Cost-effectiveness of nirmatrelvir/ritonavir for high-risk adult outpatients with COVID-19 in Japan.

INTRODUCTION: This study aimed to evaluate the cost-effectiveness of nirmatrelvir/ritonavir (Nir/Rit) for adult outpatients with COVID-19 from the perspective of a Japanese public healthcare payer. METHODS: A cost-effectiveness simulation was conducted comparing Nir/Rit for the outpatient treatment of high-risk COVID-19 patients to best supportive care (BSC) without antiviral or antibody drugs. The analytical model was divided into two phases: the treatment phase, lasting 35 days from the start of COVID-19 treatment, and the post-treatment phase. Patients who survived the treatment phase were assumed to follow a general population survival curve. Expected costs and expected quality-adjusted life years (QALYs) for both BSC and Nir/Rit were calculated for ages 40 to 80 to obtain the incremental cost-effectiveness ratio (ICER). The robustness of the results was evaluated through deterministic and probabilistic sensitivity analysis (PSA). RESULTS: The ICERs for patients aged 40, 50, 60, 70, and 80 were 18,854,276 Japanese Yen (JPY)/QALY, 8,482,034 JPY/QALY, 4,976,612 JPY/QALY, 2,636,096 JPY/QALY, and 1,597,783 JPY/QALY, respectively. In the deterministic sensitivity analysis, both the mortality risk during the treatment phase and the relative mortality risk with Nir/Rit had a high impact on ICER across all ages. In the PSA, when the willingness-to-pay (WTP) threshold was set at 5 million JPY/QALY, the probability of the ICER being below the WTP threshold was 0%, 0.2%, 45.4%, 99.9%, and 100% at ages 40, 50, 60, 70, and 80, respectively. CONCLUSION: Nir/Rit is cost-effective for older individuals aged 60 and over but not for younger age groups.

Industrially produced trans-fatty acids are potent promoters of DNA damage-induced apoptosis.

trans-Fatty acids (TFAs) are unsaturated fatty acids harboring at least one carbon-carbon double bond in trans configuration, which are categorized into two groups according to their origin: industrial and ruminant TFAs, hereafter called iTFAs and rTFAs, respectively. Numerous epidemiological studies have shown a specific link of iTFAs to various diseases, such as cardiovascular and neurodegenerative diseases. However, there is little evidence for underlying mechanisms that can explain the specific toxicity of iTFAs, and how to mitigate their toxicity. Herein, we show that iTFAs, including elaidic acid (EA) and linoelaidic acid, but not rTFAs, facilitate apoptosis induced by doxorubicin (Dox), triggering DNA double-strand breaks. We previously established that EA promotes Dox-induced apoptosis by accelerating c-Jun N-terminal kinase (JNK) activation through mitochondrial reactive oxygen species (ROS) overproduction. Consistently, iTFAs specifically enhanced Dox-induced JNK activation. Furthermore, Dox-induced pro-apoptotic signaling by iTFAs was blocked in the presence of oleic acid (OA), the geometrical cis isomer of EA. These results demonstrate that iTFAs specifically exert their toxicity during DNA damage-induced apoptosis, which could be effectively suppressed by OA. Our study provides evidence for understanding the difference in toxic actions between TFA species, and for new strategies to prevent and combat TFA-related diseases.

Effect of quantitative partial valgus stress during baseball pitching on ball velocity and subjective pitch-effort.

BACKGROUND: Excessive elbow valgus stress can often cause pitching elbow injuries, and rehabilitation is usually required before an athlete can resume playing. However, there is a lack of information on the partial load rehabilitation of pitching elbow injuries caused by valgus extension overload based on elbow valgus stress. The purpose of this study was to clarify how quantitative partial elbow valgus stress while pitching affects ball velocity and subjective pitch-effort. METHODS: Forty-six male baseball pitchers participated in this study. Each player wore a wearable device on the elbow that collected their pitch parameters. Ball velocity was measured using a radar gun. Each elbow valgus stress was measured while each player was instructed to throw 5 fastballs at full effort. Then, based on the average stress of the 5 throws (100% partial valgus stress), the 75% and 50% stresses were calculated (75% and 50% partial valgus stress, respectively). Each pitcher continued to pitch until the number of pitches thrown at the targeted elbow stress reached 5. Each player was asked about their subjective pitch-effort after completing each type of partial valgus stress pitch. Outcomes were statistically evaluated using either a 1-way repeated measures analysis of variance or 2-way analysis of variance. RESULTS: The ball velocity was 72% (95% confidence interval [CI], 69%-75%) and 58% (95% CI, 55%-61%) during the 75% and 50% partial valgus stress, respectively (P < .001). Subjective pitch-effort was 41% (95% CI, 38%-44%) and 19% (95% CI, 16%-22%) while pitching at 75% and 50% partial valgus stress, respectively (P < .001). CONCLUSIONS: It may be desirable to instruct pitchers to throw at less than 20% subjective pitch-effort of the max if they want to pitch at 50% partial valgus stress. Elbow valgus stress might correlate with ball velocity at 75% partial valgus stress pitch. These results could enable clinicians and coaches to perform safer return-to-throwing programs and prevent excessive load on the elbow.

Photocatalytic Activity of Radial Rutile Titanium(IV) Oxide Microspheres for Aerobic Oxidation of Organics.

Radial rutile TiO2 nanorod homomesocrystals (TiO2 -NR HOMCs) or the so-called "sea urchin-like TiO2 microspheres" were synthesized by using a hydrothermal method. TiO2 -NR HOMCs show photocatalytic activity for aerobic oxidative degradation of 2-naphthol under irradiation of UV- and visible light. Furthermore, extremely small iron oxide clusters were formed on the surface of TiO2 -NR HOMCs (FeOx /TiO2 -NR HOMCs) by the chemisorption-calcination technique to reduce the band gap. The FeOx -surface modification gives rise to drastic enhancement of the UV- and visible-light activity. Reversed double-beam photoacoustic spectroscopy measurements were performed for TiO2 -NR HOMCs and FeOx /TiO2 -NR HOMCs to obtain the ERDT (energy-resolved distribution of electron traps)/CBB (conduction-band bottom) patterns. The ERDT/CBB pattern of TiO2 -NR HOMCs consists of two components derived from rutile (C1) and amorphous TiO2 (C2). In the pattern, the surface electron traps in C2 exist near the CBB to be removed by the FeOx -surface modification. By taking this finding into consideration, the striking surface modification effect is ascribable to the electrocatalytic activity (or the action as an electron reservoir) of the FeOx clusters for multiple ORR, the suppression of recombination, and the increase in the visible-light harvesting efficiency.

Switching of Electron Transport Direction from the Long Axis to Short Axis in a Radial SnO2(Head)-Rutile TiO2 Nanorod(Tail) Heteromesocrystal Photocatalyst.

Heteroepitaxial growth of rutile TiO2 nanorods from SnO2 seeds yielded radial heteromesocrystals consisting of SnO2(head) and rutile TiO2 nanorod(tail) with the SnO2(head) oriented toward the center (TiO2-NR//SnO2 HEMCs). Iron oxide clusters were formed on the surface by the chemisorption-calcination technique. The FeOx-surface modification gives rise to drastic increases in the photocatalytic activity for aerobic oxidation of 2-naphthol under irradiation of UV and visible light. As a 2D-model for 3D-TiO2-NR//SnO2 HEMC, electrochemical measurements were performed for the rutile TiO2-NR array formed on a fluorine-doped tin oxide (SnO2:F) electrode. The results showed that the FeOx clusters possess electrocatalytic activity for a multielectron oxygen reduction reaction, and the high photocurrent of the electrode is remarkably reduced by the FeOx-surface modification. Consequently, the striking photocatalytic activity of FeOx/TiO2-NR//SnO2 HEMCs was ascribable to the switching of the electron transport direction necessary for the charge separation from the long axis of the TiO2 NR to the short axis.

A measure for the identification of preferred particle orientations in cryo-electron microscopy data: A simulation study.

Cryo-electron microscopy (cryo-EM) is an important experimental technique for the structural analysis of biomolecules that are difficult or impossible to crystallize. The three-dimensional structure of a biomolecule can be reconstructed using two-dimensional electron-density maps, which are experimentally sampled via the electron beam irradiation of vitreous ice in which the target biomolecules are embedded. One assumption required for this reconstruction is that the orientation of the biomolecules in the vitreous ice is isotropic. However, this is not always the case and two-dimensional electron-density maps are often sampled using preferred biomolecular orientations, which can make reconstruction difficult or impossible. Compensation for under-represented views is computationally feasible for the reconstruction of three-dimensional electron density maps, but one must know whether or not there is any missing information in the sampled two-dimensional electron density maps. Thus, a measure to identify whether a cryo-EM data is obtained from the bio-molecules adopting preferred orientations is required. In the present study, we propose a measure for which the geometry of manifold projected onto a low-dimensional space is used. To show the usefulness of the measure, we perform simulations for cryo-EM experiment of a protein. It is found that the geometry of manifold projected onto a two-dimensional space for a protein adopting a preferred biomolecular orientation is significantly different from that for a protein adopting a uniform orientation. This result suggests that the geometry of manifold projected onto a low-dimensional space can be used for the measure for the identification that the biomolecules adopt preferred orientations.

Weights, recursion relations and projective triangulations for positive geometry of scalar theories.

The story of positive geometry of massless scalar theories was pioneered in [1] in the context of bi-adjoint ϕ 3 theories. Further study proposed that the positive geometry for a generic massless scalar theory with polynomial interaction is a class of polytopes called accordiohedra [2]. Tree-level planar scattering amplitudes of the theory can be obtained from a weighted sum of the canonical forms of the accordiohedra. In this paper, using results of the recent work [3], we show that in theories with polynomial interactions all the weights can be determined from the factorization property of the accordiohedron. We also extend the projective recursion relations introduced in [4, 5] to these theories. We then give a detailed analysis of how the recursion relations in ϕ p theories and theories with polynomial interaction correspond to projective triangulations of accordiohedra. Following the very recent development [6] we also extend our analysis to one-loop integrands in the quartic theory.

Chronic Use of Theophylline and Mortality in Chronic Obstructive Pulmonary Disease: A Meta-analysis. / Uso crónico de teofilina y mortalidad en la enfermedad pulmonar obstructiva crónica: un metaanálisis.

BACKGROUND: Theophylline has been shown to improve respiratory function and oxygenation in patients with chronic obstruction pulmonary disease (COPD). However, the impact of theophylline on mortality in COPD patients has not been not sufficiently evaluated. METHOD: Two investigators independently searched for eligible articles in 4 databases. The eligibility criterion for this meta-analysis was an original research article that provided a hazard ratio for theophylline for all-cause mortality of COPD patients. Both randomized controlled trials and observational studies were accepted. After we confirmed no substantial heterogeneity (I(2)<50%), the fixed-model method with generic inverse variance was used for meta-analysis to estimate the pooled hazard ratio. RESULTS: We screened 364 potentially eligible articles. Of the 364 articles, 259 were excluded on the basis of title and abstract, and 99 were excluded after examination of the full text. Our final analysis included 6 observational studies and no randomized controlled trials. One study reported 2 cohorts. The number of patients in each cohort ranged from 47 to 46,403. Heterogeneity (I(2)=42%, P=.11) and publication bias (Begg's test r=0.21, P=.662) were not substantial. Fixed-model meta-analysis yielded a pooled hazard ratio for theophylline for all-cause death of 1.07 (95% confidence interval: 1.02-1.13, P=.003). CONCLUSION: This meta-analysis of 7 observational cohorts suggests that theophylline slightly increases all-cause death in COPD patients.

Currently Used Low-Dose Pyrazinamide Does Not Increase Liver-Injury in the First Two Months of Tuberculosis Treatment.

OBJECTIVE: In the 1950s, a high-dose (40-70 mg/kg/day) of pyrazinamide (PZA), was reported to cause drug-induced liver injury (DILI) at an unacceptable frequency. It remains unclear whether adding PZA (Z) at the currently accepted low-dose (20-25 mg/kg/day) for two months to a regimen of isoniazid (H) + rifampicin (R) + ethambutol (E) actually increases the risk of DILI. METHOD: Smear-positive tuberculosis patients were treated with daily HRE or HRZE regimen under direct observation. We used three independent models. Model 1 was analyzed with a multivariate Cox-analysis using a pre-matched cohort. Next, propensity score matching was conducted using the nearest neighbor method with caliper of 0.03. Models 2 and 3 were analyzed by univariate and multivariate Cox-analyses, respectively, with the matched cohort. DILI was assessed based on the guidelines of the American Thoracic Society. RESULTS: We reviewed the records of 383 patents (male, n=260; female n=123; mean age, 64±20 years). Among these patients, 75 patients were treated with HRE and 308 were treated with HRZE. DILI occurred in the first two months in 24% (18/75) and 8% (24/308) of the HRE-treated and HRZE-treated cases, respectively. In all three of the models, DILI was less frequent in patients treated with the HRZE regimen: Model 1, HR of 0.30 (95% confidence interval (CI) 0.14-0.68, p=0.004); Model 2, HR of 0.37 (95%CI 0.14-0.96, p=0.041); and Model 3, HR of 0.34 (95%CI 0.12-0.94, p=0.038). CONCLUSION: The addition of the currently accepted low dose (20-25 mg/kg/day) of PZA to the HRE regimen did not increase the incidence of DILI during the first two months of treatment.

Impact of Corticosteroids on Mortality in Patients with Acute Respiratory Distress Syndrome: A Systematic Review and Meta-analysis.

OBJECTIVE: The impact of corticosteroids on acute respiratory distress syndrome (ARDS) mortality remains controversial following the publication of numerous trials, observational studies and meta-analyses. An updated meta-analysis is warranted, as a few original studies on this topic have been published since the last meta-analysis. METHODS: We searched for eligible articles using four databases. In particular, we included full-length original articles providing sufficient data for evaluating the impact of corticosteroid treatment on adult ARDS mortality in the form of odds ratios. A fixed model with the confidence interval method was used. An assessment of publication bias and sensitivity analyses were also conducted. RESULTS: We included 11 of 185 articles. The pooled odds ratio for corticosteroids with respect to all-cause mortality involving 949 patients was 0.77 [95% confidence interval (CI): 0.58-1.03, p=0.079] with strong heterogeneity(I2=70%, p<0.001). The results of the sensitivity analysis, Begg-Kendall test (τ=0.53, p=0.024)and funnel plot consistently suggested the existence of strong publication bias. After six potentially unpublished cohorts were filled using Duval's trim and fill method, the pooled odds ratio shifted to 1.11 (95% CI0.86-1.44, p=0.427). In addition, the sensitivity analyses suggested that corticosteroid treatment has a different impact on mortality depending on the comorbidities and trigger events. CONCLUSION: We were unable to confirm, based on the data of published studies, the favorable impact of corticosteroid therapy on mortality in overall ARDS cases. Published articles exhibit strong publication bias,and previous meta-analyses may be affected by this publication bias. Further research focusing on pathophysiology- or trigger event-specific ARDS is anticipated.

Minimum clinically important difference in diffusing capacity of the lungs for carbon monoxide among patients with severe and very severe chronic obstructive pulmonary disease.

BACKGROUND: The minimum clinically important difference (MCID) for diffusing capacity of the lungs for carbon monoxide (DLCO) has not yet been solidly established. METHODS: We used the dataset of surgical cohort of National Emphysema Treatment Trial. Briefly, severe and very severe chronic obstructive pulmonary disease (COPD) patients who were candidate for volume reduction surgery and who could provide sufficient data at 12-month follow-up were included. We used two anchor methods using 6-minute walk distance (6MWD. MCID = 40 m) and forced expiratory volume in 1 sec (FEV1. MCID = 100 ml) as anchors, and two distribution methods. We proposed MCID with a median of estimated values. We estimated MCID for DLCO in raw value and % change from the baseline independently. RESULTS: The surgical cohort included 356 patients, whose average age was 66.6 ± 5.5 years, and the average % predicted FEV1 was 27.8 ± 7.3%. The estimated MCID for DLCO in raw value and % change from the baseline were as follows: anchor method (average, 6MWD) 1.2 ml/min/mmHg, 17%; anchor method (average, FEV1) 0.7 ml/min/mmHg, 11%; anchor method (receiver operating characteristic, 6MWD) 1.1 ml/min/mmHg, 10%; anchor method (receiver operating characteristic, FEV1) 1.2 ml/min/mmHg, 3%; distribution method (0.3 units of standard deviation), 0.9 ml/min/mmHg, 11%; distribution method (standard error of measurement), 1.1 ml/min/mmHg. The median of these values was 1.1 ml/min/mmHg and 11%. CONCLUSION: We estimated the group-level MCID for DLCO for patients with severe and very severe COPD patients as 1.1 ml/min/mmHg and 11% of baseline DLCO.

Statins reduce all-cause mortality in chronic obstructive pulmonary disease: a systematic review and meta-analysis of observational studies.

BACKGROUND: Recent observational studies have suggested that use of statins reduces mortality in patients suffering from chronic obstructive pulmonary disease. However, no meta-analysis has reported the pooled hazard ratio of statins to all-cause mortality. METHODS: We searched for eligible articles using five databases. We included randomized controlled trials and cohort studies written in English using original data reporting the hazard ratio of statins to all-cause, cardiovascular-related, cancer-related, or respiratory-related mortality. A fixed model with the confidence interval method was used. Publication bias was evaluated by funnel plot and Begg's test, and was corrected using Duval's trim and fill method. Sensitivity analyses were also conducted. RESULTS: We included 10 out of 128 articles. The pooled hazard ratio of statins to all-cause mortality involving 16269 patients was 0.81 (95% CI: 0.75-0.86, P < 0.001) with moderate heterogeneity (I2 = 52%, P = 0.032). The sensitivity analysis and funnel plot suggested the existence of publication bias. After three possibly unpublished cohorts were imputed, the pooled hazard ratio of 0.83 (95% CI: 0.78-0.88, P < 0.001) still suggested a favorable prognosis in statin-treated patients. The pooled hazard ratio of statins to cardiovascular-related, cancer-related, and respiratory-related mortality were 0.52 (95% CI: 0.27-1.01, P = 0.052), 0.57 (95% CI: 0.32-1.01, P = 0.056), and 0.55 (95% CI: 0.43-0.78, P < 0.001), respectively, although these results were not conclusive as we could not find a sufficient number of original studies dealing with those forms of mortality. CONCLUSIONS: The use of statins for patients suffering from chronic obstructive pulmonary disease may reduce all-cause mortality. This conclusion should be re-evaluated by a registered large-scale randomized controlled trial.

Three cases of mesalazine-induced pneumonitis with eosinophilia.

Oral mesalazine, or 5-aminosalicylate, is one of the first-choice medications for the treatment of ulcerative colitis and is commonly used for both induction and maintenance therapy. In a 6-month period, we treated three cases of mesalazine-induced pneumonitis. In all three cases, computed tomography images revealed upper lobe dominant bilateral peripherally localized consolidations. Such images are commonly observed in patients with cryptogenic organizing pneumonia or chronic eosinophilic pneumonia. Computed tomography images for mesalazine-induced pneumonitis have been rarely reported in the literature.

Evidence suggesting that oral corticosteroids increase mortality in stable chronic obstructive pulmonary disease.

BACKGROUND: Oral corticosteroids were used to control stable chronic obstructive pulmonary disease (COPD) decades ago. However, recent guidelines do not recommend long-term oral corticosteroids (LTOC) use for stable COPD patients, partly because it causes side-effects such as respiratory muscle deterioration and immunosuppression. Nonetheless, the impact of LTOC on life prognosis for stable COPD patients has not been clarified. METHODS: We used the data of patients randomized to non-surgery treatment in the National Emphysema Treatment Trial. Severe and very severe stable COPD patients who were eligible for volume reduction surgery were recruited at 17 clinical centers in the United States and randomized during 1998-2002. Patients were followed-up for at least five years. Hazard ratios for death by LTOC were estimated by three models using Cox proportional hazard analysis and propensity score matching. RESULTS: The pre-matching cohort comprised 444 patients (prescription of LTOC: 23.0%. Age: 66.6 ± 5.4 year old. Female: 35.6%. Percent predicted forced expiratory volume in one second: 27.0 ± 7.1%. Mortality during follow-up: 67.1%). Hazard ratio using a multiple-variable Cox model in the pre-matching cohort was 1.54 (P = 0.001). Propensity score matching was conducted with 26 parameters (C-statics: 0.73). The propensity-matched cohort comprised of 65 LTOC(+) cases and 195 LTOC(-) cases (prescription of LTOC: 25.0%. Age: 66.5 ± 5.3 year old. Female: 35.4%. Percent predicted forced expiratory volume in one second: 26.1 ± 6.8%. Mortality during follow-up: 71.3%). No parameters differed between cohorts. The hazard ratio using a single-variable Cox model in the propensity-score-matched cohort was 1.50 (P = 0.013). The hazard ratio using a multiple-variable Cox model in the propensity-score-matched cohort was 1.73 (P = 0.001). CONCLUSIONS: LTOC may increase the mortality of stable severe and very severe COPD patients.

Small, moderate, and large changes, and the minimum clinically important difference in the University of California, San Diego Shortness of Breath Questionnaire.

Minimum clinically important change of 5 points in the University of California, San Diego Shortness of Breath Questionnaire (SOBQ) is established, but cutoff values between a small, a moderate, and a large change are still unknown. We used the data set of National Emphysema Treatment Trial consisting of severe and very severe chronic obstructive pulmonary disease patients, whose mean age was 64 years. Changes from baseline to post-surgical 6-month follow-up were evaluated. The St. George's Respiratory Questionnaire was used as anchor: |∆SGRQ| < 4, meaningless change; 4 ≤ |∆SGRQ| < 8, small change; 8 ≤ |∆SGRQ| < 13, moderate change; 13 ≤ |∆SGRQ|, large change. We decided the final cutoff values for the SOBQ as medians of the three anchor methods. We also decided the range of cutoff values as the range of three values. In a cohort of surgically treated patients (N = 484), we propose value of 5 (range 5-6), 11 (range 9-15), and 16 (range 14-20) for the cutoff values between a meaningless and a small change (minimum clinically important difference), a small and a moderate change, and a moderate and a large change, respectively. In a cohort of medically treated patients, numbers of patients categorized according to ∆SOBQ scores were similar to those of the patients categorizes according to the ∆SGRQ (N = 480) or ∆Forced expiratory volume in 1 second (N = 425). We propose group-level cutoff values and range between a small, a moderate, and a large changes.

Sensitivity and specificity of the Streptococcus pneumoniae urinary antigen test for unconcentrated urine from adult patients with pneumonia: a meta-analysis.

Studies on the sensitivity and specificity of the Binax Now Streptococcus pneumonia urinary antigen test (index test) show considerable variance of results. Those written in English provided sufficient original data to evaluate the sensitivity and specificity of the index test using unconcentrated urine to identify S. pneumoniae infection in adults with pneumonia. Reference tests were conducted with at least one culture and/or smear. We estimated sensitivity and two specificities. One was the specificity evaluated using only patients with pneumonia of identified other aetiologies ('specificity (other)'). The other was the specificity evaluated based on both patients with pneumonia of unknown aetiology and those with pneumonia of other aetiologies ('specificity (unknown and other)') using a fixed model for meta-analysis. We found 10 articles involving 2315 patients. The analysis of 10 studies involving 399 patients yielded a pooled sensitivity of 0.75 (95% confidence interval: 0.71-0.79) without heterogeneity or publication bias. The analysis of six studies involving 258 patients yielded a pooled specificity (other) of 0.95 (95% confidence interval: 0.92-0.98) without no heterogeneity or publication bias. We attempted to conduct a meta-analysis with the 10 studies involving 1916 patients to estimate specificity (unknown and other), but it remained unclear due to moderate heterogeneity and possible publication bias. In our meta-analysis, sensitivity of the index test was moderate and specificity (other) was high; however, the specificity (unknown and other) remained unclear.

Long-acting beta-agonists reduce mortality of patients with severe and very severe chronic obstructive pulmonary disease: a propensity score matching study.

BACKGROUND: Long-acting beta-agonists were one of the first-choice bronchodilator agents for stable chronic obstructive pulmonary disease. But the impact of long-acting beta-agonists on mortality was not well investigated. METHODS: National Emphysema Treatment Trial provided the data. Severe and very severe stable chronic obstructive pulmonary disease patients who were eligible for volume reduction surgery were recruited at 17 clinical centers in United States during 1988-2002. We used the 6-10 year follow-up data of patients randomized to non-surgery treatment. Hazard ratios for death by long-acting beta-agonists were estimated by three models using Cox proportional hazard analysis and propensity score matching were measured. RESULTS: The pre-matching cohort was comprised of 591 patients (50.6% were administered long-acting beta-agonists. Age: 66.6 ± 5.3 year old. Female: 35.4%. Forced expiratory volume in one second (%predicted): 26.7 ± 7.1%. Mortality during follow-up: 70.2%). Hazard ratio using a multivariate Cox model in the pre-matching cohort was 0.77 (P = 0.010). Propensity score matching was conducted (C-statics: 0.62. No parameter differed between cohorts). The propensity-matched cohort was comprised of 492 patients (50.0% were administered long-acting beta-agonists. Age: 66.8 ± 5.1 year old. Female: 34.8%. Forced expiratory volume in one second (%predicted) 26.5 ± 6.8%. Mortality during follow-up: 69.1%). Hazard ratio using a univariate Cox model in the propensity-matched cohort was 0.77 (P = 0.017). Hazard ratio using a multivariate Cox model in the propensity-matched cohort was 0.76 (P = 0.011). CONCLUSIONS: Long-acting beta-agonists reduce mortality of severe and very severe chronic obstructive pulmonary disease patients.

Poor performance status is a strong predictor for death in patients with smear-positive pulmonary TB admitted to two Japanese hospitals.

BACKGROUND: Estimation of performance status (PS) has been assessed as a tool to determine which patients with newly diagnosed pulmonary TB (PTB) are most at risk of dying. This simple prediction rule has not been validated in patients with PTB with different background characteristics and from different geographic areas. METHODS: A retrospective cohort study was conducted in two Japanese hospitals in different regions and included 432 inpatients with newly diagnosed smear-positive non-multidrug-resistant lung TB without HIV infection. The patients had a mean ± SD age of 64.9 ± 19.7 years and 135 were female (31.3%). Detailed nursing charts were reviewed to estimate PS, which was graded 0 (best condition), 1, 2, 3 or 4 (worst condition), for each patient. RESULTS: Single variable and multivariable Cox regression analyses models revealed that a one-point increase in PS was associated with a 2.8-fold (95% CI 2.2-3.6) and 2.3-fold (95% CI 1.8-3.0), adjusted for age, gender, comorbidities and treatment regimen, increase in the HR for death (p < 0.001 for both models). Kaplan-Meier curves also showed a significant difference in mortality among different PS groups (p < 0.001). CONCLUSION: PS was strongly associated with mortality from PTB in the study cohort. Estimation of PS at the start of treatment for newly diagnosed PTB patients could be a useful tool in case management in resource-limited countries.

Preoperative chemotherapy is effective for stage III resectable non--small-cell lung cancer: metaanalysis of 16 trials.

BACKGROUND: The benefit of preoperative chemotherapy for resectable non-small-cell lung cancer is still controversial. PATIENTS AND METHODS: We conducted fixed-model metaanalysis including randomized controlled trials comparing 'preoperative chemotherapy plus surgery' and 'surgery alone' as a primary study with sufficient data to provide a hazard ratio for overall survival. MEDLINE and Cochrane databases were used for the study search. RESULTS: We found 16 studies. Seven included only stage III disease cases, and 9 were conducted without stage limitation. Sixteen trials involving 3728 samples observing 2326 deaths yielded a pooled hazard ratio for overall survival of 0.84 (95% confidence interval [CI], 0.77-0.91; P < .001) with moderate heterogeneity (I(2) = 40%). In sensitivity analysis, strong heterogeneity (I(2) = 69%) was found between the 7 trials covering only stage III disease and 9 trials without stage limitation. The 7 studies evaluating only stage III disease involving 1447 samples and 1068 deaths yielded a pooled hazard ratio of 0.77 (95% CI, 0.68-0.87; P < .001) with nonsignificant low heterogeneity (I(2) = 17%). No publication bias was observed throughout this study. The effect of preoperative chemotherapy differs among stages. The pooled hazard ratio comparing 'preoperative chemotherapy plus surgery' and 'surgery alone' for patients with stage III disease in our study was 0.77, which is slightly better than the pooled hazard ratio of 0.83 in the Lung Adjuvant Cisplatin Evaluation study that compared 'surgery plus postoperative chemotherapy' and 'surgery alone.' CONCLUSION: Preoperative chemotherapy plus surgery for stage III disease is more effective than previously considered.

The presence of pretreatment cavitations and the bacterial load on smears predict tuberculosis infectivity negative conversion judged on sputum smear or culture.

OBJECTIVE: There are no rules to predict the time to infectivity negative conversion based on sputum smear conversion or culture conversion during chemotherapy in smear-positive tuberculosis patients. We aimed to develop and validate rules of sputum smear grades and cavitations in the lungs due to tuberculosis. METHODS: This study was a retrospective cohort study that consisted of development (n=158, 64 ± 19 years of age) and validation (n=214, 63 ± 20 years of age) steps in different cohorts. We developed a rule with pretreatment smear grades and the existence of cavitations in the lungs due to tuberculosis as independent variables and the duration to infectivity negative conversion as the dependent variable in a Cox hazard model. The smear grade indicating the pretreatment bacterial load was classified into four grades according to the Japanese guidelines. The presence of cavitations was assessed on X-ray. Infectivity conversion was defined according to the criteria of the Japanese Ministry of Health, Labour and Welfare: a patient is currently receiving proper treatment and shows clinical improvement and sputum smears and cultures in any combination are consecutively negative three times. RESULTS: We developed an "Infectivity Conversion Score" classifying each patient with a smear grade of I though IV and assessing the existence of cavitations in the lungs due to tuberculosis. The median time to infectivity conversion in the validation cohort was 13, 22, 35 and 50 days for Infectivity Conversion Scores I through IV, respectively (p<0.001). CONCLUSION: We developed and validated Infectivity Conversion Scores.