| 1. |
- Ranebo, Mats, 1970-
(författare)
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Rotator Cuff Tears : Short- and long-term aspects on treatment outcome
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rotator cuff tear is a common disorder and there is a lack of knowledge of appropriate treatment and consequences of different treatment modalities. The overall aim of this thesis was to examine short- and long-term results of rotator cuff tear treatment.In Paper I we did a retrospective 21 to 25-year follow-up of a consecutive series of patients with partial and full-thickness rotator cuff tears, treated with acromioplasty without cuff repair. The cuff status had been documented in a specific perioperative protocol in all patients at the index operation. We did x-ray, ultrasonography and clinical scores with Constant score and Western Ontario Rotator Cuff index (WORC) at follow-up. We identified 111 patients with either a partial or a full-thickness tear, but at follow-up 21 were deceased and 11 were too ill from medical conditions unrelated to their shoulder. Out of the remaining 78 eligible patients, 69 were examined (follow-up rate 88 %) and they had a mean age at the index operation of 49 years (range 19-69 years). Forty-five had a partial tear and 24 a full-thickness tear at the index operation. At follow-up, 74% of patients with full-thickness tear had cuff tear arthropathy grade 2 or more according to the arthropathy classification of Hamada (grade 1 to 5) and 87% had developed tear progression (i.e. a larger tear). Corresponding numbers in those with a partial tear was 7 % arthropathy and 42 % tear progression, and the differences between the full-thickness group and the partial tear group was significant for both outcome measures (P<0.001 for both analyses). In those with arthropathy, the mean Constant score was 47 (standard deviation [SD], 23), the mean age and gender-adjusted Constant score 62 (SD, 27) and the mean WORC 58 % (SD, 26). Patients with a partial tear at follow-up had mean Constant score and WORC within the normal range. In multivariable analysis with logistic regression, having a full-thickness tear at the index operation was a risk factor for arthropathy (odds ratio [OR] 37.8; 95% confidence interval [CI], 8.2-175.0) and for tear progression (OR 6.09; 95% CI, 1.41-26.29).In Paper II we examined the contralateral shoulder in the same patients as in paper I and with the same methodology. Sixty-one patients were examined and 38 had had a partial tear at the index operation 21-25 years ago and 23 a full-thickness tear. The overall rate of contralateral full-thickness tears was 50.8 %, which is higher than the 16-35 % rate found in previous studies of newly diagnosed cuff patients. The rate of contralateral full-thickness tear ranged from 13.6 % in patients with a partial tear in the index shoulder at follow-up, to 90 % in patients with a full-thickness tear and arthropathy in the index shoulder. There was a significant correlation regarding conditions between shoulders in the same patient, with a Spearman coefficient of 0.72 for the number of ten-dons with a full-thickness tear, 0.31 for Hamada grade of arthropathy and 0.65 for Constant score. The number of tendons with a full-thickness tear in the index shoulder at follow-up was a risk factor for a contralateral full-thickness tear (OR 3.28; 95% CI, 1.67-6.44) in a multi-variable logistic regression model. We also found that cuff tear arthropathy was significantly more common in patients who had undergone an acromioplasty (P<0.001), a finding which is not confirmatory but may generate a hypothesis.Paper III addressed 17 to 20-year results after operation with a synthetic interposition graft for irreparable cuff tears. We used X-ray, ultrasonography and clinical scores at follow-up. We identified a consecutive series of 13 patients, one of whom was deceased at follow-up. Ten of the remaining 12 participated in a complete follow-up and 2 did only x-ray examination. Nine out of 12 (75 %; 95% CI, 43-95 %) had cuff tear arthropathy Hamada grade 2 or more in the index shoulder at follow-up. The mean Constant score was 46 (SD, 26) and the mean WORC 59 % (SD, 20). Seven out of 12 had contralateral cuff tear arthropathy, and the difference in frequency of arthropathy between shoulders was not statistically significant (P=0.667).In Paper IV we tested whether early repair of small cuff tears, involving mainly supraspinatus, would give a superior clinical result com-pared to physiotherapy without repair in a prospective randomised trial with 12 months follow-up. We used Constant score as the primary out-come, and WORC, EQ-VAS and Numerical Rating Scale for pain (NRS) as secondary outcomes. We also aimed at assessing the rate of tear progression in unrepaired shoulders and the healing rate in repaired shoulders by Magnetic Resonance Imaging (MRI) performed at 12 months. With a high grade of follow-up (100 % for 12 months Constant score and 95 % for 12 months MRI), the repair group had a 12 months median Constant score of 83 (Quartile range [QR], 25) and the conservative group 78 (QR, 22). This between-group difference in medians of 4.5 (95% CI,-5 to 9; P=0.68) was not statistically significant and we did not detect any significant differences in the secondary outcomes at 12 months. The retear rate was 6.5 % in repaired patients and 29 % of unrepaired patients had a tear enlargement >5 mm.The results in this thesis indicate that patients with small, traumatic, full-thickness tears of mainly supraspinatus have no clinical benefit of early surgical repair compared to physiotherapy alone, but in the long-term, patients with full-thickness tears have an increased risk of tear progression, cuff tear arthropathy and low clinical scores. These results are especially important in the treatment decision of repair or not in younger patients. Having a full-thickness tear is also a risk factor for having a contralateral cuff tear, a phenomenon that underlines the importance of endogenous factors in the development of rotator cuff tears. If a cuff tear is not repairable to bone, the addition of a synthetic inter-position graft does not seem to prevent cuff tear arthropathy.
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| 2. |
- Abdulrasak, Mohammed
(författare)
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EVAR of AAA: Long term outcomes, disease progression and risk stratification
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundEndovasvular aortic repair (EVAR) is the most commonly utilised technique for the treatment of abdominal aorticaneurysms (AAA) in tertiary referral centers. Detailed long-term outcomes of this technique are relatively scarce,especially for patients presenting symptomatically with AAA. Intra-operatively, proximal type Ia endoleak, involvingblood circulating into the AAA – due to poor proximal seal of the endograft to the aortic neck region – is a fearedcomplication which is usually promptly treated, given its association with post-operative AAA expansion andrupture. Aneurysmatic disease is usually considered a progressive pathology with potential for progression toareas of the aorta beyond the known aneurysmatic segment. Arterial calcifications are established as a marker foratherosclerosis, yet the association of ilio-femoral calcification with post-operative mortality after EVAR is notknown.Aims1. Evaluate the long-term results of EVAR of AAA using a single endograft2. Compare the early and late results of EVAR of symptomatically presenting patients to those treated asymptomatically3. Study the long-term results of intra-operative treatment of type Ia endoleak using large, balloon expandable stents4. Study the progression of aortic disease for patients treated with endovascular means in the postoperative period5. Assess the novel ilio-femoral calcium score as a potential predictor for overall and cardiac-specific mortality after EVARResultsEVAR of AAA yields sustainable results in the long-term, for both symptomatic and asymptomatic patients. Thereis ≈ x4 elevated early mortality in symptomatic patients as compared to asymptomatic ones. Intra-operativetreatment of type Ia endoleaks using large, balloon-expandable stents should be reserved to patients treatedacutely with EVAR. Aortic expansion beyond the sealing zone is relatively uncommon, and seems related to theforce exerted on the aortic wall by the endograft. Ilio-femoral calcium score may predict long-term overall andcardiac mortality after EVAR, albeit the relation is weak. Therefore, further studies are needed to establish thisassociation.
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| 3. |
- Byenfeldt, Marie, 1967-
(författare)
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Ultrasound based shear wave elastography of the liver : a non-invasive method for evaluation of liver disease
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Detecting liver disease at an early stage is important, given that early intervention decreases the risk of developing cirrhosis and subsequently hepatocellular cancer (HCC). The non-invasive ultrasound-based shear wave elastography (SWE) has been used clinically for a decade to assess liver stiffness. This method is reliable, rapid and can be performed in an outpatient setting without known risks for the patient. However, increased variance in SWE results has been detected, without clear explanation. Factors that affect SWE results needs to be identified. Data are insufficient regarding the reliability of SWE with different body positions and probe pressures. Men have higher SWE results than women, also for unclear reasons. Increasing the reliability of SWE is crucial for understanding how factors such as overweight and obesity, cardiovascular and antiviral medication, age, sex, smoking habits, hepatic steatosis and cirrhosis affect SWE results.Aims: The overall aim of the studies included in this thesis was to increase the reliability of SWE liver. The specific aims were to investigate patient-related factors associated with increased uncertainty in SWE results. Another aim was to investigate the influence of increased intercostal probe pressure on liver stiffness assessment with SWE liver. The final aims were to investigate the influence of postural changes, sagittal abdominal diameter (SAD) and skin-to-liver capsule distance (SCD) on SWE results, along with sex-based differences for SWE results and cardiovascular medication.Methods: All enrolled participants in these studies were consecutive patients with various liver diseases presenting at the radiology department Östersunds Hospital. The patients were examined using SWE liver method at the ultrasound unit between April 2014 and May 2018. Inclusion criteria were that participants be adults (age ≥18 years) who had provided written consent for participating in the study. The exclusion criterion was an inability to communicate. Current guidelines for SWE of the liver were used in the thesis with the following exceptions: In study II, increased intercostal probe pressure was used, and in study III, postural change was used. Study I included 188 patients; study II included 112 patients, and studies III and IV involved 200 patients. The four studies were conducted as cross-sectional and clinical trial, using quantitative methods.Results: Factors associated with low variance for SWE results were age, sex, and presence of cirrhosis, the use of antiviral and/or cardiovascular medication, smoking habits, and body mass index. Factors associated with increased uncertainty in SWE results were increased SCD and the presence of steatosis. With increased probe pressure SCD decreased and the quality of shear wave increased. The results showed that the number of required measurements can be reduced. A postural change to left decubitus decreased SCD. For patients with increased SAD and increased SWE result in the supine position, SWE result decreased with a postural change to left decubitus. The SWE results, SCD and SAD significantly differed between women and men. SWE results was higher in the presence of increased SAD (≥23 cm) among men, but not among women.Conclusions: SWE of the liver is a reliable, non-invasive method for diagnosing liver disease. Results in this thesis suggest that for patients with SCD ≥2.5 cm, shear wave measures could be of poor quality and the SWE exam less reliable. In these cases, increased probe pressure may facilitate a reliable SWE exam. With such adjustments in probe pressure, the ultrasound-based SWE method can be superior for examination in patients with overweight or obesity. An effect of SAD ≥23 cm was seen for men with liver fibrosis only, which may explain the higher SWE result for men compared to women. Depending on the severity of liver disease and SAD, a postural change to left decubitus can produce a different outcome. As SAD increased, liver stiffness did, as well. Increased SAD thus is linked to increased liver stiffness, indicating that SAD should be taken into account when performing SWE of the liver.
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| 4. |
- Malmgren, Linnea
(författare)
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Kidney Function During Ageing and its Association with Bone Mass, Fracture and Mortality
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Osteoporosis and osteoporosis related fractures are a major health care challenge both in Sweden and globally. The cost and suffering from osteoporosis are expected to increase since the population of elderly is increasing. Bone health can be affected by altered mineral homeostasis, which in its turn can be affected by reduced kidney function. However, the course of age-related decline in kidney function and its association to osteoporosis andfracture in the very elderly need further investigation since longitudinal data are scarce. Therefore, this thesis has two main aims; 1) to investigate kidney function during ageing and 2) its association to bone health in a cohort ofelderly women.Data was collected through the Malmö Osteoporosis Prospective Risk Assessment (OPRA) cohort, a prospective cohort of 1044 community dwelling women, all aged 75 and followed for ten years with reinvestigations at age 80and 85. Data on BMD, fracture and blood biochemistry was available at all three time points.Estimated kidney function greatly depends on which marker and study equation is used. The discrepancies are to such an extent that could affect whether a person is diagnosed with chronic kidney disease (CKD) or not, of particular importance in the elderly. Only women with the worst kidney function, corresponding to CKD stage 3b-5, had continuously increased mortality risk. This indicates that an age-dependent CKD definition would be of valuein elderly women.Kidney function in elderly women was associated with markers of mineral homeostasis, bone loss and BMD, but the effect size was relatively small compared to other risk factors. Also, fracture risk was increased only in womenwith mild-moderate reduction of kidney function (CKD stage 3a) and not in women with the worst kidney function (CKD stage 3b-5). Low BMD was associated with increased fracture risk independent of kidney function. Havingboth reduced kidney function and osteoporosis could present an additional risk increase.In conclusion, estimated kidney function in elderly women greatly depends on method of estimation and the results advocate for an age-adapted CKD definition. Maintaining adequate kidney function is important formaintaining bone health, although in old age it is probable that the effect size of any single specific risk factor is smaller compared with younger individuals.
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| 5. |
- Moseby-Knappe, Marion
(författare)
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Prediction of neurological outcome after cardiac arrest and targeted temperature management
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Prediction of neurological outcome in unconscious patients after cardiac arrest (CA) forms the basis for decisions on further level-of-care based on results from clinical neurological examinations, neuroimaging (CT or MRI), neurophysiology (EEG or SSEP) and blood biomarkers of brain injury. Methods must be highly specific to avoid misclassifying patients with possibilities of a good outcome. In 2015, the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM) published an algorithm to identify poor outcome patients after CA. Novel methods to analyse biomarkers of brain injury have become available and may prove superior to the recommended marker Neuron-specific enolase (NSE). Purpose: I) To describe findings on head computed tomography (CT) after CA, and evaluate the prognostic accuracy of generalised oedema. II & III) To explore the prognostic accuracies of 3 novel blood biomarkers after CA: the axonal marker serum Neurofilament light (NFL), the astrocytic Glial fibrillary acidic protein (GFAP) and the neuronal marker Ubiquitin C-terminal hydrolase (UCH-L1). IV) To assess the predictive performance of the ERC/ESICM algorithm and modifications thereof. To describe prognostic accuracies of single and combined prognostic methods as recommended by the ERC/ESICM.Methods: All patients participated in the Target Temperature after Out-of-hospital cardiac arrest (TTM) trial, a prospective international multicentre trial randomising adult patients with CA of presumed cardiac origin to targeted temperature managements of 33°C or 36°C for 24 hours. Papers I and IV are retrospective studies utilizing information from the TTM database. Serum samples studied in Papers II and III were collected prospectively at 24, 48 and 72 hours post-arrest, and stored in a biobank for batch analysis after trial completion. Primary outcome was poor neurological outcome, defined as Cerebral Performance Category Scale 3-5 (severe cerebral disability, vegetative state or death) at 6 months follow-up.Results: I) Early CT examinations ≤24h were usually normal. Subacutely, generalised oedema was the most common finding, and strongly associated with poor outcome. II) Already at 24 hours post-arrest, serum NFL analysed with an ultrasensitive assay (Simoa) predicted poor neurological outcome with higher prognostic accuracy than any prognostic method currently recommended in the ERC/ESICM algorithm. NFL also differentiatied between various levels of brain injury. II) GFAP and UCH-L1 may be useful as early markers 24h after CA, yet at 48 and 72 hours their prognostic accuracies were not superior to neuron specific enolase. GFAP and UCH-L1 were not elevated in hemolysis, which may prove an advantage compared to NSE. IV) The ERC/ESICM algorithm predicted poor outcome without false positive predictions (100% specificity) and identified approximately fourty percent of patients with poor outcome. Any two pathological findings according to the ERC/ESICM criteria predicted poor outcome without false positive predictions, regardless of level of unconsciousness. Withdrawal of life-sustaining-therapy (WLST) was common in the TTM trial and may have influenced our results.Conclusions: Prognostication after CA should always be multimodal. The current ERC/ESICM algorithm safely predicted poor outcome, but could benefit from minor modifications. Serum NFL has the potential to guide treatment decisions, both to predict poor outcome and to identify patients with a presumed good neurological prognosis where further treatment is life-saving.
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| 6. |
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| 7. |
- Hayden, Jane M.
(författare)
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The effect of intra-abdominal local anaesthetics following major gynaecological surgery. Clinical and experimental studies
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Local anaesthetics (LA), in addition to inhibition of pain signalling, also have anti-inflammatory properties. In vitro studies have demonstrated anti-proliferative and cytotoxic effect of LAs on cancer cells when administered in therapeutic concentrations. Intraperitoneal administrated LA is shown to reduce pain, improve surgical recovery and to blunt the postsurgical inflammatory response. Retrospective studies have indicated beneficial oncological outcome of regional anaesthesia on cancer recurrence when used in cancer surgery. Abdominal hysterectomy causes moderate to severe pain, and assessing new tools for pain treatment is crucial. The postoperative period of extensive surgery for advanced ovarian cancer is associated with high morbidity. When the patients have recovered from cancer surgery, chemotherapy can be initiated. New therapeutic approaches to enhanced recovery with reduced postoperative pain and inflammation is of great interest. Methods and aim: The thesis aimed to evaluate the efficacy of intra-abdominal local anaesthetics on pain, inflammatory response, serum concentration of LA and patient recovery after gynaecological surgery (study I, II and III). The aim of study IV was to determine the effects of LA on ovarian cancer cells in vitro. The clinical studies were prospective, double blind, randomized and placebo-controlled. In study I, women scheduled for abdominal hysterectomy, were randomised to local infiltration analgesia (Group LIA) or placebo (group C). Rescue analgesic consumption and opioid related side effects were analysed. In study II and III, women undergoing cytoreductive surgery for advanced ovarian cancer were randomised to receive either intraperitoneal ropivacaine (Group IPLA) or saline (Group Control) peroperatively. Inflammatory markers in serum, LA concentrations (study II), and objective measures of patient comfort, postoperative complications, pain, home readiness and time to initiation of chemotherapy (study III) were analysed. In study IV proliferation and migration in two ovarian cancer cell lines, exposed to LA in concentrations corresponding to doses used in study II and III, were analysed. Analysis of cancer stem cells (CSC) phenotypes were performed. Results: The median supplemental requirements of morphine during 0–24 hours after abdominal hysterectomy was significantly lower in group LIA compared to group C (18 mg vs. 27 mg, p = 0.028) and the median time to first analgesic injection was significantly longer in group LIA (40 min vs. 20 min, p = 0.005) (Study I). Perioperative intraperitoneal LA resulted in significantly decreased serum cortisol levels. Serum concentrations of ropivacaine were well below toxic concentrations (study II). Time to initiation of chemotherapy was significantly shorter in group IPLA (Median 21, IQR 19-29 vs. 29 days, IQR 21-40, p = 0.021). No differences in standardised recovery endpoints were found between the groups (Study III) . The laboratory study showed a significantly reduced cell number and an inhibited cell migration. Cell size were significantly increased and CSC phenotype analysis showed a reduction in all cells by up to 50% (Study IV). Discussion: Local infiltration analgesia results in a significantly lower rescue morphine consumption following abdominal hysterectomy. Intraperitoneal local anestetics can be administered in ovarian cancer cytoreductive surgery safely, without achieving toxic doses. Although IPLA do not provide further anti-inflammatory effects, the stress response is briefly blunted and there might be positive effects such as earlier start of chemotherapy. LA reduce the ability of cancer cells to metastasise. Intra-abdominal LA offers a potential to have beneficial effects on pain, recovery and circulating tumour cells after gynaecological surgery.
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| 8. |
- Djekic, Demir, 1989-
(författare)
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Novel and Traditional Risk Factors for Coronary Artery Disease : Role of Coronary Artery Calcium, Lipidomics, Psychosocial Factors and Diet
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The aim of the research reported in this thesis was to determine the association of novel and traditional risk factors with coronary artery calcium (CAC), a marker of subclinical coronary artery disease (CAD) in healthy individuals. In addition, we investigated the effects of a vegetarian, compared to a meat diet, on novel and traditional risk factors in patients with diagnosed CAD.Methods: Studies I-II evaluated the inter-laboratory reproducibility of liquid chromatography-mass spectrometry (LC-MS) lipid analysis and the association of serum lipidome with CAC in a cohort of 70 patients. Studies III and IV analysed data of 1067 participants in the pilot study of the Swedish CArdioPulmonary bioImage Study to determine associations of psychosocial (residential area, education, housing, and social support) and traditional risk factors with CAC. Cardiac computed tomography was used to obtain a coronary artery calcium score (CACS) (Studies I–IV). Study V employed a crossover design in which 31 patients with CAD were randomly allocated to a four-week vegetarian diet alternating with four weeks of an isocaloric meat diet. Enzyme-linked immunosorbent assay was used to measure oxidised LDL-cholesterol. Plasma metabolome, including choline, trimethylamine N-oxide, L-carnitine, and acetyl-carnitine, as well as plasma lipidome were determined with LC-MS. Gut microbiota and faecal short- and branched-chain fatty acids were analysed with 16S rRNA gene sequencing and gas chromatography-MS, respectively.Results: In Study I, two laboratories independently identified six lipids in common that differentiated serum of patients with CACS >250 from that of those with CACS=0. Study II, revealed higher levels of phosphatidylcholine(PC)(16:0/20:4) and lower levels of PC(18:2/18:2), PC(36:3) and phosphatidylethanolamine (PE)(20:0/18:2) in patients with CACS >250 than found in those with CACS=0. Study III showed a CACS >0 prevalence of 46.3% and 36.6% in low and high socioeconomic residential areas, respectively, but the traditional risk factor–adjusted odds ratio for CACS >0 was not significantly higher in subjects living in low socioeconomic areas. In Study III, the traditional risk factor–adjusted odds ratio for CACS >100 relative to CACS=0 was significantly higher in women with low education level and living in a rented apartment. Studies III and IV showed traditional risk factor–adjusted odds ratios for CACS >0 to be significantly higher in women with a family history of premature cardiovascular disease and low social support. No relationship of psychosocial factors with CAC was observed in men. The vegetarian diet implemented in Study V significantly lowered mean oxidized LDL-cholesterol (-2.73 U/L), total cholesterol (-0.13 mmol/L), LDL-cholesterol (-0.10 mmol/L), and body mass index (-0.21 kg/m2), as well as the relative abundance of PCs, PEs, and several microbial genera compared with the meat diet. The effect of the vegetarian diet on oxidized LDL-C was associated with higher relative abundance of Ruminococcaceae genera and of Barnesiella and reduced abundance of Flavonifractor. The vegetarian diet lowered the relative abundance of ceramide(d18:1/16:0) and triacylglycerols with saturated fatty acyl chains and raised the relative abundance of triacylglycerols with high carbon and polyunsaturated fatty acyl chains compared with the meat diet.Conclusions: Novel and traditional cardiovascular risk factors are associated with subclinical CAD. Psychosocial factors are associated with subclinical CAD in women, but not in men. Short-term intervention with a vegetarian diet in individuals with CAD can positively impact novel and traditional factors that have been associated with risk of future cardiovascular events.
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| 9. |
- Jamaly, Shabbar, 1965
(författare)
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Obesity, Weight Loss and Cardiovascular Risk
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The global prevalence of obesity is on the rise, contributing to increased incidence and prevalence of cardiovascular morbidity and mortality. Obesity has adverse effects on cardiac structure and function, directly through a hemodynamic overload, and indirectly through cardiovascular risk factors and low-grade inflammation. Still, epidemiologic studies have found that once cardiovascular disease has developed, people with obesity may experience better prognosis than those with normal weight; a phenomenon termed “the obesity paradox”. Aims: The objects of the present thesis were: 1) to investigate the effect of surgically induced long-term weight loss on the incidence of atrial fibrillation and heart failure; 2) to study possible mechanisms linking obesity to the development of heart failure; and 3) to examine the prognostic significance of different BMI categories on outcomes in a cohort of patients with ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI) Method: We analyzed data from the Swedish Obese Subjects (SOS) study, a prospective matched intervention study comparing bariatric surgery (n=2,010) and conventional obesity treatment (n=2,040). The SOS data was merged with the Swedish National Patient Register (NPR) and with the Cause of Death Register (COD). Data from the SOS obese control group was used to study the link between obesity and heart failure (n=2,040). Data from the Swedish Registry of Catheter-borne Coronary Vessel Surgery (SCAAR) (n=25,384) was merged with the COD Register to study the prognostic significance of different BMI classes. Results: Surgically induced weight loss resulted in a significantly lower incidence of atrial fibrillation and heart failure during long-term follow-up. Atrial fibrillation and myocardial infarction, as time-dependent variables, were strongly related to incident heart failure. In patients with STEMI treated with PCI, those with BMI > 30 kg/m2 had the best outcome in unadjusted analysis, but after adjustment for age and sex individuals with BMI 25-30 kg/m2 displayed the best prognosis. Underweight patients with BMI < 18.5 kg/m2 had the highest 30-day and 1-year mortality. Conclusion: In people with severe obesity, bariatric surgery induced a substantial and a sustained weight loss, which resulted in a lower incidence of atrial fibrillation and heart failure. Atrial fibrillation is probably reflected by diastolic dysfunction and myocardial infarction is likely to be related to systolic dysfunction, proposing two different mechanistic pathways for the development of heart failure. Overweight displays the lowest risk for 30-day and 1-year mortality after PCI treatment of STEMI.
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| 10. |
- Johansson Kostenniemi, Urban, 1987-
(författare)
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Bacterial meningitis in children : clinical aspects and preventive effects of vaccinations
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bacterial meningitis, one of the most severe infections a child can contract, can be caused by several different strains of bacteria. Most commonly, Haemophilus influenzae type b (Hib), Streptococcus pneumoniae and Neisseria meningitidis. These colonize the upper respiratory tract, then either cause localized infections acting as primary foci or directly spread to the brain. As preventive measure, general infant Hib and pneumococcal vaccinations were introduced in Sweden in 1993 and in 2009, respectively. Although evaluated extensively elsewhere, their long-term effects in Arctic regions are less studied. For the individual child with bacterial meningitis, treatment involves many challenges starting with correctly identifying the condition, guiding treatment, and finally identifying both short-term and long-term disabilities.In this thesis, the overall aim was to study clinical aspects of bacterial meningitis and preventive effects of vaccinations in an Arctic region. We used two datasets in the Västerbotten Region to investigate incidence rates during the time-periods adjacent to vaccine introductions. This allowed us to study the preventive effects of general infant vaccinations on bacterial meningitis in one of the Swedish Arctic regions. More precisely, we investigated changes in incidence of bacterial meningitis and sepsis during the period of 1986-2015 and of respiratory tract infections during the period of 2005-2014, in the Västerbotten Region, Sweden. We also reviewed medical records of children being treated for bacterial meningitis in the Västerbotten Region to study clinical presentation, short-term outcome, and to develop a new predictive score for identifying adverse outcome and need of invasive procedures. Additionally, by reviewing medical records and child health records from discharge and onwards we assessed long-term disabilities and evaluated clinical guidelines’ follow-up recommendations.Following introduction of general infant Hib vaccination, incidence of all-cause bacterial meningitis and Haemophilus meningitis in children aged one month to four years declined by 82.3% and 95.3%, respectively. Likewise, all-cause bacterial meningitis and pneumococcal meningitis declined by 48.0% and 67.5%, respectively, following pneumococcal vaccination. In addition, incidence of sepsis caused by H. influenzae and by S. pneumonia also decreased in the same age group. Finally, respiratory tract infections in children under five years of age decreased following pneumococcal vaccination; by 41.5% for all-cause acute otitis media, by 80.7% for sinusitis and by 28.6% for pneumonia.At admission to the hospital, difference in clinical presentation mostly depended on age. Younger children were more ill at admission but also presented with more diffuse symptoms. When evaluating clinical decision rules for detecting bacterial meningitis, none reached 100% sensitivity. The predictive score developed by us could identify all children in need of invasive procedures to manage the intracerebral pressure and were graded as excellent in the ROC analysis at this task. However, neither this score nor any other could adequately predict complications or death. Finally, permanent disabilities affected more than half of surviving children with psychiatric disease being diagnosed in 30%, and another 5% had ongoing investigations for symptoms of psychiatric disease. Notably, psychiatric disabilities were detected late, in average 14 years after having had bacterial meningitis.From these findings, we concluded that vaccinations are excellent at protecting children against bacterial meningitis, also in the Arctic region, with the added bonus of providing protection against sepsis and less severe infections such as pneumonia and acute otitis media. Further, treating children with bacterial meningitis involves several challenges starting with correctly identifying this sever disease. For this task, no clinical decision rule is perfect. When making difficult treatment decisions such as deciding on invasive procedures to manage the intracerebral pressure, the predictive score developed and tested by us, the MeningiSSS, can be very helpful. Finally, permanent disabilities may be more common than previously thought. With more than one third of survivors being affected by psychiatric disabilities, specific long-term follow-up strategies are needed to reduce suffering caused by undetected psychiatric disabilities.
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