Association between teriparatide treatment persistence and adherence, and fracture incidence in Taiwan: analysis using the National Health Insurance Research Database.

UNLABELLED: Medication persistence and adherence are critical for osteoporosis outcomes. Using the Taiwan National Health Insurance Research Database, we found that persistence and adherence to teriparatide were low in Taiwanese patients with osteoporosis and that greater persistence and adherence were associated with a lower incidence of hip and other nonvertebral fractures. INTRODUCTION: The purpose of this study was to determine the persistence and adherence to teriparatide treatment in Taiwanese patients with osteoporosis, and to examine the association between persistence and adherence to teriparatide with fracture risks. METHODS: Medical and pharmacy claims for 4,692 patients with vertebral or hip fractures and teriparatide prescriptions between 2005 and 2008 were identified (Taiwan National Health Insurance Research Database). Persistence was the time from the start of treatment to the first 90-day gap between two teriparatide prescriptions. Adherence was the number of teriparatide pens (each pen is used over 1 month) prescribed over 24 months. Association of persistence and adherence to teriparatide with fracture incidence was assessed using adjusted Cox proportional hazards models. RESULTS: The proportion of patients persisting with teriparatide for >6 months and >12 months was 44.6 and 24.9 %, respectively. Over 24 months, 53.6 % of patients were adherent for >6 months and 33.9 % were adherent for >12 months. Patients persisting for >12 months had a significantly lower incidence of hip (adjusted hazard ratio [HR], 0.61 [95 % confidence interval (CI), 0.40-0.93], P = 0.0229) and nonvertebral fracture (HR, 0.79 [95 % CI, 0.63-0.99], P = 0.0462) compared with those who persisted for ≤12 months. Patients adherent for >12 months had a lower incidence of hip (HR, 0.66 [95 % CI, 0.46-0.96], P = 0.0286) and nonvertebral fracture (HR, 0.81 [95 % CI, 0.66-0.99], P = 0.0377) compared with those adherent for ≤12 months. CONCLUSIONS: Persistence and adherence to teriparatide over 24 months were low in Taiwanese patients with osteoporosis; greater adherence and persistence were associated with a lower incidence of nonvertebral fractures.

Stigma among workers attending a hospital specialist diabetes clinic.

BACKGROUND: Stigma among sufferers of chronic diseases such as obesity, human immunodeficiency virus disease and mental health disorders has been studied. This study addresses stigma affecting workers with diabetes. AIMS: To investigate diabetes-related stigma and associated factors in a group of workers receiving care in a Singapore diabetes outpatient clinic. METHODS: Type 2 diabetes mellitus (T2DM) patients receiving subsidized care and holding full-time employment were consecutively recruited over 9 months. A questionnaire was individually administered by an interviewer. RESULTS: One hundred and twenty-five participants were recruited. Fifteen, who reported experiencing stigma, had higher median hospitalizations compared with the rest of the study group (2 (interquartile range (IQR) 0-6) versus 0 (0-1.75), P < 0.05). They were more likely to report that their diabetes affected work (8 (53%) versus 25 (23%), P < 0.05); having heard others experience diabetes-related stigma (9 (60%) versus 33 (30%), P < 0.05) and that employment prospects were affected (6 (40%) versus 18 (16%), P < 0.05), as well as having higher HbA1c (9.5% versus 8.5%, P > 0.05). Fifty-three per cent (66) of respondents reported that work affected their diabetes. There was no significant difference between the stigma and non-stigma groups in age (mean 50 years), body mass index (BMI; mean 28kg/m(2)), diabetes duration (12 years) and insulin use. CONCLUSIONS: Twelve percentage of employed T2DM outpatients reported experiencing stigma because of diabetes. This was associated with frequency of hospitalization (a surrogate for poorer health) and poorer diabetes control. Strategies to reduce stigma include optimizing diabetes control, patient support and educating employers to improve understanding of diabetes and its work implications.

Time benefits of 3D planning in orthognathic surgery: a systematic review.

This systematic review aimed to evaluate the possible time benefits when using 3-dimensional (3D) planning prior to orthognathic surgery compared with a conventional method alone. The databases utilised were PubMed, Medline, Web of Science, and the Cochrane Library. Studies were selected based on eligibility criteria and reviewed independently by two authors. A total of eight studies were included. The review concludes that there are a limited number of studies with the appropriate experimental protocols in place. Therefore, although there is low-grade evidence to suggest that 3D planning in orthognathic surgery is more time-efficient, the field would benefit from the publication of more rigorous studies.

Synchronous mucosal and intraosseous oral cavity carcinomas: a case of rare occult second primary malignancy.

Secondary primary malignancies within the head and neck region are well documented. Within this group, synchronous tumours with an index oral cancer are usually found in the oropharyngeal or laryngeal sites. We present a rare case of an index squamous cell carcinoma in the tongue with a synchronous primary intraosseous squamous cell carcinoma. We discuss the challenges associated with investigation, diagnosis and subsequent management. Treatment aims remain the same; namely, eradicating the disease using surgery, radiotherapy, chemotherapy or a combination of these modalities. It is important to acknowledge the unpredictable pattern of tumour presentation and the need to maintain a high index of suspicion.

High SUV uptake on FDG-PET/CT predicts for an aggressive B-cell lymphoma in a prospective study of primary FDG-PET/CT staging in lymphoma.

BACKGROUND: Data assessing the role of positron emission tomography (PET)/computed tomography (CT) imaging in lymphoma staging is still being accumulated and current staging is based primarily on CT. This study aims to compare the value of PET/CT over conventional CT and bone marrow biopsy (BMB) in the initial evaluation of patients with lymphoma. METHODS: Data on 122 patients with PET/CT scans as part of their initial staging were prospectively collected and reviewed. All patients had complete staging, including BMB. RESULTS: Among the 122 patients, 101 had non-Hodgkin's lymphoma (NHL) and 21 had Hodgkin's lymphoma (HL). Compared with conventional CT, PET/CT upstaged 21 (17%) cases [B-cell non-Hodgkin's lymphoma (B-NHL), 12; T-cell non-Hodgkin's lymphoma (T-NHL), 3; HL, 6]. Of significance, in 13 patients with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG)-avid splenic lesions, four had normal CT findings. A maximum FDG uptake of >10 standardized uptake value (SUV) seems to significantly correlate with an aggressive B-cell lineage (odds ratio 2.47, 95% confidence interval 2.23-2.70). Overall, PET scan was concordant with BMB results in 108 (89%) and discordant in 14 (11%) cases. In HL, our data show that PET scan and marrow results agreed in 19 of the cases (90%), being concordantly negative in 18 cases and concordantly positive in one, giving a negative predictive value (NPV) of 100%, sensitivity of 100% and specificity of 90%. Of note, all 13 with early-stage HL had negative PET/CT scan and BMB. In NHL, all 17 cases of T-NHL had concordant PET and BMB results. In patients with aggressive B-NHL, BMB and PET/CT agreed in 58 patients (92%) and disagreed in five (8%), while the corresponding rates in indolent B-cell lymphoma were 14 (67%) and seven patients (33%), respectively. All seven were falsely negative. CONCLUSIONS: PET/CT upstages 17% of cases and detects occult splenic involvement. This may have potential therapeutic and prognostic implications. SUV >10 may predict for an aggressive histology. Except for indolent B-NHL, our data show that PET scans have a good overall NPV in excluding lymphomatous bone marrow involvement. This is particularly true of early-stage HL, suggesting that BMB may be safely omitted in this group.

Complete Sets of Elastic, Dielectric, and Piezoelectric Properties of [001]-Poled Rhombohedral Pb(Zn1/3Nb2/3)O3-(4.5-7)%PbTiO3 Single Crystals.

Complete sets of elastic, dielectric, and piezoelectric properties of flux grown rhombohedral Pb(Zn1/3Nb2/3)O3-xPbTiO3 (PZN-PT; x = 0.0475 , 0.055, and 0.065) single crystals poled along [001] crystal direction have been determined in the present work. Their phase transformation temperatures, coercive fields, and mechanical quality factors are also provided. The results show that [001]-poled rhombohedral PZN-PT single crystals exhibit superior longitudinal piezoelectric properties ( k33 ≥ 0.90 , d33 ≈ 1580 -2500 pC/N). While the piezoelectric properties increase with PT content, the T RT and hence temperature stability of the crystal degrade accordingly. These unique properties, together with the property matrices provided in this work, can be used advantageously to design high-performance piezoelectric devices of longitudinal activation/sensing mode to suit various application needs.

Molecular cloning of the alpha-globin transcription factor CP2.

CP2, a transcription factor that binds the murine alpha-globin promoter, was purified and subjected to amino acid sequence analysis. Oligonucleotide primers derived from the sequence were used to obtain murine and human cDNA clones for the factor. The murine cDNA spans approximately 4 kb and contains two coextensive open reading frames (ORFs) which encode deduced polypeptides of 529 (ORF-1; molecular weight, 59,802) and 502 (ORF-2; molecular weight, 56,957) amino acids, slightly smaller than the purified factor as estimated from its mobility in sodium dodecyl sulfate-polyacrylamide gels (64,000 to 66,000). The human cDNA contains a single ORF of 501 amino acids that is nearly contiguous with murine ORF-2. Indeed, comparison of deduced human and murine amino acid sequences shows that the two polypeptides are 96.4% identical. A strictly conserved region is rich in serine and threonine (17.5%) and in proline (11%) residues (S-T-P domain). This S-T-P domain is immediately amino terminal to a string of 10 glutamines (in the human sequence) or a tract of alternating glutamine and proline residues (in the mouse sequence). Bacterial expression of the full-length (502-amino-acid) murine factor or of a core region comprising amino acids 133 to 395 generated polypeptides with the DNA binding specificity of CP2. These results confirmed the cloning of CP2 and delimited the region sufficient for specific DNA sequence recognition. Antisera produced against the core region recognized polypeptide species with Mrs of 64,000 and 66,000 in immune blots of nuclear extracts prepared from both murine and human cell lines, consistent with the size of the purified factor. Lastly, a data base search revealed that amino acids 63 to 270 of the murine factor are distantly related to a domain in the Drosophila gene regulatory factor Elf-1.

Detection of borreliacidal antibodies by flow cytometry. An accurate, highly specific serodiagnostic test for Lyme disease.

BACKGROUND: Borreliacidal antibodies can be detected in serum samples from patients with early or late Lyme disease symptoms. When these serum samples are incubated with Borrelia burgdorferi and complement, spirochetes are rapidly killed. Detection of these antibodies can be used as a serodiagnostic test. METHODS: Individual serum samples containing IgM or IgG borreliacidal antibodies were Used to develop a method for detection using flow cytometry. An additional 10 case-defined Lyme disease serum samples and 10 normal serum samples were used to confirm appropriate flow cytometric parameters. To determine specificity, 157 normal serum samples and 104 potential cross-reactive serum samples were tested for borreliacidal activity and antibodies to B burgdorferi using indirect fluorescent antibody or enzyme immunoassay. RESULTS: Flow cytometry can be used to detect borreliacidal activity within 16 to 24 hours after incubation of B burgdorferi organisms. Lyme disease serum, and complement. Significant borreliacidal activity was detected in all Lyme disease serum samples. The percentages of positive normal serum samples were comparable (6% to 10%) using all three assays. In addition, the indirect fluorescent antibody and enzyme immunoassay identified 41 (39%) and 47 (45%) potential cross-reactive serum samples as positive, respectively. In contrast, significant borreliacidal activity was not detected in any potential cross-reactive serum samples. CONCLUSION: Detection of borreliacidal antibody, unlike indirect fluorescent antibody and enzyme immunoassay, is an accurate, highly specific serodiagnostic test for detection of Lyme disease.

Linkage between tyrosine hydroxylase gene and affective disorder cannot be excluded in two of six pedigrees.

Genetic linkage between manic depression and DNA markers on the short arm of chromosome 11 was first reported in 1987 but not supported by further analyses. However, genetic markers at the tyrosine hydroxylase (TH) gene located within this region have been reported to show allelic association with the affective disorder phenotype. We present the results of a linkage analysis using polymorphic DNA segments within the TH gene and the nearby dopamine D4 receptor (DRD4) gene in 6 families multiply affected with affective disorder. Small positive Lod scores were obtained in 2 of 6 pedigrees with the TH polymorphism which may be indicative of genetic heterogeneity.

Evidence for a genetic association between alleles of monoamine oxidase A gene and bipolar affective disorder.

We present evidence of a genetic association between bipolar disorder and alleles at 3 monoamine oxidase A (MAOA) markers, but not with alleles of a monoamine oxidase B (MAOB) polymorphism. The 3 MAOA markers, including one associated with low MAOA activity, show strong allelic association with each other but surprisingly not with MAOB. Our results are significant only for females, though the number of males in our sample is too small to draw any definite conclusions. Our data is consistent with recent reports of reduced MAOA activity in patients with abnormal behavioral phenotypes. The strength of the association is weak, but significant, which suggests that alleles at the MAOA locus contribute to susceptibility to bipolar disorder rather than being a major determinant.

No evidence of association between dopamine D4 receptor variants and bipolar affective disorder.

Disturbance in the dopamine neurotransmitter system has been implicated in the pathogenesis of affective disorder. In this study, we examine the possibility that functional variants of the recently cloned dopamine D4 receptor gene contribute to the genetic component of manic depression. The polymorphism, a 48 bp tandem repeat coding for part of the third cytoplasmic loop, was detected using a PCR based method. In a first sample of 57 patients and 59 controls, we found allele 7 to be in excess in the patients. In contrast, allele 3 was less frequent in patients. A second, larger sample of 90 patients and 91 controls was utilized to test these hypotheses. Data from the two samples were then pooled together for further analyses. We calculated the power of our samples, and if the frequency of 7 repeat allele obtained from sample 1 is true, i.e., 25% (28/114) for patients and 14% (16/118) for controls, then the power of the combined sample is 62% at 5% (two-tailed) significance level. However, both observations were not replicated; we therefore conclude that variations in this repeat at the DRD4 gene do not contribute to the genetic component of manic depression.

Linkage studies on chromosome 22 in familial schizophrenia.

As part of a systematic search for a major genetic locus for schizophrenia we have examined chromosome 22 using 14 highly polymorphic markers in 23 disease pedigrees. The markers were distributed at an average distance of 6.6 cM, covering 70-80% of the chromosome. We analyzed the data by the lod score method using five plausible genetic models ranging from dominant to recessive, after testing the power of our sample under the same genetic parameters. The most positive lod score found was 1.51 under a recessive model for the marker D22S278, which is insufficient to conclude linkage. However, an excess of shared alleles in affected siblings (P < .01) was found for both D22S278 and D22S283. For D22S278, the A statistic was equal to the lod score (1.51) and therefore did not provide additional evidence for linkage allowing for heterogeneity, but the Liang statistic was more significant (P = .002). Our results suggest the possibility that the region around D22S278 and D22S283 contains a gene which contributes to the aetiology of schizophrenia.

Efficacy of donor vaccination before hematopoietic cell transplantation and recipient vaccination both before and early after transplantation.

Allogeneic hematopoietic cell transplantation is followed by humoral immunodeficiency. We evaluated whether antibody levels can be improved by recipient vaccination on day -1 and 50 and whether the levels can be further improved by donor vaccination on day -20. A total of 85 patients were randomized or assigned to one of the following strategies of immunization with Streptococcus pneumoniae polysaccharides, Haemophilus influenzae polysaccharide-protein conjugate, tetanus toxoid (protein recall antigen) and hepatitis B surface antigen (protein neo-antigen): (1) donor on day -20, recipient on days -1, +50 and +365 (D(-20)R(-1,50,365)); (2) donor nil, recipient on days -1, +50 and +365 (D(N)R(-1,50,365)); or (3) donor nil, recipient on day +365 (D(N)R(365)). For H. influenzae and tetanus, IgG levels after grafting were the highest in the D(-20)R(-1,50,365) patients, intermediate in the D(N)R(-1,50,365) patients and the lowest in the D(N)R(365) patients. For S. pneumoniae and hepatitis B, antibody levels appeared to be similar in all three patient groups. The results suggest that for polysaccharide-protein conjugate antigens or protein recall antigens, recipient immunization on days -1 and 50 improves antibody levels and that donor vaccination on day -20 further improves the levels. In contrast, neither recipient immunization on days -1 and 50 nor donor immunization on day -20 appears to be efficacious for polysaccharide antigens and poorly immunogenic protein neo-antigens.

Detection of bcl-1 gene rearrangement and B-cell clonality in mantle cell lymphoma using formalin-fixed, paraffin-embedded tissues.

Mantle cell lymphoma (MCL) has recently emerged as a distinct clinicopathologic entity with characteristic molecular genetic features. Specifically, MCL are clonal B-cell neoplasms and often harbor bcl-1 gene rearrangements. Although this genetic profile is well documented, scant or no data are available on the molecular assessment of MCL using formalin-fixed, paraffin-embedded tissue as a sample source. The polymerase chain reaction (PCR) was employed to study bcl-1 and immunoglobulin heavy chain (IgH) gene rearrangements (B-cell clonality) using formalin-fixed tissue from 12 cases of MCL. In addition, 12 cases of low grade B-cell lymphoma and 5 cases of reactive lymphocytic hyperplasia were studied as comparison controls. A hemi-nested PCR assay was developed to identify major translocation cluster (MTC) bcl-1 gene rearrangements, whereas IgH gene rearrangements were evaluated by both a single-step and hemi-nested approach. Bcl-1 gene rearrangements were amplified in 4 of 12 (33%) MCL, but in none of the controls. With the hemi-nested approach, B-cell monoclonality was demonstrated in 11 of 12 (92%) MCL; 6 of 6 (100%) small lymphocytic lymphomas; 1 of 2 marginal zone lymphomas; 1 of 4 follicular lymphomas; and 0 of 5 reactive lymphocytic hyperplasias. When one-step PCR was used for B-cell clonality assessment, the overall detection rate was lower, specifically: 8 of 12 (67%) MCL; 4 of 6 (67%) small lymphocytic lymphomas; 1 of 2 marginal zone lymphomas; 0 of 4 follicular lymphomas; and 0 of 5 reactive lymphocytic hyperplasias were identified as monoclonal. We have demonstrated that MTC bcl-1 gene rearrangements can be amplified from formalin-fixed tissue. In addition, monoclonal B-cell populations from MCL are better amplified with a hemi-nested approach rather than a single-step PCR assay. With specialized nucleic acid isolation techniques and appropriate PCR protocol design, formalin-fixed, paraffin-embedded tissue is an adequate source of DNA for assessing MTC bcl-1 and IgH gene rearrangements.

Diagnostic usefulness of antineutrophil cytoplasmic autoantibody serology. Comparative evaluation of commercial indirect fluorescent antibody kits and enzyme immunoassay kits.

Antineutrophil cytoplasmic autoantibodies (ANCAs) are increasingly used as serologic markers for pauci-immune crescentic glomerulonephritis and small vessel vasculitis. Many hospital laboratories and referral laboratories use commercial assay kits to detect ANCAs, despite inadequate documentation in the medical literature of kit performance. We evaluated the diagnostic sensitivity, specificity, and predictive value of 3 commercial indirect immunofluorescence assay (IFA) kits and 7 commercial enzyme immunoassay (EIA) kits for several ANCA subtypes. Serum samples from 396 patients with a variety of renal diseases were analyzed, including 146 patients with pauci-immune crescentic glomerulo-nephritis with or without systemic vasculitis. With 1 exception, the kits had more than 90% agreement with the reference standard and gave results similar to those of research laboratories. IFA diagnostic sensitivity ranged from 81% to 91% and EIA sensitivity from 75% to 84%. Maximum specificity was obtained with combined IFA and EIA. Diagnostic specificity was more than 70% for 2 of 3 IFA kits and at least 90% for 5 of 7 EIA kits. Predictive values varied with clinical manifestations. Most commercial IFA and EIA kits that were evaluated provide acceptably accurate analytic results.

Molecular and phenotypic spectrum of de novo Philadelphia positive acute leukemia.

The Philadelphia chromosome is present in a heterogeneous group of leukemias. It is most commonly associated with chronic myelogenous leukemia (CML) and B-lineage acute lymphoblastic leukemia (ALL) being found in more than 95% and 15-25% of cases respectively. We undertook a study to determine the morphologic, phenotypic and molecular diversity of Philadelphia positive de novo acute leukemia patients seen at our institution over the past 3 1/2 years. Twenty-one patients with de novo acute leukemia were found to have the Philadelphia chromosome by cytogenetic studies. They consisted of 3 patients with acute myelogenous leukemia (AML), 1 biphenotypic leukemia and 17 ALL patients. Of the patients with ALL, 16 were of B-lineage while 1 had a T-cell phenotype. Ten patients expressed the p210 BCR-ABL transcript alone and 10 expressed only the p190 BCR-ABL transcript. One patient had co-expression of p190 and p210 b3a2 BCR-ABL transcripts. Thus the Philadelphia chromosome can be found in a diverse cohort of morphologic and immunologic subtypes of de novo acute leukemia reflecting the heterogeneity of lineage involvement in this disease.

Clinico-biological features of 30 patients with acute promyelocytic leukemia and response to combination induction chemotherapy with all-trans retinoic acid and anthracycline.

30 adult patients with acute promyelocytic leukemia (APL) were seen at our institution overthe past 7 years. Their white cell count at presentation ranged from 400/microl to 54,900/microl. Cytogenetic studies were successful in 28 patients, of which 26(93%) were positive for t(15;17). Molecular analysis by reverse-transcription polymerase chain reaction demonstrated the PML-RARalpha fusion transcript in all 30 patients. The majority of patients had breakpoints at the 3' end with bcr1 products predominating. Complete remission rate of 92% was achieved using all-trans retinoic acid and anthracycline as induction chemotherapy in 26 patients. Of these, retinoic acid syndrome was observed in 4 cases, with 1 fatality. In conclusion, APL is a distinct entity with a highly specific molecular marker - t(15;17) translocation - that can be successfully induced into remission with all-trans retinoic acid and anthracycline in most patients.

Retreatment with chimeric CD 20 monoclonal antibody in a patient with nodal marginal zone B-cell lymphoma.

A patient with advanced and chemotherapy-refractory nodal marginal zone B-cell lymphoma was given a course of chimeric CD 20 monoclonal antibody Rituximab. Partial response was observed without any major toxicities. Retreatment with Rituximab for disease progression six months after the first course led to partial remission. Adjuvant radiotherapy was given for the residual disease and, currently, patient's disease remains stable eight months after the second course of Rituximab. This case demonstrates the therapeutic efficacy and feasibility of retreatment with Rituximab for relapsed or refractory low grade lymphoma.