| 1. |
- Bengtsson, Bonnie
(författare)
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Liver cirrhosis : epidemiology, prognosis, and cancer
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Liver cirrhosis is a major risk factor for hepatocellular carcinoma (HCC). Patients with liver cirrhosis also have a high risk to develop infections leading to deterioration of liver function and increased mortality. In this PhD-thesis, our aim was to improve the ability to predict risk of developing liver cancer and infections in patients with cirrhosis. In study I, all patients diagnosed with HCC at the Karolinska University Hospital between 2004 and 2018 were included. Patients with HCC and underlying non-alcoholic fatty liver disease (NAFLD) were characterized in detail to investigate their prognosis compared to that of other patients with HCC. In study II, we included randomly selected patients with an international classification of disease (ICD)-code corresponding to cirrhosis and cirrhosis complications registered in the national patient registry (NPR) between 2000 and 2016 to investigate the positive predictive value (PPV) of liver-related ICD-codes. In study III, all patients with cirrhosis registered in the outpatient part of the NPR were included to investigate rate and risk of HCC in cirrhosis. In study IV, we included patients with cirrhosis seen at the Hepatology clinic at the Karolinska University Hospital and obtained a blood test from the participants analyzed for fractions of mucosal-associated invariant T (MAIT) cells. Patient were followed prospectively for risk of bacterial infection and hepatic decompensation. In study I, we included 1,562 patients with HCC, and 225 (14%) of these had NAFLD. We report that NAFLD is a growing cause of HCC. One third of the patients with NAFLD-HCC had no clinical signs of cirrhosis. NAFLD patients were older than non-NAFLD patients, and non-cirrhotic NAFLD patients were even older than NAFLD patients with cirrhosis. Survival was similar between patients with NAFLD and non-NAFLD and between patients with cirrhotic and non-cirrhotic NAFLD. In study II, we found that ICD-10 codes for cirrhosis and esophageal varices had a PPV above 90%, whereas HCC had a PPV of 84%. Ascites had an unsatisfactorily low PPV of 43% for liver-related ascites, but when combined with a code indicating chronic liver disease, the PPV increased to 91%. In study III we included 15,215 individuals with cirrhosis and report that the rate of HCC in cirrhosis is 23/1,000 person-years with a lower-than-expected cumulative risk at five and ten years of 8.3% and 12.2% respectively. The cancer risk varied significantly depending on sex, age, and etiology of liver disease. In study IV, we included 106 patients with cirrhosis and found that relatively preserved MAIT cell fractions were associated with a higher risk of bacterial infections in patients with cirrhosis. In conclusion, we describe NAFLD HCC-patients with and without cirrhosis and found that patients with non-cirrhotic NAFLD are older. We suggest that any surveillance attempts in this patient group should take age into account. ICD-codes for cirrhosis and esophageal varices have a high PPV, but when using ICD-10 code for ascites to identify patients with cirrhosis, we recommend adding another code for chronic liver disease to obtain a PPV above 90%. In study III, we report that the incidence for HCC in cirrhosis and the cumulative risk at five and ten years highly depends on sex, age, and type of liver disease, indicating that HCC-surveillance should be individually tailored. In study IV, the association of bacterial infections and a relatively preserved MAIT cell fraction is an interesting finding that needs to be investigated further.
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| 2. |
- Bengtsson, Bonnie, et al.
(författare)
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Validity of administrative codes associated with cirrhosis in Sweden
- 2020
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 55:10, s. 1205-1210
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Although cirrhosisis a major cause of liver-related mortality globally, validation studies of the administrative coding for diagnoses associated with cirrhosis are scarce. We aimed to determine the validity of the International Classification of Diseases, 10th revision (ICD-10) codes corresponding to cirrhosis and its complications in the Swedish National Patient Register (NPR).Methods: We randomly selected 750 patients with ICD codes for either alcohol-related cirrhosis (K70.3), unspecified cirrhosis (K74.6) oesophageal varices (I85.0/I85.9), hepatocellular carcinoma (HCC, C22.0) or ascites (R18.9) registered in the NPR from 72 healthcare centres in 2000-2016. Hospitalisation events and outpatient visits in specialised care were included. Positive predictive values (PPVs) were calculated using the information in the patient charts as the gold standard.Results: Complete data were obtained for 630 (of 750) patients (84%). For alcohol-related cirrhosis, 126/136 cases were correctly coded, corresponding to a PPV of 93% (95% confidence interval, 95%CI: 87-96). The PPV for cirrhosis with unspecified aetiology was 91% (121/133, 95%CI: 85-95) and 96% for oesophageal varices (118/123, 95%CI: 91-99). The PPV was lower for HCC, 84% (91/109, 95%CI: 75-90). The PPV for liver-related ascites was low, 43% (56/129, 95%CI: 35-52), as this category often consisted of non-hepatic ascites. When combining the ascites code with a code for chronic liver disease, the PPV for liver-related ascites increased to 93% (50/54, 95%CI: 82-98).Conclusions: The validity of ICD-10 codes for cirrhosis, oesophageal varices and HCC is high. However, coding for ascites should be combined with a code of chronic liver disease to have an acceptable validity.
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| 3. |
- Halling, Bengt, 1959-
(författare)
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Human Lean : Combining Sense of Coherence and Lean to achieve productivity and health
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this thesis is to identify barriers to and supportive factors for Lean implementation and to investigate how application of the Sense of Coherence (SOC) theory combined with Lean philosophy may affect health and productivity. The thesis is based on five studies. The first study compared similarities and divergences in barriers to Lean described in interviews by informants in manufacturing and health care. The second study was a case study at a manufacturing firm. Interviews with managers implementing Lean revealed how their views on Lean influenced the implementation. In the third study, a literature analysis was used to conceptualize the concepts and roles of leadership and management in regard to Lean. In the fourth study it was explored how productivity, quality, work attendance and numbers of rehabilitation cases were influenced after implementation of sense of coherence theory based managerial behavior at three workplaces. The fifth study examined how the implementation of a new leadership approach based on the SOC theory combined with Lean philosophy relate to productivity, quality and levels of sick leave at a steel-producing company. The results from the studies show that the perceived difficulties and barriers are much the same in manufacturing and health care. Another finding was that managers' views on Lean influence the implementation but also that learning during the implementation process can alter their views. A third finding is that lean management is a matter of dualism, consisting of two complementary systems of action, management and leadership, which are related to the two basic principles of Lean, continuous improvement and respect for people. After application of the SOC theory combined with Lean as a basis for the managerial approach, there were improvements in productivity, quality, attendance at work and reduced levels of sick leave at all four studied workplaces, as well as fewer cases of rehabilitation at three workplaces. Several conclusions can be drawn. One is that Lean consultants with a limited approach to Lean, lack of a common organization-wide definition of Lean, and lack of supportive leadership are barriers to Lean implementation. Lean consultants with deep knowledge and capability to teach others Lean is a supportive factor. An organization-wide definition of Lean through an organization-specific Lean philosophy is another supportive factor. Managers that use both leadership and management to support people is a supportive factor to Lean. The study also shows that an application of SOC theory combined with Lean may be positively associated with health and productivity improvements. The overall conclusion is that people’s way of thinking and acting is the nucleus in Lean. To emphasize the importance of people, I suggest to call the approach of combining SOC and Lean “Human Lean.”
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| 4. |
- Jordan, Stanley C., et al.
(författare)
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Imlifidase desensitization in crossmatch-positive, highly-sensitized kidney transplant recipients : Results of an international phase 2 trial (Highdes)
- 2021
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 105:8, s. 1808-1817
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Highly-HLA sensitized patients have limited access to life-saving kidney transplantation due to a paucity of immunologically suitable donors. Imlifidase is a cysteine protease that cleaves IgG leading to a rapid decrease in antibody level and inhibition of IgG-mediated injury. This study investigates the efficacy and safety of imlifidase in converting a positive crossmatch test to negative, allowing highly sensitized patients to be transplanted with a living or deceased donor kidney.METHODS: This open-label, single arm, phase 2 trial conducted at five transplant centers, evaluated the ability of imlifidase to create a negative crossmatch test within 24 hours. Secondary endpoints included post-imlifidase DSA levels compared to pre-dose levels, renal function, and pharmacokinetic/pharmacodynamic profiles. Safety endpoints included adverse events and immunogenicity profile.RESULTS: 89.5% of the transplanted patients demonstrated conversion of baseline positive crossmatch to negative within 24 hours after imlifidase treatment. DSA most often rebounded 3-14 days post-imlifidase dose, with substantial interpatient variability. Patient survival was 100% with graft survival of 88.9% at 6 months. 38.9% had early biopsy proven antibody mediated rejection with onset 2-19 days post-transplantation. Serum IgG levels began to normalize after ~3-7 days post-transplantation. Anti-drug antibody levels were consistent with previous studies. Seven adverse events in six patients were classified as possibly or probably related to treatment and were mild-moderate in severity.CONCLUSIONS: Imlifidase was well tolerated, converted positive crossmatches to negative, and enabled patients with a median cPRA of 99.83% to undergo kidney transplantation resulting in good kidney function and graft survival at 6 months.
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