampsia and in intrauterine growth restriction. We also investigated maternal body mass index and height, as risk factors for preeclampsia. A high body mass index and a short maternal stature increase the risk of preeclampsia, of all severities. The association seems especially strong between short stature and early preeclampsia, and a high body mass index and late preeclampsia. (Study I) Using diffusion-weighted magnetic resonance imaging, we found that the placental perfusion fraction decreases with increasing gestational age in normal pregnancy. Also, the placental perfusion fraction is smaller in early preeclampsia, and larger in late preeclampsia, compared with normal pregnancies. That these differences are in opposite directions, suggests that there are differences in the underlying pathophysiology of early and late preeclampsia. (Study II) Using magnetic resonance spectroscopy, we found that the phosphodiester spectral intensity fraction and the phosphodiester/phosphomonoester spectral intensity ratio increases with increasing gestational age. Also, we found that the phosphodiester spectral intensity fraction and the phosphodiester/phosphomonoester spectral intensity ratio are higher in early preeclampsia, compared with early normal pregnancy. These findings indicate increased apoptosis with increasing gestational age in normal pregnancy, and increased apoptosis in early preeclampsia. (Study III) The placental perfusion fraction is smaller in intrauterine growth restriction than in normal pregnancy. Fetal growth, Doppler blood flow in maternal and fetal vessels, infant birth weight and plasma markers of placental function are all correlated to the placental perfusion fraction. The placental perfusion fraction examination seems therefore to offer a fast, direct estimate of the degree of placental dysfunction. (Study IV) In conclusion: Our findings in studies I-III all support the hypothesis of partly different pathophysiology between early and late preeclampsia, and suggest a strong link between early preeclampsia and placental dysfunction. Study IV shows that the placental perfusion fraction has potential to contribute to the clinical assessment of placental dysfunction.