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Journal of Veterinary Internal Medicine 2013
Topics: Animals; Diarrhea; Dog Diseases; Dogs; Exocrine Pancreatic Insufficiency; Gastrointestinal Agents; Male; Pancrelipase
PubMed: 23551120
DOI: 10.1111/jvim.12076 -
Journal of Medical Economics 2012Chronic pancreatitis (CP) is the most common cause of pancreatic exocrine insufficiency (PEI). Management of PEI due to CP is achieved through lifelong treatment with...
OBJECTIVE
Chronic pancreatitis (CP) is the most common cause of pancreatic exocrine insufficiency (PEI). Management of PEI due to CP is achieved through lifelong treatment with pancreatic enzyme replacement therapy (PERT). To the authors' knowledge, no cost-effectiveness analysis on the benefit of PERT in CP patients with PEI has been performed to date. The objective of this analysis was to examine the cost-effectiveness of Creon (pancreatin minimicrospheres [MMS]), one of the main PERTs available in Poland, in treating patients with CP-related PEI.
METHODS
The cost-effectiveness of pancreatin MMS in the treatment of patients with CP-related PEI vs no PERT treatment was estimated using a decision analysis based on clinical data from relevant studies. The model horizon was 20 years. Main outcomes included the percentage of patients with controlled PEI, survival, total medical costs, number of quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER). All costs were analysed from the Polish payer perspective.
RESULTS
The model included clinical data from 176 patients treated in five pancreatin MMS randomized trials. Treatment with pancreatin MMS resulted in a considerably higher proportion of patients with controlled PEI compared to those not treated with any PERT. Over a horizon of 20 years, the total treatment cost and the ICER for pancreatin MMS was €8223 and €6312 per QALY, respectively.
LIMITATIONS
Important limitations include the lack of long-term and comparative clinical data available. The use of 'no PERT treatment' as a comparator against pancreatin MMS treatment may not accurately reflect current practice in Poland.
CONCLUSIONS
Treatment of CP-related PEI with pancreatin MMS is cost-effective from a Polish payer perspective, with an ICER below the accepted 'willingness to pay' threshold of 3-times gross domestic product (GDP) per capita. These results are likely to apply to other European countries.
Topics: Adolescent; Adult; Aged; Cost-Benefit Analysis; Exocrine Pancreatic Insufficiency; Gastrointestinal Agents; Humans; Markov Chains; Middle Aged; Pancreatitis, Chronic; Pancrelipase; Poland; Research; Young Adult
PubMed: 23043594
DOI: 10.3111/13696998.2012.737882 -
Core Evidence 2012Pancreatic exocrine insufficiency (PEI) is often observed in patients with pancreatic diseases, including chronic pancreatitis, cystic fibrosis, and tumors, or after...
Pancreatic exocrine insufficiency (PEI) is often observed in patients with pancreatic diseases, including chronic pancreatitis, cystic fibrosis, and tumors, or after surgical resection. PEI often results in malnutrition, weight loss and steatorrhea, which together increase the risk of morbidity and mortality. Therefore, nutritional interventions, such as low-fat diets and pancreatic enzyme replacement therapy (PERT), are needed to improve the clinical symptoms, and to address the pathophysiology of pancreatic exocrine insufficiency. PERT with delayed-release pancrelipase is now becoming a standard therapy for pancreatic exocrine insufficiency because it significantly improves the coefficients of fat and nitrogen absorption as well as clinical symptoms, without serious treatment-emergent adverse events. The major adverse events were tolerable gastrointestinal tract symptoms, such as stomach pain, nausea, and bloating. Fibrosing colonopathy, a serious complication, is associated with high doses of enzymes. Several pancrelipase products have been approved by the US Food and Drug Administration in recent years. Although many double-blind, placebo-controlled trials of pancrelipase products have been conducted in recent years, these studies have enrolled relatively few patients and have often been less than a few weeks in duration. Moreover, few studies have addressed the issue of pancreatic diabetes, a type of diabetes that is characterized by frequent hypoglycemia, which is difficult to manage. In addition, it is unclear whether PERT improves morbidity and mortality in such settings. Therefore, large, long-term prospective studies are needed to identify the optimal treatment for pancreatic exocrine insufficiency. The studies should also examine the extent to which PERT using pancrelipase improves mortality and morbidity. The etiology and severity of pancreatic exocrine insufficiency often differ among patients with gastrointestinal diseases or diabetes (type 1 and type 2), and among elderly subjects. Finally, although there is currently limited clinical evidence, numerous extrapancreatic diseases and conditions that are highly prevalent in the general population may also be considered potential targets for PERT and related treatments.
PubMed: 22936895
DOI: 10.2147/CE.S26705 -
Alimentary Pharmacology & Therapeutics Sep 2012Pancreatic exocrine insufficiency (PEI) results in maldigestion, leading to abdominal pain, steatorrhoea, malnutrition and weight loss. (Randomized Controlled Trial)
Randomized Controlled Trial
Randomised clinical trial: the efficacy and safety of pancreatin enteric-coated minimicrospheres (Creon 40000 MMS) in patients with pancreatic exocrine insufficiency due to chronic pancreatitis--a double-blind, placebo-controlled study.
BACKGROUND
Pancreatic exocrine insufficiency (PEI) results in maldigestion, leading to abdominal pain, steatorrhoea, malnutrition and weight loss.
AIM
To assess the efficacy and safety of pancreatin (Creon 40000 MMS) in treating PEI due to chronic pancreatitis (CP).
METHODS
This was a 1-week, double-blind, randomised, placebo-controlled, parallel-group, multicentre study in India. Men and women ≥18 years of age with proven CP and PEI [defined as a coefficient of fat absorption (CFA) ≤80% during run-in phase] were randomised 1:1 to pancreatin or placebo (two capsules orally per main meal, one with snacks). The primary outcome measure was change in CFA from baseline to end of double-blind treatment (analysis of covariance).
RESULTS
Of 62 patients randomised (34 pancreatin, 28 placebo), 61 completed treatment; one patient in the placebo arm withdrew consent before completion. Patient characteristics were similar in both groups except for the proportion of men (pancreatin 82% vs. placebo 68%). Patients receiving pancreatin had a statistically significant greater improvement in fat absorption from baseline to the end of double-blind treatment compared with those receiving placebo, with a least squares mean change (95% CI) in CFA of 18.5% (15.8-21.2) vs. 4.1% (1.0-7.2), respectively. This resulted in a treatment difference of 14.4% (10.3-18.5); P = 0.001. Patients receiving pancreatin also had a statistically significant greater improvement in nitrogen absorption and greater reductions in mean stool fat, stool frequency and stool weight compared with those receiving placebo. Treatment-emergent adverse events occurred in 12 patients on pancreatin and in seven on placebo; none led to study discontinuation.
CONCLUSIONS
The results provide evidence for the efficacy of pancreatin (Creon 40000 MMS) in patients with pancreatic exocrine insufficiency due to chronic pancreatitis, and confirm that this formulation is well tolerated, with a good safety profile, at the dose administered.
Topics: Adult; Delayed-Action Preparations; Double-Blind Method; Exocrine Pancreatic Insufficiency; Female; Gastrointestinal Agents; Humans; India; Intestinal Absorption; Male; Microspheres; Middle Aged; Pancreatitis, Chronic; Pancrelipase; Treatment Outcome
PubMed: 22762290
DOI: 10.1111/j.1365-2036.2012.05202.x -
Molecules (Basel, Switzerland) May 2012Oxidation of low-density lipoprotein (LDL) is the principal risk factor for the development of atherosclerosis. In this study, we used several methods to investigate the...
Oxidation of low-density lipoprotein (LDL) is the principal risk factor for the development of atherosclerosis. In this study, we used several methods to investigate the ability of the acetone extract from rhizomes, stems, leaves, flowers, pericarps and seeds of Alpinia zerumbet to inhibit atherosclerosis in vitro. The seed extract had the strongest activity against tyrosinase, pancreatic lipase (PL), 15-lipoxygenase (15-LO) and LDL oxidation activities (IC₅₀ = 2.30 ± 0.02, 5.00 ± 0.07, 1.29 ± 0.07 and 15.40 ± 0.86 μg/mL, respectively), amongst all different parts. It also had similar effects to the positive controls. Most of the extracts showed partial agonistic properties towards estrogenic activity. Cholest-4-ene-3,6-dione, a steroid present only in the seed extract seems to be the compound responsible for these activities. The results showed that cholest-4-ene-3,6-dione had similar ability to curcumin and quercetin against PL and LDL oxidation (IC₅₀ = 19.50 ± 1.17 and 16.12 ± 1.43 μg/mL, respectively). Furthermore, cholest-4-ene-3,6-dione (IC₅₀ = 34.21 ± 1.31 μg/mL) had higher inhibition against 15-LO than quercetin (IC₅₀ = 54.79 ± 1.12 μg/mL).
Topics: Acetone; Alpinia; Antioxidants; Atherosclerosis; Dose-Response Relationship, Drug; Enzyme Inhibitors; Gas Chromatography-Mass Spectrometry; Humans; Inhibitory Concentration 50; Lipoproteins, LDL; Lipoxygenase Inhibitors; Monophenol Monooxygenase; Oxidation-Reduction; Pancrelipase; Plant Extracts; Seeds; Solvents
PubMed: 22634836
DOI: 10.3390/molecules17066237 -
PloS One 2012We have previously performed a genome-wide linkage study in Scandinavian Type 1 diabetes (T1D) families. In the Swedish families, we detected suggestive linkage...
BACKGROUND
We have previously performed a genome-wide linkage study in Scandinavian Type 1 diabetes (T1D) families. In the Swedish families, we detected suggestive linkage (LOD≤2.2) to the chromosome 5p13-q13 region. The aim of our study was to investigate the linked region in search for possible T1D susceptibility genes.
METHODOLOGY/PRINCIPAL FINDINGS
Microsatellites were genotyped in the Scandinavian families to fine-map the previously linked region. Further, SNPs were genotyped in Swedish and Danish families as well as Swedish sporadic cases. In the Swedish families we detected genome-wide significant linkage to the 5-hydroxytryptamine receptor 1A (HTR1A) gene (LOD 3.98, p<9.8×10(-6)). Markers tagging two separate genes; the ring finger protein 180 (RNF180) and HTR1A showed association to T1D in the Swedish and Danish families (p<0.002, p<0.001 respectively). The association was not confirmed in sporadic cases. Conditional analysis indicates that the primary association was to HTR1A. Quantitative PCR show that transcripts of both HTR1A and RNF180 are present in human islets of Langerhans. Moreover, immunohistochemical analysis confirmed the presence of the 5-HTR1A protein in isolated human islets of Langerhans as well as in sections of human pancreas.
CONCLUSIONS
We have identified and confirmed the association of both HTR1A and RFN180, two genes in high linkage disequilibrium (LD) to T1D in two separate family materials. As both HTR1A and RFN180 were expressed at the mRNA level and HTR1A as protein in human islets of Langerhans, we suggest that HTR1A may affect T1D susceptibility by modulating the initial autoimmune attack or either islet regeneration, insulin release, or both.
Topics: Chromosome Mapping; Chromosomes, Human, Pair 5; Denmark; Diabetes Mellitus, Type 1; Family Health; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Immunohistochemistry; Islets of Langerhans; Linkage Disequilibrium; Lod Score; Pancrelipase; Polymorphism, Single Nucleotide; Receptor, Serotonin, 5-HT1A; Reverse Transcriptase Polymerase Chain Reaction; Sweden; Ubiquitin-Protein Ligases
PubMed: 22563461
DOI: 10.1371/journal.pone.0035439 -
Gastroenterology & Hepatology Apr 2011
PubMed: 21857824
DOI: No ID Found -
Journal of Cystic Fibrosis : Official... Sep 2011Pancreatic enzyme replacement therapy (PERT) is critical for correction of exocrine pancreatic insufficiency (EPI) in patients with cystic fibrosis (CF). (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Pancreatic enzyme replacement therapy (PERT) is critical for correction of exocrine pancreatic insufficiency (EPI) in patients with cystic fibrosis (CF).
METHODS
This was a randomized, placebo-controlled PERT withdrawal study evaluating the efficacy and safety of PANCREAZE® (pancrelipase) in CF patients with EPI. Participants (n=49) entered an open-label, ≤ 14 day run-in phase, maintained a high-fat diet (100 ± 15 g/day), and received PANCREAZE® (10.5 or 21). Participants with a coefficient of fat absorption (CFA)≥ 80% (n=40) were then randomized (1:1) to receive either PANCREAZE® or placebo during a double-blind, ≤ 7 day withdrawal phase.
RESULTS
PANCREAZE® improved fat absorption as shown by significantly lower mean ± SD change in CFA between open-label and double-blind phases for PANCREAZE® (-1.5 ± 5.88%; p<0.001) compared to placebo (-34.1 ± 23.03%). Protein absorption was similarly improved. No unexpected adverse events were reported.
CONCLUSIONS
This study demonstrated PANCREAZE® was effective in treating EPI due to CF and was safe and well tolerated.
Topics: Adolescent; Adult; Child; Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Female; Gastrointestinal Agents; Humans; Male; Middle Aged; Pancreas, Exocrine; Pancrelipase; Placebos; Treatment Outcome; Young Adult
PubMed: 21632288
DOI: 10.1016/j.jcf.2011.04.005 -
The American Journal of Pathology Apr 2011Ectopic or tertiary lymphoid tissues (TLTs) are often induced at sites of chronic inflammation. They typically contain various hematopoietic cell types, high endothelial...
Ectopic or tertiary lymphoid tissues (TLTs) are often induced at sites of chronic inflammation. They typically contain various hematopoietic cell types, high endothelial venules, and follicular dendritic cells; and are organized in lymph node-like structures. Although fibroblastic stromal cells may play a role in TLT induction and persistence, they have remained poorly defined. Herein, we report that TLTs arising during inflammation in mice and humans in a variety of tissues (eg, pancreas, kidney, liver, and salivary gland) contain stromal cell networks consisting of podoplanin(+) T-zone fibroblastic reticular cells (TRCs), distinct from follicular dendritic cells. Similar to lymph nodes, TRCs were present throughout T-cell-rich areas and had dendritic cells associated with them. They expressed lymphotoxin (LT) β receptor (LTβR), produced CCL21, and formed a functional conduit system. In rat insulin promoter-CXCL13-transgenic pancreas, the maintenance of TRC networks and conduits was partially dependent on LTβR and on lymphoid tissue inducer cells expressing LTβR ligands. In conclusion, TRCs and conduits are hallmarks of secondary lymphoid organs and of well-developed TLTs, in both mice and humans, and are likely to act as important scaffold and organizer cells of the T-cell-rich zone.
Topics: Animals; Chemokine CXCL13; Dendritic Cells; Fibroblasts; Humans; Inflammation; Insulin; Ligands; Lymph Nodes; Lymphoid Tissue; Mice; Mice, Inbred C57BL; Mice, Transgenic; Pancrelipase; Promoter Regions, Genetic; Rats; Stromal Cells
PubMed: 21435450
DOI: 10.1016/j.ajpath.2010.12.039 -
Alimentary Pharmacology & Therapeutics May 2011Pancreatic enzyme replacement therapy (PERT) is necessary to prevent severe maldigestion and unwanted weight loss associated with exocrine pancreatic insufficiency (EPI)... (Randomized Controlled Trial)
Randomized Controlled Trial
A 6-month, open-label clinical trial of pancrelipase delayed-release capsules (Creon) in patients with exocrine pancreatic insufficiency due to chronic pancreatitis or pancreatic surgery.
BACKGROUND
Pancreatic enzyme replacement therapy (PERT) is necessary to prevent severe maldigestion and unwanted weight loss associated with exocrine pancreatic insufficiency (EPI) due to chronic pancreatitis (CP) or pancreatic surgery (PS).
AIM
To assess the long-term safety and efficacy of pancrelipase (pancreatin) delayed-release capsules (Creon) in this population.
METHODS
This was a 6-month, open-label extension of a 7-day, double-blind, placebo-controlled study enrolling patients ≥18 years old with confirmed EPI due to CP or PS who were previously receiving PERT. Patients received individualised pancrelipase doses as directed by investigators (administered as Creon 24 000-lipase unit capsules).
RESULTS
Overall, 48 of 51 patients completed the open-label phase; one withdrew due to the unrelated treatment-emergent adverse event (TEAE) of cutaneous burns and two were lost to follow-up. The mean age was 50.9 years, 70.6% of patients were male, 76.5% had CP and 23.5% had undergone PS. The mean±s.d. pancrelipase dose was 186960±74640 lipase units/day. TEAEs were reported by 22 patients (43.1%) overall. Only four patients (7.8%) had TEAEs that were considered treatment related. From double-blind phase baseline to end of the open-label period, subjects achieved a mean±s.d. body weight increase of 2.7±3.4 kg (P<0.0001) and change in daily stool frequency of -1.0±1.3 (P<0.001). Improvements in abdominal pain, flatulence and stool consistency were observed.
CONCLUSIONS
Pancrelipase was well tolerated over 6 months and resulted in statistically significant weight gain and reduced stool frequency in patients with EPI due to CP or PS previously managed with standard PERT.
Topics: Adult; Capsules; Delayed-Action Preparations; Double-Blind Method; Exocrine Pancreatic Insufficiency; Female; Gastrointestinal Agents; Humans; Male; Middle Aged; Pancreas; Pancreatitis, Chronic; Pancrelipase; Time Factors; Treatment Outcome; Weight Gain
PubMed: 21418260
DOI: 10.1111/j.1365-2036.2011.04631.x