Diagnostic delay, treatment duration and outcomes since the implementation of integrated model of tuberculosis control and their associated factors in a county in East China.

OBJECTIVE: This study assesses the diagnostic delay, treatment duration and treatment outcomes of tuberculosis (TB) patients since the implementation of the integrated model of TB control in a county in eastern China. It further identifies factors associated with diagnostic delay and treatment duration in the integrated model. METHODS: We collected data through the Chinese Tuberculosis Information Management System (TBIMS) for Cangnan County in Zhejiang Province. Chi-square and Mann-Whitney tests were adopted to identify factors associated with duration of treatment and treatment delay for TB patients within the integrated model. Multiple regression analysis was subsequently performed to confirm the identified factors. RESULTS: In the integrated model from 2012 to 2018, the median health system delay was maintained at 1 day, and the median patient delay decreased from 14 to 9 days and the median total delay decreased from 15 to 11 days. In addition, the proportion of patients who experienced patient delay > 14 days and total delay > 28 days decreased from 49% to 35% and from 32% to 29% respectively. However, the proportion of patients who had health system delay > 14 days increased from 0.2% to 13% from 2012 to 2018. The median treatment duration increased from 199 to 366 days and the number of TB patients lost to follow-up showed an overall upward trend from 2012 to 2018. The multivariable regression analysis indicated that migrant TB patients and TB patients initially diagnosed in hospitals at the prefectural level and above tended to experience total delay > 28 days (p < 0.001). Linear regression analysis confirmed that new TB patients>60 years tended to have longer treatment duration (p < 0.05). CONCLUSIONS: While our study may suggest the potential of the integrated model in early detection and diagnosis of TB, it also suggests the importance of strengthening supervision and management of designated hospitals to optimize the treatment duration and improve retention of patients in TB care. Enhancing health education for TB patients, especially amongst migrant patients, and training in TB identification and referral for non-TB doctors are also key for early TB detection and diagnosis in the integrated model.

Cost-effectiveness of trastuzumab deruxtecan for previously treated HER2-low advanced breast cancer.

OBJECTIVE: The clinical efficacy and safety profile of trastuzumab deruxtecan (T-DXd) have been demonstrated in previously treated patients with human epidermal growth factor receptor 2 (HER2)-low advanced breast cancer (BC). It is, however, necessary to evaluate the value of T-DXd considering both its clinical efficacy and its cost, given that it is high. This study aimed to evaluate the cost-effectiveness of T-DXd versus chemotherapy in patients with previously treated HER2-low advanced BC. METHODS: We used a partitioned survival model that included three mutually exclusive health states. The patients in the model were identified based on their clinical characteristics and outcomes from the DESTINY-Breast04. Probabilistic and one-way sensitivity analyses were performed to evaluate the model's robustness. Subgroup analyses were also conducted. The measures included costs, life years, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), incremental net health benefits (INHBs), and incremental net monetary benefits (INMBs). RESULTS: The ICERs of T-DXd vs. chemotherapy were $83,892/QALY, $82,808/QALY, and $93,358/QALY in all HER2-low advanced BC patients, HER2-positive (HER2+) advanced BC patients and HER2-negative (HER2-) advanced BC patients, respectively. In one-way sensitivity analysis, the cost of T-DXd and hazard ratio (HR) for progression-free survival (PFS) and overall survival (OS) were also identified as key drivers. If the price of T-DXd decreased to $17.00/mg, $17.13/mg, and $14.07/mg, it would be cost-effective at a willingness to pay (WTP) threshold of $50,000/QALY in all HER2-low advanced BC patients, HER2+ advanced BC patients and HER2- advanced BC patients, respectively. At a WTP threshold of $100,000/QALY, the probability of T-DXd being cost-effective was 81.10%, 82.27%, and 73.78% compared to chemotherapy for all HER2-low advanced BC patients, HER2+ advanced BC patients and HER2- advanced BC patients, respectively. Most subgroups of patients with HER2+ disease had a cost-effectiveness probability of > 50%. CONCLUSION: From a third-party payer's perspective in the United States, the findings of the cost-effectiveness analysis revealed that, at the current price, T-DXd is a cost-effective alternative to chemotherapy for patients with prior HER2-low advanced BC, at WTP threshold of $100,000/QALY.

Cost-effectiveness of sacituzumab govitecan in hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer.

Background: The efficiency and safety of sacituzumab govitecan (SG) for the therapy of hormone receptor-positive (HR+)/human epidermal receptor 2-negative (HER2-) metastatic breast cancer (BC) has been demonstrated. The aim of this study is to evaluate its cost-effectiveness on HR+/HER2- metastatic BC from the third-party payer perspective in the United States. Methods: We performed the cost-effectiveness of SG and chemotherapy using a partitioned survival model. TROPiCS-02 provided clinical patients for this study. We evaluated the robustness of this study by one-way and probabilistic sensitivity analyses. Subgroup analyses were also conducted. The outcomes were costs, life-years, quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefit (INHB), and incremental net monetary benefit (INMB). Results: SG treatment was related to an increase of 0.284 life years and 0.217 QALYs over chemotherapy, as well as a cost increase of $132,689, reaching an ICER of $612,772/QALY. The INHB was -0.668 QALYs, and the INMB was -$100,208. SG was not cost-effective at the willingness to pay (WTP) threshold of $150,000/QALY. The outcomes were sensitive to patient body weight and cost of SG. SG may be cost-effective at the WTP threshold of $150,000/QALY if the price is less than $3.997/mg or the weight of patients is under 19.88 kg. Based on the subgroup analysis, SG did not prove cost-effective in all subgroups at the WTP threshold of $150,000/QALY. Conclusion: From a third-party payer standpoint in the United States, SG was not cost-effective, even though it had a clinically significant advantage over chemotherapy for the treatment of HR+/HER2- metastatic BC. The cost-effectiveness of SG can be improved if the price is substantially reduced.

Chiral superstructure of aragonite similar to Turritella terebra shell induced by CTAB's adsorption chirality.

A twisted dumbbell-like chiral superstructure can be easily assembled in aragonite under the co-action of CTAB and Mg2+, producing a microstructure that is very similar to that of Turritella terebra shell. Asymmetric adsorption of the CTAB head group on aragonite, namely "adsorption chirality", is the reason for the chiral assembly.

Adsorption of Pb(II) from water by treatment with an O-hydroxyphenyl thiourea-modified chitosan.

An O-hydroxyphenyl thiourea-modified chitosan (OTCS) with excellent Pb(II) adsorption performance and selectivity was prepared as an adsorbent. The structure and morphology of the adsorbent were systematically investigated by SEM, BET, FTIR, EDX, zeta-potential measurements, XPS and XRD. The impacts of the initial Pb(II) concentration, reaction time, temperature, pH value, and coexisting ions were explored. At pH 7 and 303 K, the maximal adsorption capacity of OTCS for Pb(II) was 208.33 mg/g, which was greater than those of other adsorbing materials reported in the literature. The metal ion adsorption kinetics and isotherm models were found to obey pseudo-second-order kinetics and the Langmuir isothermal model, indicating that the adsorption process was monolayer chemisorption. The adsorption process could proceed spontaneously, and the thermodynamic results revealed that the adsorption mechanism was an endothermic reaction. The ion exchange and chelation between the sulfur, nitrogen and oxygen groups on the adsorbent and lead ions endowed the material with excellent adsorption properties. Significantly, OTCS showed excellent selectivity toward Pb(II). Therefore, the adsorbent OTCS is expected to promote the wider application of chitosan in the adsorption of Pb(II).

Selective removal of Au(III) from wastewater by pyridine-modified chitosan.

A pyridine-modified chitosan (PMCS) adsorbent with excellent adsorption performance and specific selectivity for Au(III) in wastewater was prepared. FTIR, SEM, XPS and XRD were used to study its adsorption performance, and various models were used to fit and analyze the experimental adsorption data. The maximum adsorption capacity of PMCS for Au(III) is 549.41 mg/g (298 K, pH = 4). The data analysis results prove that the PSO and Langmuir models best describe the adsorption process. Adsorption experiments in the presence of multiple ions proved that PMCS is selective for the adsorption of Au(III). The adsorption and desorption experiments showed that the adsorption rate of PMCS could still reach 94.77% after three cycles. In summary, PMCS was demonstrated to be a high-quality material for the adsorption of Au(III) from wastewater due to its excellent adsorption performance, specific selectivity and reusability.

A novel benzothiazole modified chitosan with excellent adsorption capacity for Au(III) in aqueous solutions.

A novel benzothiazole modified chitosan (BCS) with excellent Au(III) adsorption performance and selectivity was prepared as adsorbents. The structure and morphology of the adsorbents were characterized by FTIR, SEM, XRD and XPS. The adsorption property of the adsorbents for Au(III) were investigated under different reaction time, initial concentration of Au(III), temperature, pH and coexisting ions. The maximum adsorption capacity of BCS for Au(III) was 1072.22 mg/g at 298 K and optimal pH = 4, which was better than that of other adsorbents reported in literature. The adsorption kinetics and isotherm models fit the pseudo-second-order and Langmuir equations. This shows that the adsorption process of Au(III) is a monolayer chemical adsorption. The adsorption process can proceed spontaneously and belong to the endothermic reaction according to the thermodynamic results. The excellent adsorption performance is mainly attributed to the ion exchange and chelation of the nitrogen, sulfur and oxygen groups on the adsorbent with gold ions. Significantly, BCS has excellent selectivity toward Au(III) and remarkable recycle performance. With the high adsorption capacity, excellent selectivity and outstanding reusability, the BCS adsorbent could be a promising candidate to adsorb Au(III) from wastewater.

Effect of modified pomace on copper migration via riverbank soil in southwest China.

To explore the effects of modified pomace on copper migration via the soil on the banks of the rivers in northern Sichuan and Chongqing, fruit pomace (P) and ethylene diamine tetra-acetic acid (EDTA) modified P (EP) were evenly added (1% mass ratio) to the soil samples of Guanyuan, Nanbu, Jialing, and Hechuan from the Jialing River; Mianyang and Suining from the Fu River; and Guangan and Dazhou from the Qu River. The geochemical characteristics and migration rules of copper in different amended soils were simulated by column experiment. Results showed that the permeation time of copper in each soil column was categorized as EP-amended > P-amended > original soil, and the permeation time of amended soil samples at different locations was Jialing > Suining > Mianyang > Guangan > Dazhou > Nanbu > Guanyuan > Hechuan. Meanwhile, the average flow rate of copper in each soil column showed a reverse trend with the permeation time. Copper in exchangeable, carbonate, and iron-manganese oxide forms decreased with the increase of vertical depth in the soil column, among which the most evident decreases appeared in the carbonate-bonding form. The copper accumulation in different locations presented a trend of Jialing > Suining > Mianyang > Guangan > Dazhou > Nanbu > Guangyuan > Hechuan, and the copper content under the same soil showed EP-amended > P-amended > original soil. The copper proportion of the carbonate form was the highest in each soil sample, followed by the exchangeable form. The proportions of iron-manganese oxide and organic matter forms were relatively small. A significant correlation was observed between the cation exchange capacity and the copper content in exchangeable and carbonate forms. Moreover, total organic carbon and copper contents were negatively correlated.

Carbapenems versus alternative ß-lactams monotherapy or in combination for febrile neutropenia: Systematic review and meta-analysis of randomized controlled trial.

BACKGROUND: Febrile neutropenia (FN) in cancer patients can be life threatening and require the timely antimicrobial agents treatment. METHODS: To compare the effectiveness and safety of carbapenems versus ß-lactams for FN. PubMed, Medline (Ovid SP), Cochrane CENTRAL, and Embase were searched up to March 2019. FN in patients due to undergoing chemotherapy and treated with carbapenems and ß-lactams were included. Odds ratio (OR) and 95% confidence interval (CI) were estimated. RESULTS: Fifty randomized controlled trials (RCTs) studies involving 10,995 participants were included. Carbapenems were more likely to experience treatment success without modification (OR = 1.34, 95% CI = 1.24-1.46) compared with ß-lactams. Meropenem (OR = 1.36, 95% CI = 1.18-1.56; OR = 1.24, 95% CI = 1.01-1.53), imipenem/cilastatin (OR = 1.40, 95% CI = 1.19-1.65; OR = 1.31, 95% CI = 1.04-1.67) showed higher effectiveness from that by ß-lactams monotherapy or in combination with aminoglycoside, respectively. Carbapenems-aminoglycoside combination therapy does not provide an advantage over carbapenems alone. Meropenem showed similar risk of adverse events (AEs) versus ß-lactams. Imipenem/cilastatin was related to higher risk of AEs compared with ß-lactams. There was no significant difference between carbapenems and ß-lactams monotherapy or in combination. CONCLUSION: Meropenem and imipenem/cilastatin monotherapy appears to be available treatment for FN compared with ß-lactams. Imipenem/cilastatin was related to higher risk of AEs. Balancing the evidence for drug efficacy and side effects, meropenem monotherapy appears to be available treatment for FN. Individual centers should select the best matching therapy regimens according to local epidemiology and susceptibility patterns.

Panax notoginseng preparations as adjuvant therapy for diabetic kidney disease: a systematic review and meta-analysis.

Context: Panax notoginseng (Burk.) F.H. Chen (Araliaceae) preparations (PNP) are traditional Chinese medicines used as adjuvant therapeutics for diabetic kidney disease (DKD).Objective: To systematically review the efficacy of PNP as adjunct DKD therapy, including their effects on kidney function, serum lipid levels and fasting blood glucose levels.Methods: The databases PubMed, Embase, Medline, Cochrane Library, CINAHL, China Biology Medicine disc, Wanfang, VIP and China National Knowledge Infrastructure were systematically searched from the date of their inception until May 2019. Panax notoginseng, Panax notoginseng saponins, Lulutong, Xueshuantong and Xuesaitong were the key terms searched. Randomized controlled trials (RCTs) comparing the combined use of PNP and conventional medicines (CM) versus CM for DKD were included. Data were pooled using random or fixed effect models depending on heterogeneity.Results: In total, 24 RCTs involving 1918 participants were analysed. Adjunct PNP with CM was associated with reduction of albuminuria (MD -26.89 mg, 95% CI: -33.35 to -20.42), proteinuria (MD -0.32 g/24 h, 95% CI: -0.36 to -0.27), serum creatinine (MD -4.52 µmol/L, 95% CI: -8.71 to -0.32), total cholesterol (MD -1.56 mmol/L, 95% CI: -2.33 to -0.78), triglycerides (TG) (MD -0.56 mmol/L, 95% CI: -0.80 to -0.31) and low-density lipoprotein cholesterol (MD -0.94 mmol/L, 95% CI: -1.49 to -0.40) compared with CM.Conclusions: This is the first meta-analysis investigating adjuvant PNP therapy for DKD. PNP apparently exerted beneficial effects on kidney function and improved the metabolism of serum lipids by CM. Further, well-conducted, high-quality trials on DKD patients are needed to provide high-quality evidence.

Carbapenems vs alternative antibiotics for the treatment of complicated urinary tract infection: A systematic review and network meta-analysis.

BACKGROUND: Complicated urinary tract infections (cUTI) are universal reasons for hospitalization, and highly likely to develop into sepsis or septic shock. Carbapenem antibiotics with potentially higher efficacy or with fewer and milder side effects have increased in popularity, but evidence is limited by a scarcity of randomized controlled trials (RCTs) comparing different carbapenem antibiotics for cUTI. Network meta-analysis is a useful tool to compare multiple treatments when there is limited or no direct evidence available. OBJECTIVE: The aim of this study is to compare the efficacy and safety of different carbapenems with alternative antibiotics for the treatment of cUTI. METHODS: Pubmed, Medline, CENTRAL, and Embase were searched in November 2018. Studies of cUTI patients receiving carbapenem were included. We performed network meta-analysis to estimate the risk ratio (RR) and 95% credible interval (CrI) from both direct and indirect evidence; traditional meta-analysis was also performed. Primary outcomes were clinical and microbiological treatment success. RESULTS: A total of 19 studies and 7380 patients were included in the analysis. Doripenem (DOPM) was associated with lower clinical treatment success rates than other carbapenems. Although the efficacy of other carbapenems by RRs with 95% CrIs did not show statistical differences, the cumulative rank probability indicated that meropenem/vaborbactam (MV), ertapenem (ETPM), and biapenem (BAPM) had higher clinical and microbiological treatment success rates; imipenem/cilastatin (IC) and MV showed higher risk of adverse events (AEs). CONCLUSIONS: MV was associated with higher treatment success rates for cUTI, especially for cUTI caused by carbapenem-resistant uropathogens, but also with higher risk of AEs. Our findings suggest MV as a first-choice treatment of carbapenem-resistant cUTI. ETPM, BAPM, and meropenem (MEPM) is another reasonable choice for cUTI empiric therapy.

Carbapenems vs tigecycline for the treatment of complicated intra-abdominal infections: A Bayesian network meta-analysis of randomized clinical trials.

BACKGROUND: Complicated intra-abdominal infections (cIAIs) are common in clinical practice, caused by a mixture of aerobic and anaerobic bacteria, increase the risk of mortality. Carbapenems and tigecycline (TGC) are recommended for antimicrobial therapies for cIAIs. OBJECTIVE: To compare the effectiveness and safety of different carbapenems vs TGC for the treatment of cIAIs. METHODS: PubMed, Embase, Medline (via Ovid SP) and Cochrane library databases were systematically searched. We included randomized controlled trials (RCTs) comparing different carbapenems vs TGC for the treatment of cIAIs. The pooled odds ratio (OR) with 95% credible interval (CrI) was calculated by Markov chain Monte Carlo methods. We estimated summary ORs using pairwise and network meta-analysis with random effects. RESULTS: Fifteen studies involving 6745 participants were included in the analysis. Five different carbapenems and TGC were ultimately evaluated in this study. Although, the efficacy of carbapenems and TGC by ORs with corresponding 95% CrIs had not yet reached statistical differences, the cumulative rank probability indicated that clinical treatment success from best to worst was doripenem (DOPM), meropenem (MEPM), imipenem/cilastatin (IC), biapenem (BAPM), TGC and imipenem/cilastatin/relebactam (ICRB); microbiological treatment success from best to worst was DOPM, MEPM, IC, BAPM, ICRB and TGC. As for the risk of adverse events (AEs), TGC showed higher risk of AEs compared with IC (OR = 1.53, 95% CrI = 1.02-2.41), the remain antibiotic agents from lower to higher was MEPM, IC, BAPM, DOPM, ICRB and TGC. The risk of mortality from lower to higher was BAPM, DOPM, MEPM, IC, TGC and ICRB. CONCLUSION: No differences in clinical and microbiological outcomes were observed between different carbapenems and TGC. Balancing the evidence for drug efficacy and side effects, DOPM appears to be the best available treatment for cIAIs. Therefore, it is reasonable to consider that DOPM is one of the best carbapenem monotherapy for cIAIs. MEPM and IC was also associated with higher rates of clinical and microbiological treatment success following DOPM. Empiric antimicrobial treatment of patients with cIAIs should be selected in light of the local bacterial epidemiology and patterns of resistance.

Carbapenems vs ß-Lactam Monotherapy or Combination Therapy for the Treatment of Complicated Intra-abdominal Infections: Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Complicated intra-abdominal infections (cIAIs) result in significant morbidity, mortality, and cost. Carbapenem-resistant sepsis has increased dramatically in the last decade, resulting in infections that are difficult to treat and associated with high mortality rates. To prevent further antibacterial resistance, it is necessary to use carbapenem selectively. The objective of this study was to compare the effectiveness and safety of carbapenems vs alternative ß-lactam monotherapy or combination therapy for the treatment of cIAIs. METHODS: The PubMed, Embase, Medline (via Ovid SP), and Cochrane library databases were systematically searched. We included randomized controlled trials (RCTs) comparing carbapenems vs alternative ß-lactam monotherapy or combination therapy for the treatment of cIAIs. RESULTS: Twenty-two studies involving 7720 participants were included in the analysis. There were no differences in clinical treatment success (odds ratio [OR], 0.86; 95% confidence interval [CI], 0.71-1.05; I 2 = 35%), microbiological treatment success (OR, 0.88; 95% CI, 0.71-1.09; I 2 = 25%), adverse events (OR, 0.98; 95% CI, 0.87-1.09; I 2 = 17%), or mortality (OR, 0.96; 95% CI, 0.68-1.35; I 2 = 7%). Patients.treated with imipenem were more likely to experience clinical or microbiological failure than those treated with alternative ß-lactam monotherapy or combination therapy. CONCLUSIONS: No differences in clinical outcomes were observed between carbapenems and noncarbapenem ß-lactams in cIAIs. Patients treated with imipenem were more likely to experience clinical or microbiological failure than those treated with alternative ß-lactam monotherapy or combination therapy.

Safety and efficacy of combined use of propofol and etomidate for sedation during gastroscopy: Systematic review and meta-analysis.

BACKGROUND: Sedation with etomidate or propofol alone during gastroscopy has many side effects. A systematic review and meta-analysis were conducted to evaluate the safety and efficacy of the combined use of propofol and etomidate for sedation during gastroscopy. METHODS: PubMed, Embase, Medline (via Ovid SP), Cochrane library databases, CINAHL (via EBSCO), China Biology Medicine disc (CBMdisc), Wanfang, VIP, and China National Knowledge Infrastructure (CNKI) databases were systematically searched. We included randomized controlled trials (RCTs) comparing the combined use of propofol and etomidate vs etomidate or propofol alone for sedation during gastroscopy. Data were pooled using the random-effects models or fixed-effect model based on heterogeneity. RESULTS: Fifteen studies with 2973 participants were included in the analysis. Compared to propofol alone, the combined use of propofol and etomidate possibly increased recovery time (SMD = 0.14, 95% CI = 0.04-0.24; P = .005), and the risk for myoclonus (OR = 3.07, 95% CI = 1.73-5.44; P < .001), injection pain, and nausea and vomiting. Furthermore, compared to propofol alone, the combination of propofol and etomidate produced an apparent beneficial effect for mean arterial pressure (MAP) after anesthesia (SMD = 1.32, 95% CI = 0.38-2.26; P = .006), SPO2 after anesthesia (SMD = 0.99, 95% CI = 0.43-1.55; P < .001), apnea or hypoxemia (OR = 0.16, 95% CI = 0.08-0.33; P < .001), injection pain, and body movement. Further, compared to etomidate alone, the combination of propofol and etomidate reduced the risk for myoclonus (OR = 0.15, 95% CI = 0.11-0.22; P < .001), body movement, and nausea and vomiting. CONCLUSION: The combination of propofol and etomidate might increase recovery time vs that associated with propofol, but it had fewer side effects on circulation and respiration in patients undergoing gastroscopy. The combined use of propofol and etomidate can improve and produce an apparent beneficial effect on the adverse effects of propofol or etomidate alone, and it was safer and more effective than propofol or etomidate alone.