Challenges associated with electronic and in-person directly observed therapy during a randomized trial.

BACKGROUND: Electronic directly observed therapy (eDOT) has been proposed as an alternative to traditional in-person DOT (ipDOT) for monitoring TB treatment adherence. Information about the comparative performance and implementation of eDOT is limited.METHODS: The frequency of challenges during DOT, challenge type, and effect on medication observation were documented by DOT method during a crossover, noninferiority randomized controlled trial. A logistic mixed-effects model that adjusted for the study design was used to estimate the percentage of successfully observed doses when challenges occurred.RESULTS: A total of 20,097 medication doses were scheduled for observation with either eDOT (15,405/20,097; 76.7%) or ipDOT (4,692/20,097; 23.3%) for 213 study participants. In total, one or more challenges occurred during 17.3% (2,672/15,405) of eDOT sessions and 15.6% (730/4,692) of ipDOT sessions. Among 4,374 documented challenges, 27.3% (n = 1,192) were characterized as technical, 65.9% (n = 2,881) were patient-related, and 6.9% (n = 301) were program-related. Estimated from the logistic model (n = 6,782 doses, 173 participants), the adjusted percentage of doses successfully observed during problematic sessions was 21.7% (95% CI 11.2-37.8) for eDOT and 4.2% (95% CI 1.1-14.7) for ipDOT.CONCLUSION: Compared to ipDOT, challenges were encountered in a slightly higher percentage of eDOT sessions but were more often resolved to enable successful dose observation during problematic sessions.

Adverse events among persons with TB using in-person vs. electronic directly observed therapy.

BACKGROUND: We evaluated patient safety within a randomized crossover trial comparing electronic directly observed therapy (eDOT) to in-person DOT (ipDOT) in persons undergoing TB treatment in New York City, NY, USA.METHODS: Participant symptoms, symptom severity, and clinical management were documented. We assessed adverse event reports (AERs) by DOT method during the two-period crossover. Using Cox proportional-hazards mixed-effects models, we estimated the adjusted hazard ratio (aHR) of participants reporting an adverse event (AE) vs. not reporting an AE.RESULTS: Of 211 participants, 57 (27.0%) reported AEs during the two-period crossover; of these, 54.4% (31/57) were reported while using eDOT vs. 45.6% (26/57) while using ipDOT. Controlling for study group and period, the aHR for eDOT vs. ipDOT was 0.98 (95% CI 0.49-1.93). Although statistically not significant, the wide confidence intervals suggest that a significant association cannot be entirely ruled out. Gastrointestinal symptoms were most frequently reported (42.1%, 24/57). AER types and severity did not differ significantly by DOT method. Days from symptom onset to medical attention was similar across DOT methods (median: 1.0 day, IQR 0.0-2.0). No participants switched DOT methods due to AERs or monitoring concerns.CONCLUSION: Further evaluation to ascertain whether AERs differ when patients use eDOT vs. ipDOT is warranted.

Perceptions of insulin therapy amongst Asian patients with diabetes in Singapore.

AIMS: The objective of this study was to determine the prevalence of insulin refusal amongst Singaporean patients with Type 2 diabetes mellitus, to compare perceptions regarding insulin therapy use between patients who were willing to use insulin and those who were not and to identify demographic factors that might predict insulin refusal. METHODS: A cross-sectional interviewer-administered survey incorporating demographic variables and 17 perceptions regarding insulin use (14 negative and three positive) was conducted among a sample of 265 patients attending a public primary healthcare centre. RESULTS: Seven of every 10 patients expressed unwillingness to use insulin therapy (70.6%). The greatest differences in perceptions between patients willing to use insulin therapy and those who were not included fear of not being able to inject insulin correctly (47.4 vs. 70.6%), fear of pain (44.9 vs. 65.8%), belief that insulin therapy would make it difficult to fulfil responsibilities at work and home (46.2 vs. 66.8%) and belief that insulin therapy improved diabetes control (82.1 vs. 58.3%). A tertiary level of education was associated with willingness to use insulin (odds ratio 3.3, confidence interval 1.8-6.1), and significant differences in perceptions were present in patients with different educational levels. CONCLUSIONS: Insulin refusal is an important problem amongst our patients with Type 2 diabetes mellitus. Findings of this study suggest that interventions aimed at increasing insulin therapy use should focus on injection-related concerns, perceived lifestyle adaptations and correction of misconceptions. Different interventions may also be required for patients of different educational groups.

Cost savings associated with video directly observed therapy for treatment of tuberculosis.

OBJECTIVE: To calculate the per-session and annual direct program costs to implement directly observed therapy (DOT) for tuberculosis treatment and to conduct a cost attribution analysis under varying proportions of DOT utilization for four DOT types.DESIGN: Program data covering the study period from September 2014 to August 2015 in New York City (NYC) were used to conduct a retrospective bottom-up micro-costing economic evaluation. For each DOT type, potential per-session and annual program savings were estimated as the cost averted by adopting a uniform distribution of DOT alternatives. Sensitivity analyses explored aggregate cost impacts of unequal distributions.RESULTS: There was a total of 38 035 unique DOT visits, of which 12 002 (32%) were clinic-based (CDOT); 15 483 (41%) were field-based (FDOT); 7185 (19%) were live-video (LVDOT); and 3365 (9%) were recorded-video (RVDOT). The per-session direct costs (in 2016 $US) for DOT services delivered during the study period were $8.46 for CDOT; $19.83 for FDOT; $6.54 for LVDOT; and $5.35 for RVDOT. Sensitivity analyses supported the main findings.CONCLUSIONS: Significant cost savings were estimated with increased utilization of VDOT. Assuming equivalent treatment adherence, duration, completion, and adverse events across DOT types, RVDOT was the modality that most minimized cost.

The spectrum of chronic lymphoproliferative disorders in Hong Kong. A prospective study.

We report the incidence of the chronic lymphoproliferative disorders evolving with leukaemia in Hong Kong. Our findings demonstrate that B cell malignancies are significantly more frequent than mature T cell neoplasms, a picture similar to that seen in Western countries but different from other Eastern countries, eg Japan, where T cell malignancies are more frequent. In contrast to the West, where chronic lymphocytic leukaemia (CLL) is the most common disorder, in Hong Kong there is a clear predominance of B cell lymphomas in leukaemic phase accounting for two-thirds of the cases and particularly those displaying lymphoplasmacytic features or with villous lymphocytes. CLL in Hong Kong has similar clinical and laboratory features to the disease in patients from the West. Distinct disease categories, rare in the West such as the variant form of hairy cell leukaemia and T cell prolymphocytic leukaemia, are also documented. It is unclear whether the differences in prevalence of disease subtypes between Hong Kong and the West relate to different genetic background or environmental factors determinant of the development or progression of the leukaemia. Further studies investigating the genetic/molecular lesions may help to clarify whether the aetiopathogenesis of the lymphoid disorders in Hong Kong is similar to that of Western countries.

Characterising atherothrombosis in Hong Kong: results of the Hong Kong data from a global atherothrombosis epidemiological survey.

OBJECTIVES: To describe the characteristics of patients in Hong Kong with or at risk of atherothrombosis, to determine the proportion of symptomatic patients with more than one vascular bed affected, and to assess the relationship between ankle brachial index and disease severity. DESIGN: Local participation in an international prevalence study. SETTING: Five centres in Hong Kong. PARTICIPANTS: A total of 210 subjects were recruited (105 women and 105 men). Patients were divided into the symptomatic group (with current or previous atherothrombotic symptoms, n=101) and at-risk group (with no current or previous symptoms, but aged over 55 years with at least two specified risk factors, n=109). MAIN OUTCOME MEASURES: Patient characteristics were described, including the number of arterial beds affected, ankle brachial index, presence of risk factors, and medications taken. RESULTS: Of the symptomatic patients, 30% had more than one arterial bed involved. A total of 55.4% of the symptomatic group and 18.4% of the at-risk group had abnormal ankle brachial index values. Lower ankle brachial indices were associated with a greater number of affected arterial beds. Diabetes mellitus and hypertension were the most prevalent risk factors in the at-risk group. Symptomatic patients were commonly treated with antihypertensive and antiplatelet agents, whereas at-risk patients were mostly treated with antihypertensive and antidiabetic agents. Only 20% of at-risk patients were taking antiplatelet agents. CONCLUSIONS: Ankle brachial index is a useful tool for predicting those at risk of atherothrombosis. This simple measurement can be used as part of the screening process in the general practice. The role of antiplatelet agents in primary prevention of atherothrombotic events in at-risk patients deserves further attention.

Sentinel lymph node technique for breast cancer: radiation safety issues.

The radiation safety issues in the application of radioguided sentinel lymph node (SLN) biopsy are discussed, particularly the effective dose (ED) for patients undergoing lymphoscintigraphy by taking into account both the internal emission and the external transmission dose. The quantitative result can be compared with other common radiological examinations. Whole body and finger doses of surgical and pathology staff were determined by direct measurement using high-sensitivity thermoluminescent dosimeters (TLDs) and compared with the annual dose limits recommended by the International Commission on Radiological Protection (ICRP). These dosimetric observations for personnel also provide reference information to implement guidelines for the safe handling, storage, and transport of radioactive specimens at all stages of the radioguided surgery effort in order to maintain good work practices while dealing with unsealed radioactive substances.

Red blood cell alloantibodies and liver transplantation in Chinese patients.

Red blood cell (RBC) alloantibodies are present in up to 14% of white recipients of liver transplants and can cause severe delayed hemolysis. A retrospective survey showed 17 cases (8.8%) of RBC alloantibodies in 192 consecutive Chinese recipients of liver transplants, compared with a 3.7% background hospital incidence. The spectrum of RBC alloantibodies was different from that in white recipients, with no anti-D or anti-K antibodies but with a significant incidence of anti-Mi (29%) antibodies. There was significantly increased transfusion in RBC alloantibody positive cases. Delayed hemolysis also resulted in higher day-7 bilirubin levels. A total of 7 to 86 antigen-positive units were issued in five RBC alloantibody cases, including three early deaths. Seven cases in the RBC alloantibody negative group, but none in the positive group, were salvaged by regraft. Blood banks servicing transplant centers should be aware of ethnic patterns in RBC alloantibodies. Delayed hemolysis may jeopardize patient survival as a result of difficult postoperative stabilization, especially in cases requiring massive transfusion.

Red blood cell alloantibodies and liver transplantation in Chinese patients.

BACKGROUND: Red blood cell (RBC) alloantibodies are present in up to 14% of white recipients of liver transplants and can cause severe delayed hemolysis. METHODS: A retrospective survey showed 17 cases (8.8%) of RBC alloantibodies in 192 consecutive Chinese recipients of liver transplants compared with a background hospital incidence of 3.7%. RESULTS: The spectrum of RBC alloantibodies in Chinese patients was different than in white patients, with no anti-D or anti-K antibodies but a significant incidence of anti-Mi (29%) antibodies. There was a significantly increased incidence of transfusions in RBC alloantibody positive cases. Delayed hemolysis also resulted in higher day-7 bilirubin levels. A total of 7 to 86 antigen-positive units were issued in five RBC alloantibody cases, including three early deaths. Seven cases in the RBC alloantibody negative group, but none in the positive group, were salvaged by regraft. CONCLUSIONS: Blood banks servicing transplant centers should be aware of ethnic patterns in RBC alloantibodies. Delayed hemolysis may jeopardize patient survival as the result of difficult postoperative stabilization, especially in cases requiring massive transfusion.

High incidence of thrombophilia detected in Chinese patients with venous thrombosis.

Venous thromboembolism is rare in Chinese. To determine the incidence and disease profile of thrombophilia in Chinese patients with thrombosis, 52 unselected Chinese patients with documented venous thrombosis were studied for the presence of thrombophilia. Levels of antithrombin III (AT III), protein C (PC) and protein S (PS) as well as the presence of acquired lupus anticoagulant (LA) and anticardiolipin antibody (ACA) were investigated. Thirty patients were found to be abnormal. These consisted of 5 AT III deficiencies, 9 PC deficiencies, 10 PS deficiencies, 1 combined PC & PS deficiency (all in the heterozygous range), and 5 patients with LA and/or ACA. When the patients with LA and/or ACA are excluded, the incidence of hereditary thrombophilia is 25/47 i.e. 53.2% which is much higher than those reported in studies of Caucasian patients selected under strict criteria. Family studies performed in 16 cases of hereditary thrombophilia revealed involvement in 11 cases (68.7%); a total of 36 heterozygous family members were affected, most of which remain asymptomatic. Although 35 events predisposing to thrombosis (27 pregnancies, 1 oral contraceptive consumption and 7 surgical operations) were identified among these index patients, and the heterozygous family members, thrombosis was observed on only 6 occasions (17.1%). The data suggest that pregnancy and surgery do not carry the same degree of thrombotic risk in Chinese as in the Caucasian population with heterozygous AT III, PC and PS deficiency.

Thoracoscopic management of malignant pleural effusions.

Malignant pleural effusion is a common condition and often presents a challenge for treatment. We report our experience from a single institution with the use of video-assisted thoracoscopic surgery (VATS) in the management of malignant effusions. From September 1992 to April 1995, 69 patients (31 men, 38 women; age range, 38 to 76 years) underwent diagnosis and/or treatment of malignant effusions; these included 46 pleural biopsies, 34 talc insufflations, and 16 limited decortications. There was no mortality and there were no intraoperative complications. Postoperative complications occurred in seven patients (10%). Specific histologic diagnoses were obtained in all but 6 patients (87%). Malignant effusion was confirmed in 25 of 46 cases (54%). Thoracoscopic talc insufflation with or without additional decortication was successful in 32 of 34 cases (94%) in controlling recurrence of effusion after a mean follow-up of 6 months among the survivors (22 patients died during the follow-up period without effusion reaccumulation). We conclude that VATS not only provides an accurate diagnosis but also allows effective therapeutic procedures to be performed for malignant effusions that are associated with an acceptable morbidity.

Cytogenetic triclonality in acute myeloid leukemia: a morphologic, immunologic and in situ hybridization study.

Cytogenetically unrelated clones are uncommon in hematologic malignancies. We report a case of acute myeloid leukemia, which consisted morphologically of two populations of small and large blasts demonstrating immunophenotypic heterogeneity. Cytogenetic analysis showed 3 karyotypically abnormal clones: 47,XY, +14/45,XY,dic(5;17)(q11;p11),14dmin, and a near-tetraploid clone. In situ hybridization showed that the near-tetraploid clone corresponded to the large blasts, and the near-diploid clones the small blasts, therefore demonstrating a direct relationship between cell size and DNA content. The diverse morphologic, immunologic and cytogenetic heterogeneity observed in our case suggested hematopoietic oligoclonality.

Bone marrow necrosis masquerading as interferon toxicity in chronic myeloid leukemia.

Bone marrow necrosis (BMN) is a rare pathologic entity associated with a wide variety of diseases. We describe a patient with chronic myeloid leukemia on interferon treatment, who developed BMN with symptoms and signs masquerading as interferon toxicity. This is followed by a literature review of BMN in CML.

Rhodizonate and croconate dianions as divergent hydrogen-bond acceptors in the self-assembly of supramolecular structures.

The C5O5(2-) and relatively unstable C6O6(2-) dianions, each serving as a hub for binding with a set of convergent NH donor groups of four phenylurea molecules, have been generated in situ and stabilized in nearly isostructural hydrogen-bonded host lattices.

Vitamin B12 deficiency--need for a new guideline.

OBJECTIVES: Many patients with vitamin B12 deficiency do not have anemia or macrocytosis, but the prevalence of B12 deficiency in patients without macrocytosis is not known. METHODS: We investigated the prevalence of B12 deficiency among patients with normocytosis and microcytosis and recommended a screening strategy. All patients (n = 3714) with serum B12 measured at the Prince of Wales Hospital in 1996 were reviewed. The prevalence of serum B12 less than 140 pmol/L was determined for the following patient subgroups: younger than 70 y, older than 70 y, anemic, non-anemic, macrocytic, normocytic, microcytic, documented iron deficiency, and documented thalassemia. RESULTS: The prevalence of B12 deficiency (<140 pmol/L) ranged from 4.8% to 9.8% among the different subgroups. CONCLUSIONS: Whatever screening criteria were used, a significant number of B12-deficient patients will be missed. Therefore, there may be a case for universal vitamin B12 screening.

UV-light-induced mutations in synchronous CHO cells.

Asynchronous and synchronous CHO cells were irradiated with germicidal UV light to determine the fluence response curve for cell killing, and the induction of resistance to 6-thioguanine, ouabain, and diphtheria toxin. For asynchronous populations the data show a sigmoidal response for induced reproductive death, as has been seen by others, with a D0 of 6 J/m2 and an extrapolation number of 2.5. The induction of mutations appears to be a linear function for all three mutagenic markers up to a dose of 17 J/m2. Reproductive death induced in the synchronous populations is a function of the time at which exposure occurs in the cell cycle, with late G1 and early S being the sensitive stages. The induction of resistance to 6TG, ouabain, and diphtheria toxin (DT) all seem to depend on the time of exposure in the cell cycle. As in the case of UV-induced reproductive death, the more sensitive periods for mutation induction appear also to be the G1 and early S period of the cell cycle, with the largest cyclic variation occurring for induced DT resistance. A comparison of the results reported here for the UV exposure with exposures of synchronous CHO cells to X-rays and ethylnitrosourea suggests that there are different age-specific responses to mutation induction for each agent, and that there are often different age responses for different mutagenic endpoints with the same mutagen.

Design and performance of a new continuous-flow sample-introduction system for flame infrared-emission spectrometry: Applications in process analysis, flow injection analysis, and ion-exchange high-performance liquid chromatography.

A new sample introduction system for the analysis of continuously flowing liquid streams by flame infrared-emission (FIRE) spectrometry has been developed. The system uses a specially designed purge cell to strip dissolved CO(2) from solution into a hydrogen gas stream that serves as the fuel for a hydrogen/air flame. Vibrationally excited CO(2) molecules present in the flame are monitored with a simple infrared filter (4.4 mum) photometer. The new system can be used to introduce analytes as a continuous liquid stream (process analysis mode) or on a discrete basis by sample injection (flow injection analysis mode). The key to the success of the method is the new purge-cell design. The small internal volume of the cell minimizes problems associated with purge-cell clean-out and produces sharp, reproducible signals. Spent analytical solution is continuously drained from the cell, making cell disconnection and cleaning between samples unnecessary. Under the conditions employed in this study, samples could be analyzed at a maximum rate of approximately 60/h. The new sample introduction system was successfully tested in both a process analysis- and a flow injection analysis mode for the determination of total inorganic carbon in Waco tap water. For the first time, flame infrared-emission spectrometry was successfully extended to non-volatile organic compounds by using chemical pretreatment with peroxydisulfate in the presence of silver ion to convert the analytes into dissolved carbon dioxide, prior to purging and detection by the FIRE radiometer. A test of the peroxydisulfate/Ag(+) reaction using six organic acids and five sugars indicated that all 11 compounds were oxidized to nearly the same extent. Finally, the new sample introduction system was used in conjunction with a simple filter FIRE radiometer as a detection system in ion-exchange high-performance liquid chromatography. Ion-exchange chromatograms are shown for two aqueous mixtures, one containing six organic acids and the second containing six mono-, di-, and trisaccharides.