A model-based cost-effectiveness analysis of osteoporosis screening and treatment strategy for postmenopausal Japanese women.

Although an osteoporosis screening program has been implemented as a health promotion project in Japan, its cost-effectiveness has yet to be elucidated fully. We performed a cost-effectiveness analysis and found that osteoporosis screening and treatment would be cost-effective for Japanese women over 60 years. INTRODUCTION: The purpose of this study was to estimate the cost-effectiveness of osteoporosis screening and drug therapy in the Japanese healthcare system for postmenopausal women with no history of fracture. METHODS: A patient-level state transition model was developed to predict the outcomes of Japanese women with no previous fracture. Lifetime costs and quality-adjusted life years (QALYs) were estimated for women who receive osteoporosis screening and alendronate therapy for 5 years and those who do not receive the screening and treatments. The incremental cost-effectiveness ratio (ICER) of the screening option compared with the no screening option was estimated. Sensitivity analyses were performed to examine the influence of parameter uncertainty on the base case results. RESULTS: The ICERs of osteoporosis screening and treatments for Japanese women aged 50-54, 55-59, 60-64, 65-69, 70-74, and 75-79 years were estimated to be $89,242, $64,010, $40,596, $27,697, $17,027, and $9771 per QALY gained, respectively. Deterministic sensitivity analyses showed that several parameters such as the disutility due to vertebral fracture had a significant influence on the base case results. Applying a willingness to pay of $50,000 per QALY gained, the probability that the screening option became cost-effectiveness estimated to 50.9, 56.3, 59.1, and 64.7 % for women aged 60-64, 65-69, 70-74, and 75-79 years, respectively. Scenario analyses showed that the ICER for women aged 55-59 years with at least one clinical risk factor was below $50,000 per QALY. CONCLUSIONS: In conclusion, dual energy X-ray absorptiometry (DXA) screening and alendronate therapy for osteoporosis would be cost-effective for postmenopausal Japanese women over 60 years. In terms of cost-effectiveness, the individual need for osteoporosis screening should be determined by age and clinical risk factors.

Economic evaluation of osteoporosis liaison service for secondary fracture prevention in postmenopausal osteoporosis patients with previous hip fracture in Japan.

A model-based cost-effectiveness analysis was performed to evaluate the cost-effectiveness of secondary fracture prevention by osteoporosis liaison service (OLS) relative to no therapy in patients with osteoporosis and a history of hip fracture. Secondary fracture prevention by OLS is cost-effective in Japanese women with osteoporosis who have suffered a hip fracture. INTRODUCTION: The purpose of this study was to estimate, from the perspective of Japan's healthcare system, the cost-effectiveness of secondary fracture prevention by OLS relative to no therapy in patients with osteoporosis and a history of hip fracture. METHODS: A patient-level state transition model was developed to predict lifetime costs and quality-adjusted life years (QALYs) in patients with or without secondary fracture prevention by OLS. The incremental cost-effectiveness ratio (ICER) of secondary fracture prevention compared with no therapy was estimated. Sensitivity analyses were performed to examine the influence of parameter uncertainty on the base case results. RESULTS: Compared with no therapy, secondary fracture prevention in patients aged 65 with T-score of -2.5 resulted in an additional lifetime cost of $3396 per person and conferred an additional 0.118 QALY, resulting in an ICER of $28,880 per QALY gained. Deterministic sensitivity analyses showed that treatment duration and offset time strongly affect the cost-effectiveness of OLS. According to the results of scenario analyses, secondary fracture prevention by OLS was cost-saving compared with no therapy in patients with a family history of hip fracture and high alcohol intake. CONCLUSIONS: Secondary fracture prevention by OLS is cost-effective in Japanese women with osteoporosis who have suffered a hip fracture. In addition, secondary fracture prevention is less expensive than no therapy in high-risk patients with multiple risk factors.

Successful control of an outbreak of colonization by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae sequence type 258 in a neonatal intensive care unit, Italy.

This article reports an outbreak of colonization by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) sequence type (ST) 258 in a neonatal intensive care unit (NICU) in Palermo, Italy. KPC-Kp ST258 was detected by an active surveillance culture programme. Between 18th September and 14th November 2012, KPC-Kp was isolated from 10 out of 54 neonates admitted in the outbreak period. No cases of infection were recorded. Male sex was associated with colonization, whereas administration of ampicillin- sulbactam plus gentamicin was protective. Infection control interventions interrupted the spread of KPC-Kp without the need to close the NICU to new admissions.

Imported leprosy in Italy.

BACKGROUND: Leprosy is far from being eliminated with more than 200,000 new cases detected (NCD)/year. OBJECTIVE: Retrospective analysis between 2003 and 2009 to compare the New Case Detected Rate (NCDR) observed in Italy in the immigrant population with the NCDR of the same population in their country of origin to verify if the cases observed are those expected or not. METHODS: Leprosy statistics were retrieved from the Italian leprosy register and from official WHO data. RESULTS: The NCD in Italy were lower than expected, from 2003 when the expected number of NCD was 40.5 between the legally resident immigrants, but only one case was diagnosed (98% of lower from the expected), to 2009 when four NCD were diagnosed and 41 were expected (90% lower from expected). CONCLUSIONS: This study points out a discrepancy between the observed and the expected cases of leprosy in Italy. Specifically, the number of NCD was less than expected for each studied year. Of course our data do not represent a validation, but only an indication of the leprosy diagnosis in Italy. Difficulty in accessing the health systems, fear of segregation, ignorance and illegal immigrant status with consequent fear of police arrest are possible explaining factors. The critical issue anyhow is the medical expertise. The role of the dermatologist is fundamental. For these reasons, there is still a need for wide spread leprosy teaching programmes. Although with few limitations, this study represents a first approach to validate the accuracy in leprosy diagnosis in Italy.

A case of ''silk route disease'' in a patient from Congo.

The authors describe a case of Behçet's syndrome or ''silk route disease'' in a patient from the Democratic Republic of Congo. The patient arrived in hospital suffering from an acute episode of febrile erythema nodosum, which was diagnosed as type 2 leprosy reaction. His history reported recurrent oral aphthae and during hospitalization ulcers on the scrotum and pathergy were observed. A diagnosis of Behçet's disease was made. The patient is HLA B51 negative and the scientific literature confirms that testing for the presence of this allele is negative in the 10 cases of Behçet's disease reported from Sub-Saharan countries.

Tuberculoid leprosy and Type 1 lepra reaction.

A patient is described with tuberculoid leprosy and Type 1 (lepra) reaction from Sicily a non-endemic region, who lived previously in Manila from 2000 to 2005. The skin lesions became acutely inflamed and edematous. The plaques were painless to touch or pinprick, and there was swelling of the nerves in the fibro-osseous tunnels under the surface of the skin, including both the ulnar nerve at the elbow, and the posterior tibial nerve (medial malleolus). During the course of electro-neurographic studies, conduction velocity in the motory nerves indicated a slowing-down. The diagnosis of leprosy was confirmed by residence in an endemic area for about 5 years, by simultaneous skin lesions and peripheral nerve abnormalities, and by skin biopsy. Outside of endemic areas, diagnosis remains a challenge for physicians for mainly two reasons. Firstly, the incubation period of leprosy is uniquely long among bacterial diseases and varies from a month to over 40 years. Secondly, outside leprosy-endemic areas, the diagnosis of leprosy is usually not considered, and patients are likely to be examined by a wide range of specialists. Physicians outside endemic areas should consider leprosy as a possible differential diagnosis if a patient from leprosy-endemic regions presents with painless skin lesions, nerve enlargement, or persistent skin lesions.

Monitoring of T-cell repertoire was useful for predicting graft-versus-host disease prognosis in a patient with chronic myelogeneous leukemia after allogeneic bone marrow transplantation.

We analyzed 24 T-cell receptor (TCR)beta chain subfamilies (Vbeta) and the chimerism of a patient with chronic myelogeneous leukemia who underwent allogeneic bone marrow transplantation (allo-BMT). The patient developed liver dysfunction at day 19 leading to worsening of his condition. He died on day 91 of hepatic failure. Complete donor chimerism was observed after day 19. The average complexity score of TCR-Vbeta, which was low on day 19 (5.50), because much lower on day 82 (3.77). The average value of normal volunteers is 7.69. Neither immunosuppressive therapy nor antiviral therapy was effective to treat his hepatic dysfunction. A liver specimen at autopsy showed necrotic tissue with invasion of lymphocytes under the endothelial cells of the bile ducts. These findings suggest that the liver dysfunction was due to graft-versus-host disease (GVHD). Careful monitoring of chimerism and TCR-Vbeta complexity may help to predict the prognosis of GVHD after allogeneic BMT.

Treatment with low-dose cytosine arabinoside followed by administration of macrophage colony-stimulating factor prolongs the survival of patients with RAEB, RAEB-T, or leukemic phase myelodysplastic syndrome: a pilot study.

The treatment of patients with aggressive subclasses of myelodysplastic syndrome (MDS) remains a challenge. In an effort to improve the survival of patients with refractory anemia with excess blasts (RAEB), RAEB in transformation (RAEB-t), or acute myelogenous leukemia transformed from MDS (MDS-AML), we conducted a small trial in which 28 such patients were treated with low-dose cytosine arabinoside (LDAraC) followed by administration of macrophage colony-stimulating factor (M-CSF). The overall rate of response to the treatment was 61%, including 39% with a complete response, which is higher than rates obtained in previous studies in which LDAraC alone was administered to patients with MDS. Median survival was 23.5 months in cases of RAEB, 16.7 months in cases of RAEB-t, and 19.7 months in cases of MDS-AML. The overall survival of the study group appeared to be prolonged in comparison with a historical control group of patients treated with LDAraC alone. It is suggested that M-CSF added to the administration of LDAraC plays an active role in the therapy. No therapy-related death occurred. Some unique actions of M-CSF were suggested in this trial. It is concluded that therapy with LDAraC + M-CSF is a useful treatment option for patients with aggressive subclasses of MDS and MDS-AML to provide better response and survival.

Ras and signal transducer and activator of transcription (STAT) are essential and sufficient downstream components of Janus kinases in cell proliferation.

Cytokines exert their activities in cell growth and differentiation by binding specific cell membrane receptors. Janus kinases (JAKs) are cytoplasmic protein tyrosine kinases that physically interact with intracellular domains of the cytokine receptors and they play crucial roles in transducing signals triggered by the cytokine-receptor interaction. We have previously shown that conditional activation of JAK through membrane-proximal dimerization confers cytokine-independence on interleukin-3 (IL-3)-dependent Ba / F3 lymphoid cells and that the cytokine-independent proliferation is completely inhibited by dominant negative Ras. In this work, we demonstrate that ectopic expression of a dominant negative form of Stat5, a major signal transducer and activator of transcription (STAT) expressed in Ba / F3 cells, also inhibits JAK-triggered mitogenesis. In contrast, overexpression of constitutively active Ras or conditional activation of Stat5 by chemical dimerization fails to confer cytokine-independence. However, concomitant activation of ectopic Ras and Stat5 molecules in Ba / F3 cells suffices for cell proliferation in the absence of IL-3. Our results indicate that Ras and STAT are essential and sufficient components of JAK-triggered mitogenesis. Our findings further indicate that the cytokine signal bifurcates into Ras and STAT pathways following JAK activation.

Evolution to acute myeloblastic leukemia from chronic neutrophilic leukemia with dysplastic features in granulocytic lineage.

We experienced the case of an 82-year-old man with chronic neutrophilic leukemia (CNL) with dysplastic features in the granulocytic lineage which subsequently progressed to acute myeloblastic leukemia (AML) with myelofibrosis. The patient had hepatosplenomegaly, but there was no evident cause of neutrophilic leukocytosis. The cytogenetic study showed that he had a normal karyotype. Concentrations of the serum granulocyte colony-stimulating factor (G-CSF) were not detectable. Two years after the diagnosis of CNL, blastic transformation to AML occurred with myelofibrosis and significant morphological abnormalities in neutrophils. The blasts were positive for myeloperoxidase, CD33, CD34, and HLA-DR, and the presence of dysplasia within the granulocytic lineage suggested that he had an abnormality at the level of the granulocyte-committed progenitors. Heterogeneous origins of CNL might lead to various clinicopathological features in each case.

Possible role of granulocyte colony-stimulating factor in increased serum soluble interleukin-2 receptor-alpha levels after allogeneic bone marrow transplantation.

Serum soluble interleukin-2 receptor - alpha (sIL-2R) levels markedly increased at the engraftment period in patients who underwent allogeneic bone marrow transplantation (BMT). Since serum G-CSF levels increased during G-CSF administration and decreased after the cessation, increased sIL-2R levels appeared to be induced by G-CSF administration. There was no increase in sIL-2R levels in a patient given macrophage colony-stimulating factor (M-CSF). The sIL-2R levels at the engraftment period and the onset of acute graft-versus-host disease (GVHD) were higher in patients who developed acute GVHD during G-CSF administration than in those who developed acute GVHD after G-CSF cessation. This finding suggests that G-CSF administration may possibly augment acute GVHD. However, it appears to be unlikely, because in the entire population, 18 of 35 patients had acute GVHD while only 6 of 17 patients had acute GVHD during G-CSF administration. Further analysis is still needed in order to draw definite conclusions. Preconditioning regimens did not appear to affect the sIL-2R levels, when the variable frequencies of methotrexate (MTX) administration were compared.

[Acute biliary pancreatitis. Therapeutic trends]. / La pancreatite biliare acuta. Nostro orientamento terapeutico.

BACKGROUND: Treatment of biliary pancreatitis includes suppression of the biliary cause by cholecystectomy and common bile duct clearance. Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy for eradication of biliary stones and laparoscopic cholecystectomy (L.C.) for residual gallbladder stones would be ideal but were once considered to be contraindicated by most surgeons. The timing of definitive biliary tract surgery and the role of ERCP have been the focus of discussion in recent years. METHODS: During a two-year study period 51 patients with acute biliary pancreatitis were studied. Seven patients (14%) underwent emergency laparotomy, necrosectomy, cholecystectomy, exploration of the common bile duct and T-tube insertion, because unstable clinical conditions, with evidence of pancreatic and peripancreatic necrosis on CT-scan. Elective open cholecystectomy and CBD exploration were performed in 7 patients after the resolution of acute pancreatitis during the same hospital admission. RESULTS: Early ERCP and L.C. were associated with favourable outcomes. 33 patients underwent ERCP preoperatively: 17 within 72 hours of admission and 16 after signs of clinical improvement. Laparoscopic cholecystectomy performed 3-25 days after admission was successful in 27 of 29 patients. Postsphincterectomy bleeding occurred in one patient and was treated successfully by endoscopic epinephrine injection. For median hospital stay and recurrence there were statistical differences between early and delayed ERCP. CONCLUSIONS: ERCP and sphincterectomy have a certain role in conjunction with laparoscopic cholecystectomy in the management of patients with acute biliary pancreatitis, particularly in institutions where there is easy access to expert interventional endoscopic techniques. This policy should reduce the risk of cholangitis and recurrent pancreatitis.

A novel human RasGAP-like gene that maps within the prostate cancer susceptibility locus at chromosome 1q25.

We report the molecular cloning of a human cDNA that encodes a molecule having striking homology with Ras-specific GTPase-activating proteins (RasGAPs). Among previously described RasGAPs, the cDNA product is most closely related to Caenorhabditis elegans GAP-2, including a predicted coiled-coil structure near the carboxyl terminus. Expression of the cDNA in Saccharomyces cerevisiae defective in one of two RasGAPs, Ira2, complemented loss of the Ira2 function, indicating that the cDNA product functions as a RasGAP. The RasGAP-like gene is located on the human chromosome 1q25, the locus that appears to contain a hereditary prostate cancer susceptible gene, HPC1.

The important balance between cytokines derived from type 1 and type 2 helper T cells in the control of graft-versus-host disease.

We have investigated cytokine mRNA expression in the peripheral blood mononuclear cells of 20 patients who received allogeneic hematopoietic stem cell transplants to assess the cytokine network after transplantation. IL-4 mRNA expression decreased in five of five (100%) patients with > or = grade III (severe) acute GVHD and increased in 10 of 22 (45%) patients without severe GVHD. In contrast, IL-12 mRNA expression increased in two of two (100%) patients with severe GVHD, but increased in only six of 18 (33%) patients without severe GVHD. Furthermore, IL-10 and/or IL-13 mRNA expression increased in 19 of 22 (86%) patients without severe GVHD, but increased in only one of three (33%) patients with severe GVHD. In patients with allogeneic PBSCT who had severe acute GVHD, the cytokine mRNA expression in patients with allogeneic PBSCT, who had no severe GVHD, showed a similar pattern to that in patients with allogeneic BMT. IL-4 mRNA expression increased in three of five (60%) patients and IL-10 and/or IL-13 mRNA expression increased in five of five (100%) patients. In contrast, IL-12 mRNA expression increased in only one of three (33%) patients. Serum IL-4 concentration in allogeneic PBSCT patients in the early engraftment phase was relatively high, while serum IL-12 concentration was low. These findings suggest that severe GVHD may be related to the cytokine imbalance between type 1 helper T (Th1) cells and type 2 helper T (Th2) cells.