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  • 1.
    Ahl, Rebecka
    et al.
    Örebro University, School of Medical Sciences. Division of Trauma and Emergency Surgery, Department of Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Barmparas, Galinos
    Division of Acute Care Surgery and Surgical Critical Care, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, USA.
    Riddez, Louis
    Division of Trauma and Emergency Surgery, Department of Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Ley, Eric J.
    Division of Acute Care Surgery and Surgical Critical Care, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, USA.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Division of Trauma and Emergency Surgery, Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Division of Trauma and Emergency Surgery, Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Mohseni, Shahin
    Örebro University, School of Medical Sciences. Örebro University Hospital. Division of Trauma and Emergency Surgery, Department of Surgery, Örebro University Hospital, Örebro, Sweden; Division of Trauma and Emergency Surgery, Department of Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Does beta-blockade reduce the risk of depression in patients with isolated severe extracranial injuries?2017In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 41, no 7, p. 1801-1806Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Approximately half of trauma patients develop post-traumatic depression. It is suggested that beta-blockade impairs trauma memory recollection, reducing depressive symptoms. This study investigates the effect of early beta-blockade on depression following severe traumatic injuries in patients without significant brain injury.

    METHODS: Patients were identified by retrospectively reviewing the trauma registry at an urban university hospital between 2007 and 2011. Severe extracranial injuries were defined as extracranial injuries with Abbreviated Injury Scale score ≥3, intracranial Abbreviated Injury Scale score <3 and an Injury Severity Score ≥16. In-hospital deaths and patients prescribed antidepressant therapy ≤1 year prior to admission were excluded. Patients were stratified into groups based on pre-admission beta-blocker status. The primary outcome was post-traumatic depression, defined as receiving antidepressants ≤1 year following trauma.

    RESULTS: Five hundred and ninety-six patients met the inclusion criteria with 11.4% prescribed pre-admission beta-blockade. Patients receiving beta-blockers were significantly older (57 ± 18 vs. 42 ± 17 years, p < 0.001) with lower Glasgow Coma Scale score (12 ± 3 vs. 14 ± 2, p < 0.001). The beta-blocked cohort spent significantly longer in hospital (21 ± 20 vs. 15 ± 17 days, p < 0.01) and intensive care (4 ± 7 vs. 3 ± 5 days, p = 0.01). A forward logistic regression model was applied and predicted lack of beta-blockade to be associated with increased risk of depression (OR 2.7, 95% CI 1.1-7.2, p = 0.04). After adjusting for group differences, patients lacking beta-blockers demonstrated an increased risk of depression (AOR 3.3, 95% CI 1.2-8.6, p = 0.02).

    CONCLUSIONS: Pre-admission beta-blockade is associated with a significantly reduced risk of depression following severe traumatic injury. Further investigation is needed to determine the beneficial effects of beta-blockade in these instances.

  • 2.
    Ahl, Rebecka
    et al.
    Örebro University, School of Medical Sciences. Department of Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Matthiessen, Peter
    School of Medical Science, Örebro University, Örebro, sweden; Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Sjölin, Gabriel
    Örebro University, School of Medical Sciences. Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department of Surgery, Örebro University Hospital, Örebro, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Mohseni, Shahin
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery.
    The Effects of Beta-Blocker Therapy on Mortality After Elective Colon Cancer SurgeryManuscript (preprint) (Other academic)
  • 3.
    Giesecke, Peter
    et al.
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
    Frykman, Viveka
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
    Wallin, Göran K.
    Örebro University, School of Medical Sciences. Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden; Department of Surgery, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Lönn, Stefan
    Department of Research and Development, Region Halland, Halmstad, Sweden.
    Discacciati, Andrea
    Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
    Törring, Ove
    Department of Clinical Research and Education, Karolinska Institute, Stockholm, Sweden.
    Rosenqvist, Mårten
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
    All-cause and cardiovascular mortality risk after surgery versus radioiodine treatment for hyperthyroidism2018In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 105, no 3, p. 279-286Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Little is known about the long-term side-effects of different treatments for hyperthyroidism. The few studies previously published on the subject either included only women or focused mainly on cancer outcomes. This register study compared the impact of surgery versus radioiodine on all-cause and cause-specific mortality in a cohort of men and women.

    METHODS: Healthcare registers were used to find hyperthyroid patients over 35 years of age who were treated with radioiodine or surgery between 1976 and 2000. Comparisons between treatments were made to assess all-cause and cause-specific deaths to 2013. Three different statistical methods were applied: Cox regression, propensity score matching and inverse probability weighting.

    RESULTS: Of the 10 992 patients included, 10 250 had been treated with radioiodine (mean age 65·1 years; 8668 women, 84·6 per cent) and 742 had been treated surgically (mean age 44·1 years; 633 women, 85·3 per cent). Mean duration of follow-up varied between 16·3 and 22·3 years, depending on the statistical method used. All-cause mortality was significantly lower among surgically treated patients, with a hazard ratio of 0·82 in the regression analysis, 0·80 in propensity score matching and 0·85 in inverse probability weighting. This was due mainly to lower cardiovascular mortality in the surgical group. Men in particular seemed to benefit from surgery compared with radioiodine treatment.

    CONCLUSION: Compared with treatment with radioiodine, surgery for hyperthyroidism is associated with a lower risk of all-cause and cardiovascular mortality in the long term. This finding was more evident among men.

  • 4.
    Giesecke, Peter
    et al.
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Rosenqvist, Mårten
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Frykman, Viveka
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Friberg, Leif
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Surgery, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Höijer, Jonas
    Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Lönn, Stefan
    Research and Development, Region Halland, Halmstad, Sweden.
    Törring, Ove
    Department of Clinical Research and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
    Increased Cardiovascular Mortality and Morbidity in Patients Treated for Toxic Nodular Goiter Compared to Graves' Disease and Nontoxic Goiter2017In: Thyroid, ISSN 1050-7256, E-ISSN 1557-9077, Vol. 27, no 7, p. 878-885Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Previous research has suggested an increased risk of death and cardiovascular disease in patients treated for hyperthyroidism. However, studies on this subject are heterogeneous, often based on old data, or have not considered the impact that treatment for hyperthyroidism might have on cardiovascular risk. It is also unclear whether long-term prognosis differs between Graves' disease and toxic nodular goiter. The aim of this study was to use a very large cohort built on recent data to assess whether improvements in cardiovascular care might have changed the prognosis over time. The study also investigated the impact of different etiologies of hyperthyroidism.

    METHODS: This was an observational register study for the period 1976-2012, with subjects followed for a median period of 18.4 years. Study patients were Stockholm residents treated for Graves' disease or toxic nodular goiter with either radioactive iodine or surgery (N = 12,239). This group was compared to Stockholm residents treated for nontoxic goiter (N = 3685), with adjustments made for age, sex, comorbidities, and time of treatment. Comparisons were also made to the general population of Stockholm. Outcomes were assessed in terms of all-cause and cardiovascular mortality as well as cardiovascular morbidity.

    RESULTS: The hazard ratios (HR) for all-cause mortality and for cardiovascular mortality were 1.27 [confidence interval (CI) 1.20-1.35] and 1.29 [CI 1.17-1.42], respectively, for hyperthyroid patients compared to those with nontoxic goiter. For cardiovascular morbidity, the HR was 1.12 [CI 1.06-1.18]. Patients aged ≥45 years who were treated for toxic nodular goiter were generally at greater risk than others, and those included from the year 1990 and onwards were at greater risk than those included earlier. Increased all-cause mortality, as well as cardiovascular mortality and morbidity, were also seen in comparisons with the general population.

    CONCLUSIONS: This is the first large study to indicate that the long-term risk of death and cardiovascular disease in hyperthyroid subjects is due to the hyperthyroidism itself and not an effect of confounding introduced by its treatment. Much of the excess risk is confined to individuals treated for toxic nodular goiter. Despite advances in cardiovascular care during recent decades, hyperthyroidism is still a diagnosis associated with increased cardiovascular morbidity and mortality.

  • 5.
    Meehan, Adrian David
    et al.
    Örebro University, School of Medical Sciences. Department of Geriatrics, Örebro University Hospital, Örebro, Sweden.
    Humble, Mats B.
    Örebro University, School of Medical Sciences. Psychiatric Research Centre, Örebro University Hospital, Örebro, Sweden.
    Yazarloo, Payam
    Department of Psychiatry, Ryhov Hospital, Jönköping, Sweden .
    Järhult, Johannes
    Department of Surgery, Ryhov Hospital, Jönköping, Sweden .
    Wallin, Göran
    Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Reply to comments From Dr Lozano, et al - Concerning the prevalence of lithium-associated hyperparathyroidism2016In: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 36, no 2, p. 191-192Article in journal (Refereed)
  • 6.
    Meehan, Adrian David
    et al.
    Örebro University, School of Medical Sciences. Department of Geriatrics, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Udumyan, Ruzan
    Örebro University, School of Medical Sciences.
    Kardell, Mathias
    Section of Psychiatry and Neurochemistry, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Sahlgrenska University Hospital, Gothenburg, Sweden.
    Landén, Mikael
    Section of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden: Sahlgrenska University Hospital, Gothenburg, Sweden.
    Järhult, Johannes
    Department of Surgery, Ryhov Hospital, Jönköping, Sweden.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Department of Surgery, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Lithium-Associated Hypercalcemia: Pathophysiology, Prevalence, Management2018In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 42, no 2, p. 415-424Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Lithium-associated hypercalcemia (LAH) is an ill-defined endocrinopathy. The aim of the present study was to determine the prevalence of hypercalcemia in a cohort of bipolar patients (BP) with and without concomitant lithium treatment and to study surgical outcomes for lithium-associated hyperparathyroidism.

    METHODS: Retrospective data, including laboratory results, surgical outcomes and medications, were collected from 313 BP treated with lithium from two psychiatric outpatient units in central Sweden. In addition, data were collected from 148 BP without lithium and a randomly selected control population of 102 individuals. Logistic regression was used to compare odds of hypercalcemia in these respective populations.

    RESULTS: The prevalence of lithium-associated hypercalcemia was 26%. Mild hypercalcemia was detected in 87 out of 563 study participants. The odds of hypercalcemia were significantly higher in BP with lithium treatment compared with BP unexposed to lithium (adjusted OR 13.45; 95% CI 3.09, 58.55; p = 0.001). No significant difference was detected between BP without lithium and control population (adjusted OR 2.40; 95% CI 0.38, 15.41; p = 0.355). Seven BP with lithium underwent surgery where an average of two parathyroid glands was removed. Parathyroid hyperplasia was present in four patients (57%) at the initial operation. One patient had persistent disease after the initial operation, and six patients had recurrent disease at follow-up time which was on average 10 years.

    CONCLUSION: The high prevalence of LAH justifies the regular monitoring of calcium homeostasis, particularly in high-risk groups. If surgery is necessary, bilateral neck exploration should be considered in patients on chronic lithium treatment. Prospective studies are needed.

  • 7.
    Meehan, Adrian
    et al.
    Örebro University, School of Medical Sciences.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Järhult, Johannes
    Ryhov Hospital, Jönköping, Sweden.
    Characterization of Calcium homeostasis in Lithium-treated Patients: Disturbances reveal both hypercalcemia and hypocalcemiaManuscript (preprint) (Other academic)
  • 8.
    Sjölin, Gabriel
    et al.
    Örebro University, School of Medical Sciences.
    Holmberg, Mats
    Karolinska Universitetssjukhuset, ANOVA, Stockholm, Sweden.
    Törring, Ove
    Karolinska Institute, Stockholm County, Stockholm, Sweden.
    Byström, Kristina
    Örebro Lans Landsting, Dept. of Medicine, Örebro, Örebro, Sweden.
    Khamisi, Selwan
    Akademiska sjukhuset, Dept. of Endocrinology and diabetes, Uppsala, Sweden.
    de Laval, Dorota
    Blekingesjukhuset i Karlskrona, Department of Medicine, Karlskrona, Sweden.
    Abraham-Nordling, Mirna
    Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Stockholm County, Sweden.
    Calissendorff, Jan
    Karolinska Universitetssjukhuset, Dept. of Endocrinology, Metabolism and Diabetes, Stockholm, Sweden.
    Lantz, Mikael
    Lund University, Lund, Sweden.
    Hallengren, Bengt
    Lund University, Lund, Sweden.
    Filipsson Nyström, Helena
    Sahlgrenska Academy, Dept. of Endocrinology, Göteborg, Sweden.
    Wallin, Göran
    Örebro University, School of Medical Sciences. Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden.
    The long-term outcome of treatment for Graves' hyperthyroidism2019In: Thyroid, ISSN 1050-7256, E-ISSN 1557-9077Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The treatment efficacy of antithyroid drug therapy(ATD), radioactive iodine(I131) or surgery for Graves' hyperthyroidism is well described. However, there are few reports on the long-term total outcome of each treatment modality as how many require levothyroxine supplementation, the need of thyroid ablation or the individual patient's estimation of their recovery.

    METHODS: We conducted a pragmatic trial to determine the effectiveness and adverse outcome in a patient cohort newly diagnosed with Graves' hyperthyroidism between 2003-2005(n=2430). The patients were invited to participate in a longitudinal study spanning 8±0.9years(mean±SD) after diagnosis. We were able to follow 1186(60%) patients that had been treated with ATD, I131 or surgery. We determined the mode of treatment, remission rate, recurrence, quality of life, demographic data, comorbidities and lifestyle factors through questionnaires and review of the individual medical history records.

    RESULTS: At follow-up the remission rate after first line treatment choice with ATD was 45.3%(351/774), with I131therapy 81.5%(324/264) and with surgery96.3%(52/54). Among those patients who had a second course of ATD 29.4% achieved remission. The total number of patients who had undergone ablative treatment was 64.3%(763/1186), of which 23%(278/1186) had received surgery, 43%(505/1186) I131therapy including 2%(20/1186) who received both surgery and I131. Patients who received ATD as first treatment and possibly additional ATD had 49.7%risk(385/774) of having undergone ablative treatment at follow-up. Levothyroxine replacement was needed in 23%(81/351) of the initially ATD treated in remission, in 77.3%(204/264) of the I131treated and in 96.2%(50/52) of the surgically treated patients. Taken together after 6-10 years, and all treatment considered, normal thyroid hormone status without thyroxine supplementation was only achieved in 35.7%(423/1186) of all patients and in only 40.3% of those initially treated with ATD. The proportion of patients that did not feel fully recovered at follow-up was25.3%.

    CONCLUSION: A patient selecting ATD therapy as the initial approach in the treatment of Graves' hyperthyroidism should be informed that they have only a 50.3%chance of ultimately avoiding ablative treatment and only a 40%chance of eventually being euthyroid without thyroid medication. Surprisingly, 1in4 patients did not feel fully recovered after 6-10 years. The treatment for Graves' hyperthyroidism, thus has unexpected long-term consequences for many patients.

  • 9.
    Törring, Ove
    et al.
    Karolinska Institutet, Institution for Clinical Science and Education, Stockholm, Sweden .
    Watt, Torquil
    Copenhagen University Hospital Rigshospitalet, Department of Medical Endocrinology, Copenhagen, Danmark, Denmark .
    Sjölin, Gabriel
    Örebro University, School of Medical Sciences. Department of Surgery.
    Byström, Kristina
    Örebro University, School of Medical Sciences.
    Abraham-Nordling, Mirna
    Karolinska Institute, Institute of molecular medicine and surgery, Colorectal surgery, Karolinska University Hospital, Stockholm, Sweden .
    Calissendorff, Jan
    Dept. of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden.
    Cramon, Per
    Copenhagen University Hospital Rigshospitalet, Department of Endocrinology, Copenhagen, Denmark .
    Filipsson Nyström, Helena
    Dept. of Endocrinology, Sahlgrenska University Hospital, Göteborg, Sweden .
    Hallengren, Bengt
    Dept. of Endocrinology, Skånes University Hospital, Malmö, Sweden.
    Holmberg, Mats
    ANOVA, Karolinska University Hospital, Stockholm, Sweden.
    Khamisi, Selwan
    Dept. of Endocrinology, Uppsala University Hospital, Uppsala, Sweden .
    Lantz, Mikael
    Lund University, Department of Clinical Sciences, Diabetes & Endocrinology, Department of Endocrinology, Skåne University Hospital, Malmö, Sweden .
    Wallin, Göran
    Örebro University, School of Medical Sciences. Karolinska Institutet, Department of Molecular Medicine and Surgery, Stockholm, Sweden; Örebro University, Dept of Surgery, Faculty of Medicine and Health, Sweden, Sweden .
    Impaired Quality of Life After Radioiodine Therapy Compared to Antithyroid Drugs or Surgical Treatment for Graves’ Hyperthyroidism: A Long-Term Follow-Up with the Thyroid-Related Patient-Reported Outcome Questionnaire and 36-Item Short Form Health Status Survey2019In: Thyroid, ISSN 1050-7256, E-ISSN 1557-9077, Vol. 29, no 3, p. 322-331Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Hyperthyroidism is known to have a significant impact on the quality of life (QoL) at least in the short term. The purpose of the present study was to assess QoL in patients at 6-10 years after treatment for Graves' disease (GD) with radioiodine (RAI) to those treated with thyroidectomy or antithyroid drugs (ATD) as assessed with both a thyroid-specific (ThyPRO) and general (SF-36) QoL surveys.

    METHODS: We evaluated 1186 GD patients in a sub-cohort from an incidence study 2003-2005 which had been treated according to routine clinical practice at seven participating centers. Patients were included if they had returned the ThyPRO (n=975) and/or the SF-36 questionnaire (n=964) and informed consent at follow-up. Scores from ThyPRO were compared with scores from a general population sample (n=712), using multiple linear regression adjusting for age and gender as well as multiple testing. Treatment related QoL outcome for ATD, RAI and surgery were compared including adjustment for the number of treatments received, sex, age and co-morbidity.

    RESULTS: Regardless of treatment modality, patients with GD had worse thyroid-related QoL 6-10 years after diagnosis compared with the general population. Patients treated with RAI had worse thyroid-related and general QoL than patients treated with ATD or thyroidectomy on the majority of QoL-scales. Sensitivity analyses supported the relative negative comparative effects of RAI treatment on QoL in patients with hyperthyroidism.

    CONCLUSIONS: Graves' disease is associated with a lower QoL many years after treatment compared to the general population. In a previous, small RCT we did not show any difference in patient satisfaction years after ATD, RAI or surgery. We now report that in a large non-randomized cohort, patients who received RAI had adverse scores on ThyPRO and SF-36. These findings in a Swedish population are limited by comparison to normative data from Denmark, by older age and possibly a more prolonged course in those patients who received radioiodine, and a lack of information regarding thyroid status at the time of evaluation. The way RAI may adversely affect QoL is unknown but since the results may be important for future considerations regarding treatment options for GD they need to be substantiated in further studies.

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