[Analysis of early diagnosis and prevention techniques for occupational pneumoconiosis based on patent perspectives in China's coal industry].

Occupational pneumoconiosis in the coal industry is an occupational disease that seriously endangers coal miners' health. Early diagnosis and prevention techniques are significant in controlling its incidence rate and reducing its harm. This article takes the patent data related to the early diagnosis and prevention of occupational pneumoconiosis in the coal industry, published from 1985 to 2021, as the research object. It uses tools such as the Derwent Data Analyzer (DDA) software, the Patyee Database, and the PatSnap Database to analyze the technological development trend and characteristics in this field from aspects of growth trend, primary patent holders, IPC classification layout, value, and research and development hotspots. The results show that the number of patent applications in this field indicates a rapid growth trend, mainly in the hands of Shandong Energy Group Co. Ltd., Shandong University of Science and Technology, China University of Mining and Technology, and other institutions or enterprises. Patent technology mainly involves spray dust reduction, dust removal fans, dust masks, and other aspects with high patent value and innovation ability. This article provides a new perspective and reference for preventing, diagnosing, and treating occupational pneumoconiosis in the coal industry.

[Clinical efficacy of 585 nm Q-switched laser treatment on inflammatory lesion and postinflammatory erythema of acne vulgaris].

OBJECTIVE: To evaluate the efficacy and safety of 585 nm Q-switched laser in the treatment of acne inflammatory lesions and postinflammatory erythema. METHODS: A total of 25 patients with moderate facial acne, symmetrical distribution of inflammatory lesions and postinflammatory erythema on both sides of the face, were enrolled. Among the 25 patients, 22 patients completed all the treatment and evaluation, and 3 patients were lost to follow-up. 585 nm Q-switched laser was used on a randomly selected side of the face for three times of treatment at a 2 week interval. The evaluations were made before each treatment, 2 and 4 weeks after the last treatment, therefore the evaluation time points were before the treatment, weeks 2, 4, 6, and 8, respectively, for a total of 5 times. Acne severity was assessed using the investigator' s global assessment (IGA) score, and erythema severity was assessed using the investigator' s subjective erythema score and narrow-spectrum reflectance spectrophotometer at each follow-up. RESULTS: After 3 times of treatment, there was statistically significant difference between the IGA score in week 8 and before treatment on both sides(Z=2.64, P < 0.01; Z=2.67, P < 0.01). There was no significant difference in IGA score between the treatment side and the control side before treatment and in week 8 (P=0.59, P=0.26). There was statistically significant difference between the investiga-tor' s subjective erythema score in week 8 and before treatment on the treatment side(Z=4.24, P < 0.01), while no significant difference was showed on the control side(Z=1.73, P=0.08). In week 8, the investigator's subjective erythema score of the treatment side was lower than that of the control side (Z=3.61, P < 0.01). The erythema index of the treatment side was significantly decreased at 5 time points (P < 0.01), and the index decreased significantly in week 8 compared with the index before treatment (P < 0.01), while the erythema index of the control side was not significantly different at 5 time points. The treatment related adverse events included erythema and edema after treatment and pain during treatment, the severity was mild to moderate, which resolved spontaneously within 1 to 3 days. Nine patients were very satisfied with the treatment, 7 patients were satisfied, and 6 patients considered average. CONCLUSION: 585 nm Q-switched laser has some effect in the treatment of postinflammatory erythema, and it ensures good tolerance and safety. There was no statistically significant difference between the treatment side and the control side on the improvement of acne inflammatory lesions.

[Efficacy and safety of carotid endarterectomy combined with endovascular therapy in hybrid operating room for patients with segmental atherosclerotic internal carotid artery occlusion].

The current study aimed to investigate the efficacy and safety of carotid endarterectomy combined with endovascular therapy in hybrid operating room for patients with segmental atherosclerotic internal carotid artery occlusion, and share the experience of preoperative screening of patients suitable for vascular reconstruction. A total of 20 patients with internal carotid artery occlusion (ICAO) who were admitted to the Department of Neurosurgery, General Hospital of Tianjin Medical University from May 2018 to May 2020 were collected, and 15 patients met the inclusion criteria. All patients received hybrid surgery. The total success rate of recanalization was 14/15, and only 1 patient developed ICA re-occlusion at 1 year follow up.Therefore, carotid endarterectomy combined with endovascular treatment in hybrid operating room was an alternative treatment for patients with segmental atherosclerotic internal carotid artery occlusion.

[Clinical efficacy and safety of endobronchial one-way valves for the treatment of bronchopleural fistula].

Objective: To investigate the efficacy and safety of interventional endobronchial one-way valves (EBV) for the treatment of peripheral bronchopleural fistula (BPF). Methods: A total of 33 patients with peripheral BPF who underwent EBV implantation in Endoscopy Center of Shanghai Pulmonary Hospital from August 2017 to December 2021 were selected as the research objects. All the patients were diagnosed with peripheral BPF before the implantation surgery. The detailed medical records of the patients were collected, and the etiology, lesion location, treatment method and operation process, treatment efficacy and postoperative complications were analyzed to evaluate the efficacy and safety of EBV implantation. Results: Of the 33 patients in our study, 26 were male and 7 were female. The median age was 54.7 (28-86) years. There were 18 cases of BPF after thoracic surgery (54.5%), 6 cases of chronic obstructive pulmonary disease complicated with spontaneous pneumothorax (18.2%), and 12 cases of pulmonary tuberculosis and non-tuberculous mycobacterial infection with spontaneous pneumothorax (36.4%). A total of 63 valves were inserted in the 33 cases, and a maximum of valves and at least one were inserted in a single case. The lesions were located in the right lower lobe in 16 cases (48.5%) and the left upper lobe in 12 cases (36.4%). Of the 33 patients undergoing EBV placement, 22 (66.7%) were successful, with chest drainage tube indwelling duration of (88.5±36.6) days and (29.6±11.4) days, respectively, before and after EBV treatment. The time from EBV placement to successful withdrawal of EBV was (102.2±31.3) days. During a postoperative follow-up of 6 months after EBV treatment, the main complications were 29 cases with attachment of secretions to the EBV (90.6%) and 13 cases (40.6%) with mild granulation proliferation. In addition, there were five patients with moderate to severe granulation proliferation (15.6%), one with valve displacement or shedding (3.1%), and one with bleeding (3.1%). Conclusions: In this study, the success rate of EBV placement and occlusion was 66.7%. Transbronchoscopic EBV placement in the treatment of peripheral BPF is a effective treatment with relatively minor complications.

Adherence to Pre-exposure Prophylaxis in Black Men Who Have Sex with Men and Transgender Women in a Community Setting in Harlem, NY.

While oral pre-exposure prophylaxis (PrEP) has proven efficacious for HIV prevention, consistent use is necessary to achieve its intended impact. We compared effectiveness of enhanced PrEP (enPrEP) adherence support to standard of care (sPrEP) among Black MSM and TGW attending a community clinic in Harlem, NY. EnPrEP included peer navigation, in-person/online support groups, and SMS messages. Self-reported adherence over previous 30 days, collected in quarterly interviews, was defined as ≥ 57%. Crude and adjusted analyses examined factors associated with adherence. A total of 204 participants were enrolled and randomized; 35% were lost to follow-up. PrEP adherence was 30% at 12-months; no intervention effect was observed (p = 0.69). Multivariable regression analysis found that lower adherence was associated with low education and depressive symptoms. We found that an enhanced adherence intervention did not improve PrEP adherence. Findings point to the need for innovative methods to improve PrEP adherence among Black MSM and TGW.Clinical Trial Registration NCT02167386, June 19, 2014.

Profiles of gut microbiota in children with obesity from Harbin, China and screening of strains with anti-obesity ability in vitro and in vivo.

AIMS: The purpose of this study was to investigate the characteristics of gut microbiota of children with obesity in Harbin, China and to screen anti-obesity strains in vitro and in vivo. METHODS AND RESULTS: The gut microbiota of children with obesity and normal-weight children were investigated by high-throughput sequencing, and based on the different composition in gut microbiota, the strains with potential anti-obesity properties were screened in vitro and in vivo. Compared with normal-weight children, the Firmicutes to Bacteroidetes ratio in children with obesity decreased. Moreover the relative abundances of Lactobacillus and Bifidobacterium in children with obesity were decreased, while the relative abundance of Akkermansia increased. After a series of screening in vitro and in vivo, nine strains were found inhibiting the body weight gain of HFD-fed mice, of which two strains showed significant effects (P < 0·05). CONCLUSIONS: There were significant changes in gut microbiota of children with obesity from Harbin, China. The obtained strains showed obvious anti-obesity effects, and the screening methods used in this study were effective. SIGNIFICANCE AND IMPACT OF THE STUDY: This study enriched the research results on the characteristics of gut microbiota of children with obesity in different regions of the world. Moreover we established a new and effective method for screening anti-obesity strains, and obtained effective strains.

[A comparison study of cognitive-behavioral therapy alone versus combination with tapered hypnotic agents in patients with chronic insomnia].

Objective: To investigate the efficacy of cognitive-behavioral therapy for insomnia (CBT-i) or combination with tapered hypnotic agents. Methods: Seventy-five patients were randomized into either CBT-i group (n=37) or combination group (n=38). The duration of treatment lasted for 8 weeks. The efficacy was evaluated by Pittsburgh sleep quality index (PSQI), Beck depression index (BDI) , Beck anxiety inventory (BAI) and sleep diary variables at baseline, middle and end of treatment. Results: (1)Compared with the results at baseline, the total scores of PSQI,BDI and BAI in both groups significantly decreased at the end of treatment: CBT-i group, PSQI (4.7±2.5) vs. (12.9±3.5); BDI (3.2±4.4) vs. (9.7±6.4); BAI (4.2±5.6) vs. (10.7±8.1); and combination group, PSQI (5.8±2.8) vs. (13.9±3.1); BDI (4.5±4.8) vs. (13.8±8.7); BAI (4.4±4.0) vs. (14.1±6.3) (all P<0.01). (2) Compared with the results at baseline, subjective sleep quality (SQ), sleep onset latency (SOL), sleep efficiency (SE), sleep disturbance (SD) and used sleep medication (USM) in PSQI in combination group significantly decreased at week 4 and 8 (all P<0.05) . The total sleep time (TST) and daytime dysfunction (DF) in PSQI significantly decreased at week 8 (both P<0.05) . (3) Compared with combination group, improvement of SOL and SE in CBT-i group was superior (both P=0.01). Conclusions: CBT-i for chronic insomnia is effective in both CBT-i alone and combination with tapered hypnotic agents. CBT-i group is superior in improving SOL and SE. Combination regimen in our study can significantly reduce the doses of medication.

[Breastfeeding promotion strategies study on preterm infants in the neonatal intensive care unit].

OBJECTIVE: To explore the effect of breastfeeding promotion strategies on neonatal clinical outcomes of preterm infants during hospitalization in the neonatal intensive care unit (NICU). METHODS: We developed breastfeeding promotion strategies, including the establishment of a multidisciplinary breastfeeding steering team, breastfeeding support of families and society, family-integrated care, kangaroo mother care, donor human milk bank, and so on. Preterm infants meeting the inclusion standard, less than 32 weeks gestational age, who were admitted to NICU from November 2015 to February 2017 were enrolled, and the eligible infants were divided into two groups (control group and intervention group) before and after policy implementation. The data of preterm infants including breastfeeding related outcomes (time to initiation of enteral feeding, time to initiation of breastfeeding, time to achieve full breastfeeding, time to achieve full enteral feeding and rate of breastfeeding), growth (extrauterine growth restriction) and complications were compared between the two groups. RESULTS: One hundred and twenty-three preterm infants were enrolled, including 61 in the control group and 62 in the intervention group. There were no significant differences in gender, gestational age, birth weight, intrauterine growth retardation (IUGR) and admission disease status between the two groups (P>0.05). Compared with the control group, there were significantly earlier time to initiation of enteral feeding [15.37 (10.00, 22.13) h vs. 20.25 (12.88, 26.33) h, P<0.01], time to achieve full breastfeeding [91.00 (69.75, 103.00) h vs. 94.00 (80.37, 118.75) h, P=0.04], and time to achieve full enteral feeding [12 (11, 15) d vs. 14 (12, 18) d, P<0.01] in the intervention group. Otherwise, there were no significant differences in time to initiation of breastfeeding, hospital stay, extrauterine growth restriction (EUGR) occurance rate of weight, the rate of breastfeeding, motality, and the incidence of complications including feeding intolerance, neonatal necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) (P>0.05). CONCLUSION: The breastfeeding promotion strategie was a quality improvement of ordinary breastfeeding protocol. It had significantly reduced time to initiation of enteral feeding, time to achieve full breastfeeding and time to achieve full enteral feeding for preterm infants in NICU. Further research is needed to confirm whether the strategies can improve the breastfeeding rate and reduce the occurrence of the complications, such as NEC, BPD, and ROP.

[Investigation on the current status of the cultivation of the master of public health (MPH) in colleges in China].

In order to understand the status of the cultivation of the masters of public health (MPH) in colleges in China and improve the cultivation model, an electronic questionnaire survey were conducted among 22 schools of public health in colleges. The result showed that the size and the enrolment scale of Chinese MPH students were relatively small, and the training objectives were still unclear. There was no obvious difference between the curriculum setting for MPH and academic master degree. The practical skill-oriented courses and emergency response ability of public health practice were insufficient. The cultivation model of MPH should be improved in future.

[Cardioversion efficacy of nifekalan in patients with sustained atrial fibrillation after radiofrequency ablation].

Objective: To evaluate the efficacy and safety of nifekalan (NIF) on cardioversion in atrial fibrillation (AF) patients post radiofrequency ablation, and investigate the relevant factors related to the cardioversion efficacy of NIF. Methods: We screened patients with sustained AF rhythm after radiofrequency ablation between November 2016 and July 2018. Participants were treated with intravenous NIF 0.4 mg/kg within 5-10 minutes after ablation. We observed the adverse reaction, and monitored the rhythm, heart rate, QT interval and QTc interval before the medication and at 5, 10, 20, 120 min after the medication. According to the drug outcome of NIF, patients were divided into conversion group and non-conversion group, related factors affecting conversion efficacy were evaluated using logistic regression analysis. Results: (1)A total of 116 patients were enrolled in the study (63 males and 53 females, mean age was (64±18) years). Among them, 72 patients were converted to sinus rhythm, and the overall successful rate was 62.1%. There were 84 patients with persistent AF, of which 50 cases (59.2%) were restored to sinus rhythm. There were 32 patients with paroxysmal AF, 22 cases (68.8%) of them were restored to sinus rhythm. The conversion time was 1.5 to 12 (6.8±3.4)min. (2) In 116 patients, the QT interval and QTc interval were significantly longer after medication than before the drug administration (P<0.01), and peaked at about 10th min, and restored to the level before drug administration at about 120th min. (3) There were 8 cases of bradycardia (6.9%), 3 cases of frequent and short ventricular tachycardia (2.6%). (4) The duration of atrial fibrillation was shorter and left atrial diameter was smaller in the cardioversion group than in the non-cardioversion group (both P<0.05). There were no significant differences in gender, disease history, atrial fibrillation type and structural heart disease between the two groups (P>0.05). (5) Multifactorial logistic regression analysis showed that the duration of atrial fibrillation (OR=0.980, 95%CI 0.966-0.994, P=0.004) and the left atrial diameter (OR=0.888, 95%CI 0.814-0.967, P=0.007) were the factors that influence the cardioversion efficacy of NIF on atrial fibrillation post ablation. Conclusions: The total effective rate of NIF was 62.1% in patients witrh sustained AF post radiofrequency ablation, was 68.8% in patients with paroxysmal AF. Besides, NIF has the advantage of short conversion time and few adverse reactions. Left atrium diameter and AF duration were relevant factors that influence the efficacy of NIF of cardioversion in patients with sustained AF after radiofrequency ablation.

Rosacea treatment update: recommendations from the global ROSacea COnsensus (ROSCO) panel.

BACKGROUND: Rosacea is currently treated according to subtypes. As this does not adequately address the spectrum of clinical presentation (phenotypes), it has implications for patient management. The ROSacea COnsensus panel was established to address this issue. OBJECTIVES: To incorporate current best treatment evidence with clinical experience from an international expert panel and establish consensus to improve outcomes for patients with rosacea. METHODS: Seventeen dermatologists and three ophthalmologists reached consensus on critical aspects of rosacea treatment and management using a modified Delphi approach. The panel voted on statements using the responses 'strongly disagree', 'disagree', 'agree' or 'strongly agree'. Consensus was defined as ≥ 75% 'agree' or 'strongly agree'. All voting was electronic and blinded. RESULTS: The panel agreed on phenotype-based treatments for signs and symptoms presenting in individuals with rosacea. First-line treatments were identified for individual major features of transient and persistent erythema, inflammatory papules/pustules, telangiectasia and phyma, underpinned by general skincare measures. Multiple features in an individual patient can be simultaneously treated with multiple agents. If treatment is inadequate given appropriate duration, another first-line option or the addition of another first-line agent should be considered. Maintenance treatment depends on treatment modality and patient preferences. Ophthalmological referral for all but the mildest ocular features should be considered. Lid hygiene and artificial tears in addition to medications are used to treat ocular rosacea. CONCLUSIONS: Rosacea diagnosis and treatment should be based on clinical presentation. Consensus was achieved to support this approach for rosacea treatment strategies.

[Contemporary use of ticagrelor in patients with acute coronary syndrome after discharge].

Objective: To investigate the degree and determinants of using ticagrelor among discharged patients with acute coronary syndrome (ACS). Methods: Patients with ACS in Fuwai hospital who were given ticagrelor after discharge between Jan. 2015 to Jun. 2015 were analyzed.The clinical characteristics and adherence to ticagrelor of these patients were collected by reviewing the electronic medical records and telephone interview.Date were statistically-analyzed. Results: Among all screened 404 patients, 158 (39.1%) patients prematurely stopped ticagrelor within 12 months, while 119(29.5%) patients switched from ticagrelor to clopidogrel.Unavailable locally (34.8%), economic reasons (17.7%) and hemorrhagic events (18.4%) were the main causes of the premature discontinuation of ticagrelor.Univariate analysis showed left main disease (P=0.04) and the frequency of outpatient follow-up (P<0.01) as relative factors for prematurely stopping ticagrelor outside hospital after discharge.Multivariate analysis revealed medical insurance payment (OR 1.79, 95%CI 1.03-3.11) and the frequency of outpatient follow-up (OR 0.61, 95%CI 0.43-0.86) as independent predictors of prematurely stopping ticagrelor outside hospital.Prematurely stopping ticagrelor has no significant effect on the ischemic events (myocardial infaction or stroke) (P=0.76). Conclusion: Social cinditions is the main factor for the persistence to ticagrelor among ACS patients after dischcrge.Medical insurance payment and low frequency of outpatient follow-up were independent predictors of prematurely stopping ticagrelor and it may not have impact on ischemic events.

[Clinical efficacy and safety of thrombolytic treatment with reteplase in patients with intermediate-risk acute pulmonary embolism].

Objective: To assess the efficacy and safety of thrombolytic treatment with reteplase in patients with intermediate-risk acute pulmonary embolism. Methods: Ten consecutive patients with intermediate-risk acute pulmonary embolism who received thrombolytic treatment with reteplase at Thrombosis and Vascular Medicine Center, Fuwai Hospital from March to November in 2016 were included.Vital signs, right ventricular diameter, systolic pulmonary artery pressure, and biochemical markers were assessed before and after thrombolytic therapy with reteplase, and bleeding complications were also observed during 3 months follow up. Results: (1) For the efficacy outcomes: at 48 hours after thrombolytic treatment with reteplase, echocardiography-derived diameter of right ventricular was significant reduced from (27.9±3.8) mm to (24.8±2.6) mm (P=0.03), systolic pulmonary artery pressure decreased from (63.9±21.6) mmHg(1 mmHg=0.133 kPa) to (34.4±19.8) mmHg (P=0.02). Heart rate and breathing rate were also decreased significantly (both P<0.05), blood pressure remained unchanged post therapy.Hypoxemia was quickly corrected with an significant elevation of PaO(2) and SaO(2) ((65.2±14.3) mmHg vs. (80.0±9.6) mmHg, P=0.006; (90.8±3.5)% vs. (95.2 ±1.6)%, P=0.002 respectively). PaCO(2) was also increased significantly (P<0.05). Serum NT-proBNP and cTnI were decreased significantly (both P<0.05). There was no recurrent pulmonary embolism or deep-vein thrombosis during the 3 months follow-up. (2) For the safety outcomes: a thrombolytic relevant hemoptysis (about 70 ml) occurred in 1 patient, and was controlled by PCC therapy.No other clinically relevant events were observed during thrombolytic treatment. Eight patients were followed more than 3 months, there was no major bleeding complication or death during the follow up period. Conclusion: Treatment of intermediate-risk acute pulmonary embolism with reteplase is effective and safe and there are no obvious side effects.

[Adverse effects of low dose exposures to cadmium below renal damage level should be emphasized for human health effect studies].

Currently, the pollution of heavy metal, including lead, cadmium (Cd) and mercury, was one of the major environmental problems in China. Cd could cause adverse effects on kidney, bone, lung and reproductive system. Most of the past researches focused on renal damage effect, and some evidences suggestedadverse effects on bone, tumor, cardiovascular diseases, diabetes and mineral elements, etc, which was occurred at low dose exposures to Cd below renal damage level. An important content of human health effect Studies on exposures to Cd is to follow up the development and consequences of adverse effects after long-term exposure to environmental Cd and then reduction or cessation of its exposure among this population. In this paper, the progress and development trend of long-term environmental exposure to Cd and its health damage effect were reviewed.

[Efficiency and influencing factors of ultrasound-guided radiofrequency ablation as treatment in hepatic malignant tumors].

OBJECTIVE: To evaluate the efficiency and influencing factors of ultrasound-guided percutaneous radiofrequency ablation (RFA) as treatment of hepatic malignant tumors. METHODS: Clinical data and follow-up radiographic images of patients with hepatic malignant tumors who had undergone treatment with ultrasound-guided percutaneous RFA at our hospital between March 2012 and March 2014 were reviewed. Rates of incomplete ablation, recurrence, and tumor progression were calculated, and the factors affecting each were analyzed. RESULTS: Four hundred and twelve lesions were ablated in a total of 392 ultrasound-guided percutaneous RFA procedures applied to 360 patients. The average tumor size was 2.51±1.10 cm. During at least 3 months of follow-up, the complete ablation rate was 86.11% (310/360), the recurrence rate was 7.78% (28/360), and the progression rate was 6.1% (22/360). Tumors with vessel-proximal location, size of ≥ 3 cm and ≥ 3 month presence had significantly higher rates of residual lesions after ablation (χ(2) = 4.431, 10.889 and 8.000, respectively; p<0.05). Tumors with ≥ 3 month presence had significantly higher rates of recurrence and progression (χ(2) = 29.032 and 22.092, P < 0.05). CONCLUSION: Ultrasound-guided percutaneous RFA can effectively control local progression of hepatic malignant tumors. Tumor size, length of presence, and vessel-proximal location are influencing factors of complete ablation rate, while length of presence is also an influencing factor for the recurrence and progression rates.

Randomised controlled trial on the effectiveness of home-based walking exercise on anxiety, depression and cancer-related symptoms in patients with lung cancer.

BACKGROUND: Although exercise has been addressed as an adjuvant treatment for anxiety, depression and cancer-related symptoms, limited studies have evaluated the effectiveness of exercise in patients with lung cancer. METHODS: We recruited 116 patients from a medical centre in northern Taiwan, and randomly assigned them to either a walking-exercise group (n=58) or a usual-care group (n=58). We conducted a 12-week exercise programme that comprised home-based, moderate-intensity walking for 40 min per day, 3 days per week, and weekly exercise counselling. The outcome measures included the Hospital Anxiety and Depression Scale and the Taiwanese version of the MD Anderson Symptom Inventory. RESULTS: We analysed the effects of the exercise programme on anxiety, depression and cancer-related symptoms by using a generalised estimating equation method. The exercise group patients exhibited significant improvements in their anxiety levels over time (P=0.009 and 0.006 in the third and sixth months, respectively) and depression (P=0.00006 and 0.004 in the third and sixth months, respectively) than did the usual-care group patients. CONCLUSIONS: The home-based walking exercise programme is a feasible and effective intervention method for managing anxiety and depression in lung cancer survivors and can be considered as an essential component of lung cancer rehabilitation.

Efficacy and safety of lixisenatide once daily vs. placebo in people with Type 2 diabetes insufficiently controlled on metformin (GetGoal-F1).

AIMS: To assess the efficacy and safety of one- and two-step dose-increase regimens of lixisenatide once daily in participants with Type 2 diabetes mellitus insufficiently controlled with metformin. METHODS: This was a randomized, double-blind, placebo-controlled, parallel-group, multi-centre study enrolling participants with Type 2 diabetes (n = 484) treated with metformin. Participants were randomized to receive either lixisenatide in a one-step dose increase or a two-step dose increase vs. placebo for 24 weeks, followed by a ≥ 52-week variable double blind period. Primary outcome was HbA1c reduction at week 24. RESULTS: Lixisenatide one-/two-step once daily significantly improved HbA1c at week 24 compared with placebo (P < 0.0001) and allowed more participants to achieve HbA1c < 53 mmol/mol (< 7.0%) (P ≤ 0.0005). Improvements were observed in fasting plasma glucose (-0.5/-0.6 vs. +0.1 mmol/l; P < 0.001) and body weight (-2.6/-2.7 vs. -1.6 kg; P < 0.005). At week 24, adverse events were reported by 67.7/70.8/65.6% of participants treated with lixisenatide one-/two-step/placebo, respectively--nausea and vomiting being reported most frequently. Symptomatic hypoglycaemia occurred in 1.9/2.5% of participants on one-/two-step lixisenatide and 0.6% with placebo, with no severe episodes. Lixisenatide continued to be efficacious and well tolerated during the variable double-blind extension period of at least 52 weeks. CONCLUSIONS: Lixisenatide one- or two-step dose-increase regimens significantly improved glycaemic control and decreased body weight over 24 weeks and during a long-term extension period without increasing hypoglycaemia. The study confirmed that tolerability in the one-step group was at least similar to the two-step dose increase, with nausea/vomiting and hypoglycaemia frequency being lower in the one-step regimen.