Uppsala University Hospital Research Articles

A case–control study of risk factors for urinary acquisition of Klebsiella pneumoniae producing CTX-M-15 in an outbreak situation in Sweden

A retrospective case-control study was initiated at Uppsala University Hospital in 2006 during a major outbreak caused by a Klebsiella pneumoniae strain producing CTX-M-15. To identify risk factors associated with acquisition of the outbreak strain in the urinary tract, 52 case patients with a urine culture positive for the outbreak strain between 1 May and 31 December 2005 were enrolled. Case patients were matched 1:2 with concurrently hospitalized control patients with significant growth of susceptible Escherichia coli in a urine sample. Conditional logistic regression analyses identified hospital stay >or=9 days (odds ratio (OR) 18.8, 95% confidence interval (CI) 5.74-61.2), nasogastric feeding tube (OR 18.0, 95% CI 2.28-142) and diarrhoea (OR 9.62, 95% CI 3.30-28.1) as risk factors with high ORs. The odds of previous use of cephalosporins were 7.58 (95% CI 3.13-18.4) times higher in case patients compared with the controls. Several multivariable models were evaluated to reduce bias from confounding. These models identified prolonged period of hospitalization, diarrhoea, malignancy and antibiotic use as the most important risk factors for acquisition of the outbreak strain, factors that are often found in elderly patients with a poor functional status.

Large differences in levodopa dose requirement in Parkinson’s disease: men use higher doses than women

The characteristics of levodopa dosing are not well described in the literature. The aims were to investigate the use of levodopa in a nationwide Swedish survey and to study the characteristics of low-dose and high-dose patients with Parkinson's disease (PD) in a university hospital. Patients with >or= 1 and >or= 2 purchases of levodopa during 2007 were selected from the prescribed drug register. Daily levodopa doses were estimated. Records of 504 patients with PD who visited the neurology clinic at Uppsala University Hospital during 2006-2007 were examined to select a low-dose group (< or = 400 mg levodopa daily, n = 21) and a high-dose group (>or= 1200 mg daily, n = 26) with at least 5 years of PD duration. In total, 33 534 levodopa users with > or = 1 levodopa purchase were found. Daily levodopa dose range was large; median daily dose was 465 mg for men and 395 mg for women (P < 0.0001). Almost half (46%) of the patients used < 400 mg levodopa daily. Significantly, more men were treated with doses >or= 1200 mg daily. Dose and age correlated negatively (P < 0.0001). Patients with high dose at 5 years PD duration continuously increased their dosage the following years, whereas low-dose patients did not. The occurrence of dyskinesias was about the same in both groups despite the large difference in levodopa dose. We conclude that the levodopa requirement in PD ranges considerably, and that men use higher levodopa dose than women. Levodopa requirement is constant during the progression of the disease in low-dose patients but increases in high-dose patients.

Fibrinogen and histidine‐rich glycoprotein in early‐onset preeclampsia

To determine whether plasma levels of fibrinogen and the placental tissue distributions of fibrinogen and histidine-rich glycoprotein (HRG) differ between early- and late-onset preeclampsia. The study comprised 18 women with early-onset (gestational weeks 24-32) and 19 women with late-onset (gestational weeks 35-42) preeclampsia. As controls concerning the plasma levels of fibrinogen, we used samples from non-pregnant fertile women, healthy pregnant women at gestational weeks 24-32 and healthy pregnant women at gestational weeks 35-42. Placental samples from women with healthy pregnancies at gestational weeks 35-42 served as controls in the immunohistochemical staining. Uppsala University Hospital, Uppsala. Plasma fibrinogen levels were analyzed and the placental tissue expression of fibrinogen and HRG determined by immunohistochemistry. Plasma level of fibrinogen was increased in early-onset, but not late-onset, preeclampsia. Levels of fibrinogen were significantly lower, and that of HRG significantly higher, in placentas from women with early-onset preeclampsia as compared with control placentas (p = 0.01 and 0.001). HRG and fibrinogen might be involved in the hypercoagulability and the angiogenic imbalance seen in early-onset preeclampsia.

Four-Fold Increase in Direct Costs of Stroke Survivors With Spasticity Compared With Stroke Survivors Without Spasticity

The prevalence of spasticity after first-ever stroke is approximately 20%, but there are no health economic studies on costs associated with spasticity after stroke. The objective of our study was to estimate direct costs of stroke with spasticity for patients surviving up to 1 year after the stroke event in comparison to costs of stroke without spasticity. A representative sample of patients with first-ever stroke hospitalized at Uppsala University Hospital was eligible for our cross-sectional survey. All direct costs during 1 year were identified for each patient, including costs for hospitalization (acute and rehabilitation), primary health care, medication, and costs for municipality services. Swedish currency was converted to Purchasing Power Parities US dollar (PPP$). Median age (interquartile range) was 73 years (18), and the proportion of women was 48%. The majority of the direct costs (78%) was associated with hospitalization, whereas 20% was associated with municipality services during 1 year after a first-ever stroke. Only 1% of all direct costs were related to primary health care and 1% to medication. The level of costs for patients with stroke was correlated with the presence of spasticity as measured with the modified Ashworth scale (r(s)=0.524) and with the degree of disability as measured with modified Rankin Scale (r(s)=0.624). The mean (median, interquartile range) direct cost for stroke patients with spasticity was PPP$ 84,195 (72,116, 53,707) compared with PPP$ 21,842 (12,385, 17,484) for patients with stroke without spasticity (P<0.001). Direct costs for 12-month stroke survivors are 4 times higher than direct costs for patients with stroke without spasticity during the first year after the event.

Social and biological determinants of reproductive success in Swedish males and females born 1915–1929

To investigate whether early life characteristics predict subsequent reproductive success in a post-demographic transition population; to ascertain the pathways mediating any observed effects; and to examine whether any of the...

Health‐related self‐assessed quality of life in young people at a Youth Centre in Sweden

To study the self-reported health of young people visiting a Youth Centre (YC) at a University hospital, describe possible gender differences and to compare the results with those in previous Swedish reports on similar age groups using the same instrument. All young people who visited a YC at a particular, randomly chosen time, were verbally asked to fill out a questionnaire, Short Form 36. The interviews were conducted during a 12-month period to lessen the impact of seasonal variations. A YC at the department for obstetrics and gynaecology, Uppsala University hospital. A total of 1495 young people aged 14-25 years who visited the YC. The study population (n = 1495). Response rate was 96%. This population reported lower overall scores compared with the normative Swedish population from 1992. Further, females scored significantly lower than males on all subscales (p < 0.001), except for 'Physical Functioning'. The lowest scores were reported for the subscales Vitality, Role Emotional and Mental Health. This study describes physical functioning and mental health among young people visiting a YC. The results indicate a worsening of the perceived physical and MH in young individuals, especially in young women. Further studies are needed to monitor changes in MH and quality of life over time in this group and assess the effects of interventions. This study enhances the importance of a holistic approach towards health and health promotion comprising both physical and mental health issues.

Primary patency of percutaneously inserted self-expanding metallic stents in patients with malignant biliary obstruction

BackgroundEffective bile duct drainage is crucial to the health-related quality of life of patients with jaundice caused by obstruction of the bile duct by inoperable malignant tumours. MethodsAll patients who were treated at Uppsala University Hospital, Sweden with percutaneous stenting between 2000 and 2005 were identified retrospectively. Data on the location of the obstruction and type of stent used, date and cause of death and date of stent failure were abstracted from the patients' notes. Stent patency was defined as the duration from the insertion of the stent to the date of failure. In cases in which the cause of death was directly related to failure of the stent, the date of death was defined as the patency endpoint. ResultsA total of 64 patients (34 women, 30 men) were identified. Their mean age was 71 years (standard deviation 11 years). The median length of patency was 11.4 months. Stent diameter >10mm and distal stricture were found to be associated with significantly longer patency time in univariate Cox proportional hazard analysis. In multivariate Cox proportional hazard analysis, only location of the stricture was found to be independently and significantly associated with patency time. DiscussionPercutaneous stenting is a good alternative for patients with obstructive jaundice and a life expectancy ≤1 year. It may give instant relief from the symptoms associated with jaundice. Patency time may be prolonged by using stents with a diameter ≥10mm. However, patency time was found to be lower for hilar tumours.

CFTR and tight junctions in cultured bronchial epithelial cells

a Department of Medical Cell Biology, Uppsala University, Box 571, SE-75123 Uppsala, Sweden b Department of Clinical Pathology and Cytology, Uppsala University Hospital, 75185 Uppsala, Sweden c Department of Pharmacy, Uppsala University, 75123 Uppsala, Sweden d Department of Public Health and Caring Sciences, Family Medicine and Clinical Epidemiology Section, Uppsala University, 75105 Uppsala, Sweden e School of Health and Medical Sciences, Orebro University, University Hospital, 70185 Orebro, Sweden

The impact of early twentieth century illegitimacy across three generations. Longevity and intergenerational health correlates

This study contributes to the understanding of how social mortality patterns are reproduced across generations by documenting associations of women's marital status at childbirth in the beginning of last century with selected health indicators across three subsequent generations of their offspring, and by highlighting a special set of plausible mechanisms linked to this particular event in history. We use the Multigenerational Uppsala Birth Cohort Study (UBCoS) database consisting of 12,168 individuals born at Uppsala University Hospital in 1915–1929 (UG1), their children (UG2) and grandchildren (UG3). Results showed that men and women born outside wedlock (BOW) in early twentieth century Sweden were at an increased risk of adult mortality compared to those who were born in wedlock (BIW), and the men were also significantly less likely to reach their 80th birthday. The question of childhood social disadvantage and its long-term consequences for health is then taken one step further by examining their offspring in two subsequent generations in terms of four specific anthropometric and psychological outcomes at the time of military conscription, all known to predict disease and mortality later in life. Results showed that sons of men BOW as well as sons and grandsons of women BOW had significantly lower psychological functioning and cognitive ability. Regarding body mass index and height, however, significant associations were found only among descendants of men BOW. The anthropometric and psychological disadvantages found among descendents of individuals BOW were partly mediated by their social class background. The four outcomes observed early in the lives of UG2s and UG3s do in fact constitute early health determinants, each potentially influencing longevity and mortality risk in these generations. We conclude that the social disadvantage imposed on those BOW in early twentieth century Sweden appears to be reproduced as a health disadvantage in their children and grandchildren, with likely consequences for mortality among these.

Researchers 'Astonished' by Anorexia Death Rates

Back to table of contents Previous article Next article Clinical & Research NewsFull AccessResearchers 'Astonished' by Anorexia Death RatesJoan Arehart-TreichelJoan Arehart-TreichelSearch for more papers by this authorPublished Online:6 Feb 2009https://doi.org/10.1176/pn.44.3.0020Anorexia nervosa, as psychiatrists know only too well, is a dangerous illness with a high rate of premature death.But exactly how dangerous has become clearer—the result of a nationwide longitudinal study conducted by Swedish scientists.The study team reported two major findings. The first was that compared with the general population, anorexia patients were at a heightened risk of death not only after hospitalization but many years later. The second was that their long-term risk of death came not just from anorexia but from a number of other causes as well.The scientists were “astonished” by these findings, they wrote in their report published in the January British Journal of Psychiatry.Thanks to the unique personal identification numbers assigned to all Swedish residents, and to the national cause-of-death records and national hospital-discharge records that Sweden maintains, these researchers were able to assess death from natural and unnatural causes in a nation-wide cohort of Swedish women with anorexia nervosa. The researchers studied the records of some 6,000 patients covering a 30-year period (1973 to 2003).Out of the cohort studied, 265 died during the 30-year follow-up. The most frequent causes of death were suicide (responsible for 32 percent of the deaths), anorexia (19 percent of the deaths), and cancer (11 percent of the deaths). The remaining 38 percent of deaths were caused by other illnesses or by homicide. The average age at death for the 265 anorexia patients who died was 34.The researchers also compared findings for their anorexia patients during the 30-year follow-up period with those of the general Swedish population. For example, compared with the general population during this time, anorexia subjects were 19 times more likely to have died from psychoactive substance use, primarily alcohol use, 14 times more likely to have died from suicide; 12 times more likely to have died from respiratory diseases, 11 times more likely to have died from urogenital diseases, five times more likely to have died from gastrointestinal diseases, and two times more likely to have died from either cardiovascular disease or from cancer.Altogether, anorexia patients were six times more likely to have died during the 30-year follow-up period than was the general population.“These results underline the need for careful follow-up of anorexia nervosa patients,” Fotios Papadopoulos, M.D., Ph.D., a general psychiatry resident at Sweden's Uppsala University Hospital and the lead investigator, told Psychiatric News. For instance, anorexia patients' five-fold increase in deaths due to gastrointestinal diseases may have been due, at least in part, to the indirect effects of alcohol abuse since 4 out of 6 deaths in this category were from liver cirrhosis. Moreover, other researchers have found that a number of patients with anorexia do not have alcohol problems during the first part of their illness, yet develop them later. Thus, anorexia patients should be carefully monitored for signs that they may be developing alcohol dependence.Some good news also emerged from the study, the researchers noted, in that the death rates for patients first admitted to the hospital from 1987 to 2003 for anorexia were substantially lower than those for patients first admitted to the hospital for anorexia from 1973 to 1979. The researchers believe that this downward trend reflects improved psychiatric and other medical care for anorexia patients in recent years.The study was funded by the Swedish Research Council.An abstract of “Excess Mortality, Causes of Death, and Prognostic Factors in Anorexia Nervosa” is posted at<http://bjp.rcpsych.org/cgi/content/abstract/194/1/10>.▪ ISSUES NewArchived

Cancer of the parotid gland; long-term follow-up. A single centre experience on recurrence and survival

Background. The aim of the study was to investigate the results of treatment of malignant parotid gland tumours at a single centre during a 56 year period, focusing on tumour control and survival. Patients and methods. At Uppsala University Hospital, Sweden, 144 patients (73 male and 71 female) with parotid cancer were treated between 1948 and 2004. The mean and median ages were 62 and 65 years, respectively (range 16–89 years). Surgery was the primary treatment in 113 (78%) patients followed by radiotherapy in 81. Postoperative radiotherapy in doses of 64–66 Gy, where the intention was curative and delivered with either split course or not, was administered to a majority of patients after 1970. The split-course mode was practised between 1970 and 1989. The median follow-up time was 8.3 years for patients still alive. There were 57 (40%) relapses, of which 40 were local recurrences with 26 inside the treatment volume.Results. The overall 5-year survival was 53%. The majority of tumour-related deaths appeared in the first 3–5 years after diagnosis. Age, co-morbidity, the presence of lymph node metastases, adenoid cystic carcinoma and extent of disease were important for outcome; gender, however, was not. We found no difference in the survival between patients following split course therapy versus continuous fractionation. No difference could be seen in the survival of patients treated in the 1970s versus the 1990s. Conclusions. Age, nodal engagement, a higher T-stage, adenoid cystic carcinoma histopathology, facial palsy and intercurrent disease worsen the outcome of patients, whereas gender does not. Treatment principles at our hospital have been surgery followed by radiotherapy since the early 1970s even though a split course technique was practised during a part of this period. Survival has not improved markedly. Thus, there is scope for improvement for this group of patients.

Clinical teaching improvement: The transportability of the Stanford Faculty Development Program

Background: The Stanford Faculty Development Center (SFDC) at Stanford University developed a teaching improvement course for medical teachers that has been widely disseminated using a train-the-trainer model. We were curious to see if cultural factors might influence the applicability and impact of the course when delivered to non-American participants by a facilitator from that culture.Methods: A Swedish anaesthesiologist at Uppsala University Hospital, Sweden, was trained in October 2004 at Stanford University. From January 2005 to March 2007 he delivered five faculty development seminar series at Uppsala University Hospital to 40 physicians from different departments. Participants rated the usefulness of the seminar series and retrospective pre- and post-seminar ratings were used to assess effects on participants’ teaching skills and behaviours.Results: Participants rated the seminars as highly useful (M = 4.8, SD = 0.4). Participants’ ratings of their teaching ability indicated significant increases across a variety of clinical and non-clinical teaching settings (p < 0.001), and positive changes in teaching behaviours were found for all seven educational categories assessed (p < 0.001).Conclusions: This faculty development model is highly transportable to medical teachers in Sweden, and capable of producing positive results, consistent with those found in the United States.

In Search of Excellence in Anesthesiology

In Search of Excellence in Anesthesiology

Uppsala University Hospital 300 years—a survey of the surgical development

Professor Lars Roberg, the initiator of the Nosocomium Academicum (1708), our first university hospital in Sweden, claimed that ‘no-one who does not understand surgery is a completely trained doctor’. However, it was not until the end of 19th century that modern surgery was born.The Academic Hospital was opened in 1867, and at the turn of that century Uppsala had a flourishing period under the influence of Karl Gustav Lennander, professor of surgery. In 1889 he performed the first appendectomy in Scandinavia.At the end of the 19th century the surgical tree began to branch out. In Uppsala gynaecology and obstetrics was the first to be an independent speciality (1891). It was followed by ophthalmology (1894) with Allvar Gullstrand as professor and head of the department. Gullstrand received the Nobel Prize in medicine in 1911. A separate department for diseases of the ear, nose, and throat was founded in 1916 with the Nobel laureate Robert Bárány as head.Thoracic surgery began in Uppsala in the 1940s with lung surgery and was separated from general surgery in 1958 with Viking Olov Björk as head of the department. Björk introduced open heart surgery in Uppsala.In 1951 reconstructive plastic surgery was organized by Tord Skoog, who devoted special interest to operations for cleft lip and palate surgery.Neurosurgery was established in 1962, and Uppsala has held a prominent position in the development of modern neurointensive care.During the 1970s general surgery became subspecialized into gastrointestinal, endocrine, and vascular surgery. At the same time fracture surgery was transferred to the orthopaedists, and urological surgery became an independent speciality. Transplantation surgery was introduced in Uppsala in 1967, when Professor Lars Thorén performed the first kidney transplantation. Today Uppsala has a leading position in transplantation of pancreatic islets cells.

Amplitude-Integrated EEG in the Newborn

Th value of amplitude-integrated electroencephalography (aEEG) in the newborn is explored by researchers at Washington University, St Louis; Wilhelmina Children’s Hospital, Utrecht, Netherlands; and Uppsala University Hospital, Sweden.

Reference values for clinical chemistry tests during normal pregnancy

Reference values are usually defined based on blood samples from healthy men or nonpregnant women. This is not optimal as many biological markers changes during pregnancy and adequate reference values are of importance for correct clinical decisions. There are only few studies on the variations of laboratory tests during normal pregnancies, especially during the first two trimesters. It is thus a need to establish such reference values. Longitudinal study of laboratory markers in normal pregnancies. Uppsala University Hospital, Sweden. Healthy pregnant females. We have studied 25 frequently used laboratory tests during 52 normal pregnancies. Each woman was sampled up to nine times and the samples were divided according to collection time into the following groups: gestational week 7-17; week 17-24; week 24- 28; week 28-31; week 31-34; week 34-38; predelivery (0-2 weeks before delivery) and postpartum (> 6 weeks after delivery). The 2.5 and 97.5 percentiles for these markers were calculated according to the recommendations of the International Federation of Clinical Chemistry on the statistical treatment of reference values. Reference intervals are reported for plasma alanine aminotransferase, albumin, alkaline phosphatase, pancreas amylase, apolipoprotein A1, apolipoprotein B, aspartate aminotransferase, bilirubin, calcium, chloride, creatinine, cystatin C, ferritin, gamma-glutamyltransferase, iron, lactate dehydrogenase, magnesium, phosphate, potassium, sodium, transferrin, triglycerides, thyroid-stimulating hormone, urate and urea during these pregnancy periods. Most of the analytes change during normal pregnancy. It is thus of importance to use special reference values during pregnancy.

Cerebrospinal fluid shunt infections in children over a 13-year period: anaerobic cultures and comparison of clinical signs of infection with Propionibacterium acnes and with other bacteria

Shunt infections represent a major problem with risk for sequelae and even death. The aim in this retrospective study was to analyze the incidence, origin, and clinical presentation of shunt infections, with special reference to the results of cultures for anaerobic organisms performed in addition to the usual tests, to prolonged incubation times, and to infections caused by Propionibacterium acnes. The medical records of 237 hydrocephalic children (age range 0-15 years) in whom operations were performed by a pediatric surgeon at Uppsala University Hospital during a 13-year period were reviewed. Thirty-four verified or suspected intraventricular shunt infections and 5 distal catheter infections occurred after 474 operations. Skin bacteria, such as coagulase-negative staphylococci ([CoNS], 19 patients), Staphylococcus aureus (7 patients), and P. acnes (6 patients) predominated. The addition of anaerobic cultures and prolonged incubation times increased the verification of shunt infection by more than one third. Children with P. acnes infection were significantly older, had a lower body temperature, fewer cerebrospinal fluid (CSF) leukocytes, a higher CSF/blood glucose ratio, more distal catheter infections, and other sources of infection. Four had an abdominal pseudocyst. Children < 1 year of age and infected with CoNS were more affected than older children with systemic and local symptoms. In children with distal catheter infection and growth of propionibacteria at the time of the distal catheter and valve replacement, no follow-up antibiotic treatment was necessary. Addition of anaerobic cultures and prolonged incubation times led to an increase in the detection of shunt infections. Infections caused by propionibacteria often result in mild symptoms that may be overlooked if adequate anaerobic cultures are not obtained.

Does the strength of the association between foetal growth rate and ischaemic heart disease mortality differ by social circumstances in early or later life?

Objective:To study whether the effect of size at birth on the risk of ischaemic heart disease (IHD) death is modified by social circumstances in childhood or in adulthood.Design:A cohort study....

The first major extended‐spectrum β‐lactamase outbreak in Scandinavia was caused by clonal spread of a multiresistant Klebsiella pneumoniae producing CTX‐M‐15

Between May and December 2005, 64 multidrug-resistant isolates of Klebsiella pneumoniae were detected from patients admitted to Uppsala University Hospital. This represented a dramatic increase in ESBL-producing K. pneumoniae compared to previous years. To investigate the epidemiology and to characterize the resistance mechanisms of the isolates, a study was initiated. Antibiotic susceptibility was determined by means of the Etest and the disc diffusion method. Extended-spectrum beta-lactamase (ESBL) production was identified by clavulanic acid synergy test and confirmed with PCR amplification followed by DNA sequencing. DNA profiles of the isolates were examined with pulsed-field gel electrophoresis (PFGE). All isolates were resistant or exhibited reduced susceptibility to cefadroxil, cefuroxime, cefotaxime, ceftazidime, aztreonam, piperacillin/tazobactam, ciprofloxacin, tobramycin, and trimethoprim-sulfamethoxazole. They produced ESBL of the CTX-M-15 type, and the involvement of a single K. pneumoniae clone was shown. This is the first major clonal outbreak of multiresistant ESBL-producing K. pneumoniae in Scandinavia. The outbreak demonstrates the epidemic potential of enterobacteria containing ESBLs of the CTX-M type, even in a country with a relatively low selective pressure and a low prevalence of multiresistant bacteria.

Selective Screening for Abdominal Aortic Aneurysm among Patients Referred to the Vascular Laboratory

Patients examined for peripheral arterial disease at the vascular laboratory, Uppsala University Hospital, are since 1993 screened for abdominal aortic aneurysm (AAA). The objective of this study was to study the prevalence of AAA found at this selective high-risk screening. All files in the vascular laboratory were retrospectively reviewed. Of 9296 persons examined with arterial duplex between 1993 and October 2005, 5924 were screened for AAA. The primary target vessel was the carotid arteries in 3772 subjects, the renal arteries in 1529 subjects and the lower extremity arteries in 1457 subjects. An AAA was defined as an infrarenal aortic diameter >/=30mm. 179 subjects were found to have an AAA. In a logistic regression model male gender, age and duplex-verified arterial stenosis were independently associated with AAA (odds ratio 3.2, 2.0/20 years and 2.0, respectively, p<0.001). In men <60 years the AAA prevalence was 0.9% (95% confidence interval 0.2-1.6%) when arterial stenosis was absent and 1.5% (0.0-3.2%) when present. In men >/=60 years the AAA prevalence was 4.0% (3.0-5.1%) when no arterial stenosis was found and 7.3% (5.7-8.9%) when found. The corresponding prevalences in women were 0%, 0%, 1.2% (0.5-1.8%), and 3.1% (1.9-4.3%), respectively. Men >/=60 years referred for arterial examination have a significant risk of having an AAA while only women >/=65 years with a duplex verified arterial stenosis have a sufficient risk of having an AAA. Studies to evaluate the benefit of selective high-risk screening are warranted.