| 1. |
- Andersson, H. Ingemar, 1950-, et al.
(författare)
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Characteristics of subjects with chronic pain, in relation to local and widespread pain report : a prospective study of symptoms, clinical findings and blood tests in subgroups of a geographically defined population
- 1996
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Ingår i: Scandinavian Journal of Rheumatology. - 0300-9742 .- 1502-7732. ; 25:3, s. 146-154
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Tidskriftsartikel (refereegranskat)abstract
- The relation between reported chronic pain and clinical findings was studied by comparing survey data six months before and eighteen months after a clinical examination. Studied individuals (n = 165) were randomly selected from subsamples of an initial survey (n = 1806) to a general population. Among individuals reporting chronic pain 85% were assessed to have chronic pain at the examination. Diagnoses were found in 22% of examined pain individuals. Myofascial pain syndrome and myalgia were the most common findings. Compared with located neck-shoulder pain, widespread pain had a greater impact on the individual, a worse prognosis regarding pain duration and working capacity, and revealed a raised serum urate level of unclear significance. Although no specific cause of pain is found in individuals with widespread pain it is important to identify and treat this group due to the great effects on functional capacity and the worse prognosis.
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| 2. |
- Andersson, H. Ingemar, 1950-, et al.
(författare)
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Chronic pain in a geographically defined general population : studies of differences in age, gender, social class, and pain localization.
- 1993
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Ingår i: The Clinical Journal of Pain. - 0749-8047 .- 1536-5409. ; 9:3, s. 174-182
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To establish basic epidemiological data on chronic pain (duration > 3 months) in a defined population. Relationships between age, gender, and social class were tested. DESIGN: A survey of pain symptoms, including location, intensity, duration, and functional capacity, was conducted by means of a mail questionnaire. SETTING: General populations in two Swedish primary health care districts. Medical care was provided in a state health system. SUBJECTS: A random sample (from the population register) of 15% of the population aged 25-74 (n = 1,806). The response rate was 90%. OUTCOME MEASURES: Descriptive epidemiologic data in relation to objectives of the study. RESULTS: Without sex differences, 55% (95% confidence interval, 53-58%) of the population had perceived persistent pain for 3 months and 49% for 6 months. Among individuals with chronic pain, 90% localized their pain to the musculoskeletal system to a variable extent. Women experienced more multiple localizations of pain and had pain in the neck, shoulder, arm, and thigh to a greater extent than men. Prevalence of pain increased by age up to 50-59 years for both genders and then slowly decreased. The neck-shoulder area was the most common site of pain (30.2%), followed by the lower back (23.2%). Even in the youngest age groups more than one of four reported chronic pain. Blue-collar workers and employers (including farmers) reported chronic pain to a greater extent than other groups. In 13% of the population, manifest pain problems were associated with reduced functional capacity. CONCLUSION: Chronic pain symptoms are common but unevenly distributed in a general population. The results may influence planning and consultation in primary health care as well as warranting selective prevention activities.
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| 3. |
- Andersson, H. Ingemar, et al.
(författare)
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Chronic pain in a geographically defined general population : studies of differences in age, gender, social class, and pain localization.
- 1993
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Ingår i: The Clinical Journal of Pain. - 0749-8047. ; 9:3, s. 174-182
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To establish basic epidemiological data on chronic pain (duration > 3 months) in a defined population. Relationships between age, gender, and social class were tested. DESIGN: A survey of pain symptoms, including location, intensity, duration, and functional capacity, was conducted by means of a mail questionnaire. SETTING: General populations in two Swedish primary health care districts. Medical care was provided in a state health system. SUBJECTS: A random sample (from the population register) of 15% of the population aged 25-74 (n = 1,806). The response rate was 90%. OUTCOME MEASURES: Descriptive epidemiologic data in relation to objectives of the study. RESULTS: Without sex differences, 55% (95% confidence interval, 53-58%) of the population had perceived persistent pain for 3 months and 49% for 6 months. Among individuals with chronic pain, 90% localized their pain to the musculoskeletal system to a variable extent. Women experienced more multiple localizations of pain and had pain in the neck, shoulder, arm, and thigh to a greater extent than men. Prevalence of pain increased by age up to 50-59 years for both genders and then slowly decreased. The neck-shoulder area was the most common site of pain (30.2%), followed by the lower back (23.2%). Even in the youngest age groups more than one of four reported chronic pain. Blue-collar workers and employers (including farmers) reported chronic pain to a greater extent than other groups. In 13% of the population, manifest pain problems were associated with reduced functional capacity. CONCLUSION: Chronic pain symptoms are common but unevenly distributed in a general population. The results may influence planning and consultation in primary health care as well as warranting selective prevention activities.
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| 4. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 5. |
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| 6. |
- Dreyer, Bo, et al.
(författare)
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Spectrum of USH2A mutations in Scandinavian patients with Usher Syndrome type II
- 2008
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Ingår i: Human Mutation. - : Wiley-Liss. - 1059-7794 .- 1098-1004. ; 29:3, s. 451-451
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Tidskriftsartikel (refereegranskat)abstract
- Usher syndrome type II (USH2) is an autosomal recessive disorder, characterised by moderate to severe high-frequency hearing impairment, normal balance function and progressive visual impairment due to retinitis pigmentosa. Usher syndrome type IIa, the most common subtype, is defined by mutations in the USH2A gene encoding a short and a recently discovered long usherin isoform comprising 21 and 73 exons, respectively. More than 120 different disease-causing mutations have been reported, however, most of the previous reports concern mutations restricted to exons 1-21 of the USH2A gene. To explore the spectrum of USH2A disease-causing mutations among Scandinavian USH2 cases, patients from 118 unrelated families of which 27 previously had been found to carry mutations in exons 1-21 were subjected to extensive DNA sequence analysis of the full size USH2A gene. Altogether, 122 USH2A DNA sequence alterations were identified of which 57 were predicted to be disease-causing, 7 were considered to be of uncertain pathogenicity and 58 were predicted to be benign variants. Of 36 novel pathogenic USH2A mutations 31 were located in exons 22-73, specific to the long isoform. USH2A mutations were identified in 89/118 (75.4%) families. In 79/89 (88.8%) of these families two pathogenic mutations were identified whereas in 10/89 (11.2%) families the second mutation remained unidentified. In 5/118 (4.2%) families the USH phenotype could be explained by mutations in the USH3A gene. The results presented here provide a comprehensive picture of the genetic aetiology of Usher syndrome type IIA in Scandinavia as it is known to date.
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| 7. |
- Eklund, Arne, 1957-
(författare)
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Laparoscopic or Open Inguinal Hernia Repair - Which is Best for the Patient?
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Inguinal hernia repair is the most common operation in general surgery. Its main challenge is to achieve low recurrence rates. With the introduction of mesh implants, first in open and later in laparoscopic repair, recurrence rates have decreased substantially. Therefore, the focus has been shifted from clinical outcome, such as recurrence, towards patient-experienced endpoints, such as chronic pain. In order to compare the results of open and laparoscopic hernia repair, a randomised multicentre trial - the Swedish Multicentre trial of Inguinal hernia repair by Laparoscopy (SMIL) - was designed by a study group from 11 hospitals. Between November 1996 and August 2000, 1512 men aged 30-70 years with a primary inguinal hernia were randomised to either laparoscopic (TEP, Totally ExtraPeritoneal) or open (Lichtenstein) repair. The primary endpoint was recurrence at five years. Secondary endpoints were short-term results, frequency of chronic pain and a cost analysis including complications and recurrences up to five years after surgery. In total, 1370 patients, 665 in the TEP and 705 in the Lichtenstein group, underwent operation. With 94% of operated patients available for follow-up after 5.1 years, the recurrence rate was 3.5% in the TEP and 1.2% in the Lichtenstein group. Postoperative pain was lower in the TEP group up to 12 weeks after operation, resulting in five days less sick leave and 11 days shorter time to full recovery. Patients in the TEP group had a slightly increased risk of major complications. Chronic pain was reported by 9-11% of patients in the TEP and 19-25% in the Lichtenstein group at the different follow-up points. Hospital costs for TEP were higher than for Lichtenstein, while community costs were lower due to shorter sick leave. By avoiding disposable laparoscopic equipment, the cost for TEP would be almost equal compared with Lichtenstein. In conclusion, both TEP and Lichtenstein repair have advantages and disadvantages for the patient. Depending on local resources and expertise both methods can be used and recommended for primary inguinal hernia repair.
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| 8. |
- Hakkaart, C, et al.
(författare)
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Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers
- 2022
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 1061-
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Tidskriftsartikel (refereegranskat)abstract
- The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09–1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.
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| 9. |
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| 10. |
- Mark, Daniel B., et al.
(författare)
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Comprehensive Quality-of-Life Outcomes With Invasive Versus Conservative Management of Chronic Coronary Disease in ISCHEMIA
- 2022
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Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 145:17, s. 1294-1307
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) compared an initial invasive treatment strategy (INV) with an initial conservative strategy in 5179 participants with chronic coronary disease and moderate or severe ischemia. The ISCHEMIA research program included a comprehensive quality-of-life (QOL) substudy.METHODS: In 1819 participants (907 INV, 912 conservative strategy), we collected a battery of disease-specific and generic QOL instruments by structured interviews at baseline; at 3, 12, 24, and 36 months postrandomization; and at study closeout. Assessments included angina-related QOL (19-item Seattle Angina Questionnaire), generic health status (EQ-5D), depressive symptoms (Patient Health Questionnaire-8), and, for North American patients, cardiac functional status (Duke Activity Status Index).RESULTS: Median age was 67 years, 19.2% were female, and 15.9% were non-White. The estimated mean difference for the 19-item Seattle Angina Questionnaire Summary score favored INV (1.4 points [95% CI, 0.2-2.5] over all follow-up). No differences were observed in patients with rare/absent baseline angina (SAQ Angina Frequency score >80). Among patients with more frequent angina at baseline (SAQ Angina Frequency score <80, 744 patients, 41%), those randomly assigned to INV had a mean 3.7-point higher 19-item Seattle Angina Questionnaire Summary score than conservative strategy (95% CI, 1.6-5.8) with consistent effects across SAQ subscales: Physical Limitations 3.2 points (95% CI, 0.2-6.1), Angina Frequency 3.2 points (95% CI, 1.2-5.1), Quality of Life/Health Perceptions 5.3 points (95% CI, 2.8-7.8). For the Duke Activity Status Index, no difference was estimated overall by treatment, but in patients with baseline SAQ Angina Frequency scores <80, Duke Activity Status Index scores were higher for INV (3.2 points [95% CI, 0.6-5.7]), whereas patients with rare/absent baseline angina showed no treatment-related differences. Moderate to severe depression was infrequent at randomization (11.5%-12.8%) and was unaffected by treatment assignment.CONCLUSIONS: In the ISCHEMIA comprehensive QOL substudy, patients with more frequent baseline angina reported greater improvements in the symptom, physical functioning, and psychological well-being dimensions of QOL when treated with an invasive strategy, whereas patients who had rare/absent angina at baseline reported no consistent treatment-related QOL differences.
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| 11. |
- Maron, David J., et al.
(författare)
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Initial Invasive or Conservative Strategy for Stable Coronary Disease
- 2020
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 382:15, s. 1395-1407
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Tidskriftsartikel (refereegranskat)abstract
- Background: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain.Methods: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction.Results: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32).Conclusions: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, .) Patients with stable coronary disease were randomly assigned to an initial invasive strategy with angiography and revascularization if appropriate or to medical therapy alone. At 3.2 years, there was no significant difference between the groups with respect to the estimated rate of ischemic events. The findings were sensitive to the definition of myocardial infarction.
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| 12. |
- Newman, Jonathan D., et al.
(författare)
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Biomarkers and cardiovascular events in patients with stable coronary disease in the ISCHEMIA Trials
- 2023
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Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 266, s. 61-73
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Tidskriftsartikel (refereegranskat)abstract
- ImportanceBiomarkers may improve prediction of cardiovascular events for patients with stable coronary artery disease (CAD), but their importance in addition to clinical tests of inducible ischemia and CAD severity is unknown.ObjectivesTo evaluate the prognostic value of multiple biomarkers in stable outpatients with obstructive CAD and moderate or severe inducible ischemia.Design and settingThe ISCHEMIA and ISCHEMIA CKD trials randomized 5,956 participants with CAD to invasive or conservative management from July 2012 to January 2018; 1,064 participated in the biorepository.Main outcome measuresPrimary outcome was cardiovascular death, myocardial infarction (MI), or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. Secondary outcome was cardiovascular death or MI. Improvements in prediction were assessed by cause-specific hazard ratios (HR) and area under the receiver operating characteristics curve (AUC) for an interquartile increase in each biomarker, controlling for other biomarkers, in a base clinical model of risk factors, left ventricular ejection fraction (LVEF) and ischemia severity. Secondary analyses were performed among patients in whom core-lab confirmed severity of CAD was ascertained by computed cardiac tomographic angiography (CCTA).ExposuresBaseline levels of interleukin-6 (IL-6), high sensitivity troponin T (hsTnT), growth differentiation factor 15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP), lipoprotein a (Lp[a]), high sensitivity C-reactive protein (hsCRP), Cystatin C, soluble CD 40 ligand (sCD40L), myeloperoxidase (MPO), and matrix metalloproteinase 3 (MMP3).ResultsAmong 757 biorepository participants, median (IQR) follow-up was 3 (2-5) years, age was 67 (61-72) years, and 144 (19%) were female; 508 had severity of CAD by CCTA available. In an adjusted multimarker model with hsTnT, GDF-15, NT-proBNP and sCD40L, the adjusted HR for the primary outcome per interquartile increase in each biomarker was 1.58 (95% CI 1.22, 2.205), 1.60 (95% CI 1.16, 2.20), 1.61 (95% 1.22, 2.14), and 1.46 (95% 1.12, 1.90), respectively. The adjusted multimarker model also improved prediction compared with the clinical model, increasing the AUC from 0.710 to 0.792 (P < .01) and 0.714 to 0.783 (P < .01) for the primary and secondary outcomes, respectively. Similar findings were observed after adjusting for core-lab confirmed atherosclerosis severity.Conclusions and relevanceAmong ISCHEMIA biorepository participants, biomarkers of myocyte injury/distension, inflammation, and platelet activity improved cardiovascular event prediction in addition to risk factors, LVEF, and assessments of ischemia and atherosclerosis severity. These biomarkers may improve risk stratification for patients with stable CAD.
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| 13. |
- Reynolds, Harmony R., et al.
(författare)
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Sex Differences in Revascularization, Treatment Goals, and Outcomes of Patients With Chronic Coronary Disease : Insights From the ISCHEMIA Trial
- 2024
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Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundWomen with chronic coronary disease are generally older than men and have more comorbidities but less atherosclerosis. We explored sex differences in revascularization, guideline‐directed medical therapy, and outcomes among patients with chronic coronary disease with ischemia on stress testing, with and without invasive management.Methods and ResultsThe ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial randomized patients with moderate or severe ischemia to invasive management with angiography, revascularization, and guideline‐directed medical therapy, or initial conservative management with guideline‐directed medical therapy alone. We evaluated the primary outcome (cardiovascular death, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) and other end points, by sex, in 1168 (22.6%) women and 4011 (77.4%) men. Invasive group catheterization rates were similar, with less revascularization among women (73.4% of invasive‐assigned women revascularized versus 81.2% of invasive‐assigned men; P<0.001). Women had less coronary artery disease: multivessel in 60.0% of invasive‐assigned women and 74.8% of invasive‐assigned men, and no ≥50% stenosis in 12.3% versus 4.5% (P<0.001). In the conservative group, 4‐year catheterization rates were 26.3% of women versus 25.6% of men (P=0.72). Guideline‐directed medical therapy use was lower among women with fewer risk factor goals attained. There were no sex differences in the primary outcome (adjusted hazard ratio [HR] for women versus men, 0.93 [95% CI, 0.77–1.13]; P=0.47) or the major secondary outcome of cardiovascular death/myocardial infarction (adjusted HR, 0.93 [95% CI, 0.76–1.14]; P=0.49), with no significant sex‐by‐treatment‐group interactions.ConclusionsWomen had less extensive coronary artery disease and, therefore, lower revascularization rates in the invasive group. Despite lower risk factor goal attainment, women with chronic coronary disease experienced similar risk‐adjusted outcomes to men in the ISCHEMIA trial.
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| 14. |
- Rosenberg, Mark, et al.
(författare)
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Vision zero in disease eradication
- 2022
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Ingår i: The Vision Zero Handbook: Theory, Technology and Management for a Zero Casualty Policy. - Cham : Springer International Publishing. ; , s. 1165-1193
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Road safety has come a long way in our lifetimes, and there are steps in this progress that mark their place in history. Many of these were technical innovations, such as seat belts, electronic stability control, and geofencing for vehicle speed control. Also important, though perhaps fewer in number, were innovations in strategies to achieve change. These include the public health model of Dr. William Haddon, the introduction of Vision Zero, the World Report on Road Traffic Injury Prevention from WHO and the World Bank, and more recently, the Decade of Action 2011-2020. I am sure that the work and recommendations presented in this report will deserve their place in a "Hall of Fame" for strategic innovation in saving lives across the globe.
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| 15. |
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