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.

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.

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.

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.

Promotion of seasonal influenza vaccination among staff in residential care homes for elderly in Hong Kong.

Annual influenza epidemics continue to cause worldwide morbidity, mortality and societal disruption, especially among the aged residents of residential care homes for the elderly (RCHEs). Vaccination remains the most effective measure to prevent influenza and its associated complications. The seasonal influenza vaccine uptake rates among RCHE staff were much lower than that among residents. In order to increase uptake of influenza vaccination among RCHE staff in Hong Kong, this study developed and evaluated amultimodal vaccine promotion program (VPP) based on identified factors affecting vaccination acceptance or refusal within the Hong Kong Chinese context. Vaccine acceptance was found to be significantly associated with belief in vaccine efficacy, duration of service, staff group and providing direct care to residents. The focus group study revealed that RCHE staff's belief in the efficacy and safety of the vaccine played a major role in vaccine acceptance. VPP effectiveness was evaluated with a cluster randomised controlled trial among RCHEs with staff vaccination rates below 50%. Compared with 2008/09, the 2009/10 mean staff vaccination rates increased significantly in both the intervention (39.4% to 59.6% (P < 0.001)) and control groups (36.3% to 47.6% (P = 0.008)). RCHE staff in the intervention group had a higher vaccination rate than in the control group (59.6% versus 47.6%, P = 0.072). This program reinforces the importance of a comprehensive and culturally sensitive approach to promote influenza vaccination for RCHE staff.

Presence of extensive intraductal component in patients undergoing breast conservative surgery predicts presence of residual disease in subsequent completion mastectomy.

BACKGROUND: Local recurrence remains a serious problem among patients undergoing breast conservative surgery. This study aimed at identifying risk factors for residual disease after breast conservative surgery. METHODS: This retrospective study was based on patients with invasive breast cancer who have received breast conservative surgery and subsequent completion mastectomy. All patients had a clear resection margin in the initial operation. We analyzed the association between the presence of residual disease during completion mastectomy and the following risk factors: T staging, young age, and presence of extensive intraductal component (EIC), a close margin, lymphovascular permeation (LVP), positivity of estrogen receptor, progesterone receptor, and c-erbB-2. RESULTS: Residual disease was encountered in 21 (45.7%) of 46 patients; EIC was present in 28 patients (60.9%), of whom 17 had residual disease. Presence of EIC during breast conservation surgery was associated with a higher risk of residual disease during completion mastectomy (P = 0.011). Other variables were not statistically significant risk factors for presence of residual disease. No local recurrence was recorded in our cohort, and the disease-free survival and overall survival after completion mastectomy were similar for patients who had residual disease and those who had not. CONCLUSIONS: The presence of EIC is a significant risk factor for residual disease in patients after breast conservative surgery. Our findings may suggest the indicated value of completion mastectomy in patients with EIC during initial breast conservative surgery to decrease the risk of subsequent local failure.

A new labdane diterpene from Leonurus heterophyllus.

A new labdane diterpene, heteronone B (1), together with a known labdane diterpene, heteronone A (2), have been isolated from the aerial part of Leonurus heterophyllus. Their structures were established mainly by 1D and 2D NMR analysis and the stereochemistry of 2 was confirmed by single-crystal X-ray diffraction analysis.

Als2-deficient mice exhibit disturbances in endosome trafficking associated with motor behavioral abnormalities.

ALS2 is an autosomal recessive form of spastic paraparesis (motor neuron disease) with juvenile onset and slow progression caused by loss of function of alsin, an activator of Rac1 and Rab5 small GTPases. To establish an animal model of ALS2 and derive insights into the pathogenesis of this illness, we have generated alsin-null mice. Cytosol from brains of Als2(-/-) mice shows marked diminution of Rab5-dependent endosome fusion activity. Furthermore, primary neurons from Als2(-/-) mice show a disturbance in endosomal transport of insulin-like growth factor 1 (IGF1) and BDNF receptors, whereas neuronal viability and endocytosis of transferrin and dextran seem unaltered. There is a significant decrease in the size of cortical motor neurons, and Als2(-/-) mice are mildly hypoactive. Altered trophic receptor trafficking in neurons of Als2(-/-) mice may underlie the histopathological and behavioral changes observed and the pathogenesis of ALS2.

Living donor liver transplantation for hepatitis C related hepatocellular carcinoma in a haemophilia A patient.

We report the first case of unrelated living liver transplantation for hepatitis C related hepatocellular carcinoma (HCC) in a Chinese patient with haemophilia A. The development of cirrhosis and HCC was insidious in this patient, who has previously failed interferon treatment despite low viral load and genotype 6a. With factor VIII and novoseven support, there were no operative complications and there was no need for blood transfusion. Postoperative pegulated interferon treatment resulted in viral clearance with no increased cellular rejection. The use of living donors represent a potential life saving therapeutic options for hepatitis C virus related complications in haemophiliac, especially in countries of organ shortage. Careful patient and donor choice, meticulous surgical expertise and proper counselling, however, are prudent requirements.

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.

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.

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.

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.