Medical and financial burden of acute intermittent porphyria

Introduction

A small proportion of patients with acute intermittent porphyria (AIP) suffer from recurrent porphyric attacks, with a severely diminished quality of life. In this retrospective case-control study, the burden of disease is quantified and compared among three AIP patient subgroups: cases with recurrent attacks, cases with one or occasional attacks and asymptomatic carriers.

Methods

Data from patient records and questionnaires were collected in patients between 1960 and 2016 at the Erasmus Medical Center, Rotterdam, the Netherlands. We collected symptoms related to porphyria, porphyria related complications, attack frequency, hospitalisation frequency, hospitalisation days related to acute porphyric attacks, frequency of heme infusions and medical healthcare costs based on hospitalisations and heme therapy.

Results

In total 11 recurrent AIP cases, 24 symptomatic AIP cases and 53 AIP carriers as controls were included. All recurrent patients reported porphyria related symptoms, such as pain, neurological and/or psychiatric disorders, and nearly all developed complications, such as hypertension and chronic kidney disease. In the recurrent cases group, the median lifelong number of hospitalisation days related to porphyric attacks was 82 days per patient (range 10–374), and they spent a median of 346 days (range 34–945) at a day-care facility for prophylactic heme therapy; total follow-up time was 243 person-years (PYRS). In the symptomatic non-recurrent group the median lifelong number of hospitalisation days related to porphyric attacks was 7 days per patient (range 1–78), total follow-up time was 528 PYRS. The calculated total medical healthcare cost for recurrent cases group was €5.8 million versus €0.3 million for the symptomatic cases group.

     

Screening for hepatocellular carcinoma in acute intermittent porphyria: a 15-year follow-up in northern Sweden

Abstract. Innala E, Andersson C (Umeå University, Umeå, Sweden). Screening for hepatocellular carcinoma in acute intermittent porphyria: a 15‐year follow‐up in northern Sweden. J Intern Med 2011; 269 : 538–545. Objectives. To evaluate the benefit of screening for hepatocellular carcinoma (HCC) in gene carriers of acute intermittent porphyria (AIP) and estimate the annual incidence of HCC in this group. Subjects. All AIP gene carriers aged ≥55 years from the northernmost county in Sweden, Norrbotten, were invited for screening in this prospective study every 1–1.5 years during the period 1994–2009. We registered all HCC cases amongst AIP gene carriers in the northern region of Sweden (four counties). We compared gene carriers with repeated screening intervals of <2 years (Group A) with controls (Group B; i.e. gene carriers who had never been screened, those screened for the first time or screened at intervals of >2 years, or dropouts). The screening included radiological examination of the liver and relevant laboratory tests. Results. A total of 62 AIP subjects participated in the study, comprising 33% of the total AIP population aged >55 years in the northern region of Sweden. HCC was diagnosed in 22 AIP subjects (12 men and 10 women), mean age 69 (59–82) years. Amongst these subjects, 73% had experienced prior AIP attacks. The incidence rate ratio for HCC was 64 (52 in men and 93 in women). There were no cases of hepatitis B/C or alcohol abuse. Liver cirrhosis was rare. Liver resection could be performed in most subjects in Group A. Fourteen patients died of HCC, one in Group A and 13 in Group B. Compared with those who were not screened regularly, screening was associated with improved 3‐year and 5‐year survival (P = 0.005 and 0.038). Conclusions. Screening for HCC in carriers of AIP enables early diagnosis and a choice of potentially curative treatments with improved prognosis. We recommend annual screening using liver imaging for AIP gene carriers >50 years of age.     

Effects of diabetes mellitus on patients with acute intermittent porphyria

Objectives. To study the effects of diabetes mellitus in patients with acute intermittent porphyria (AIP). Haeme deficiency in the liver of AIP patients stimulates an increase in ALA-synthase which triggers an escalating metabolic chain reaction, leading to an increase in the porphyrin content. This reaction can be reduced by treating AIP patients with haeme arginate or with glucose. Design. A population-based study of all patients >18 years of age having DNA-verified AIP (n = 328) living in the two most northerly counties of Sweden (Norrbotten and Västerbotten, with 550 000 inhabitants) of whom 16 had type 2 diabetes. Prevalence of diabetes was studied retrospectively in 26 AIP patients with hepatocellular carcinoma (HCC). Results. None of the patients showed symptoms of AIP after the onset of their diabetes. Three patients had had recurrent, severe attacks for many years but when their diabetes became manifest, their urinary ALA and PBG levels decreased and the AIP symptoms resolved, to the relief of the patients. Amongst the 26 AIP patients with HCC, only one with signs of diabetes was identified (impaired glucose tolerance test). Conclusions. This study raises the possibility that diabetes mellitus may be beneficial for patients with severe AIP.     

The epidemiology of hepatocellular carcinoma in patients with acute intermittent porphyria

Objective. To describe the epidemiology, pathogenesis and clinical features of hepatocellular carcinoma (HCC) in patients with acute intermittent porphyria (AIP).
Design. A retrospective population-based mortality study.
Subjects. All inhabitants who died between 1978–1990 (2122) including 33 with AIP, in two municipalities in northern Sweden with a high prevalence of AIP.
Interventions. Death certificates and hospital records were examined. Histological re-examination of paraffin-embedded specimens from patients with HCC was performed and hepatitis B virus content analysed.
Results. HCC was found in 27% of patients with AIP versus 0.2% of the deceased non-AIP subjects, P< 0.0001. HCC was more common in women (men:women 1:2) and in manifest AIP (manifest: latent 2:1). Liver cirrhosis was more common in AIP patients (12%), especially in women, compared with controls (0.5%), P <0.0001.
Conclusions. AIP patients seem to have an increased risk of developing HCC. This tumour is more common in patients with manifest AIP and in women, a reversal of the usually reported gender ratio for HCC. No cause for developing HCC other than AIP was found. The pathogenesis may be explained by abnormalities in porphyrin metabolism and by intrinsic production of mutagenic substances, resulting in a condition of systemic overload of oxidative stress, enhancing mutation rate and liver cell injury. Liver cirrhosis appears to be more common in AIP patients and may be a preliminary stage to HCC. All AIP gene carriers aged 55 should be screened for HCC.     

Use of gonadotropin-releasing hormone analog with tibolone to prevent cyclic attacks of acute intermittent porphyria

A 25-year-old woman with a 10-year history of recurrent attacks of acute abdominal pain just before menstrual periods had acute intermittent porphyria (AIP) diagnosed when she was 23.5 years old. Many acute attacks required hospitalization. Suppression of the menstrual cycle with a gonadotropin-releasing hormone analog (GnRHa; triptorelin) and tibolone administration as add-back therapy resulted in absence of acute porphyric attacks. The patient had no acute attacks over a 1-year follow-up period. This case suggests that long-term GnRHa therapy with tibolone add-back may be a therapeutic option for patients with AIP.     

Signs of neuropathy in the lower legs and feet of patients with acute intermittent porphyria

OBJECTIVE: To assess signs of distal neuropathy in patients with acute intermittent porphyria (AIP). DESIGN: A population-based study. SUBJECTS: All patients with DNA-verified AIP >/= 18 years of age in the four most northerly counties of Sweden. INTERVENTION: Validated neuropathic signs and tests such as monofilament test, neuropathic pain, dry feet, extensor digitorum brevis (EDB) test, loss of forefoot arch, hammer toes and ulceration. RESULTS: A total of 356 patients were registered and 339 of them (95%) participated in the neuropathy study. The chronic neurological signs were symmetrical and similar to those in type 1 diabetic patients. Significant impairment was found concerning perception, EDB test, lower leg pain, ankle and knee tendon reflexes, but not concerning dry feet, loss of forefoot arch and hammer toes, on comparing patients with manifest versus latent AIP. The neurological signs were more severe in the diabetic patients (n = 298). Five AIP patients had permanent quadriplegia after severe attacks. CONCLUSIONS: Patients with manifest AIP had significantly more signs of distal chronic, symmetrical neuropathy of axonal type than did patients with latent AIP. More grave neurological lesions appear to develop after severe attacks.     

Genetic and biochemical characterization of 16 acute intermittent porphyria cases with a high prevalence of the R173W mutation

Summary Acute intermittent porphyria (AIP) is a metabolic disease with a variable prevalence among different countries. In some areas of southern Europe it remains to be fully evaluated. We undertook a genetic and biochemical study of 16 unrelated Spanish AIP patients and relatives. The genetic analyses showed they harboured the following mutations in the porphobilinogen deaminase gene: R173W, G111R, L278P, L238P, R116W, R26C, 340insT, 730delCT, 691del30bp, and IVS14+1g>a. The mutation R173W was found in 6 patients (37.5%), including the only patients of our series with >3 recurrent porphyria attacks. While in clinical remission, all AIP patients exhibited sustained increased excretion of porphyrins and precursors. PBG excretion showed a high between-subject variation and was not related to erythrocyte PBG deaminase activity. The study of family members allowed the identification of 22 asymptomatic AIP carriers. These included 8 persons harbouring the R173W mutation belonging to four different families. Six of these latent AIP subjects showed increased PBG elimination, and in two the urinary levels were >10-fold the normal limit. These results reinforce the hypothesis that the R173W mutation may have a high biochemical and clinical penetrance among AIP patients. Competing interests: None declared     

Acute intermittent porphyria in women: clinical expression,use and experience of exogenous sex hormones. A population-based study in northern Sweden

OBJECTIVE: To describe the clinical expression of acute intermittent porphyria (AIP) in women, their use of exogenous sex hormones, and the effects on AIP. DESIGN: A retrospective population-based study. SUBJECTS: All women aged > or =18 years (n = 190) with DNA-diagnosed AIP in northern Sweden. RESULTS: A total of 166 women (87%) participated; 91 (55%) had manifest AIP. Severe attacks were reported by 82%; 39% reported recurrent premenstrual AIP attacks and 22% reported chronic AIP symptoms. Oral hormonal contraceptives had been used by 58% of all these women and by 50 with manifest AIP (57%). Twelve women (24%) associated oral contraceptives as precipitating AIP attacks; in nine cases their first attack. One woman experienced relief from AIP symptoms. On commencing their treatment, 72% of the women with manifest AIP had not yet suffered their first attack. Twenty-two women (25%) aged > or =45 years had used hormonal replacement therapy (HRT) at menopause to remedy climacteric symptoms (the percutaneous route was most frequently used); no AIP attack was precipitated. HRT to remedy vaginal dryness was used by 26 women (28%) aged > or =45 years without triggering an AIP attack. Miscarriages were more frequent in women with manifest AIP (50%) than in the latent group (30%, P = 0.014). CONCLUSIONS: About half of the women with AIP had used oral hormonal contraceptives. As 25% of women with manifest AIP reported attacks associated with such drugs, caution must still be recommended. Menopausal HRT only rarely affected the disorder. Miscarriage was more common amongst women with manifest AIP.     

Prognosis of acute porphyria: occurrence of acute attacks, precipitating factors, and associated diseases.

We evaluated the prognosis of acute porphyria among 206 adult Finnish patients with acute intermittent porphyria (AIP) or variegate porphyria (VP). The series represents all known patients with these porphyrias in Finland. Of the 47 patients who had a total of 117 acute attacks during the period 1967-1989, 6 died during an attack and 21 attacks were associated with paresis; the frequency of severe attacks was significantly smaller than before 1967 (p = 0.00002). Most pareses and deaths occurred because of a delay in diagnosis and inappropriate treatment of porphyria. For those patients who were symptom-free at the time of diagnosis (1365 follow-up years), the risk of the first subsequent attack was significantly smaller than for those who had had an acute attack before the diagnosis of porphyria (1047 follow-up years, p = 0.005). In addition, milder symptoms of porphyria were more common among those who had had previous attacks than among those who had not (p less than 0.00001). In AIP the risk of attacks correlated with the excretion of porphobilinogen in the urine during remission among adults (p = 0.03); a low rate of excretion predicted freedom from acute attacks. A regular use of many precipitating drugs was never associated with symptoms of porphyria. Two percent of the surgical operations and 4% of the pregnancies were associated with acute attacks. Nearly one-third of the women had symptoms of porphyria associated with the menstrual cycle, but these seldom proceeded to an acute attack. Forty-six percent of the women had used sex-hormone preparations regularly; 2 of them (4.5%) experienced associated acute attacks. Patients with AIP or VP showed increased incidences of hepatocellular carcinoma, and probably also chronic renal failure and hypertension.     

An analysis of 112 acute porphyric attacks in Cape Town, South Africa: Evidence that acute intermittent porphyria and variegate porphyria differ in susceptibility and severity

Four forms of porphyria may present clinically with the acute attack, an episodic, severe, and potentially life-threatening manifestation characterized by abdominal and neurologic symptoms. We describe our experience with 112 consecutive attacks observed and treated in 25 patients with the 2 most common forms of acute porphyria in Cape Town, South Africa; 25 attacks in 10 patients with variegate porphyria and 87 attacks in 14 patients with acute intermittent porphyria. The remaining patient experienced more than 100 sequential, severe, and poorly remitting attacks, which are not included in our analysis. In our population, the relative risk of an acute attack in acute intermittent porphyria compared with that in variegate porphyria was 14.3 (confidence intervals, 6.3-32.7). Patients with variegate porphyria were significantly older (median age at first attack, 30 yr) than those with acute intermittent porphyria (median age at first attack, 23.5 yr; p < 0.0001), and demonstrated an equal sex ratio, whereas the male:female ratio in acute intermittent porphyria was 2:12 (p < 0.0001). There was a significant difference in the incidence of factors precipitating the acute attack. Drug exposure was a frequent precipitant of the acute attack in variegate porphyria, whereas hormonal factors were more important in acute intermittent porphyria (p < 0.00001). Patients with acute intermittent porphyria also showed a trend to earlier and more frequent recurrent acute attacks following the initial admission. Mean urine precursor levels, blood pressure, pulse rate, and heme arginate requirement were all significantly higher in patients with acute intermittent porphyria. No significant difference in the frequency of serious complications or in outcome could be shown. We describe our experience with treatment with heme arginate, and provide evidence that heme arginate results in a prompt and statistically significant improvement in symptoms. The incidence of serious complications and mortality in this series was low, confirming a trend to an increasingly good prognosis for patients with acute porphyria who receive expert treatment.     

正铁血红素治疗急性间歇性血卟啉症

目的 探讨正铁血红素对急性间歇性血卟啉症的治疗作用。方法 ２例ＡＩＰ均具有典型症状，尿Ｗａｔｓｏｎ－Ｓｃｈｗａｗｒｔｚ试验阳性，葡萄糖疗法对其明显效果，给予正铁血纱剂Ｐａｎｈｅｍａｔｉｎ治疗，２００ｍｇ／天，静脉输注，连用５天。结果 腹绞痛在用药２－３天后均迅速缓解。例１抽搐症状明显减轻，例１在６个月后症状复发，再次用药仍有效，随访２年昨发；例２接受随访１年，未见复发。     

Clinicopathologic study on complications of orthotopic liver transplantation in 54 patients with chronic hepatitis B viral infection

Objective

To study the complication incidence of 54 patients with chronic HBV infection following orthotopic liver transplantation (OLT) and risk factors associated with HBV recurrence and hepatocellular carcinoma (HCC) recurrence or metastasis post-OLT.

Methods

The light-microscopic appearance of hepatic allograft biopsies in 54 patients with chronic HBV infection following OLT was examined. The related clinical data were analyzed. The incidence and occurrence time of post-OLT complications were studied. Furthermore, the relationship between hepatitis B virus recurrence and acute rejection and the relationship among HCC recurrence/metastasis, acute rejection, tumor diameter, and portal vein invasion were particularly studied.

Results

Frequent complications of patients with chronic HBV infection following OLT were acute rejection [38 (70.4 %); occurrence time: 5–365 days], chronic rejection [1 (1.9 %); occurrence time: 10.7 months], bile duct complications [24 (44.4 %);occurrence time: 7–940 days], HBV recurrence [7 (13.0 %); occurrence time: 1–540 days], HCV infection [3 (5.6 %); occurrence time: 60 days, 60 days, 33 months], CMV infection [8 (14.8 %); occurrence time: 67–90 days], and HCC recurrence or metastasis [17 (31.5 %); occurrence time: 2–41 months]. At the end of 1 year post-OLT, 95 % of patients with post-hepatitis B cirrhosis were alive. At the end of 3 years post-OLT, 85 % of patients with post-hepatitis B cirrhosis were alive. However, at the end of 1 year post-OLT, 67.6 % of patients with post-hepatitis B HCC were alive. At the end of 3 years post-OLT, 50 % of patients with post-hepatitis B HCC were alive. The number of acute rejection episodes in patients with recurrent HBV infection and in those without recurrent HBV infection was 0.86 ± 1.46 times/patient and 1.07 ± 0.90 times/patient, respectively (p > 0.05); the number of moderate acute rejection episodes (RAI score ≥4) in patients with recurrent HBV infection and in those without recurrent HBV infection was 0.29 ± 0.49 times/patient and 0.50 ± 0.63 times/patient (p > 0.05). Incidence of patients with ≥3 episodes of acute rejection in patient with recurrent HBV infection and in those without recurrent HBV infection was 14.3 and 10.6 % (p > 0.05). Furthermore, the number of acute rejection episodes in patients with HCC recurrence or metastasis and in those without HCC recurrence or metastasis was 1.12 ± 0.93 times/patient and 1.06 ± 1.39 times/patient, respectively (p > 0.05). The number of moderate acute rejection episodes (RAI score ≥4) in patients with HCC recurrence or metastasis and in those without HCC recurrence or metastasis was 0.65 ± 0.79 times/patient and 0.65 ± 1.06 times/patient, respectively (p > 0.05). Incidence of patients with ≥3 episodes of acute rejection in patients with HCC recurrence or metastasis and in those without HCC recurrence or metastasis was 5.9 and 17.6 %, respectively (p > 0.05). The tumor diameter in patients with HCC recurrence or metastasis was 6.72 ± 3.40 cm; however, that in patients without HCC recurrence or metastasis was 3.55 ± 2.17 cm (p = 0.0047). The incidence of portal vein invasion in patients with HCC recurrence or metastasis and in those without HCC recurrence or metastasis was 68.75 and 33.3 %, respectively (p = 0.006).

Conclusion

There was no significant difference between HBV recurrence and acute rejection post-liver transplantation in patients with chronic HBV infection. There was no significant difference between HCC recurrence and acute rejection. The tumor diameter in patients with HCC recurrence or metastasis was significantly greater than that in patients with no HCC recurrence or metastasis. Portal vein invasion was significantly more frequent in patients with HCC recurrence or metastasis than in those with no HCC recurrence or metastasis.     

Prevalence and incidence of rheumatoid arthritis in South Korea

Several studies of rheumatoid arthritis (RA) incidence and prevalence indicate that occurrence of the disease varies significantly among different populations. We aimed to estimate the prevalence and incidence of RA in South Korea. We used Korean National Health Insurance (NHI) claims data to estimate the prevalence of RA in 2007–2009 and the incidence of RA in 2008. On the basis of our previous validation study, the presence of RA was defined by the diagnostic code for RA with biologic or non-biologic disease-modifying anti-rheumatic drugs in the same claim in each year. To estimate the incidence of RA, we identified cases of RA in 2008 and set the 12-month period prior to 2008 as a disease-free period. Among the incident case of 2008, only patients who continued treatment in 2009 were defined as true incident case of RA in 2008. The corresponding prevalence estimates were 0.26 % (95 % CI 0.25–0.27) in 2006, 0.27 % (95 % CI 0.26–0.28) in 2007, and 0.27 % (95 % CI 0.26–0.28) in 2008. The incidence of RA in 2008 was estimated at 42/100,000 (95 % CI 29.3–54.7) in the general population of South Korea. Data gathered nationwide through the NHI yielded estimates of RA prevalence and incidence in South Korea. This study is the first report of nationwide prevalence and incidence of South Korea and those are comparable to values for other countries in Asia.     

Clinical and biochemical characteristics and genotype-phenotype correlation in 143 Finnish and Russian patients with acute intermittent porphyria

Acute intermittent porphyria (AIP), resulting from a deficiency of porphobilinogen deaminase (PBGD) in heme biosynthesis, is genetically heterogeneous and manifests with variable penetrance. The clinical outcome, prognosis, and correlation between PBGD genotype and phenotype were investigated in 143 Finnish and Russian AIP patients with 10 mutations (33G-->T, 97delA, InsAlu333, R149X, R167W, R173W, R173Q, R225G, R225X, 1073delA). Thirty-eight percent of the patients had experienced 1 or more acute attacks during their lives. The proportion of symptomatic patients has decreased dramatically from 49% to 17% among patients diagnosed before and after 1980, respectively. Patients with the R167W and R225G mutations showed lower penetrance (19% and 11%, respectively) and recurrence rate (33% and 0%, respectively) than patients with other mutations (range, 36%-67% and 0%-66%, respectively). Moreover, urinary excretions of porphyrins and their precursors were significantly lower in these patients (porphobilinogen [PBG], 47 +/- 10 vs. 163 +/- 21 micromol/L, p < 0.001; uroporphyrin, 130 +/- 40 vs. 942 +/- 183 nmol/d, p < 0.001). Erythrocyte PBGD activity did not correlate with PBG excretion in remission or with the clinical severity of the disease. Mutations R167W and R225G resulted in milder biochemical abnormalities and clinical symptoms indicating a milder form of AIP in these patients. In all AIP patients, normal PBG excretion predicted freedom from acute attacks. The risk of symptoms was highest for female patients with markedly increased PBG excretion (>100 micromol/L). Proper counseling contributed to the prevention of subsequent attacks in 60% of previously symptomatic and in 95% of previously symptom-free patients.     

Porphyrien – was ist gesichert?

Porphyrias are caused by enzyme defects of heme biosynthesis. According to their clinical presentation and to each affected pathway, they are categorized into acute and non-acute as well as hepatic and erythropoietic porphyrias. Acute hepatic porphyrias, e.g. acute intermittent porphyria (AIP), porphyria variegata (VP), hereditary coproporphyria (HCP) and 5?aminolevulinic acid dehydratase-deficient porphyria (ALADP) are characterized by accumulation of the porphyrin precursors 5?aminolevulinic acid (ALA) and porphobilinogen (PBG) that correlate with severe abdominal, psychiatric, neurological or cardiovascular symptoms. Additionally, skin photosensitivity can occur in VP and less frequently, in HCP. Decisive for the diagnosis of acute hepatic porphyrias are a >4-fold elevated urinary excretion of ALA in ALADP and ALA and PBG in all other acute porphyrias. First-line treatment of an acute porphyria attack includes intensive care with pain management, sufficient caloric supply, strict avoidance of porphyrinogenic drugs and elimination of other triggering factors. Heme therapy is indispensable in case of developing neurological symptoms and clinical worsening despite first-line measures. Non-acute porphyrias, mainly porphyria cutanea tarda (PCT), erythropoietic protoporphyria (EPP) and X?linked protoporphyria (XLP) display accumulation of porphyrins in the skin and/or liver resulting in photosensitivity up to possible liver damage. Patients with PCT benefit from iron depletion, low-dose chloroquine treatment and/or hepatitis C virus elimination. Afamelanotide is associated with better sunlight tolerance in patients with EPP and XLP. Moreover, innovative therapies that highly selectively address dysregulated steps of the heme biosynthetic pathway are currently under clinical trial.     

Unsuspected pulmonary embolism in cancer patients: a narrative review with pooled data

Detection of pulmonary embolism (PE) is not uncommon in patients undergoing computed tomography (CT) for routine staging of malignancy. Several studies have been conducted in recent years to evaluate the impact of unsuspected pulmonary embolism (UPE) on the prognosis and management of cancer patients. We aimed at summarizing the available evidence, to improve the understanding of the frequency and clinical significance of UPE in terms of survival, recurrent venous thromboembolism (VTE) and major bleeding. Medline was searched up to the end of September 2013, by using the terms “unsuspected pulmonary embolism” OR “incidental pulmonary embolism” OR “asymptomatic pulmonary embolism”. We found 552 out of 35,990 cancer patients diagnosed with UPE (14 studies), for a mean weighted prevalence of 1.82 % (95 % CI 1.47–2.21). When comparing cancer patients diagnosed with UPE to those presenting with symptomatic PE, we found a pooled OR of 0.96 (95 % CI 0.58–1.57) for mortality (3 studies), 0.87 (95 % CI 0.47–1.60) for recurrent VTE (4 studies) and 0.90 (95 % CI 0.43–1.88) for major bleeding (4 studies). In conclusion, UPE represents a non-infrequent finding on CT scans ordered for reasons other than suspected PE and is a challenging clinical situation in the management of cancer patients. Even if UPE is generally milder in the short term, it may share a similar impact on survival and recurrent VTE, as compared to symptomatic PE. Large collaborative projects and, hopefully, interventional trials are needed to clarify the best management strategies.     

Incidence and predictors of ischemic stroke during hospitalization for congestive heart failure

Heart failure (HF) increases the risk of ischemic stroke. Data regarding the incidence and predictors of ischemic stroke during hospitalization for HF are limited. The study population of this retrospective cohort study consisted of patients with congestive HF, consecutively admitted to our center from October 2010 to April 2014. We excluded patients complicated with acute myocardial infarction, infective endocarditis, and takotsubo cardiomyopathy. We also excluded those with dialysis or mechanical circulatory support. We investigated the incidence of ischemic stroke during hospitalization for HF. Thereafter, we divided the patients without oral anticoagulants at admission into two groups: patients with ischemic stroke and those without it, and explored the predictors of ischemic stroke. A total of 558 patients (287 without atrial fibrillation (AF), 271 with AF) were enrolled. The mean age was 76.8 ± 12.3 years, and 244 patients (44 %) were female. The mean left-ventricular ejection fraction was 47.4 %. Oral anticoagulants were prescribed in 147 patients (8 without AF, 139 with AF). During hospitalization (median length 18 days), symptomatic ischemic stroke (excluding catheter-related) occurred in 15 patients (2.7 % of the total, 8 without AF, 7 with AF). Predictors significantly associated with increased risk of ischemic stroke in patients without oral anticoagulants were as follows; short-term increases in blood urea nitrogen after admission (at day 3; odds ratio (per 1 md/dl): 1.06, 95 % confidence interval (CI) 1.01–1.11, p = 0.02, and at day 7; odds ratio: 1.03, 95 % CI 1.00–1.07, p = 0.03, respectively), and previous stroke (odds ratio; 3.33, 95 % CI 1.01–11.00, p = 0.04). The incidence of ischemic stroke during hospitalization for HF was high, even in patients without AF. Previous stroke and short-term increases in blood urea nitrogen was significantly associated with the incidence of ischemic stroke.     

Trends in incidence of acute pancreatitis in a Swedish population: is there really an increase?

BACKGROUND AND AIMS: Recent reports have suggested an increasing incidence of acute pancreatitis, and changing patterns of risk factors, over the past decades. The aim of this study was to investigate trends in the incidence of acute pancreatitis, and risk factors related to the disease, in a general population over a 15-year period. METHODS: Clinical, autopsy, and forensic records for all patients with a first attack of acute pancreatitis in Malm?, Sweden, from 1985 to 1999, were validated retrospectively. Evidence for diagnosis was reconsidered and plausible cause was assessed. The incidence of gallstone disease, lung cancer, and alcohol-related conditions in the background population were retrieved from hospital diagnosis records and cancer and cause-of-death registries. RESULTS: A total of 929 first attacks of acute pancreatitis were identified. The total incidence of acute pancreatitis increased by 3.9% per year (95% confidence interval [CI], 2.1-5.8). The incidence of gallstone-related pancreatitis increased by 7.6% per year (95% CI, 4.0-11.4), and this correlated with an increase in the incidence of other gallstone-related conditions ( r = 0.68; P = 0.005). Alcohol-related pancreatitis decreased by -5.1% per year (95% CI, -7.4 to -2.8), and this correlated with a decrease in the incidence of delirium tremens ( r = 0.75; P = 0.001), mortality from cirrhosis ( r = 0.81; P < 0.001), and incidence of lung cancer ( r = 0.57; P = 0.026). CONCLUSIONS: There was a statistically significant increase in the incidence of acute pancreatitis. Gallstone-related pancreatitis increased, and alcohol-related pancreatitis decreased. Both of these trends were statistically significant and correlated with trends in the incidence of other conditions associated with either gallstone disease or alcohol abuse.