Optimal Treatment Regimen For Patients Research Articles

Apixaban versus low molecular weight heparin in patients with cancer-associated venous thromboembolism: a systematic review and meta-analysis.

The optimal treatment regimen for patients with cancer-associated venous thromboembolism (CA-VTE) remains unclear. Therefore, the authors sought to compare the outcomes of (VKAs) versus direct apixaban and low molecular weight heparin (LMWH) in patients with CA-VTE. MEDLINE, Embase, and Cochrane Central databases were searched for randomized controlled trials (RCTs) and observational studies comparing the efficacy and safety of apixaban and LMWH in patients with CA-VTE. Major bleeding, clinically relevant non-major bleeding (CRNMB), recurrence of pulmonary embolism (PE), deep venous thrombosis (DVT) and bleeding-related mortality were among outcomes of interest. Mantel-Haenszel weighted random-effects model was used to calculate relative risks (RRs) with 95% CIs. The analysis included 12011 patients from 3 RCTs and 2 observational studies. Compared to LMWH, apixaban significantly decreased the risk of major bleeding [RR 0.67 (95% CI 0.54, 0.83); P=0.0003, I2=0%] without significantly changing the risk of clinically relevant non-major bleeding [RR 0.96 (95% CI 0.64, 0.1.45); P=0.85, I2=57%]. Patients on apixaban had a noticeably reduced the risk of recurrence of PE than those taking LMWH, according to a meta-analysis [RR 0.56 (95% CI 0.32, 0.99); P=0.05, I2=0%]. There was no discernible difference between apixaban and LMWH in bleeding-related mortality events [RR 0.20 (95% CI 0.01, 4.18); P=0.30, I2=NA%], and recurrence of DVT [RR 0.60 (95% CI 0.22, 1.59); P=0.23, I2=32%]. Due to its lower risk of severe bleeding and reduced PE recurrence, apixaban may be a preferable treatment option for CA-VTE, but additional research is required to validate these conclusions and evaluate its long-term efficacy and safety.

Pathogenesis and modern methods for treatment of hip infectious arthritis: a review

Background. One of the little-studied but long-known problems is determining the optimal treatment regimen for patients with infectious arthritis of the hip joint. Existing studies offer various methods of conservative and surgical treatment, which, however, do not have a fundamental evidence base. The polyetiology and variability of the clinical manifestations of infectious arthritis of the hip joint and the severity of the consequences in case of incorrectly chosen tactics require a differentiated approach to treatment and development of certain diagnostic and treatment algorithms. The aim of the review – to identify pathogenesis factors that are significant for the choice of treatment tactics and to analyze modern methods of treating infectious arthritis of the hip joint based on the data from available medical literature. Methods. For analysis, we selected 90 foreign and domestic sources published between 1997 and 2023. Inclusion criteria were: clinical studies, analytical reviews and meta-analyses of the literature. The search was performed in eLIBRARY, PubMed and Google Scholar databases. Results. The analysis showed that, despite the comparable effectiveness and advantages of individual treatment methods, their use is limited to certain indications, and the choice of the optimal one for a particular patient should take into account many etiopathogenetic factors, clinical, laboratory and instrumental data, the role of which is still insufficiently studied. Currently, throughout the world the “gold standard” for radical surgical treatment remains the technique of two-stage hip arthroplasty using an antibacterial spacer. However, encouraging results of alternative treatment methods require continued search for ways to optimize diagnostic and therapeutic tactics.

Current view of the management of patients with endometrial hyperplasia: A review

Endometrial hyperplasia (EH) is a spectrum of morphological changes in the endometrium characterized by the proliferation of glands and an increase in the gland-stromal ratio. The relevance of this disease is due to its high prevalence (10–55%). The clinical significance of EH is related to the increased risk of endometrioid cancer. One of the leading causes of EH is absolute or relative hyperestrogenism and progesterone deficiency that does not eliminate the proliferative effect of estrogens. The risk group for EH includes women with early menarche, late menopause, infertility, anovulation, polycystic ovary syndrome, obesity, type 2 diabetes mellitus, hypertension, Lynch syndrome, estrogen-producing ovarian tumors, as well as those receiving estrogen monotherapy or tamoxifen. Most leading experts believe that therapy should include surgery followed by drug therapy aimed at eliminating risk factors to reduce the risk of EH recurrence. Despite numerous research findings demonstrating the benefits of a particular treatment modality and the consequent presence of these modalities in clinical guidelines, the potential benefits of alternative therapies are still being discussed. This issue requires further study and the selection of optimal treatment regimens for patients with EH.

Factor Xa inhibitors vs. warfarin in patients with Hughes syndrome: a systematic review and meta-analysis of randomized controlled trials.

The optimal treatment regimen for patients with Hughes syndrome remains unclear. Therefore, the authors sought to compare the outcomes of warfarin vs. factor Xa inhibitors in patients with Hughes syndrome. MEDLINE, Embase, and Cochrane Central databases were searched for randomized controlled trials (RCTs) comparing 8 efficacy and safety of warfarin and factor Xa inhibitors in patients with Hughes syndrome. Recurrent thrombosis, all-cause mortality, stroke, adverse reactions, and bleeding were among 10 outcomes of interest. Mantel-Haenszel weighted random-effects model was used to calculate 11 relative risks (RRs) with 95% CIs. The analysis included 625 patients from four RCTs and one post-hoc analysis. Meta-analysis showed a statistically non-significant difference between factor Xa inhibitors and warfarin in the recurrent thrombosis risk (arterial or venous) [RR 2.77 (95%, CI 0.79, 9.65); P=0.11, I2=50%]. Consistent results were revealed among patients with a previous history of arterial thrombosis [RR 2.76 (95% CI 0.93, 8.16); P=0.75, I2=0%], venous thrombosis [RR 1.71 (95% CI 0.60, 4.84); P=0.31, I2=15%] and patients who were triple antiphospholipid antibodies (aPL) positive [RR 4.12 (95% CI 0.46, 37.10); 21 P=0.21, I2=58%]. Factor Xa inhibitors were significantly associated with an increased risk of stroke [RR 8.51 (95% CI 2.35, 13.82); P=0.47, I2=0%]. Factor Xa inhibitors exhibited an increased risk of stroke among patients with Hughes syndrome. In addition, although not significant, the higher RRs among patients on factor Xa inhibitors may indicate a higher risk of thrombotic events associated with factor Xa inhibitors.

Effectiveness of rivaroxaban in preventing cerebral venous thromboembolism: a systematic review and meta-analysis.

Cerebral venous thromboembolism (CVT) poses a significant risk of venous infarction and haemorrhage, which can lead to neurological deficits and, in severe cases, even death. The optimal treatment regimen for patients with CVT remains unclear. MEDLINE, Embase, Google Scholar, Web of Science (WoS), and Cochrane Central databases were searched for randomized controlled trials (RCTs) and observational studies assessing the efficacy and safety of rivaroxaban in patients with CVT. All-site venous thromboembolism (VTE), risk of clinically relevant non-major bleeding, incidence of partial recanalization, complete recanalization and major haemorrhage were among outcomes of interest. Mantel-Haenszel weighted random-effects model was used to calculate relative risks (RRs) with 95% CIs. The analysis included 1 RCT and 3 observational studies containing 211 patients. Compared to vitamin K antagonists (VKAs), rivaroxaban did not significantly decrease the all-site VTE [RR 0.31 (95% CI 0.01, 8.43); P=0.49, I2=0%]. Compared with VKAs, patients on rivaroxaban did not show a significantly reduced risk of recurrent cerebral venous thrombosis. In terms of incidence of partial recanalization, there was no discernible difference between rivaroxaban and VKAs [RR 0.90 (95% CI 0.66, 1.22); P=0.49, I2=0%]. There was no discernible difference in incidence of complete recanalization [RR 0.98 (95% CI 0.32, 3.03); P=0.97, I2=28%] and incidence of major haemorrhage [RR 0.19 (95% CI 0.01, 4.54); P=0.30]. Rivaroxaban was found to have similar efficacy to VKAs. Due to its lower risk of severe bleeding and no need for INR monitoring, rivaroxaban may be a preferable treatment option for CVT.

Score based on contrast-enhanced ultrasound predict central lymph node metastasis in papillary thyroid cancer.

To investigate the association between contrast-enhanced ultrasound (CEUS) features of PTC and central lymph node metastasis (CLNM) and to develop a predictive model for the preoperative identification of CLNM. This retrospective study evaluated 750 consecutive patients with PTC from August 2020 to April 2023. Conventional ultrasound and qualitative CEUS features were analyzed for the PTC with or without CLNM using univariate and multivariate logistic regression analysis. A nomogram integrating the predictors was constructed to identify CLNM in PTC. The predictive nomogram was validated using a validation cohort. A total of 684 patients were enrolled. The 495 patients in training cohort were divided into two groups according to whether they had CLNM (pCLNM, n= 191) or not (nCLNM, n= 304). There were significant differences in terms of tumor size, shape, echogenic foci, enhancement direction, peak intensity, and score based on CEUS TI-RADS between the two groups. Independent predictive US features included irregular shape, larger tumor size (≥ 1.0cm), and score. Nomogram integrating these predictive features showed good discrimination and calibration in both training and validation cohort with an AUC of 0.72 (95% CI: 0.68, 0.77) and 0.79 (95% CI: 0.72, 0.85), respectively. In the subgroup with larger tumor size, age ≤ 35 years, irregular shape, and score > 6 were independent risk factors for CLNM. The score based on preoperative CEUS features of PTC may help to identify CLNM. The nomogram developed in this study provides a convenient and effective tool for clinicians to determine an optimal treatment regimen for patients with PTC.

Efficacy of ablation therapy on clinical outcomes in patients with atrial fibrillation: a systematic review and meta-analysis.

Optimal treatment regimen for patients with atrial fibrillation (AF) remains unclear. Therefore, the authors sought to compare the outcomes of ablation therapy versus pharmacological regimens in patients with AF. MEDLINE, Embase, and Cochrane Central databases were searched for randomized controlled trials and observational studies comparing clinical outcomes between of ablation and pharmacological therapy in patients with AF. Stroke, all-cause mortality, cardiovascular mortality, cardiovascular hospitalization, heart failure (HF), and bleeding were among outcomes of interest. Mantel-Haenszel weighted random-effects model was used to calculate relative risks (RRs) with 95 % CIs. The analysis included ~200000 patients from 4 randomized controlled trials and 7 observational studies. Meta-analysis showed statistically significant reduction in stroke among patients on ablation therapy [hazard ratio (HR) 0.51, 95% CI (0.43, 0.60), P<0.00001, I2=10%], all-cause mortality [HR 0.64, 95% CI (0.45, 0.93), P=0.02, I2=58%], cardiovascular mortality [HR 0.35, 95% CI (0.25, 0.50), P<0.0001, I2=0%], and HF [HR 0.40, 95% CI (0.31, 0.53), P<0.00001, I2=30%]. However, no significant difference was revealed in the risk of cardiovascular hospitalization [HR 1.04, 95% CI (0.88, 1.23), P=0.66, I2=89%] and bleeding [HR 1.11, 95% CI (0.97, 1.27), P=0.13, I2=0%]. Ablation significantly reduces the risk of stroke, cardiovascular mortality, all-cause mortality, and HF in AF patients, compared with medical therapy alone, supporting its use in clinical practice.

First-line treatment options for advanced gastric/gastroesophageal junction cancer patients with PD-L1-positive: a systematic review and meta-analysis.

Literature search through major databases in English and Chinese: PubMed, Embase, Cochrane library, web of Science and CNKI updated on 10 March 2023. Randomized controlled trials were selected to investigate chemotherapy plus programmed death 1 inhibitor versus chemotherapy. A total of 7 randomised controlled trials including 5788 participants were included. The overall survival (hazard ratio=0.79;95% CI: 0.74-0.85, P<0.01), progression-free survival (hazard ratio=0.72; 95% CI: 0.67-0.77, P<0.01) and objective response rate (risk ratio=1.24,95% CI: 1.18-1.31, P<0.05) were longer than chemotherapy alone in the pooled analysis. For subgroup analyses of overall survival, programmed death 1 inhibitors plus chemotherapy had a significant advantage in patients with combined positive score greater than or equal to 5, in Asia, in men and in those younger than 65 years (P<0.01), as were immune-mediated adverse events (odds ratio=8.86;95% CI: 1.26-62.47,P<0.05) and treatment-related grade 3-5 adverse events (odds ratio=1.40,95% CI:1.20-1.62, P<0.01). Programmed death 1 inhibitors plus chemotherapy have significant antitumour activity compared to chemotherapy alone. However, it is riskier in terms of toxicity than chemotherapy. The authors recommend programmed death 1 inhibitors plus chemotherapy as the optimal treatment regimen for patients with positive programmed death ligand 1 expression, in Asia, male and less than 65 years of age. More well-designed studies are needed to investigate the efficacy and safety of different immune plus chemotherapy drug doses and regimens.

Predictors of mortality for dermatomyositis patients positive with anti-melanoma differentiation-related gene 5 and optimal treatment.

To explore the risk factors of early death in dermatomyositis patients positive with anti-melanoma differentiation-related gene 5 antibody (anti-MDA5-DM). To explore the optimal treatment regimen for patients with anti-MDA5-DM. Patients with newly onset anti-MDA5-DM from June 2018 to October 2021 in our centre were retrospectively reviewed for 6 months. Patients were divided into five groups based on initial treatments. The major outcome was mortality in 6 months. Secondary outcomes included remission and severe infection. A total of 214 patients were included in the study. During 6 month follow-up, 63 patients (30.14%) died, 112 patients (53.59%) achieved remission, 52 patients (24.88%) experienced serious infection and 5 patients (2.34%) were lost. Independent risk factors of mortality in the first 6 months after diagnosis were as follows: age> 53 years, skin ulcer, peripheral blood lymphocyte count (LYMP)≤ 0.6×109/L, lactate dehydrogenase (LDH) > 500 U/L, C reactive protein (CRP) > 5mg/L, anti-Ro52 antibody and ground-glass opacity (GGO) score> 2. On the contrary, prophylactic use of the compound sulfamethoxazole (SMZ Co) was independent protective factor. The five-category treatment was not an independent influencing factor of early death, but subgroup analysis found that patients with rapidly progressive interstitial lung disease (RPILD) responded better to a triple combination of high-dose glucocorticoids (GC), calcineurin inhibitors (CNI) and cyclophosphamide (CYC) or a triple combibation of GC, CNI and tofacitinib (TOF). Advanced age, skin ulcer, lymphopenia, anti-Ro52 antibody and higher levels of LDH, CRP and GGO score increase the risk of early death for MDA5-DM, while prophylactic use of SMZ Co is protective. Aggressive therapy with combined immunosuppressants may improve the short-term prognosis of anti-MDA5-DM with RPILD.

A Real-World Study of Optimal Treatment with Anlotinib First-Line Therapy in Advanced Hepatocellular Carcinoma.

PurposeTo observe the efficacy and safety of anlotinib as a first-line treatment for patients with advanced hepatocellular carcinoma (aHCC) in a real-word environment, explore the optimal treatment regimen for patients with aHCC using anlotinib as a first-line treatment.Patients and MethodsData from 62 patients with aHCC who received anlotinib single-drug first-line therapy between February 2019 and November 2021. Patients received anlotinib monotherapy, which may be interrupted or discontinued or changed in the event of unacceptable or severe adverse events (AEs) or failure to inhibit tumor progression. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate(ORR), disease control rate (DCR), overall survival (OS), and safety.ResultsAmong the 62 patients, in the best overall response assessment, there were 12 with complete response (CR; 19.4%), 17 with partial response (PR; 27.4%), 25 with stable disease (SD; 40.3%), and 8 with progressive disease (PD; 14.5%). The ORR and DCR were 46.8% and 87.1%, respectively. Among the 11 patients who received tyrosine kinase inhibitors (TKIs) combined with programmed death 1 (PD-1) inhibitors after disease progression, three (27.3%) had CR, one (9.1%) had PR, three (27.3%) had SD, and four (36.4%) had PD. Therefore, the ORR and DCR were 36.4% and 63.6%, respectively. The median PFS for anlotinib monotherapy was 7.37 months (95% confidence interval [CI]: 5.88–8.86) and the median OS did not reach. AEs occurred in 95.2% of patients during anlotinib monotherapy, with the most common being thrombocytopenia (51.6%). The incidence of grade ≥3 AEs was 38.7%.ConclusionAnlotinib is effective and well-tolerated as a first-line treatment for patients with aHCC. Treatment with TKIs and PD-1 inhibitors after disease progression has also shown preliminary efficacy and safety; therefore, sequential therapy with anlotinib-TKIs and PD-1 inhibitors may be an effective treatment for patients with aHCC.

Multimodality Treatment including Surgery Related to the Type of N2 Involvement in Locally Advanced Non-Small Cell Lung Cancer.

Simple SummaryMultimodality therapy for locally advanced non-small cell lung cancer (NSCLC) is a complex and controversial issue, especially regarding optimal treatment regimens for patients with ipsilateral positive mediastinal nodes (N2 disease). Is the landscape in this hotly debated stage changing the role for surgery as immunotherapy and targeted therapies are being investigated and implemented? A review on multimodality therapeutic options for stage IIIA-N2 NSCLC is presented.For patients with locally advanced non-small cell lung cancer (NSCLC) or positive N1 nodes, multimodality treatment is indicated. However, the optimal management of patients presenting with ipsilateral positive mediastinal nodes (N2 disease) has not been determined yet. Different treatment regimens consisting of chemotherapy, radiation therapy, and surgery have been proposed and implemented previously. In more recent years, immunotherapy and targeted therapies have been added as therapeutic options. The role of surgery is currently redefined. Recent studies have shown that surgical resection after induction immunotherapy or targeted therapy is feasible and yields good short-term results. In this review, we summarize the latest data on multimodality treatment options for stage IIIA-N2 locally advanced NSCLC, depending on the extent of nodal involvement.

Antibody-mediated rejection in heart transplantation

The role of antibody-mediated rejection in predicting survival among heart recipients has been studied in clinical transplantology for over 20 years. This condition is a significant risk factor for heart failure and graft vasculopathy. Antibody-mediated rejection results from activation of the humoral immune system and production of donorspecific antibodies that cause myocardial injury through the complement system. The presence of donor-specific antibodies is associated with lower allograft survival. Treatment of antibody-mediated rejection should take into account the rejection category and the presence or absence of graft dysfunction. The main principle of treatment is to suppress humoral immunity at different levels. World clinical practice has made significant inroads into the study of this issue. However, further research is required to identify and develop optimal treatment regimens for patients with humoral rejection in cardiac transplantation.

Surgery after Induction Targeted Therapy and Immunotherapy for Lung Cancer.

Simple SummaryFor patients with locally advanced non-small cell lung cancer (NSCLC) or positive N1 nodes, multimodality treatment is indicated. However, the optimal management of patients presenting with ipsilateral positive mediastinal nodes (N2 disease) has not been determined yet. Different treatment regimens consisting of chemotherapy, radiation therapy, and surgery have been proposed and implemented previously. In more recent years, immunotherapy and targeted therapies have been added as therapeutic options. The introduction of these newer modalities has raised questions on the role of surgery after targeted therapy or immunotherapy. Recent studies have shown that surgical resection after induction immunotherapy or targeted therapy is indeed feasible, but is associated with a higher risk of conversion and increased morbidity due to hilar inflammation. In this review, we summarize the latest data on outcomes of patients undergoing surgical resection after induction immunotherapy and/or targeted therapy. Treatment outcomes have to be carefully evaluated to determine the contribution of surgery in multimodality treatment regimens including immunotherapy and targeted therapies.Multimodality therapy for locally advanced non-small cell lung cancer (NSCLC) is a complex and controversial issue, especially regarding optimal treatment regimens for patients with ipsilateral positive mediastinal nodes (N2 disease). Many trials investigating neoadjuvant immunotherapy and targeted therapy in this subpopulation have shown promising results, although concerns have risen regarding surgical feasibility. A thorough literature review was performed, analyzing all recent studies regarding surgical morbidity and mortality. Despite the fact that two major trials investigating this subject were terminated early, the overall consensus is that surgical management seems feasible. However, dissection of hilar vessels may be challenging due to hilar fibrosis. Further research is necessary to identify the role of surgery in these multimodality treatment regimens, and to define matters such as the optimal treatment regimen, the dosage of the different agents used, the interval between induction therapy and surgery, and the role of adjuvant therapy.

Predicting optimal treatment regimens for patients with HR+/HER2- breast cancer using machine learning based on electronic health records

Aim: To predict optimal treatments maximizing overall survival (OS) and time to treatment discontinuation (TTD) for patients with metastatic breast cancer (MBC) using machine learning methods on electronic health records. Patients/methods: Adult females with HR+/HER2-MBC on first- or second-line systemic therapy were eligible. Random survival forest (RSF) models were used to predict optimal regimen classes for individual patients and each line of therapy based on baseline characteristics. Results: RSF models suggested greater use of CDK4 & 6 inhibitor-based therapies may maximize OS and TTD. RSF-predicted optimal treatments demonstrated longer OS and TTD compared with nonoptimal treatments across line of therapy (hazard ratios=0.44∼0.79). Conclusion: RSF may help inform optimal treatment choices and improve outcomes for patients with HR+/HER2-MBC.

Assessment of treatment options for patients with hepatitis C virus recombinant form 2k/1b.

Hepatitis C virus (HCV) intergenotype recombinant form (RF) 2k/1b has been actively circulating in HCV-infected patients, and the prevalence of this RF virus in the Republic of Georgia is one of the highest reported worldwide. The aim of this study was to define the optimal treatment regimen for patients with RF_2k/1b. We analyzed the data of 2735 patients who started treatment at the Medical Center Mrcheveli within Georgia's hepatitis C elimination program from May 2015 through December 2019. The patients were treated with sofosbuvir (SOF)-based regimens. For identification of RF_2k/1b variants, refinement of standard (INNO-LiPA) genotyping results for all patient samples assigned the unspecific HCV genotypes (GT) 2a/2c was carried out by sequencing of core and non-structural protein 5B genes. Overall, 444 patients, representing 66% of GT2 and 16% of the total samples, were RF_2k/1b. Treatment of patients with RF_2k/1b with SOF/ledipasvir and SOF/velpatasvir was highly effective and viral cure rates did not differ among genotypes treated with the same regimen: RF_2k/1b, 99% (343/346); GT1, 99% (876/885); GT2, 96% (156/162); and GT3, 99% (545/552). A separate comparison analysis of sustained virologic response rate, treated with SOF plus ribavirin, showed significantly higher sustained virologic response (96%) in patients with confirmed GT2 (by sequencing) compared to unspecified GT2 (by INNO-LiPA) (79%) (P < 0.05). Sofosbuvir-based regimens are highly effective for treatment of RF 2k/1b patients, and with availability of new pan-genotypic direct-acting antivirals, genotyping to identify RF 2k/1b patients might not be necessary.

Hearing Outcomes of Treatment for Acute Noise-induced Hearing Loss: A Systematic Review and Meta-analysis.

To determine the efficacy of various treatment modalities used for acute noise-induced hearing loss (aNIHL) from acute acoustic trauma (AAT) via a systematic review and meta-analysis. PubMed, Cochrane, and Scopus databases. The scientific literature was searched up to October 2018 for articles evaluating hearing outcomes after treatment of aNIHL. The following were extracted: Oxford level of evidence, number of patients, mean age, time to presentation, source of noise exposure, method of treatment/intervention, baseline hearing threshold, posttreatment hearing threshold, hearing gain, proportion of patients with no recovery, partial recovery, or complete recovery, and treatment complications. Sixteen studies with 932 patients met inclusion criteria for systematic review and four studies with 187 patients were included in the meta-analysis. Treatment modalities identified were steroids, vascular agents, nootropics, antioxidants, vitamins, cell apoptosis inhibitors, and hyperbaric oxygen therapy. Meta-analysis demonstrated significant improvement in mean hearing threshold for patients with high-frequency hearing loss, those treated within 48 hours, and those receiving treatment with a nootropic agent. Significant heterogeneity was present in experimental design among included studies and many were of lower levels of evidence. More prospective, large scale, randomized, double-blinded, placebo-controlled clinical trials are required to determine optimal treatment regimens for patients suffering from aNIHL caused by AAT.

Long-term bedaquiline-related treatment outcomes in patients with extensively drug-resistant tuberculosis from South Africa

Optimal treatment regimens for patients with extensively drug-resistant tuberculosis (XDR-TB) remain unclear. Long-term prospective outcome data comparing XDR-TB regimens with and without bedaquiline from an endemic setting are lacking.We prospectively followed-up 272 South African patients (49.3% HIV-infected; median CD4 count 169 cells·µL-1) with newly diagnosed XDR-TB between 2008 and 2017. Outcomes were compared between those who had not received bedaquiline (pre-2013; n=204) and those who had (post-2013; n=68; 80.9% received linezolid in addition).The 24-month favourable outcome rate was substantially better in the bedaquiline versus the non-bedaquiline group (66.2% (45 out of 68) versus 13.2% (27 out of 204); p<0.001). In addition, the bedaquiline group exhibited reduced 24-month rates of treatment failure (5.9% versus 26.0%; p<0.001) and default (1.5% versus 15.2%; p<0.001). However, linezolid was withdrawn in 32.7% (18out of 55) of patients in the bedaquiline group because of adverse events. Admission weight >50 kg, an increasing number of anti-TB drugs and bedaquiline were independent predictors of survival (the bedaquiline survival effect remained significant in HIV-infected persons, irrespective of CD4 count).XDR-TB patients receiving a backbone of bedaquiline and linezolid had substantially better favourable outcomes compared to those not using these drugs. These data inform the selection of XDR-TB treatment regimens and roll-out of newer drugs in TB-endemic countries.

Successful Treatment of HCV/TB co-infected Patient With Sofosbuvir and Daclatasvir: A Case Report

Aim: This case report suggests proper management of patients co-infected with both HCV and TB. Patients &amp; methods: A 77-year-old female patient visited a primary care physician for a routine follow-up because she had past history of HCV in 2011, but she was successfully treated with interferon-therapy. She experienced HCV relapse in 2016 but did not respond to sofosbuvir and ribavirin and it was later on confirmed that she had TB which made the treatment of HCV more challenging. Results: This is the first evidence that highlights sofosbuvir, daclatasvir and ribavirin as an optimal treatment regimen for patients co-infected with TB. Furthermore, it is necessary to treat TB before initiating HCV treatment because of risk of hepatotoxicity. Conclusion: Co-infection of TB in HCV patients alters treatment response toward nucleotide analog inhibitor, sofosbuvir, an approved anti-HCV drug with high rate of sustained virological response.

Irritable bowel syndrome (IBS): a treatable form of peripheral neuropathy

Irritable bowel syndrome (IBS) has long been considered a diagnosis of exclusion with no clear pathogenesis. With an estimated prevalence of 20% in the Western world, understanding this disease has been a major topic of interest in the medical and non-medical community. Data suggests the pathogenesis is multifactorial. More recently, the role of the mesentery, both on a structural and neurological level, has been postulated as well as the necessity of healthy gut flora. These are emerging as key factors in ensuring adequate levels of serotonin in the intestine, in turn regulating bowel motility. With IBS affecting a large patient population, further research is required to characterise relationships between the mesentery, peripheral nerves, bowel flora and gut motility to help identify an optimal treatment regimen for patients with IBS.

Optimal treatment regimen for patients with HBeAg-positive chronic hepatitis B after suboptimal response to 24 weeks of Peg-IFN α-2a

Objective: To investigate the optimal treatment regimen for patients with HBeAg-positive chronic hepatitis B (CHB) after suboptimal response to 24 weeks of pegylated interferon (Peg-IFN) α-2a. Methods: A total of 188 patients with HBeAg-positive CHB who had suboptimal response to 24 weeks of Peg-IFN α-2a were randomly divided into entecavir group (n = 93) and telbivudine group (n = 95). The two groups received entecavir 0.5 mg/d and telbivudine 0.6 g/d, respectively, for 208 weeks. After 208 weeks of treatment, the following indices were assessed: HBeAg clearance rate and seroconversion rate, hepatitis B virus (HBV) DNA clearance rate (HBV DNA < 500 IU/ml), safety, and drug resistance rate. The data were subjected to intention-to-treat (ITT) analysis and per protocol (PP) analysis. Univariate and multivariate logistic regression analyses were performed for the drugs used and baseline characteristics in patients with or without HBeAg seroconversion, and stratification analysis was performed based on the baseline HBeAg level. Results: Six cases in the entecavir group and four cases in the telbivudine group did not complete the treatment. Sequential entecavir and telbivudine were well tolerated and safe for all patients. There was a significant difference in HBV DNA clearance rate at 52 weeks of treatment between the entecavir group and the telbivudine group (ITT analysis: 93.55% [87/93] vs 77.89% [74/95], χ (2) = 9.363, P = 0.002; PP analysis: 93.10% [81/87] vs 76.92% [70/91], χ (2) = 9.049, P = 0.003). The suppression rates of HBV DNA at 208 weeks of treatment were 95.70% (89/93) vs 92.63% (88/95) (ITT analysis) and 95.40% (83/87) vs 92.31% (84/91) (PP analysis). There was a significant difference in HBeAg seroconversion rate at 208 weeks of treatment between the entecavir group and the telbivudine group (ITT analysis: 38.71% [36/93] vs 62.11% [59/95], χ (2) = 10.290, P = 0.001; PP analysis: 41.38% [36/87] vs 64.84% [59/91], χ (2) = 9.833, P = 0.002). Univariate and multivariate logistic regression analyses suggested that sequential use of telbivudine, male sex, and the baseline level of HBeAg were significantly associated with HBeAg seroconversion at 208 weeks of treatment (P = 0.003, hazard ratio [HR] = 0.386; P = 0.009, HR = 0.303; P = 0.001, HR = 3.502). Conclusion: For patients with HBeAg-positive CHB after suboptimal response to 24 weeks of Peg-IFNα-2a, sequential use of telbivudine is the optimal treatment regimen according to the baseline level of HBeAg (baseline guidance). The incidence of HBeAg seroconversion during 208 weeks of sequential treatment can be significantly increased according to the HBeAg decline curve in early treatment (24 weeks) and 104 weeks (response guidance).