Clinical standards for the management of adverse effects during treatment for TB.

BACKGROUND: Adverse effects (AE) to TB treatment cause morbidity, mortality and treatment interruption. The aim of these clinical standards is to encourage best practise for the diagnosis and management of AE.METHODS: 65/81 invited experts participated in a Delphi process using a 5-point Likert scale to score draft standards.RESULTS: We identified eight clinical standards. Each person commencing treatment for TB should: Standard 1, be counselled regarding AE before and during treatment; Standard 2, be evaluated for factors that might increase AE risk with regular review to actively identify and manage these; Standard 3, when AE occur, carefully assessed and possible allergic or hypersensitivity reactions considered; Standard 4, receive appropriate care to minimise morbidity and mortality associated with AE; Standard 5, be restarted on TB drugs after a serious AE according to a standardised protocol that includes active drug safety monitoring. In addition: Standard 6, healthcare workers should be trained on AE including how to counsel people undertaking TB treatment, as well as active AE monitoring and management; Standard 7, there should be active AE monitoring and reporting for all new TB drugs and regimens; and Standard 8, knowledge gaps identified from active AE monitoring should be systematically addressed through clinical research.CONCLUSION: These standards provide a person-centred, consensus-based approach to minimise the impact of AE during TB treatment.

Clinical standards for the dosing and management of TB drugs.

BACKGROUND: Optimal drug dosing is important to ensure adequate response to treatment, prevent development of drug resistance and reduce drug toxicity. The aim of these clinical standards is to provide guidance on 'best practice´ for dosing and management of TB drugs.METHODS: A panel of 57 global experts in the fields of microbiology, pharmacology and TB care were identified; 51 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all participants.RESULTS: Six clinical standards were defined: Standard 1, defining the most appropriate initial dose for TB treatment; Standard 2, identifying patients who may be at risk of sub-optimal drug exposure; Standard 3, identifying patients at risk of developing drug-related toxicity and how best to manage this risk; Standard 4, identifying patients who can benefit from therapeutic drug monitoring (TDM); Standard 5, highlighting education and counselling that should be provided to people initiating TB treatment; and Standard 6, providing essential education for healthcare professionals. In addition, consensus research priorities were identified.CONCLUSION: This is the first consensus-based Clinical Standards for the dosing and management of TB drugs to guide clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment to improve patient care.

Analysis of efficacy and safety of core-needle biopsy versus fine-needle aspiration cytology in patients with cervical lymphadenopathy and salivary gland tumour.

In this study, we compared the diagnostic accuracy and safety of fine-needle aspiration cytology and core-needle biopsy in patients with cervical lymphadenopathy or salivary gland tumour, and provided a basis for selecting the appropriate diagnostic method in clinical situations. A total of 278 patients were included in this study. The sensitivities of fine-needle aspiration cytology and core-needle biopsy were 66.7% and 100%, respectively, and negative predictive values were 92.6% and 100%, respectively, for diagnosing malignancy. In diagnosing lymphoma, fine-needle aspiration cytology gave false-negative results in all patients. In diagnosing tuberculous lymphadenopathy, the sensitivities of fine-needle aspiration cytology and core-needle biopsy were 33.3% and 91.15%, respectively, and the negative predictive values were 90.0% and 95.1%, respectively. The sensitivities of fine-needle aspiration cytology and core-needle biopsy were 42.9% and 100% in diagnosing malignant salivary gland tumours, and the negative predictive values were 91% and 100%, respectively. The results of this study showed that core-needle biopsy was superior in diagnosing and distinguishing critical diseases such as malignant lymphadenopathy and tuberculosis in patients with cervical lymphadenopathy and salivary gland tumour.

Efficacy of ultrasound-guided core needle gun biopsy in diagnosing cervical lymphadenopathy.

OBJECTIVE: Ultrasound-guided fine needle aspiration cytology (US-FNA) is useful for diagnosing cervical lymphadenopathy. However, FNA, has a high false negative rate, especially in patients with lymphoma. Ultrasound-guided core needle gun biopsy (US-CNB) has recently become important for diagnosing cancers, but its value remains undetermined. This study evaluates the efficacy of US-CNB, performed in an outpatient setting, in diagnosing cervical lymphadenopathy and the spectrum of related diseases. MATERIALS AND METHODS: This retrospective study included 79 subjects who were not squamous cell carcinoma suspects and did not have a history of malignancy between January 2006 and July 2009. A US-CNB was performed on enlarged cervical lymph nodes (>1.0cm) in all subjects. Diagnostic sensitivity, specificity, and accuracy of US-CNB in differentiating between malignant and benign lymphadenopathy were evaluated. All enrolled subjects underwent a planned US-FNA before the study US-CNB was performed. Results of US-CNB and US-FNA were compared. RESULTS: The correct histopathological diagnoses were made in 73 of 79 subjects (91.1%) using US-CNB samples. Of these, the most common diagnoses were reactive hyperplasia (26 subjects), Kikuchi's disease (17 subjects), tuberculous lymphadenitis (15 subjects), lymphoma (8 subjects), and metastatic carcinoma (3 subjects). The US-CNB was very good at differentiating between malignant and benign lymphadenopathy, with a diagnostic sensitivity, specificity, and accuracy of 91.6%, 100%, and 98.6%, respectively. Additionally, US-CNB was more accurate than US-FNA in identifying lymphoma (88.8% vs. 11.1%) and Kikuchi's disease (89.4% vs. 29.4%). No US-CNB related-complications were observed. CONCLUSION: The US-CNB is safe, effective, and has a high diagnostic yield for cervical lymphadenopathy. The US-CNB may also be useful for diagnosing lymphoma and Kikuchi's disease.

Prognostic significance of tumour progression and human papillomavirus in advanced tonsillar cancer classified as stage IVa.

OBJECTIVE: To identify clinical factors that can explain the differences in treatment outcome, and examine the value of human papillomavirus infection as a prognostic biomarker in stage IVa tonsillar carcinomas. METHODS: Fifty-nine patients with tonsillar carcinoma classified as stage IVa were retrospectively analysed for survival outcomes according to various clinical factors. Human papillomavirus infection was evaluated using a human papillomavirus DNA chip test and immunohistochemical staining for p16 and p53. RESULTS: Lower disease-free survival rates were associated with increasing local invasiveness and nodal status. Although human papillomavirus positivity and p16 expression was more common in locally advanced tonsillar carcinomas with advanced nodal status, the overall survival rate was better for patients with human papillomavirus positive, p16-positive tumours. CONCLUSION: The disease-free survival rate may differ according to local tumour invasiveness and nodal status, even for stage IVa tonsillar cancers. Human papillomavirus infection may be a useful biomarker for predicting treatment outcomes for stage VIa tumours.

Response characteristics for thermal and pressure devices commonly used for monitoring nasal and oral airflow during sleep studies.

We examined thermocouple and pressure cannulae responses to oral and nasal airflow using a polyester model of a human face, with patent nasal and oral orifices instrumented with a dual thermocouple (F-ONT2A, Grass) or a dual cannula (0588, Braebon) pressure transducer (± 10 cm H2O, Celesco) system. Tidal airflow was generated using a dual compartment facemask with pneumotachographs (Fleisch 2) connected to the model orifices. During nasal breathing: thermocouple amplitude = 0.38 Ln [pneumotachograph amplitude] + 1.31 and pressure cannula amplitude = 0.93 [pneumotachograph amplitude](2.15); during oral breathing: thermocouple amplitude = 0.44 Ln [pneumotachograph amplitude] + 1.07 and pressure cannula amplitude = 0.33 [pneumotachograph amplitude](1.72); (all range ∼ 0.1-∼ 4.0 L s(-1); r(2) > 0.7). For pneumotachograph amplitudes <1 L s(-1) (linear model) change in thermocouple amplitude/unit change in pneumotachograph amplitude was similar for nasal and oral airflow, whereas nasal pressure cannula amplitude/unit change in pneumotachograph amplitude was almost four times that for oral. Increasing oral orifice area from 0.33 cm(2) to 2.15 cm(2) increased oral thermocouple amplitude/unit change in pneumotachograph amplitude by ∼ 58% but decreased pressure cannula amplitude/unit change in pneumotachograph amplitude by 49%. For pneumotachograph amplitudes up to 1 L s(-1), alterations in inspiratory/expiratory ratios or total respiratory time did not affect the sensitivity of either nasal or oral pressure cannulae or the nasal thermocouple, but the oral thermocouple sensitivity was influenced by respiratory cycle time. Different nasal and oral responses influence the ability of these systems to quantitatively assess nasal and oral airflow and oro-nasal airflow partitioning.

A macrophage-specific synthetic promoter for therapeutic application of adiponectin.

Foam cell formation from macrophage is a major cause of atherosclerosis. An efficient macrophage-specific promoter is required for the targeting to macrophages. In this study, we develop a macrophage-specific synthetic promoter for the therapeutic application of adiponectin (APN), an antiatherogenic gene. Synthetic promoter-146 (SP146), registered on the NCBI website (http://www.ncbi.nlm.nih.gov/nuccore/DQ107383), was tested for promoter activities in two non-macrophage cell lines (293 T, HeLa) and a macrophage cell line (RAW264.7, bone marrow-derived macrophages). To enforce macrophage specificity, partial elements of p47(phox) including the PU.1 site with various lengths (-C1, -C2 and -C3) were inserted next to the synthetic promoters. SP146-C1 showed the highest specificity and efficacy in RAW264.7 cells and was selected for development of an APN-carrying macrophage-specific promoter. Green fluorescent protein (GFP)- or APN-expressing lentivirus under SP146-C1 (Lenti-SP-GFP or Lenti-SP-APN, respectively) showed the highest expression efficacy in RAW264.7 cells compared with the non-macrophage cell lines. APN overexpression in RAW264.7 cells successfully inhibited intracellular lipid accumulation, and atherosclerotic lesions and lipid accumulation were significantly reduced by Lenti-SP-APN in ApoE-/- atherosclerosis mice. In conclusion, the synthetic promoter SP146-C1, combined with a p47(phox) promoter element, was successfully developed to target macrophage, and macrophage-specific introduction of APN under SP146-C1 was shown to ameliorate the atherosclerotic pathology.

Effect of voice therapy after phonomicrosurgery for vocal polyps: a prospective, historically controlled, clinical study.

OBJECTIVE: This study aimed to evaluate the efficacy of post-operative voice therapy after phonomicrosurgery for vocal polyp removal. METHODS: The study retrospectively enrolled 55 consecutive patients who had undergone voice therapy after phonomicrosurgery for vocal polyp removal occurring between June 2010 and June 2011. A historical group of 63 similar patients not receiving voice therapy was used as an external control. We compared voice analysis parameters and Voice Handicap Index scores for the two groups. RESULTS: Most objective and subjective voice outcome parameters were significantly improved after surgical treatment. Although the study and control groups showed no significant difference regarding objective parameters (using acoustic and aerodynamic analysis) or the subjective parameters assessed using the grade-roughness-breathiness-asthenia-strain scale, the study group had significantly better final Voice Handicap Index scores. CONCLUSION: Following surgery for vocal polyps, post-operative voice therapy can improve patients' vocal discomfort, emotional responses and everyday self-perception.

Genetic analysis of duck circovirus in Pekin ducks from South Korea.

The genetic organization of the 24 duck circovirus (DuCV) strains detected in commercial Pekin ducks from South Korea between 2011 and 2012 is described in this study. Multiple sequence alignment and phylogenetic analyses were performed on the 24 viral genome sequences as well as on 45 genome sequences available from the GenBank database. Phylogenetic analyses based on the genomic and open reading frame 2/cap sequences demonstrated that all DuCV strains belonged to genotype 1 and were designated in a subcluster under genotype 1. Analysis of the capsid protein amino acid sequences of the 24 Korean DuCV strains showed 10 substitutions compared with that of other genotype 1 strains. Our analysis showed that genotype 1 is predominant and circulating in South Korea. These present results serve as incentive to add more data to the DuCV database and provide insight to conduct further intensive study on the geographic relationships among these virus strains.

Systemic sclerosis sine scleroderma associated with Wolff-Parkinson-White syndrome.

The term "systemic sclerosis sine scleroderma" (ssSSc) has been used to designate a rare progressive systemic sclerosis of visceral organs without skin manifestations. A variety of visceral organs, including the gastrointestinal tract, lung, heart, and kidney, can be involved. We describe a case of 59-year-old female patient with both Wolff-Parkinson-White (WPW) syndrome and ssSSc. She was diagnosed as having ssSSc with Raynaud's phenomenon, anti-nuclear antibody (ANA) and anti-topoisomerase antibody positivity, interstitial pulmonary infiltrates, suspected pulmonary hypertension, subclinical oesophageal dysmotility but no skin thickening. She had a history of paroxysmal tachycardia together with Raynaud's phenomenon and exercise-induced dyspnoea. Electrophysiological study confirmed WPW syndrome with left posterior bypass tract. This case highlights cardiac arrhythmia caused by WPW syndrome as a clinical manifestation of the heart in ssSSc.

A case of successful primary coronary intervention for the total occlusion of left main stem with the aid of abciximab.

A 61-yr-old male patient presented with severe chest pain with cardiogenic shock due to an extensive anterolateral myocardial infarction. Two-dimensional echocardiogram showed severe left ventricular systolic dysfunction (ejection fraction=17%). Emergent coronary angiogram obtained immediately after placing temporary pacing electrode revealed total thrombotic occlusion in the left main stem. We performed direct coronary intervention using kissing balloon technique with the aid of Abciximab (ReoPro) infusion. Residual stenosis with thrombus remained even after high pressure balloon dilatations, therefore we placed two stents, one in the ostia of left anterior descending (LAD) and the other in left circumflex artery (LCX). Coronary angiogram after kissing stents showed improved LAD and LCX flows without residual stenosis. Chest pain resolved and blood pressure normalized after coronary intervention. The whole procedure time was 15 min. Follow-up coronary angiogram taken one week later showed patent previous stented arteries, and echocardiography demonstrated 40% of left ventricular ejection fraction. The clinical course for one-year follow-up was uneventful.

A case of torsade de pointes associated with hypopituitarism due to hemorrhagic fever with renal syndrome.

We describe a 51-yr-old man presenting with syncope due to torsade de pointes. The torsade de pointes was refractory to conventional medical therapy, including infusion of isoproterenol, MgSO4, potassium, lidocaine, and amiodarone. His past history, physical findings, and hormone study confirmed that QT prolongation was caused by anterior hypopituitarism that developed as a sequela of hemorrhagic fever with renal syndrome. The long QT interval with deep inverted T wave was completely normalized 4 weeks after starting steroid and thyroid hormone replacement. Hormonal disorders should be considered as a cause of torsade de pointes, because this life-threatening arrhythmia can be treated by replacing the missing hormone.

Huge calcified aneurysm of the sinus of Valsalva.

Aneurysms of the sinus of Valsalva often remain undiagnosed until they rupture. A 61-year-old man had a huge, heavily calcified unruptured aneurysm, originating from the right sinus of Valsalva, detected incidentally on a chest radiograph taken for the diagnosis of cardiomegaly. Two-dimensional echocardiography revealed pericardial effusion with a huge calcified mass compressing the right ventricular outflow tract. The Doppler color-flow echocardiogram showed blood flow from the aortic root into the aneurysm. A chest computed tomographic scan revealed a large thrombosed aneurysm originating from the aortic root and measuring 10x10 cm. After pericardiocentesis, cardiac catheterization was performed, which showed that the right ventricular systolic pressure had elevated to 80 mmHg. Aortic root aortography demonstrated a huge unruptured calcified aneurysm in the sinus of Valsalva arising from the right coronary sinus. The patient underwent surgical correction to prevent aneurysmal rupture and to relieve the right ventricular outflow obstruction.

Clinical characteristics of unexplained sudden cardiac death in Korea.

In Western countries, sudden cardiac death (SCD) is closely related to coronary artery disease, but in Korea the clinical characteristics of SCD are not well determined. Over a 4-year period (June 1995 to May 1999), 186 cases of SCD, ranging in age from 16 to 75 years, were admitted to the Chonnam National University Hospital. In 82 (44.1%) of these, neither symptoms nor evidence of structural heart disease was found and so their clinical characteristics were investigated. There were 66 (80.5%) men and 16 (19.5%) women (male/female ratio = 4.1:1). The mean age was 50 +/- 14 years: 19 (23.2%) were in their 40s, 21 (25.6%) in their 50s, and 17 (20.7%) in their 60s. The time of circulatory collapse witnessed in 68 cases of SCD showed 2 peaks: between midnight and 03.00h (n=16, 23.5%) and between 09.00h and midday (n=15, 22.1%). Unexplained SCD occurred at home in 48 (64.9%) cases and on the street in 12 (16.2%); it occurred during normal daily routine activity in 23 (39.6%) and during sleep in 15 (25.9%). Thirty-three patients (40.2%) experienced various prodromal symptoms, including chest discomfort (n=13, 15.9%) and dyspnea (n=8, 9.8%). The electrocardiogram taken on arrival recorded asystole in 65 (79.3%) and ventricular fibrillation in 17 (20.7%). Idiopathic ventricular fibrillation was diagnosed in 14 (10 men, 4 women; 45 +/- 11 years) of 21 patients who recovered spontaneous circulation. Five (6.1%) patients were discharged alive, and an implantable cardioverter-defibrillator was implanted in 2. Unexplained SCD is common in Korea and develops predominantly in middle-aged males around midnight or in the late morning usually with no prodromal symptoms (59.8%). Idiopathic ventricular fibrillation is thought to be one of the important causes.

Successful management of intractable coronary spasm with a coronary stent.

Although the long-term survival of patients suffering from coronary spasm is usually excellent, serious complications can develop, such as disabling pain, myocardial infarction, ventricular tachyarrhythmias, atrioventricular block and sudden cardiac death. A 40-year-old man who had intractable chest pain from coronary artery spasm suffered ventricular fibrillation and an acute anterior myocardial infarction upon first admission. The patient underwent a coronary angiogram, which revealed a spontaneous focal spasm at the proximal left anterior descending coronary artery (LAD). He was treated by the combination of nitrate and calcium channel blocker, but continued to complain of severe chest pain despite intensive medical therapy and he had to be treated in the emergency room 5 times during an 8-month follow-up period. An ergonovine coronary angiogram was performed and an intracoronary ultrasound examination, which revealed a focal spasm at the same site of the proximal LAD with a small amount of localized eccentric atheromatous plaque. A coronary artery stent was placed in the proximal LAD and his symptoms resolved. A follow-up coronary angiogram was performed 3 years after stenting and the stent remained patent without any in-stent restenosis or spasm.

The reliability and acceptability of telemedicine for patients with schizophrenia in Korea.

We conducted a pilot study to evaluate telemedicine for patients with schizophrenia. The telemedicine system was connected over the ordinary telephone network at 33 kbit/s. A computer-based patient record was used to view patient summaries and to allow nursing notes to be entered at the patient's home. Fifteen patients with schizophrenia were assessed over the telemedicine system and 15 patients were assessed face to face, using the Brief Psychiatric Rating Scale (BPRS). Our low-bandwidth telemedicine system appeared to be as reliable as higher-bandwidth ISDN systems. In addition, the patients' acceptance of the telemedicine interview, in terms of comfort, ease of self-expression, quality of interpersonal relationship and usefulness, was good in most cases. The only factors significantly affecting the patients' level of acceptance of their particular type of interview were the assessment type (i.e. whether the patient had had a telemedicine assessment or not) and their BPRS score. Since the system was of low cost and was easy to interface with a notebook computer, it could be used support other home-health nursing services.