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- Ahl, Rebecka, 1987-
(author)
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The Association Between Beta-Blockade and Clinical Outcomes in the Context of Surgical and Traumatic Stress
- 2019
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Doctoral thesis (other academic/artistic)abstract
- Traumatic injury and major abdominal surgery are areas in general surgery associated with high rates of morbidity and mortality. The overall colorectal cancer surgery mortality rate is around 4%, with that for emergency surgery more than twice as high as for planned. Surgical morbidity varies between 25% and 45%. Around half of trauma patients develop low mood. In one quarter of patients this becomes permanent. Depression is known to impede physical rehabilitation and recovery. The onset of physiological stress, driven by adrenergic hyperactivity following traumatic and surgical injury is hypothesized to contribute to these adverse outcomes. Interest has therefore been sparked into blocking adrenergic receptor activation.Papers I and II investigated the role of beta-blocker therapy in preventing post-traumatic depression following severe traumatic brain injury (Paper I) and severe extracranial injury (Paper II). The Karolinska University Hospital Trauma Registry was used to identify patients admitted between 2007 and 2011. In Paper I (n = 545), patients on pre-injury beta-blocker therapy were matched to beta-blocker naïve patients with equivalent injury burden. Results revealed that beta-blocked patients exhibited a 60% reduced risk of needing antidepressant therapy within one year of trauma. In Paper II (n = 596), the lack of beta-blocker use before extracranial trauma was linked to a three-fold increase in the risk of antidepressant initiation.Papers III-V explored the role of pre-operative beta-blocker therapy in patients undergoing surgery for colorectal cancer between 2007 and 2016, identified using the nationwide Swedish Colorectal Cancer Registry. Paper III (n = 3,187) identified a 69% reduction in the risk of 30-day mortality in beta-blocked patients. Paper IV (n = 22,337) outlined long-term survival benefits for patients on beta-blocker therapy prior to undergoing elective surgery for colon cancer. Beta-blocked patients showed a risk reduction of 42% for 1-year all-cause mortality and 18% for 5-year cancerspecific mortality. Similarly, patients on beta-blocker therapy who underwent surgery for rectal cancer demonstrated improved survival up to one year after surgery with a risk reduction of 57% and a reduction in anastomotic failure and infectious complications in Paper V (n = 11,966).
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| 2. |
- Dehlaghi Jadid, Kaveh, 1985-
(author)
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Long-term outcome, socioeconomic aspects and postoperative inflammatory response in minimally invasive rectal cancer surgery
- 2024
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Doctoral thesis (other academic/artistic)abstract
- In Sweden, more than 2,200 individuals are diagnosed with rectal cancer each year and surgical resection is the cornerstone of treatment. Minimally invasive surgery (MIS) was introduced for abdominal rectal cancer resection in the 1990s. Proven advantages of MIS in the short term include less intraoperative bleeding, less postoperative pain, faster postoperative mobilization, and shorter hospital stay. Large randomized studies have also shown that MIS is not inferior to OPEN with regard to the oncological short-term or long-term outcome.The aim of this thesis was to increase the knowledge of MIS from a Swedish perspective regarding long-term oncological outcome, socioeconomic aspects, and the postoperative inflammatory response in curative abdominal rectal cancer surgery.Study I included all patients who were diagnosed with clinical stage I-III rectal cancer during 2010-2016. More than 8,300 patients were identified via the Swedish Colorectal Cancer Registry (SCRCR). The study had a so-called non-inferiority design and investigated overall 5-year survival. The results showed that survival was not worse in patients who underwent minimally invasive surgery in comparison to patients who underwent open surgery.Study II included all patients who were diagnosed with pathological stage I-III cancer of the colon 2010-2016. More than 11,000 patients were identified via the SCRCR. The study was designed in the same way as Study I. The results demonstrated that minimally invasive surgery was not inferior to open surgery.Study III analysed the potential impact of socioeconomic status, measured as level of education and household income, regarding the likelihood of receiving minimally invasive surgery. All patients who underwent curative abdominal rectal resection surgery during 2010-2016 were included. More than 8,000 patients were identified. The results showed that patients with the highest level of education and those in the highest income quartile were more likely to be operated on with minimally invasive technique.Study IV analysed the inflammatory response, measured as serum C-reactive protein during postoperative days 1-5, in all 520 patients undergoing abdominal rectal resection in Örebro between 2011 and 2021. Following exclusions based on postoperative adverse events, 382 patients remained for final analysis. The study demonstrated a trend for a less pronounced inflammatory response in patients operated with robot-assisted laparoscopy compared with conventional laparoscopy.
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| 3. |
- Meehan, Adrian, 1973-
(author)
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Lithium-associated hyperparathyroidism : Prevalence, Pathophysiology, Management
- 2018
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Doctoral thesis (other academic/artistic)abstract
- Lithium has been used in the treatment of bipolar disorder, formerly called manic depression, for nearly seven decades. Lithium-associated hyperparathyroidism (LHPT) is an ill-defined and less well known possible side-effect of chronic lithium therapy and was first described in 1973. The condition has been considered to be rare, though there exists conflicting evidence as to its prevalence, its pathophysiological background, and, if and when identified, what the appropriate medical or surgical treatment should be. The principal aim of this thesis was to understand and more comprehensively characterise this condition through studying a large patient cohort, with regards its prevalence, development, and additionally by providing an evaluation of surgical management up until now.In Study I a population of 423 lithium-treated out-patients (251 women, 172 men) were recruited from Jönköping and Örebro County. We found that 18% met the criteria for hyperparathyroidism (HPT) and that a further 21% had intermittent episodes of hypercalcaemia. We then examined, in Study II, the effects of lithium only in patients with bipolar disorder and compared them, firstly, to patients with bipolar disorder without lithium and, secondly, to a control population. In total, 563 individuals participated in the study. Hypercalcaemia was found to be strongly associated to lithium therapy (adjusted OR 13.45; 95% CI 3.09, 58.55; p=0.001). Study III is a descriptive study of calcium homeostasis in 297 lithium-treated patients from Jönköping where three main groups could be discerned: 178 were normocalcaemic (60%), 102 hypercalcaemic (34%), and 17 hypocalcaemic (6%). Many patients demonstrate robust fluctuations in serum calcium intermittently. Of those with suspected LHPT, 31% had urinary calcium excretion values be-low 1.2 mmol/24hrs. Study IV analysed surgical results of 78 parathyroidectomies in 71 patients with concurrent lithium therapy. In strong contrast to surgical outcomes in those with primary HPT, the overall cure-rate was lower (58%) and the predominant histological diagnosis was hyperplasia (52%). Two patients had double adenomas.Factors which should be particularly taken into consideration while monitoring lithium-treated patients are age, gender and lithium-duration.
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| 4. |
- Sjölin, Gabriel, 1979-
(author)
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Hyperthyroidism : a chronic disease?
- 2021
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Doctoral thesis (other academic/artistic)abstract
- During 2003-2005, approximately 3,000 de novo hyperthyroid patients were collected in Sweden and became one of the world's largest hyperthyroidism studies. This dissertation shows that many people diagnosed with hyperthyroidism live with its impacts even after excess of thyroid hormone has ended. These include repeated recurrences, multiple treatments, replacement therapy, little sense of recovery, and reduced Quality Of life(QoL). Patients were categorised into two groups, Graves' disease (GD) and toxic nodular goitre (TNG), studied separately. Overall, just over 1,400 patients, or 60% of dispatches, answered the questionnaires. 1186 GD, 237 TNG. Most patients were women and GD's mean age was around 40 years, while TNG patients were 20 years older, reflecting the same patternas previous studies. The incidence of 27/100,000 persons per year might not seem large, but considering the proposed chronic nature of hyperthyroidism, prevalence is high (0.7%). Around two in three people diagnosed with hyperthyroidism will live with thyroid hormone replacement. This could be attributed, that GD patients over time receive more ablative treatment, despite the fact that less receive it as the first treatment. Another explanation the recurrence risk of ATD-treated patients exceeds 50%. Levothyroxine treatment did not vary between TNG treatments. Repeated, often multiple, treatments in TNG patients are rarely described. This implies TNG may be more complex than anticipated. Hyperthyroid patients have worse QoL 6-10 years following diagnosis than the general public. RAI treated patients with GD had more affected long-term thyroid-specific and generic QoL than ATD and surgical patients. Surprisingly, there was no clear QoL difference between GD and TNG. GD is often seen as a severe condition than TNG, as TNG has a milder course of disease. Hyperthyroidism has long-term impacts, affecting a relatively large population. This dissertation's findings indicate a chronic nature of hyperthyroidism.
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| 5. |
- Ahl, Rebecka, 1987-, et al.
(author)
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Effects of beta-blocker therapy on mortality after elective colon cancer surgery : a Swedish nationwide cohort study
- 2020
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In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 10:7
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Colon cancer surgery remains associated with substantial postoperative morbidity and mortality despite advances in surgical techniques and care. The trauma of surgery triggers adrenergic hyperactivation which drives adverse stress responses. We hypothesised that outcome benefits are gained by reducing the effects of hyperadrenergic activity with beta-blocker therapy in patients undergoing colon cancer surgery. This study aims to test this hypothesis.DESIGN: Retrospective cohort study.SETTING AND PARTICIPANTS: This is a nationwide study which includes all adult patients undergoing elective colon cancer surgery in Sweden over 10 years. Patient data were collected from the Swedish Colorectal Cancer Registry. The national drugs registry was used to obtain information about beta-blocker use. Patients were subdivided into exposed and unexposed groups. The association between beta-blockade, short-term and long-term mortality was evaluated using Poisson regression, Kaplan-Meier curves and Cox regression.PRIMARY AND SECONDARY OUTCOMES: Primary outcome of interest was 1-year all-cause mortality. Secondary outcomes included 90-day all-cause and 5-year cancer-specific mortality.RESULTS: The study included 22 337 patients of whom 36.1% were prescribed preoperative beta-blockers. Survival was higher in patients on beta-blockers up to 1 year after surgery despite this group being significantly older and of higher comorbidity. Regression analysis demonstrated significant reductions in 90-day deaths (IRR 0.29, 95% CI 0.24 to 0.35, p<0.001) and a 43% risk reduction in 1-year all-cause mortality (adjusted HR 0.57, 95% CI 0.52 to 0.63, p<0.001) in beta-blocked patients. In addition, cancer-specific mortality up to 5 years after surgery was reduced in beta-blocked patients (adjusted HR 0.80, 95% CI 0.73 to 0.88, p<0.001).CONCLUSION: Preoperative beta-blockade is associated with significant reductions in postoperative short-term and long-term mortality following elective colon cancer surgery. Its potential prophylactic effect warrants further interventional studies to determine whether beta-blockade can be used as a way of improving outcomes for this patient group.
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