This study aims to investigate the antimicrobial ability and mechanism analysis of Lactobacillus species against carbapenemase-producing Enterobacteriaceae (CPE). Five Lactobacillus spp. strains and 18 CPE clinical isolates were collected. Their anti-CPE effects were assessed by agar well diffusion and broth microdilution assay, as well as time-kill test. Finally, the specific anti-CPE mechanism, especially for the effect of organic acids was determined using broth microdilution method. All of five Lactobacilli isolates displayed the potent activity against most CPE isolates with mean zones of inhibition ranging 10.2-21.1 mm. The anti-CPE activity was not affected by heating, catalase, and proteinase treatment. Under the concentration of 50% LUC0180 cell-free supernatant (CFS), lactic acid, and mix acid could totally inhibit the growth of carbapenem-resistant Klebsiella pneumoniae (CPE0011), and acetic acid could inhibit 67.8%. In contrast, succinic acid and citric acid could not inhibit the growth of CPE0011. While we decreased the concentration to 25%, only lactic acid and mix acid displayed 100% inhibition. In contrast, succinic acid, citric acid and acetic acid did not show any inhibitory effect. Lactobacillus strains exhibit potent anti-CPE activity, and lactic acid produced by Lactobacillus strains is the major antimicrobial mechanism.

Background:EMPEROR-Reduced trial provides promising evidence on the efficacy of empagliflozin adding to the standard treatment in patients with heart failure and reduced ejection fraction (HFrEF). This study aimed to investigate the cost-effectiveness of add-on empagliflozin vs. standard therapy alone in HFrEF from the perspective of the Asia-Pacific healthcare systems.Methods:A Markov model was constructed to simulate HFrEF patients and to project the lifetime direct medical costs and quality-adjusted life years (QALY) of both therapies. Transitional probabilities were derived from the EMPEROR-Reduced trial. Country-specific costs and utilities were extracted from published resources. Incremental cost-effectiveness ratio (ICER) against willingness to pay (WTP) threshold was used to examine the cost-effectiveness. A series of sensitivity analyses was performed to ensure the robustness of the results.Results:The ICERs of add-on empagliflozin vs. standard therapy alone in HFrEF were US$20,508, US$24,046, US$8,846, US$53,791, US$21,543, and US$20,982 per QALY gained in Taiwan, Japan, South Korea, Singapore, Thailand, and Australia, respectively. Across these countries, the probabilities of being cost-effective for using add-on empagliflozin under the WTP threshold of 3-times country-specific gross domestic product per capita were 93.7% in Taiwan, 95.6% in Japan, 96.3% in South Korea, 94.2% Singapore, 51.9% in Thailand, and 95.9% in Australia. The probabilities were reduced when shortening the time horizon, assuming the same cardiovascular mortality for both treatments, and setting lower WTP thresholds.Conclusion:Adding empagliflozin to HFrEF treatment is expected to be a cost-effective option among the Asia-Pacific countries. The cost-effectiveness is influenced by the WTP thresholds of different countries.

Neuropathic pain (NP) can occur as a chronic complication of leprosy neuropathy. NP epidemiology and its impact on patients have not been well documented. This study investigates NP prevalence and impact in the years after patients are declared “released from treatment” (RFT) following multidrug therapy (MDT) completion. In this cross-sectional study, 85 RFT patients were recruited within leprosy referral services in Nepal. The Douleur Neuropathique 4 Questionnaire (DN4) was used to screen for NP. Pain severity, impacts on patients’ daily activities and mental health were measured by using the Brief Pain Inventory (BPI), Screening of Activity Limitation and Safety Awareness (SALSA), and General Health Questionnaire-12 (GHQ-12) respectively. 96% surveyed had been treated for multibacillary leprosy. 44 (52%) complained of pain of which 30 (68%) were diagnosed with NP. NP was not associated with age, gender, or presence of skin lesions or nerve symptoms at leprosy diagnosis. 70% of patients with NP had either history of or ongoing reactions and 47% had grade 2 disability. Nerve tenderness (p = 0.023) and current reactions (p = 0.018) were significant risk factors for NP. Patients with NP suffered significantly higher intensity pain (p = 0.023) and daily life interference (p = 0.003) and were more likely to have moderate to extreme daily activity limitations (p = 0.005). 13 (43%) exhibited psychological distress, and medications only reduced moderate degree (50–60%) of pain. In our study, 35% of RFT patients had ongoing NP. Risk factors include nerve tenderness and reaction. They suffer from more daily life interference and psychological distress. Leprosy patient care should include recognition and management of NP. Leprosy could present with chronic neuropathic pain, which might severely disturb daily life and mental health of leprosy-infected patients. This complication could also occur even years after antibiotics therapy completion, and we noticed that it is associated with recent leprosy reactions and nerve tenderness on physical examination. This is the first study that describes the epidemiology of neuropathic pain in leprosy patients in Nepal. More than one-third of leprosy patients who had completed multidrug therapy, are still suffering from neuropathic pain, and this study demonstrated that it has caused a great impact to their daily activities and psychological status. Therefore, prompt recognition and management of neuropathic pain are mandatory while taking care of the patients with leprosy.

Pre-exposure prophylaxis (PrEP) for prevention of human immunodeficiency virus infection is proved to be effective and has been implemented worldwide. This article introduces the guideline development and revised recommendations and guidance on PrEP provision in the updated Taiwan PrEP guideline. The Taiwan PrEP guideline writing group searched randomized controlled trials and guidelines published before October 2017 through Medline/PubMed, Cochrane Database, Embase and ClinicalTrials.gov database. Keywords included pre(-)exposure prophylaxis, PrEP, Truvada, tenofovir, HIV, and AIDS. Each selected article was assessed by two authors using the Grading of Recommendations Assessment, Development and Evaluation. External reviewers were invited to independently evaluate the revised manuscript per the Appraisal of Guidelines for Research and Evaluation II. Before publication, a public consultation was held to reach consensus on the updated guideline among providers, civil society, and Taiwan Centers for Disease Control. Four systematic reviews and 28 original articles were reviewed by Taiwan PrEP writing group. The second version of the Taiwan PrEP guideline was released in March 2018. We recommended daily PrEP use for the following populations: strong recommendation and high quality of evidence for men who have sex with men (MSM) and transgender women (TGW), as well as heterosexual serodiscordant couples; weak recommendation and high quality of evidence for people who inject drugs, while weak recommendation and moderate quality of evidence for at-risk heterosexual men and women. There is high-quality evidence for event-driven PrEP in MSM and likely TGW, and we additionally recognized these key populations could benefit from such dosing regimen.