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1.
J Phys Ther Sci ; 31(1): 24-28, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30774200

RESUMEN

[Purpose] To present an efficient treatment regimen for patients with cervicogenic headache by comparatively analyzing the neck disability index (NDI) and cervical muscle activity after an exercise intervention. [Participants and Methods] Thirty patients with cervicogenic headache were assigned to the cranio-cervical flexion group (n=15) and cranio-cervical flexion plus transcranial direct current stimulation (tDCS) group (n=15). Intervention was administered for four weeks, after which the participants' NDI and sternocleidomastoid muscle activity were measured. [Results] The treatment group demonstrated a significantly greater change in NDI after the intervention compared to the control group. The treatment group also showed a significantly greater change in sternocleidomastoid muscle activity than the control group. [Conclusion] Our results show that applying tDCS during cranio-cervical flexion exercise can strengthen the sternocleidomastoid muscle more effectively while improving pain and associated functions in patients with cervicogenic headache. These results would contribute towards developing a more efficient treatment for patients with cervicogenic headache.

2.
J Phys Ther Sci ; 30(3): 361-364, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29581652

RESUMEN

[Purpose] The purpose of this study was to examine the effects of extracorporeal shock wave therapy (ESWT) on upper extremity muscle tone in chronic stroke patients. [Subjects and Methods] For this study, 30 stroke patients participated in this study and they were divided into ESWT group and sham-ESWT group, each group consisted of 15 patients. ESWT and sham-ESWT was performed by the patients for two times a week, for eight weeks. MyotonPRO was used to measure muscle tone. [Results] According to the results of the comparisons between the groups, after intervention, upper extremity muscle tone were significantly higher in the ESWT group than in the sham-ESWT group. [Conclusion] This study showed that ESWT is effective for improving decrease of muscle tone in chronic stroke patients.

3.
J Phys Ther Sci ; 29(10): 1836-1840, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29184301

RESUMEN

[Purpose] The present study aimed to conduct a comparative analysis of changes in mechanical characteristics of cervical muscles and cervical posture in patients with cervicogenic headache following exercise program intervention in order to present effective treatment methods for such patients. [Subjects and Methods] A total of 30 patients with cervicogenic headache were recruited and 15 patients were allocated to cervical stretching exercise group and 15 to cervical stretching exercise and cranio-cervical flexion exercise group. After 3 weeks of exercise intervention, craniovertebral angle and tone (Hz) and stiffness (N/m) of the suboccipital and upper trapezius muscles were measured. [Results] After the exercise program intervention, a greater amount of change in tone of suboccipital and upper trapezius muscles was found in the experimental group, as compared to the control group, but the difference was not statistically significant. Greater amount of change in muscle stiffness and craniovertebral angle was found in the experimental group, as compared to the control group. [Conclusion] Findings of the present study showed that cranio-cervical exercise was an effective form of exercise for changing muscle characteristics and posture in patients with cervicogenic headache. Such findings will be helpful in providing effective treatments for patients with cervicogenic headache.

4.
J Phys Ther Sci ; 29(2): 332-335, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28265168

RESUMEN

[Purpose] This study aimed to compare and analyze the mechanical properties of the upper cervical muscles in patients with cervicogenic headache to identify efficient methods of treatment and diagnosis. [Subjects and Methods] A total of 40 subjects including 20 healthy individuals and 20 patients with cervicogenic headache were selected. A MyotonPRO device was used to measure the tone (Hz), stiffness (N/m), and elasticity (log decrement) of the suboccipital muscles and upper trapezius of the subjects. [Results] There was no significant difference between the 2 groups in the elasticity of the suboccipital muscles and upper trapezius. However, there was a statistically significant difference in tone and stiffness. [Conclusion] This study showed that the tone and stiffness of the suboccipital muscles and upper trapezius in patients with cervicogenic headache had increased compared to healthy subjects.

5.
J Phys Ther Sci ; 28(11): 3145-3148, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27942137

RESUMEN

[Purpose] This study aims to analyze the factors that affect the quality of life of children with cerebral palsy. [Subjects and Methods] The study subjects were 138 children, aged 7-12, who suffer from cerebral palsy. Factors affecting subjects' quality of life were evaluated using the ICF-CY; quality of life was evaluated using the KIDSCREEN 52 - Health-Related Quality of Life questionnaire. Multiple regression analysis was conducted. [Results] The factors related to physical functions that affect subjects' quality of life were mental function, sensory function and pain, genitourinary and reproductive function, as well as neuromusculoskeletal and movement-related functions. Factors related to activities and participation were learning and applying knowledge, self-care, interpersonal interactions and relationships, major life areas, and community, social and civic life. Lastly, factors related to the environment were products and technology, natural environment and human made changes to environment, and attitude. [Conclusion] In order to improve the quality of life of children with cerebral palsy, the compound effects of several factors should be comprehensively considered without being limited to a specific variable from physical function. And children should be provided with ample opportunities to participate in diverse activities and their physical functions, as well as the environmental factors, should improve.

6.
J Phys Ther Sci ; 28(8): 2289-92, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27630416

RESUMEN

[Purpose] The purpose of this study was to examine the correlation between quadriceps muscle activity and balance and gait in stroke patients. [Subjects and Methods] Fifty-five stroke patients (30 males 25 females; mean age 58.7 years; stroke duration 4.82 months; Korean mini-mental state examination score 26.4) participated in this study. MP100 surface electromyography, BioRescue, and LUKOtronic were used to measure the quadriceps muscle activity, balance, and gait, respectively. [Results] There was a significant correlation between quadriceps muscle activity (vastus lateralis % reference voluntary contraction, vastus medialis % reference voluntary contraction) and balance (limits of stability) and gait (gait velocity) but there was none between vastus lateralis % reference voluntary contraction, vastus medialis % reference voluntary contraction. [Conclusion] An increase in quadriceps muscle activity will improve balance and gait ability. To improve function in stroke patients, training is needed to strengthen the quadriceps muscles.

7.
J Phys Ther Sci ; 28(7): 2055-8, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27512263

RESUMEN

[Purpose] The purpose of this study was to examine the effect of virtual reality-based eccentric training on lower extremity muscle activity and balance in stroke patients. [Subjects and Methods] Thirty stroke patients participated, with 15 patients allotted to each of two eccentric training groups: one using a slow velocity (group I) and one using a fast velocity (group II). The virtual reality-based eccentric training was performed by the patients for 30 minutes once a day, 5 days a week, for 8 weeks using an Eccentron system. Surface electromyography was used to measure the lower extremity muscle activity, while a BioRescue was used to measure balancing ability. [Results] A significant difference in lower extremity muscle activation and balance ability was observed in group I compared with group II. [Conclusion] This study showed that virtual reality-based eccentric training using a slow velocity is effective for improving lower extremity muscle activity and balance in stroke patients.

8.
J Nanosci Nanotechnol ; 15(9): 7164-8, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26716303

RESUMEN

Nano silica ball (NSB) core polymethylmethacrylate (PMMA) shell hybrid nanocomposites were synthesized by atomic transfer radical polymerization (ATRP) method for the application to the clearcoat to enhance scratch resistance. The characteristics of the synthesized inorganic/organic hybrid material were examined by scanning electron microscope (SEM), particle size analysis, Fourier transform infrared (FTIR) spectroscopy and thermo gravimetric analysis-differential scanning calorimetry (TGA-DSC). The scratch resistance and light transmittance of the clearcoat were measured by a nano-scratch tester and UV-visible spectroscopy, respectively. The average particle size of the NSB-PMMA hybrid compounds was 30 nm with narrow size distribution. Even 0.1 wt% loading of NSB-PMMA in the clearcoat dramatically enhanced the scratch resistance, about 40% increase in the force of the first fracture, while slightly reduced the light transmittance, about 5% only.

9.
J Phys Ther Sci ; 27(9): 2891-3, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26504319

RESUMEN

[Purpose] The purpose of this study was to investigate the effects of Nordic walking and walking on spatiotemporal gait parameters and ground reaction force. [Subjects] The subjects of this study were 30 young adult males, who were divided into a Nordic walking group of 15 subjects and a walking group of 15 subjects. [Methods] To analyze the spatiotemporal parameters and ground reaction force during walking in the two groups, the six-camera Vicon MX motion analysis system was used. The subjects were asked to walk 12 meters using the more comfortable walking method for them between Nordic walking and walking. After they walked 12 meters more than 10 times, their most natural walking patterns were chosen three times and analyzed. To determine the pole for Nordic walking, each subject's height was multiplied by 0.68. We then measured the spatiotemporal gait parameters and ground reaction force. [Results] Compared with the walking group, the Nordic walking group showed an increase in cadence, stride length, and step length, and a decrease in stride time, step time, and vertical ground reaction force. [Conclusion] The results of this study indicate that Nordic walking increases the stride and can be considered as helping patients with diseases affecting their gait. This demonstrates that Nordic walking is more effective in improving functional capabilities by promoting effective energy use and reducing the lower limb load, because the weight of the upper and lower limbs is dispersed during Nordic walking.

10.
J Phys Ther Sci ; 27(9): 2943-5, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26504330

RESUMEN

[Purpose] The aims of this study were to determine (1) the significance of walking and foot pressure in stroke patients, and (2) the association between changes in postural alignment of stroke patients. [Subjects and Methods] Foot pressure and walking ability based on postural alignment were measured in 50 stroke patients. Trunk imbalance, trunk rotation, pelvic tilt, kyphosis, lordosis were measured using DIERS formetric4D (DIERS International GmbH, Schlangenbad, Germany), which anlalyzes 3-dimensional spinal structure in order to measure postural alignment. To determine foot pressure, the support rate of weight and, average foot pressure were measured using DIERS pedoscan (DIERS International GmbH, Schlangenbad, Germany) apparatus as a pressure platform. [Results] DIERS formetric 4D, DIERS pedoscan, and a 10 m walking test were utilized to measure foot pressure and walking ability relative to changes in postural alignment in participating stroke patients. [Conclusion] This study confirmed the significance of foot pressure and walking ability as related postural alignment, indicating that postural alignment education and a recovery therapy program for functional improvement of stroke patients should be provided together.

11.
J Phys Ther Sci ; 27(5): 1485-90, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-26157246

RESUMEN

[Purpose] This study aimed to examine the expression of transforming growth factor ß1 (TGF-ß1) and type I collagen by applying high voltage pulsed current stimulation (HVPCS) with a visible contraction intensity to white rats with induced wounds. [Subjects] Thirty-six white rats were used for this study. HVPCS with a non-visible contraction intensity was applied to experimental group I, and HVPCS with a visible contraction intensity was applied to experimental group II. Placebo stimulation was applied to the control group. [Methods] After wounds were triggered, the intervention appropriate for each group was applied. Changes in the size of their wounds and expression of TGF- ß1 and type I collagen were measured on the third, fifth, and seventh days. [Results] Comparison of the sizes of the wounds among the groups showed that the most significant decreases were found in experimental group II on the fifth and seventh days. TGF-ß1 expression comparison revealed that experimental group II had the most expression on the fifth day. [Conclusion] HVPCS with a visible contraction intensity was effective in promoting wound healing by increasing expression of TGF-ß1 and synthesis of type I collagen.

12.
Sci Transl Med ; 6(265): 265ra166, 2014 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-25473034

RESUMEN

Definitive clinical trials of new chemotherapies for treating tuberculosis (TB) require following subjects until at least 6 months after treatment discontinuation to assess for durable cure, making these trials expensive and lengthy. Surrogate endpoints relating to treatment failure and relapse are currently limited to sputum microbiology, which has limited sensitivity and specificity. We prospectively assessed radiographic changes using 2-deoxy-2-[(18)F]-fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) at 2 and 6 months (CT only) in a cohort of subjects with multidrug-resistant TB, who were treated with second-line TB therapy for 2 years and then followed for an additional 6 months. CT scans were read semiquantitatively by radiologists and were computationally evaluated using custom software to provide volumetric assessment of TB-associated abnormalities. CT scans at 6 months (but not 2 months) assessed by radiologist readers were predictive of outcomes, and changes in computed abnormal volumes were predictive of drug response at both time points. Quantitative changes in FDG uptake 2 months after starting treatment were associated with long-term outcomes. In this cohort, some radiologic markers were more sensitive than conventional sputum microbiology in distinguishing successful from unsuccessful treatment. These results support the potential of imaging scans as possible surrogate endpoints in clinical trials of new TB drug regimens. Larger cohorts confirming these results are needed.


Asunto(s)
Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico por imagen , Tuberculosis Resistente a Múltiples Medicamentos/terapia , Adulto , Algoritmos , Método Doble Ciego , Femenino , Fluorodesoxiglucosa F18 , Humanos , Pulmón/diagnóstico por imagen , Masculino , Metronidazol/uso terapéutico , Imagen Multimodal , Variaciones Dependientes del Observador , Estudios Prospectivos , Curva ROC , Interpretación de Imagen Radiográfica Asistida por Computador , Sensibilidad y Especificidad , Programas Informáticos , Esputo/microbiología , Resultado del Tratamiento
13.
BMC Infect Dis ; 14: 360, 2014 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-24990578

RESUMEN

BACKGROUND: Tuberculosis remains an important health concern in many countries. The aim of this study was to identify predictors of unfavorable outcomes at the end of treatment (EOT) and at the end of study (EOS; 40 months after EOT) in South Korea. METHODS: New or previously treated tuberculosis patients were recruited into a prospective observational cohort study at two hospitals in South Korea. To identify predictors of unfavorable outcomes at EOT and EOS, logistic regression analysis was performed. RESULTS: The proportion of multidrug-resistant tuberculosis (MDR-TB) was 8.2% in new cases and 57.9% in previously treated cases. Of new cases, 68.6% were cured, as were 40.7% of previously treated cases. At EOT, diabetes, ≥3 previous TB episodes, ≥1 significant regimen change, and MDR-TB were significantly associated with treatment failure or death. At EOS, age ≥35, body-mass index (BMI) <18.5, diabetes, and MDR-TB were significantly associated with treatment failure, death, or relapse. Among cases that were cured at EOT, age ≥50 and a BMI <18.5 were associated with subsequent death or relapse during follow-up to EOS. Treatment interruption was associated with service sector employees or laborers, bilateral lesions on chest X-ray, and previous treatment failure or treatment interruption history. CONCLUSIONS: Risk factors for poor treatment outcomes at EOT and EOS include both patient factors (diabetes status, age, BMI) and disease factors (history of multiple previous treatment episodes, MDR-TB). In this longitudinal, observational cohort study, diabetes mellitus and MDR-TB were risk factors for poor treatment outcomes and relapse. Measures to help ensure that the first tuberculosis treatment episode is also the last one may improve treatment outcomes. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT00341601.


Asunto(s)
Tuberculosis Pulmonar/epidemiología , Adulto , Antituberculosos/uso terapéutico , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , República de Corea/epidemiología , Factores de Riesgo , Insuficiencia del Tratamiento , Resultado del Tratamiento , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Pulmonar/tratamiento farmacológico
14.
BMC Med Genet ; 15: 40, 2014 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-24690209

RESUMEN

BACKGROUND: The well-known genetic polymorphisms in ADH1B(His47Arg) and ALDH2(Glu487Lys) have dramatic effects on the rate of metabolizing alcohol and acetaldehyde. We investigated possible involvement of these functional polymorphisms in other common complex-trait diseases. METHODS: The genetic effects of these two polymorphisms on hepatitis, asthma, type-2 diabetes mellitus (T2DM), and tuberculosis (TB) were examined in a Korean population. RESULTS: We demonstrated that the well-known functional polymorphism of a primary alcohol-metabolizing enzyme (ALDH2 Glu487Lys) has a strong genetic association with the risk of TB. The frequency of the minor allele (ALDH2*487Lys) was found to be much lower in TB patients (freq. = 0.099/n = 477) than among controls (freq. = 0.162/n = 796) (P = 0.00001, OR (95% confidential interval) = 0.57 (0.45-0.74)). Our data may indicate that TB was once an endemic disease, which exerted selection pressure for higher frequencies of ALDH2*487Lys in Asian populations. In addition, the calculated attributable fraction (AF) indicates that 39.5% of TB patients can attribute their disease to the detrimental effects of ALDH2Glu487Glu. CONCLUSION: Our results suggest that this polymorphism is one of the genetic components of TB, at least in the Korean population.


Asunto(s)
Aldehído Deshidrogenasa/genética , Polimorfismo Genético , Tuberculosis Pulmonar/genética , Adulto , Anciano , Anciano de 80 o más Años , Aldehído Deshidrogenasa Mitocondrial , Sustitución de Aminoácidos , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , República de Corea , Factores de Riesgo , Análisis de Secuencia de ADN , Tuberculosis Pulmonar/enzimología , Adulto Joven
15.
Antimicrob Agents Chemother ; 57(8): 3903-9, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23733467

RESUMEN

Pulmonary lesions from active tuberculosis patients are thought to contain persistent, nonreplicating bacilli that arise from hypoxic stress. Metronidazole, approved for anaerobic infections, has antituberculosis activity against anoxic bacilli in vitro and in some animal models and may target persistent, nonreplicating bacilli. In this double-blind, placebo-controlled trial, pulmonary multidrug-resistant tuberculosis subjects were randomly assigned to receive metronidazole (500 mg thrice daily) or placebo for 8 weeks in addition to an individualized background regimen. Outcomes were measured radiologically (change on high-resolution computed tomography [HRCT]), microbiologically (time to sputum smear and culture conversion), and clinically (status 6 months after stopping therapy). Enrollment was stopped early due to excessive peripheral neuropathies in the metronidazole arm. Among 35 randomized subjects, 31 (15 metronidazole, 16 placebo) were included in the modified intent-to-treat analysis. There were no significant differences by arm in improvement of HRCT lesions from baseline to 2 or 6 months. More subjects in the metronidazole arm converted their sputum smear (P = 0.04) and liquid culture (P = 0.04) to negative at 1 month, but these differences were lost by 2 months. Overall, 81% showed clinical success 6 months after stopping therapy, with no differences by arm. However, 8/16 (50%) of subjects in the metronidazole group and 2/17 (12%) of those in the placebo group developed peripheral neuropathy. Subjects who received metronidazole were 4.3-fold (95% confidence interval [CI], 1.1 to 17.1) more likely to develop peripheral neuropathies than subjects who received placebo. Metronidazole may have increased early sputum smear and culture conversion but was too neurotoxic to use over the longer term. Newer nitroimidazoles with both aerobic and anaerobic activity, now in clinical trials, may increase the sterilizing potency of future treatment regimens.


Asunto(s)
Antituberculosos/administración & dosificación , Antituberculosos/uso terapéutico , Metronidazol/administración & dosificación , Metronidazol/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adulto , Antituberculosos/efectos adversos , Antituberculosos/farmacocinética , Área Bajo la Curva , Intervalos de Confianza , Método Doble Ciego , Femenino , Humanos , Pulmón/microbiología , Pulmón/patología , Masculino , Metronidazol/efectos adversos , Metronidazol/farmacocinética , Mycobacterium tuberculosis/aislamiento & purificación , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Índice de Severidad de la Enfermedad , Esputo/microbiología , Resultado del Tratamiento , Adulto Joven
16.
Respiration ; 86(6): 472-8, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23689646

RESUMEN

BACKGROUND: Few studies have investigated the impact of diabetes mellitus (DM), a globally increasing metabolic disease, on treatment outcomes and long-term survival in patients with multidrug-resistant forms of tuberculosis (MDR-TB). OBJECTIVES: We analyzed outcomes in a large cohort to assess the impact of DM on treatment outcomes of patients with MDR-TB. METHODS: MDR-TB patients newly diagnosed or retreated between 2000 and 2002 and followed for 8-11 years were retrospectively analyzed with respect to the effect of DM as a comorbidity on their treatment outcome and long-term survival. RESULTS: Of 1,407 patients with MDR-TB, 239 (17.0%) had coexisting DM. The mean age and body mass index were higher in MDR-TB patients with DM [MDR-TBDM(+)] than in those without DM [MDR-TBDM(-)]. Patients with MDR-TB and a comorbidity of DM had a significantly lower treatment success rate than those without a history of DM (36.0 vs. 47.2%, p = 0.002). In addition, DM was the negative predictor for MDR-TB treatment success in multivariate analyses [odds ratio 0.51, 95% confidence interval (CI) 0.26-0.99]. Mean survival times were also lower in MDR-TBDM(+) than in MDR-TBDM(-) patients (102 vs. 114 months, p = 0.001), with DM as a significant predictor of poor long-term survival in multivariate analyses (hazard ratio 1.59, 95% CI 1.01-2.50). CONCLUSIONS: Among MDR-TB patients, DM was a relatively common comorbidity. In patients undergoing treatment for MDR-TB and followed for 8-11 years, it was found to be independently associated with an increased risk of both treatment failure and death.


Asunto(s)
Diabetes Mellitus/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Índice de Masa Corporal , Estudios de Cohortes , Comorbilidad , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , República de Corea/epidemiología , Estudios Retrospectivos , Insuficiencia del Tratamiento , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adulto Joven
17.
N Engl J Med ; 367(16): 1508-18, 2012 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-23075177

RESUMEN

BACKGROUND: Linezolid has antimycobacterial activity in vitro and is increasingly used for patients with highly drug-resistant tuberculosis. METHODS: We enrolled 41 patients who had sputum-culture-positive extensively drug-resistant (XDR) tuberculosis and who had not had a response to any available chemotherapeutic option during the previous 6 months. Patients were randomly assigned to linezolid therapy that started immediately or after 2 months, at a dose of 600 mg per day, without a change in their background regimen. The primary end point was the time to sputum-culture conversion on solid medium, with data censored 4 months after study entry. After confirmed sputum-smear conversion or 4 months (whichever came first), patients underwent a second randomization to continued linezolid therapy at a dose of 600 mg per day or 300 mg per day for at least an additional 18 months, with careful toxicity monitoring. RESULTS: By 4 months, 15 of the 19 patients (79%) in the immediate-start group and 7 of the 20 (35%) in the delayed-start group had culture conversion (P=0.001). Most patients (34 of 39 [87%]) had a negative sputum culture within 6 months after linezolid had been added to their drug regimen. Of the 38 patients with exposure to linezolid, 31 (82%) had clinically significant adverse events that were possibly or probably related to linezolid, including 3 patients who discontinued therapy. Patients who received 300 mg per day after the second randomization had fewer adverse events than those who continued taking 600 mg per day. Thirteen patients completed therapy and have not had a relapse. Four cases of acquired resistance to linezolid have been observed. CONCLUSIONS: Linezolid is effective at achieving culture conversion among patients with treatment-refractory XDR pulmonary tuberculosis, but patients must be monitored carefully for adverse events. (Funded by the National Institute of Allergy and Infectious Diseases and the Ministry of Health and Welfare, South Korea; ClinicalTrials.gov number, NCT00727844.).


Asunto(s)
Acetamidas/uso terapéutico , Antituberculosos/uso terapéutico , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Oxazolidinonas/uso terapéutico , Acetamidas/efectos adversos , Acetamidas/farmacocinética , Adulto , Antituberculosos/efectos adversos , Antituberculosos/farmacocinética , Farmacorresistencia Bacteriana , Quimioterapia Combinada , Femenino , Humanos , Estimación de Kaplan-Meier , Linezolid , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , Oxazolidinonas/efectos adversos , Oxazolidinonas/farmacocinética , Esputo/microbiología , Adulto Joven
18.
PLoS Med ; 9(8): e1001300, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22952439

RESUMEN

BACKGROUND: Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB. METHODS AND FINDINGS: Three recent systematic reviews were used to identify studies reporting treatment outcomes of microbiologically confirmed MDR-TB. Study authors were contacted to solicit individual patient data including clinical characteristics, treatment given, and outcomes. Random effects multivariable logistic meta-regression was used to estimate adjusted odds of treatment success. Adequate treatment and outcome data were provided for 9,153 patients with MDR-TB from 32 observational studies. Treatment success, compared to failure/relapse, was associated with use of: later generation quinolones, (adjusted odds ratio [aOR]: 2.5 [95% CI 1.1-6.0]), ofloxacin (aOR: 2.5 [1.6-3.9]), ethionamide or prothionamide (aOR: 1.7 [1.3-2.3]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.3 [1.3-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 2.7 [1.7-4.1]). Similar results were seen for the association of treatment success compared to failure/relapse or death: later generation quinolones, (aOR: 2.7 [1.7-4.3]), ofloxacin (aOR: 2.3 [1.3-3.8]), ethionamide or prothionamide (aOR: 1.7 [1.4-2.1]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.7 [1.9-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 4.5 [3.4-6.0]). CONCLUSIONS: In this individual patient data meta-analysis of observational data, improved MDR-TB treatment success and survival were associated with use of certain fluoroquinolones, ethionamide, or prothionamide, and greater total number of effective drugs. However, randomized trials are urgently needed to optimize MDR-TB treatment. Please see later in the article for the Editors' Summary.


Asunto(s)
Antituberculosos/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adulto , Intervalos de Confianza , Femenino , Humanos , Masculino , Oportunidad Relativa , Recurrencia , Insuficiencia del Tratamiento
19.
N Engl J Med ; 366(23): 2151-60, 2012 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-22670901

RESUMEN

BACKGROUND: Delamanid (OPC-67683), a nitro-dihydro-imidazooxazole derivative, is a new antituberculosis medication that inhibits mycolic acid synthesis and has shown potent in vitro and in vivo activity against drug-resistant strains of Mycobacterium tuberculosis. METHODS: In this randomized, placebo-controlled, multinational clinical trial, we assigned 481 patients (nearly all of whom were negative for the human immunodeficiency virus) with pulmonary multidrug-resistant tuberculosis to receive delamanid, at a dose of 100 mg twice daily (161 patients) or 200 mg twice daily (160 patients), or placebo (160 patients) for 2 months in combination with a background drug regimen developed according to World Health Organization guidelines. Sputum cultures were assessed weekly with the use of both liquid broth and solid medium; sputum-culture conversion was defined as a series of five or more consecutive cultures that were negative for growth of M. tuberculosis. The primary efficacy end point was the proportion of patients with sputum-culture conversion in liquid broth medium at 2 months. RESULTS: Among patients who received a background drug regimen plus 100 mg of delamanid twice daily, 45.4% had sputum-culture conversion in liquid broth at 2 months, as compared with 29.6% of patients who received a background drug regimen plus placebo (P=0.008). Likewise, as compared with the placebo group, the group that received the background drug regimen plus 200 mg of delamanid twice daily had a higher proportion of patients with sputum-culture conversion (41.9%, P=0.04). The findings were similar with assessment of sputum-culture conversion in solid medium. Most adverse events were mild to moderate in severity and were evenly distributed across groups. Although no clinical events due to QT prolongation on electrocardiography were observed, QT prolongation was reported significantly more frequently in the groups that received delamanid. CONCLUSIONS: Delamanid was associated with an increase in sputum-culture conversion at 2 months among patients with multidrug-resistant tuberculosis. This finding suggests that delamanid could enhance treatment options for multidrug-resistant tuberculosis. (Funded by Otsuka Pharmaceutical Development and Commercialization; ClinicalTrials.gov number, NCT00685360.).


Asunto(s)
Antituberculosos/uso terapéutico , Nitroimidazoles/uso terapéutico , Oxazoles/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adolescente , Adulto , Antituberculosos/efectos adversos , Antituberculosos/farmacocinética , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/crecimiento & desarrollo , Mycobacterium tuberculosis/aislamiento & purificación , Nitroimidazoles/efectos adversos , Nitroimidazoles/farmacocinética , Oxazoles/efectos adversos , Oxazoles/farmacocinética , Esputo/microbiología , Análisis de Supervivencia , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Adulto Joven
20.
Tuberculosis (Edinb) ; 91(4): 300-7, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21514229

RESUMEN

The immune responses of multidrug-resistant tuberculosis (MDR-TB) patients undergoing lung resection surgery were investigated in order to understand the mechanism of strong immune suppression in MDR-TB. We examined changes in cell-mediated immune response (CMI) of a total of sixteen MDR-TB patients, three of them extensively drug-resistant tuberculosis (XDR-TB) patients, after the removal of the heavily diseased lung section. The IFN-γ response to Mycobacterium tuberculosis culture filtrate proteins (Mtb-CFP), one of the most important CMI to defend TB, showed a statistically significant elevation in 2-4 months after operation when compared to the preoperative CMI in patients who were converted into AFB negative and cured in two years' follow-up, suggesting that the recovery of CMI may be one of the key factors in the successful treatment of MDR-TB. Interestingly, IL-10 response to Mtb-CFP was also elevated in 2-4 months after surgery in cured patients although both proliferative response and PBMC composition were not significantly changed. Infection with first- or second-line drugs resistant Mtb reduces the efficiency of chemotherapeutic treatment of MDR-TB to about 50%. Thus, this study suggests that chemotherapeutic treatment of MDR-TB may be more effective when combined with accompanying therapy that increases CMI, includes lung resection surgery.


Asunto(s)
Antituberculosos/uso terapéutico , Citocinas/metabolismo , Inmunidad Celular , Tuberculosis Resistente a Múltiples Medicamentos/inmunología , Adolescente , Adulto , Antituberculosos/efectos adversos , Proliferación Celular , Quimioterapia Combinada , Femenino , Humanos , Interferón gamma/metabolismo , Interleucina-10/metabolismo , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/cirugía , Adulto Joven
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