Publications by authors named "Pettersson B"

242 Publications

A new reimbursement system for innovative pharmaceuticals combining value-based and free market pricing.

Appl Health Econ Health Policy 2012 Jul;10(4):217-25

School of Economics, Lund University, Lund, Sweden.

Sweden has experienced a national value-based pricing (VBP) system for innovative outpatient drugs operated by the Pharmaceutical Benefits Board - LFN (now called the Dental and Pharmaceutical Benefits agency - TLV) since 2002. VBP has the character of a monopoly system, leading to reimbursement decisions where usage of new medicines is limited to subgroups and not the population for which the drug is approved. VBP relies on a broad societal perspective, encouraging innovations by signaling to firms that value-adding treatments are demanded. However, the VBP system is operated without a drug budget responsibility. The budget responsibility lies at the regional level, not operating VBP, thus an intrinsic conflict is built into the system. The aim of this article is to suggest a modification to the current reimbursement system in Sweden where payment for pharmaceuticals is split between the regional and national levels. The system is expected to make new innovative pharmaceuticals accessible to a larger number of patients and provide more consumer surplus without reducing the producer surplus. In short, the county councils pay the marginal cost of production while the state pays for the innovation.
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http://dx.doi.org/10.2165/11633930-000000000-00000DOI Listing
July 2012

Some bitter-sweet reflections on the Ottawa Charter commemoration cake: a personal discourse from an Ottawa rocker.

Authors:
Bosse Pettersson

Health Promot Int 2011 Dec;26 Suppl 2:ii173-9

Public Health Policy, Swedish Ministry of Health and Social Affairs, Sweden.

The Ottawa Charter both gave health promotion a solid framework and health promoters an identity. Yet, health promotion has far from reached its potential in being internalized in public health politics. Advocacy for health is one of the core missions for health promotion and the 25-year celebration of the Ottawa Charter offers a free ride, instead of being a missed opportunity. WHO has not met the expectations in taking advantage of the momentum and outcomes from the long series of global health promotion conferences. The series represents a lifeline for health promotion. Concepts like healthy public policy, supportive environments, social determinants, health and human rights, whole of government, globalization and others have been elaborated and framed in a health promoting context. The downside is that the footprints have not been bold, in particular not internationally. An upside is the development of research and science, underscored by a rapid development of scientific journals, textbooks, academic institutions and posts. A question arising is whether practise and policy making are left behind, since implementation on a grand scale still is lacking? Further and future efforts must be devoted to explore the processes and art of policy making. There is a need for more narratives and more health promoters involving themselves in policy making and politics. Health promotion is as relevant for the twenty-first century as ever. The challenges and opportunities are evident; the increasing global burden of non-communicable diseases, ageing populations, harmful use of alcohol, social determinants and fair societies improved governance and more. Health promotion can add value and WHO can step up its engagement.
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http://dx.doi.org/10.1093/heapro/dar080DOI Listing
December 2011

Utilization and costs of lipid modifying therapies following health technology assessment for the new reimbursement scheme in Sweden.

Health Policy 2012 Jan 23;104(1):84-91. Epub 2011 Nov 23.

The Center for Medical Technology Assessment, CMT Linköping University, Sweden. Billie

Introduction: A new reimbursement scheme (RS) for lipid modifying therapies (LMT) was implemented in Sweden in June 2009. Products on the market were continued, restricted or excluded in the new RS. The aim of this study was to compare utilization, costs and switching behavior in patients treated with LMT before and after the new RS.

Materials And Methods: This is a quasi-experimental study using data on dispensed LMT and costs from a database on dispensed individual prescriptions in Sweden. Segmented regression analyses were used to assess utilization and costs of LMT.

Results: Number of patients treated with products with restricted reimbursement increased in level (P=0.0336) following the changes in the scheme, while decreased in level (P<0.0001) for products excluded from the RS. Patients initially treated with products excluded from the RS discontinued to a greater extent, and switched to higher doses of the same substance or to generic simvastatin. The total annual costs decreased moderately.

Conclusions: The decreasing trend in utilization of low-dose atorvastatin and rosuvastatin was accelerated and so was the increasing trend in utilization of generic simvastatin following the new RS. Switching to higher doses and discontinuation increased and expected savings were overestimated.
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http://dx.doi.org/10.1016/j.healthpol.2011.10.010DOI Listing
January 2012

Cervical cancer in the screening era: who fell victim in spite of successful screening programs?

J Gynecol Oncol 2011 Jun;22(2):76-82

Gynecological Oncology, Radiumhemmet, Department of Oncology, Karolinska University Hospital, Solna, Karolinska Institute, Stockholm, Sweden.

Objective: To compare profiles of a prescreening and screening cohort of women with cervical cancer regarding histopathology and clinical variables in order to identify those remaining at risk despite successful screening programs. By analyzing these profiles we hope to improve future screening methods.

Methods: The prescreening and screening cohorts consisted of 5,046 and 1,174 women, respectively, treated for cervical cancer at the Department of Gynecological Oncology at Radiumhemmet, Karolinska University Hospital, during the periods 1944-1957 and 1990-2004.

Results: Mean age increased from 48.9 years to 55.3 years in the cohorts treated 1944-1957 and 1990-2004, respectively. The percentage of patients older than 69 years was 5.4% and 27.3% in the prescreening and screening period, respectively. A shift towards earlier stages at diagnosis, a reduction of squamous cervical cancer and an increase of adenocarcinoma were observed in the screening cohort. The percentage of adenocarcinoma was about 6 times higher among younger patients. Cases of stump cancer and cervical cancer associated with pregnancy have declined. Eighty-seven women in the screening cohort had a history of treatment for in situ carcinoma by conization; 28% of these cases developed cervical cancer within one year after conization.

Conclusion: The profile changed in the screening era indicating a need to refine screening for improved detection of in older women. This study, one of the largest clinical series of cervical cancer, provides an important baseline with which later studies can be compared to evaluate the effects of human papillomavirus vaccine and other important changes in this field.
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http://dx.doi.org/10.3802/jgo.2011.22.2.76DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152759PMC
June 2011

Public health associations can make a difference: a tribute to the Canadian contributions and some future challenges for public health associations.

J Public Health Policy 2011 Aug 12;32(3):380-90. Epub 2011 May 12.

Swedish National Institute of Public Health.

This commentary addresses the 25th anniversary of the Canadian Public Health Association's international program 'Strengthening of Public Health Associations' and its importance for the World Federation of Public Health Associations. Furthermore, it points out future challenges for public health associations throughout the world, on social determinants and fair societies, global governance, non-communicable diseases and chronic conditions, harmful use of alcohol, healthy ageing, and millennium development goals post-2015. The suggestions for keys to success are to expand the advocacy role, to improve the collaboration with public health practitioners, and to develop the interface between evidence and policymaking.
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http://dx.doi.org/10.1057/jphp.2011.24DOI Listing
August 2011

External pelvic and vaginal irradiation versus vaginal irradiation alone as postoperative therapy in medium-risk endometrial carcinoma--a prospective randomized study.

Int J Radiat Oncol Biol Phys 2012 Mar 14;82(3):1249-55. Epub 2011 Jun 14.

Department of Gynecological Oncology, Örebro University Hospital, Örebro, Sweden.

Purpose: To evaluate the value of adjuvant external beam pelvic radiotherapy as adjunct to vaginal brachytherapy (VBT) in medium-risk endometrial carcinoma, with regard to locoregional tumor control, recurrences, survival, and toxicity.

Methods And Materials: Consecutive series of 527 evaluable patients were included in this randomized trial. Median follow-up for patients alive was 62 months. The primary study endpoints were locoregional recurrences and overall survival. Secondary endpoints were recurrence-free survival, recurrence-free interval, cancer-specific survival, and toxicity.

Results: Five-year locoregional relapse rates were 1.5% after external beam radiotherapy (EBRT) plus VBT and 5% after vaginal irradiation alone (p = 0.013), and 5-year overall survival rates were 89% and 90%, respectively (p = 0.548). Endometrial cancer-related death rates were 3.8% after EBRT plus VBT and 6.8% after VBT (p = 0.118). Pelvic recurrences (exclusively vaginal recurrence) were reduced by 93% by the addition of EBRT to VBT. Deep myometrial infiltration was a significant prognostic factor in this medium-risk group of endometrioid carcinomas but not International Federation of Gynecology and Obstetrics grade or DNA ploidy. Combined radiotherapy was well tolerated, with serious (Grade 3) late side effects of less than 2%. However, there was a significant difference in favor of VBT alone.

Conclusions: Despite a significant locoregional control benefit with combined radiotherapy, no survival improvement was recorded, but increased late toxicity was noted in the intestine, bladder, and vagina. Combined RT should probably be reserved for high-risk cases with two or more high-risk factors. VBT alone should be the adjuvant treatment option for purely medium-risk cases.
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http://dx.doi.org/10.1016/j.ijrobp.2011.04.014DOI Listing
March 2012

Carcinoma of the cervical stump: fifty years of experience.

Oncol Rep 2011 Jun 22;25(6):1651-4. Epub 2011 Mar 22.

Gynecological Oncology Radiumhemmet, Department of Oncology, Karolinska University Hospital, Solna, Stockholm, Sweden.

A series of patients with carcinoma of the cervical stump in relation to age, clinical stage, histopathology, changes in relative incidence, treatment outcome and long-term survival, were studied and the findings were compared with matched controls that have an intact uterus and cancer of the cervix. Of 8,028 women treated for invasive cervical carcinoma between 1959-2004, 161 were diagnosed with stump cancer, accounting for 2.0% of all cervical cancers. The mean time interval between subtotal hysterectomy and stump cancer diagnosis was 17.6 years, with a range of 1-46 years. In 80% of cases, symptoms drove the patient to seek medical attention and postcoital, intermenstrual or postmenopausal bleeding was the main reason. Among 161 stump cancer cases 89% were squamous cell carcinoma (SCC) and the remaining 17 cases were adenocarcinomas (AC). Cumulative cause-specific survival rate was significantly worse for adenocarcinoma than for squamous cell carcinoma (SCC) of the cervical stump (Log-rank p = 0.027, Cox-Mantel p = 0.015, Cox F-test p = 0.01). The stump cancer cases show a worse stage profile compared with the cancer cases in intact uterus. We conclude that the total effect of stump cancers following subtotal hysterectomies is not to be neglected.
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http://dx.doi.org/10.3892/or.2011.1228DOI Listing
June 2011

One-pot Eschenmoser episulfide contractions in DMSO: applications to the synthesis of fuligocandins A and B and a number of vinylogous amides.

J Org Chem 2011 Mar 22;76(6):1554-61. Epub 2011 Feb 22.

Unit of Organic Chemistry, Department of Biosciences at Novum, Karolinska Institute, SE-141 57 Huddinge, Sweden.

Practical total syntheses of the natural products fuligocandin A (2a) and fuligocandin B (3) have been achieved through a convergent strategy depending on the Eschenmoser episulfide contraction as a key step. Conducting the reaction in DMSO proved to be an efficient and general method for the synthesis of a variety of vinylogous amides, such as azepan-2-ylidenepropan-2-one.
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http://dx.doi.org/10.1021/jo101864nDOI Listing
March 2011

Thionations using a P4S10-pyridine complex in solvents such as acetonitrile and dimethyl sulfone.

J Org Chem 2011 Mar 22;76(6):1546-53. Epub 2011 Feb 22.

Unit of Organic Chemistry, Department of Biosciences at Novum, Karolinska Institute, SE-141 57 Huddinge, Sweden.

Tetraphosphorus decasulfide (P(4)S(10)) in pyridine has been used as a thionating agent for a long period of time. The moisture-sensitive reagent has now been isolated in crystalline form, and the detailed structure has been determined by X-ray crystallography. The thionating power of this storable reagent has been studied and transferred to solvents such as acetonitrile in which it has proven to be synthetically useful and exceptionally selective. Its properties have been compared with the so-called Lawesson reagent (LR). Particularly interesting are the results from thionations at relatively high temperatures (∼165 °C) in dimethyl sulfone as solvent. Under these conditions, for instance, acridone and 3-acetylindole could quickly be transformed to the corresponding thionated derivatives. Glycylglycine similarly gave piperazinedithione. At these temperatures, LR is inefficient due to rapid decomposition. The thionated products are generally cleaner and more easy to obtain because in the crystalline reagent, impurities which invariably are present in the conventional reagents, P(4)S(10) in pyridine or LR, have been removed.
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http://dx.doi.org/10.1021/jo101865yDOI Listing
March 2011

tRNA accumulation and suppression of the bldA phenotype during development in Streptomyces coelicolor.

Mol Microbiol 2011 Mar 27;79(6):1602-14. Epub 2011 Jan 27.

Department of Cell and Molecular Biology, Box 596, Biomedical Centre, SE-751 24 Uppsala, Sweden.

Streptomyces coelicolor undergoes distinct morphological changes as it grows on solid media where spores differentiate into vegetative and aerial mycelium that is followed by the production of spores. Deletion of bldA, encoding the rare tRNA(Leu) UAA, blocks development at the stage of vegetative mycelium formation. From previous data it appears that tRNA(Leu) UAA accumulates relatively late during growth while two other tRNAs do not. Here, we studied the expression of 17 different tRNAs including bldA tRNA, and the RNA subunit of the tRNA processing endoribonuclease RNase P. Our results showed that all selected tRNAs and RNase P RNA increased with time during development. However, accumulation of bldA tRNA and another rare tRNA(Leu) isoacceptor started at an earlier stage compared with the other tRNAs. We also introduced the bldA tRNA anticodon (UAA) into other tRNAs and introduced these into a bldA deletion strain. In particular, one such mutant tRNA derived from the tRNA(Leu) CAA isoacceptor suppressed the bldA phenotype. Thus, the bldA tRNA scaffold is not critical for function as a regulator of S. coelicolor cell differentiation. Further substitution experiments, in which the 5'- and 3'-flanking regions of the suppressor tRNA were changed, indicated that these regions were important for the suppression.
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http://dx.doi.org/10.1111/j.1365-2958.2011.07543.xDOI Listing
March 2011

Self-reported experience of hypoglycemia among adults with type 2 diabetes mellitus (Exhype).

Diabetes Res Clin Pract 2011 Apr 30;92(1):19-25. Epub 2010 Dec 30.

Center for Medical Technology Assessment, Linköping University, Sweden.

Aims: To evaluate the experience of hypoglycemia in patients treated with metformin in combination with sulphonylureas (SUs) and the impact on patients' quality of life (QoL) and worry about hypoglycemia.

Methods: This was a national, cross-sectional, multicenter study. Patients with type 2 diabetes treated with metformin and SU dual therapy were recruited by 54 investigators between January 2009 and August 2009. The patients were asked to complete a QoL instrument, the EuroQol-5 Dimensions questionnaire (EQ-5D), and the Hypoglycemia Fear Survey (HFS-II). Investigators completed a web-based case report form on laboratory values, medical history and anti-diabetic treatment.

Results: A total of 430 patients (60% male) were included in the study. Mean age was 69 years. Approximately one fifth of the patients experienced moderate or worse symptoms of hypoglycemia. Patients who experienced moderate or worse hypoglycemia had lower QoL as measured by the weighted EQ-5D summary score (0.81 vs. 0.88; p<0.001) than patients who experienced mild or no hypoglycemia.

Conclusions: Experience of hypoglycemia was found to be associated with lower QoL in patients with type 2 diabetes on dual treatment with metformin and sulphonylurea. This should be taken into consideration when selecting treatment for these patients in clinical practice.
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http://dx.doi.org/10.1016/j.diabres.2010.12.005DOI Listing
April 2011

Renal angiomyoadenomatoid tumor.

Urology 2011 Aug 4;78(2):327-8. Epub 2010 Dec 4.

Department of Urology, Countess of Chester Foundation NHS Foundation Trust, Cheshire, United Kingdom.

Renal angiomyoadenomatoid tumor is a distinct pathologic entity that can mimic clear cell renal adenocarcinoma in presentation. The nature and behavior of these tumors are not well understood, and they require long-term follow-up to clarify their neoplastic potential.
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http://dx.doi.org/10.1016/j.urology.2010.08.033DOI Listing
August 2011

Prevalence of lipid abnormalities before and after introduction of lipid modifying therapy among Swedish patients with dyslipidemia (PRIMULA).

BMC Public Health 2010 Nov 29;10:737. Epub 2010 Nov 29.

Center for Medical Technology Assessment, Linköping University, Linköping, Sweden.

Background: Data on the prevalence of dyslipidemia and attainment of goal/normal lipid levels in a Swedish population are scarce. The objective of this study is to estimate the prevalence of dyslipidemia and attainment of goal/normal lipid levels in patients treated with lipid modifying therapy (LMT).

Methods: This longitudinal retrospective observational study covers time periods before and after treatment. Data were collected from 1994-2007 electronic patient records in public primary healthcare centers in Uppsala County, Sweden. Patients were included if they had been treated with LMT and had at least one lipid abnormality indicating dyslipidemia and if complete lipid profile data were available. Thresholds levels for lipids were defined as per Swedish guidelines.

Results: Among 5,424 patients included, at baseline, the prevalence of dyslipidemia (≥1 lipid abnormality) was by definition 100%, while this figure was 82% at follow-up. At baseline, 60% had elevated low-density lipoprotein (LDL-C) combined with low high-density lipoprotein (HDL-C) and/or elevated triglycerides (TG s), corresponding figure at follow-up was 36%. Low HDL-C and/or elevated TGs at follow-up remained at 69% for patients with type 2 diabetes mellitus (T2DM), 50% among patients with coronary heart disease (CHD) and 66% among patients with 10 year CHD risk >20%. Of the total sample, 40% attained goal levels of LDL-C and 18% attained goal/normal levels on all three lipid parameters.

Conclusions: Focusing therapy on LDL-C reduction allows 40% of patients to achieve LDL-C goal and helps reducing triglyceride levels. Almost 60% of patients experience persistent HDL-C and/or triglyceride abnormality independently of LDL-C levels and could be candidates for additional treatments.
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http://dx.doi.org/10.1186/1471-2458-10-737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3009647PMC
November 2010

Cleavage of model substrates by archaeal RNase P: role of protein cofactors in cleavage-site selection.

Nucleic Acids Res 2011 Feb 8;39(3):1105-16. Epub 2010 Oct 8.

Department of Cell and Molecular Biology, Biomedical Centre, Uppsala University SE-751 24, Uppsala, Sweden.

RNase P is a catalytic ribonucleoprotein primarily involved in tRNA biogenesis. Archaeal RNase P comprises a catalytic RNase P RNA (RPR) and at least four protein cofactors (RPPs), which function as two binary complexes (POP5•RPP30 and RPP21• RPP29). Exploiting the ability to assemble a functional Pyrococcus furiosus (Pfu) RNase P in vitro, we examined the role of RPPs in influencing substrate recognition by the RPR. We first demonstrate that Pfu RPR, like its bacterial and eukaryal counterparts, cleaves model hairpin loop substrates albeit at rates 90- to 200-fold lower when compared with cleavage by bacterial RPR, highlighting the functionally comparable catalytic cores in bacterial and archaeal RPRs. By investigating cleavage-site selection exhibited by Pfu RPR (±RPPs) with various model substrates missing consensus-recognition elements, we determined substrate features whose recognition is facilitated by either POP5•RPP30 or RPP21•RPP29 (directly or indirectly via the RPR). Our results also revealed that Pfu RPR + RPP21•RPP29 displays substrate-recognition properties coinciding with those of the bacterial RPR-alone reaction rather than the Pfu RPR, and that this behaviour is attributable to structural differences in the substrate-specificity domains of bacterial and archaeal RPRs. Moreover, our data reveal a hierarchy in recognition elements that dictates cleavage-site selection by archaeal RNase P.
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http://dx.doi.org/10.1093/nar/gkq732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3035440PMC
February 2011

Physicians' experiences of palliative care for heart failure patients.

Eur J Cardiovasc Nurs 2011 Mar 14;10(1):64-9. Epub 2010 May 14.

Department of Nursing, Umeå University, Campus Skellefteå, 93187 Skellefteå, Sweden.

Background: Although heart disease is the single most common cause of death knowledge about palliative care for this group of patients is deficient.

Aim: The aim of this study was to describe physicians' experiences of palliative care for heart failure patients.

Methods: Fifteen physicians at a medical geriatrics clinic were interviewed. The interviews were analysed using thematic content analysis.

Results: The results show that the physicians are confronted with patients with an unpredictable disease trajectory, including patients with severe symptoms, uncertainty about anticipating the course of dying and encountering close relative's anxiety and frustration. The physicians face difficult situations regarding whether to continue or withdraw care and medical treatment which means deciding concerning 'active' medical treatment, cardio pulmonary resuscitation and an implantable cardioverter-defibrillator (ICD). The physicians acknowledge the necessity for better structured follow-ups and cooperation with outpatient settings. They recognize that there is a lack of follow-ups and continuity of care and treatment at the hospital, involving their passing on or retaining responsibility for the patients' medical care.

Conclusion: From the physicians' view clarification of who is principally responsible for the patient's medical care, being involved throughout the disease trajectory and cooperating more closely with palliative care services are necessary to further improve the way in which care is delivered to patients dying of heart failure.
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http://dx.doi.org/10.1016/j.ejcnurse.2010.04.005DOI Listing
March 2011

Invasive carcinoma of the uterine cervix associated with pregnancy: 90 years of experience.

Cancer 2010 May;116(10):2343-9

Department of Gynecological Oncology Radiumhemmet, Karolinska University Hospital, Solna, Karolinska Institute, Stockholm, Sweden.

Background: This study is a representation of 90 years of experience with carcinoma of the uterine cervix in pregnancy. The objective was to retrospectively study changes in the distribution of cervical carcinoma (CC) by age, disease stage, histopathology, survival, and the development of second primary cancers.

Methods: Altogether, 18,474 women with newly diagnosed CC were examined and treated at the Radiumhemmet between 1914 and 2004, including 9247 women who were of a childbearing age (<50 years) and 219 women who were pregnant.

Results: The mean patient age declined from 35 years (during 1914-1943) to 32.2 years (during 1960-2004). Similarly, the age range changed from ages 23 to 51 years (during 1914-1943) to ages 21 to 47 years (during 1960-2004). The relative incidence for all women aged <50 years who were treated for CC dropped considerably from 4.2% (during 1914-1943) to 1.2% (during 1960-2004), which translated into a reduction of by approximately 66%. At the time of diagnosis, stage I CC was observed in 75.6% of patients during 1960 to 2004 compared with 24.8% of patients during 1914 to 1943. The 10-year actuarial survival rate improved significantly during the study period from 27% (1914-2004) to 79% (1960-2004). The 10-year cause-specific cumulative actuarial survival rate for 41 women who were treated during 1960 to 2004 did not differ statistically from the rate for an age-matched, stage-matched, and histopathology-matched control series from the total cohort of women with CC who were treated at the Radiumhemmet during the same period (log-rank test; P = .85).

Conclusions: During the study period, the incidence of CC during pregnancy declined, the cases were discovered at earlier stages, and survival improved. Furthermore, there was no increase in second primary cancers, and pregnancy did not appear to influence prognosis.
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http://dx.doi.org/10.1002/cncr.24971DOI Listing
May 2010

[Important to keep the principle of value-based pricing of drugs].

Lakartidningen 2009 Oct 28-Nov 3;106(44):2862-4

Lunds universitet.

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December 2009

Sporulation in mycobacteria.

Proc Natl Acad Sci U S A 2009 Jun 16;106(26):10781-6. Epub 2009 Jun 16.

Department of Cell and Molecular Biology, Biomedical Center, Uppsala University, Uppsala SE-751 24, Sweden.

Mycobacteria owe their success as pathogens to their ability to persist for long periods within host cells in asymptomatic, latent forms before they opportunistically switch to the virulent state. The molecular mechanisms underlying the transition into dormancy and emergence from it are not clear. Here we show that old cultures of Mycobacterium marinum contained spores that, upon exposure to fresh medium, germinated into vegetative cells and reappeared again in stationary phase via endospore formation. They showed many of the usual characteristics of well-known endospores. Homologues of well-known sporulation genes of Bacillus subtilis and Streptomyces coelicolor were detected in mycobacteria genomes, some of which were verified to be transcribed during appropriate life-cycle stages. We also provide data indicating that it is likely that old Mycobacterium bovis bacillus Calmette-Guérin cultures form spores. Together, our data show sporulation as a lifestyle adapted by mycobacteria under stress and tempt us to suggest this as a possible mechanism for dormancy and/or persistent infection. If so, this might lead to new prophylactic strategies.
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http://dx.doi.org/10.1073/pnas.0904104106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2705590PMC
June 2009

The Swedish personal identity number: possibilities and pitfalls in healthcare and medical research.

Eur J Epidemiol 2009 6;24(11):659-67. Epub 2009 Jun 6.

Department of Paediatrics, Orebro University Hospital, Orebro, Sweden.

Swedish health care and national health registers are dependent on the presence of a unique identifier. This paper describes the Swedish personal identity number (PIN) and explores ethical issues of its use in medical research. A ten-digit-PIN is maintained by the National Tax Board for all individuals that have resided in Sweden since 1947. Until January 2008, an estimated 75,638 individuals have changed PIN. The most common reasons for change of PIN are incorrect recording of date of birth or sex among immigrants or newborns. Although uncommon, change of sex always leads to change of PIN since the PIN is sex-specific. The most common reasons for re-use of PIN (n = 15,887), is when immigrants are assigned a PIN that has previously been assigned to someone else. This is sometimes necessary since there is a shortage of certain PIN combinations referring to dates of birth in the 1950s and 1960s. Several ethical issues can be raised pro and con the use of PIN in medical research. The Swedish PIN is a useful tool for linkages between medical registers and allows for virtually 100% coverage of the Swedish health care system. We suggest that matching of registers through PIN and matching of national health registers without the explicit approval of the individual patient is to the benefit for both the individual patient and for society.
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http://dx.doi.org/10.1007/s10654-009-9350-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773709PMC
April 2010

Synthesis of 1,4-benzodiazepin-3-ones and 1,5-benzodiazocin-4-ones by addition of Grignard reagents to derivatives of o-aminobenzonitrile.

Org Biomol Chem 2009 Mar 5;7(6):1184-91. Epub 2009 Feb 5.

Karolinska Institute, Department of Biosciences at Novum, Unit of Organic Chemistry, SE-141 57, Huddinge, Sweden.

Addition of organometallics to N-(alpha-haloacyl)-o-aminobenzonitrile resulted in the formation of 2,5-disubstituted 1,4-benzodiazepin-3-ones, whereas N-(beta-haloacyl)-o-aminobenzonitrile gave 2,6-disubstituted 1,5-benzodiazocin-4-ones under similar conditions. Initial cylization of N-(beta-haloacyl)-o-aminobenzonitrile to obtain the corresponding lactam (e.g.alpha,alpha-dimethyl-N-(2-cyanophenyl)-beta-lactam) increased the yield of 1,5-benzodiazocin-4-ones significantly. Somewhat surprisingly, addition of lithium reagents to N-(beta-haloacyl)-o-aminobenzonitrile gave 4,4-disubstituted quinazolines via Grob fragmentation.
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http://dx.doi.org/10.1039/b819260jDOI Listing
March 2009

The presence of a C-1/G+73 pair in a tRNA precursor influences processing and expression in vivo.

J Mol Biol 2008 Sep 3;381(5):1089-97. Epub 2008 Jul 3.

Department of Cell and Molecular Biology, Box 596, Biomedical Center, SE-751 24 Uppsala, Sweden.

To understand whether 5' and 3' structural elements of the region corresponding to the mature tRNA affect the expression of the tRNA, we examined several bacterial genomes for tRNA genes where the expression might be potentially affected by structural elements located outside of the mature tRNA. In Pseudomonas aeruginosa, our analysis suggested that the tRNA(Trp) is transcribed together with a putative stem-loop structure followed by a uridine tract immediately downstream of the tRNA region. This structural element, resembling a Rho-independent transcription terminator, might therefore influence the expression and processing of tRNA(Trp). Moreover, the secondary structure suggested that the discriminator base in the tRNA(Trp) precursor can pair with either the C at position -1, the 3' terminal residue in the 5' leader, or the C immediately 5' of the uridine tract of the putative Rho-independent transcription terminator. Here, we present in vivo data demonstrating the importance of residue -1 and the positioning of the putative transcription terminator for the expression of correctly 5' processed P. aeruginosa tRNA(Trp) in Escherichia coli. Interestingly, we also detected a difference in the appearance of correctly 5' processed P. aeruginosa tRNA(Trp) in E. coli compared to the situation in P. aeruginosa.
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http://dx.doi.org/10.1016/j.jmb.2008.06.077DOI Listing
September 2008

Transforming Ottawa Charter health promotion concepts into Swedish public health policy.

Authors:
Bosse Pettersson

Promot Educ 2007 ;14(4):244-9

Swedish National Institute of Public Health.

Swedish public health policy clearly illustrates how the concept of the Ottawa Charter for health promotion can be utilized at a national level. The impact has been more implicit than explicit. Public health has a long history in Sweden and much of the present and future is, and will be, linked to traditional values and structures. International input, however, has been essential to prompt new approaches and change. Health inequalities remain the major shortcoming. The Swedish system offers universal access to healthcare in a decentralized system. Still, primary healthcare, and the health services as a whole have not yet sufficiently embraced the idea of health promotion. Political attention to modern public health at the Prime Minister level was established in late 1980s. Since, continuous initiatives in terms of organization, infrastructure and funding have taken place. With regard to funding, a vast majority of the resources allocated to health promotion will be found outside the health sector. An interesting observation is that the Swedish public health policy with its 11 objective domains remains the same, also after a change of government. Future challenges include maintaining and developing an intersectoral mechanism for implementation, allocating more resources for intervention research to strengthen knowledge-based health promotion, and developing tools for coping better with the challenges of globalisation identified in the Bangkok Charter.
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http://dx.doi.org/10.1177/10253823070140041201DOI Listing
April 2008

Surgical treatment of postinfarction left ventricular pseudoaneurysm.

Ann Thorac Surg 2007 Feb;83(2):526-31

Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, Ohio 44195, USA.

Background: Left ventricular pseudoaneurysm from myocardial infarction is rare and is associated with a high risk of rapid enlargement and rupture. The purposes of this study were to describe its clinical presentation, assess the accuracy of diagnostic imaging modalities, and determine operative and late surgical results.

Methods: From January 1986 through December 2001, 30 patients aged 50 to 85 years (mean, 68; 70% male) underwent left ventricular pseudoaneurysm repair. Two surgical approaches were used: primary repair (n = 5, 17%) and patch closure (n = 25, 83%). Twenty-one patients (70%) had concomitant procedures, including coronary revascularization (n = 17, 57%) and mitral valve surgery (n = 9, 30%); 8 patients (29%) underwent emergent surgery. Clinical presentation, preoperative imaging data, and surgical outcomes were abstracted from medical records or obtained by patient follow-up.

Results: The most common clinical presentations were heart failure (n = 22, 73%) and angina (n = 11, 41%). Pseudoaneurysm was rarely suspected at clinical presentation. Contrast ventriculography was diagnostic in 54% of patients in whom it was performed, as opposed to 97% for two-dimensional echocardiography (p = 0.2). Postoperative intra-aortic balloon pump was required in 7 patients (23%). Hospital mortality was 20%, and late survival was 73%, 59%, and 45% at 1, 5, and 8 years, respectively.

Conclusions: Left ventricular pseudoaneurysm should be suspected in postinfarction patients with unexplained heart failure. Echocardiography is usually diagnostic and is superior to ventriculography. The surgical mortality rate is elevated in this complex patient population. Long-term survival is also poor, mainly because of underlying ischemic cardiomyopathy.
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http://dx.doi.org/10.1016/j.athoracsur.2006.06.080DOI Listing
February 2007

Extended use of extracorporeal membrane oxygenation after lung transplantation.

J Thorac Cardiovasc Surg 2006 Oct;132(4):954-60

Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic, Cleveland, Ohio 44195, USA.

Objectives: Extracorporeal membrane oxygenation (ECMO) for severe graft failure after lung transplantation is accepted immediately postoperatively; extending its use is controversial. We evaluated our post-lung transplant ECMO experience, which included extended indication, to (1) determine its prevalence, risk factors, indications, and timing, (2) compare complications and outcomes of these patients with those not requiring it, and (3) identify risk factors, including indications, for mortality.

Methods: From February 1990 to October 2005, 474 patients underwent lung transplantation; postoperative ECMO support was instituted for severe graft failure 23 times in 22 patients (4.0%). Indications for ECMO and its timing were obtained by reviewing medical records and survival by systematic follow-up.

Results: No factor evaluated predicted severe graft failure leading to ECMO. The most common indication for ECMO was early graft failure (13 patients); however, it was also used for pneumonia or sepsis (6) and acute rejection (4). ECMO was initiated at a median arterial oxygen tension/inspired oxygen fraction of 59 at a median of 2 days postoperatively and was maintained for a median of 4 days. The most common complications were renal failure (57%) and bleeding (43%). ECMO was effective in salvaging patients with rejection and early graft failure (survival at 1, 3, 6, and 12 months: 62%, 54%, 49%, and 41%), but ineffective for pneumonia or sepsis (survival at these intervals: 9%, 4%, 4%, and 3%).

Conclusions: ECMO can be extended beyond early severe graft failure to acute rejection and can be considered after the immediate postoperative period. Survival after ECMO in patients with pneumonia or sepsis is poor.
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http://dx.doi.org/10.1016/j.jtcvs.2006.06.010DOI Listing
October 2006

Surgical treatment of pseudoaneurysm of the thoracic aorta.

J Thorac Cardiovasc Surg 2006 Aug;132(2):379-85

Department of Thoracic and Cardiovascular Surgery, The Cleveland Clinic Foundation, Cleveland, Ohio.

Objectives: To examine the clinical profiles, operative outcomes, and late results of patients with pseudoaneurysm of the thoracic aorta.

Methods: From 1990 to 2002, 60 patients underwent repair of aortic pseudoaneurysm: ascending aorta in 70%, ascending aorta and arch in 15%, descending aorta in 10%, and arch alone in 5%. Mean age was 53 +/- 15 years, and 70% were men. Of these, 50 (83%) had undergone previous cardiac surgery, including 22 (37%) composite valve graft operations. The preferred cannulation site was femoral-femoral (n = 27, 45%), with deep hypothermic circulatory arrest in 62% and retrograde cerebral perfusion in 33%; more recently, however, axillary cannulation has been preferred.

Results: Principal etiologies were graft infection in ascending aorta pseudoaneurysm and trauma in descending aorta pseudoaneurysm. Fifteen patients (25%) presented with chest pain, 13 (22%) with heart failure, and 20% with moderate or severe aortic regurgitation. The pseudoaneurysm was resected and the aorta replaced (n = 45, 75%) or repaired (n = 15, 25%) using various methods. Hospital mortality was 6.7% (n = 4). Reexploration for bleeding was required in 8.3%, and 3.3% had postoperative stroke. At 30 days, 5 years, and 10 years, survival was 94%, 74%, and 60% and freedom from reoperation was 95%, 77%, and 67%, respectively.

Conclusions: Most patients with aortic pseudoaneurysm require ascending aorta and/or arch replacement, which can be accomplished with low operative mortality and morbidity. Long-term survival and freedom from reoperation in these young patients parallel those expected for complex cardiac and aortic disease.
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http://dx.doi.org/10.1016/j.jtcvs.2006.03.052DOI Listing
August 2006

Surgery for permanent atrial fibrillation: impact of patient factors and lesion set.

Ann Thorac Surg 2006 Aug;82(2):502-13; discussion 513-4

Atrial Fibrillation Innovation Center (AFIC), The Cleveland Clinic Foundation, Cleveland, Ohio, USA.

Background: Whether a complete Cox-maze procedure is needed to ablate permanent atrial fibrillation in patients undergoing concomitant cardiac surgery is unknown. Our objective was to assess the effectiveness of different lesion sets in such patients.

Methods: From November 1991 to January 2004, 575 patients underwent surgical treatment of permanent atrial fibrillation (duration > 6 months); mitral valve disease was the primary indication for surgery in 74%. Procedures included pulmonary vein isolation alone (n = 68, 12%), pulmonary vein isolation with left atrial connecting lesions (n = 265, 46%), and Cox-maze (n = 242, 42%). Rhythm documented on 5,120 postoperative electrocardiograms was used to estimate time-related prevalence of, and risk factors for, atrial fibrillation.

Results: Prevalence of postoperative atrial fibrillation peaked at 46% two weeks after operation, declining to 24% at one year. Patient-related risk factors for increased prevalence included older age (p < 0.0001), larger left atrium (p < 0.0001), and longer duration of preoperative atrial fibrillation (p = 0.0008). The Cox-maze procedure and lesion sets resembling it created with alternative energy sources had a similarly low prevalence of late postoperative atrial fibrillation; in contrast, pulmonary vein isolation and lesion sets that did not include a lesion to the mitral anulus were less effective.

Conclusions: This study suggests that in cardiac surgical patients with permanent atrial fibrillation the left atrial lesion set should include wide pulmonary vein isolation, at least one connection between right and left pulmonary veins, and a connection to the mitral anulus. Availability of alternative energy sources to create lesions sets has virtually eliminated the need for the cut-and-sew Cox-maze procedure.
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http://dx.doi.org/10.1016/j.athoracsur.2006.02.030DOI Listing
August 2006

Duration of testosterone suppression after a 9.45 mg implant of the GnRH-analogue buserelin in patients with localised carcinoma of the prostate a 12-month follow-up study.

Eur Urol 2006 Sep 27;50(3):483-9. Epub 2006 Mar 27.

Department of Urology, Faculty of Health Sciences University Hospital, Linköping, Sweden.

Objectives: (1) To determine the duration of androgen deprivation after a single buserelin implant 9.45 mg in the neoadjuvant setting in combination with curative radiation therapy of carcinoma of the prostate, and (2) to evaluate the time to recovery of gonadal function, and the incidence and duration of hypogonadal symptoms.

Methods: We prospectively evaluated 21 men with carcinoma of the prostate who received one implant of 9.45 mg buserelin subcutaneously. Release of buserelin, changes in serum testosterone concentration, hot flushing and sexual function over a 12-month study period were recorded.

Results: Testosterone was suppressed below the castration limit (0.58 ng/ml=2 nmol/l) for 224 days (range, 139-309). The mean time to first return of testosterone above the castration limit was 246 days (range, 168-344); 50% of pre-treatment value was reached after 285 days (range, 218-370). The prevalence of hot flushing was 19 of 21 patients (90%) at 12 weeks. At the end of the study period, serum testosterone had reached 80% (range, 33%-166%) of pre-treatment concentration, sexual interest was present in 52%, erection was possible in 60%, and hot flushing remained in 24%.

Conclusion: A single injection of 3-month buserelin implant 9.45 mg suppresses serum testosterone below the castration limit for at least 6 months. Testosterone secretion recovers by 8-12 months. Hypogonadal symptoms decreased with the restoration of serum testosterone secretion. These data are clinically relevant regarding the dose schedule for buserelin and the patient information provided.
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http://dx.doi.org/10.1016/j.eururo.2006.03.001DOI Listing
September 2006

Does use of a right internal thoracic artery increase deep wound infection and risk after previous use of a left internal thoracic artery?

J Thorac Cardiovasc Surg 2006 Mar;131(3):609-13

Department of Thoracic and Cardiovascular Surgery, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

Objective: To determine whether adding right internal thoracic artery to previous left internal thoracic artery bypass at reoperation increases deep sternal wound infection and hospital mortality, particularly in diabetic patients.

Methods: Reoperations (n = 2875; 2381 men) in patients with previous left internal thoracic artery bypass were performed between January 1990 and January 2003; 1939 (67%) had no repeat internal thoracic artery grafting, 923 (32%) received an additional right internal thoracic artery graft, and 13 (0.5%) had bilateral internal thoracic artery grafting with reuse of the left internal thoracic artery. Of the patients, 352 (12%) were insulin-treated and 590 (21%) non-insulin-treated diabetics. Multivariable logistic regression analysis was used to identify preoperative variables associated with right versus non-right internal thoracic artery use in diabetics and nondiabetics and to formulate propensity models. Propensity scores were used for matching and adjusted multivariable analyses of deep wound infection and hospital mortality.

Results: Deep wound infection occurred in 3.0% (7/230) of diabetics receiving right internal thoracic artery grafts, 2.2% (5/230) of propensity-matched diabetics receiving non-right internal thoracic artery grafts (P = .6), in 1.1% (6/538) of nondiabetics receiving right internal thoracic artery grafts, and in 1.0% (5/538) of matched non-diabetic patients receiving non-right internal thoracic artery grafts (P = .8). Corresponding hospital mortality in these matched groups was 1.7% (4/230) versus 6.1% (14/230) for diabetics (P = .02) and 2.6% (14/538) versus 3.5% (19/538) for nondiabetics (P = .4). Risk factors for deep wound infection included higher weight (P = .0003), higher New York Heart Association functional class (P = .03), and less severe left anterior descending disease (P = .03). Risk factors for death were (P < .02) emergency operation, mitral valve replacement, and greater number of saphenous vein grafts.

Conclusions: Use of the right internal thoracic artery for reoperations does not increase the risk of deep wound infections in diabetics or nondiabetics and does not increase mortality.
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http://dx.doi.org/10.1016/j.jtcvs.2005.09.055DOI Listing
March 2006

Noise exposure and subjective hearing symptoms among school children in Sweden.

Noise Health 2005 Apr-Jun;7(27):27-37

Department of Audiology, Sahlgrenska University Hospital, Sahlgrenska Academy, Göteborg, Sweden.

Objective: The aim of the present study was to evaluate factors of importance for the experience of temporary threshold shift (TTS), noise- induced tinnitus (NIT), spontaneous tinnitus (ST) in school children.

Subjects And Methods: A total of 671 students aged 13-16 years old were asked to fill in a questionnaire containing items concerning TTS, NIT, ST, hearing loss (HL), heredity for HL, noise exposure, history of otitis media, symptoms of anxiety and depression, psychosocial factors and habits, life satisfaction, chronic medical conditions, age, gender and height. The questionnaire was filled in during school hours.

Results: Correlations were found with exercise and eating habits, sleep disturbances, BMI, depressive and anxiety disorders, heredity for HL and noise exposure dosage. The risk for TTS was nine times higher in students who reported having a verified hearing loss than in subjects without subjective or verified complaints of hearing loss. The risk for NIT was approximately four times higher in the group who visited concerts 6-12 times per year as compared to those who never attended concerts. There was almost a threefold increase in the risk for ST in the group that sometimes experienced TTS, as compared to those without TTS, and a tenfold increase in risk for ST in those who reported having a verified hearing loss.

Conclusion: In school children, exposure to leisure noise is correlated with tinnitus and the risk increases with increasing noise exposure. Sensitivity to subjective hearing loss has similar risk factors as seen for metabolic syndrome and we suggest that this sensitivity may be another side of metabolic syndrome.
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http://dx.doi.org/10.4103/1463-1741.31635DOI Listing
January 2006
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