Outcomes of long-acting injectable antipsychotics use in pregnancy:A literature review

BACKGROUND Women with a history of serious psychotic disorders are at increased risk of disease relapse during pregnancy.Long-acting injectable(LAI)antipsychotics have been widely used to improve adherence and prevent relapse in patients with various severe psychotic disorders,but there is a lack of high-quality data from previous research on the safety of LAI antipsychotics during pregnancy.AIM To summarize relevant data on maternal,pregnancy,neonatal,and developmental outcomes from published cases of LAI antipsychotic use in pregnancy.METHODS A literature search was performed through November 11,2023,using three online databases:PubMed/MEDLINE,Scopus,and Web of Science.Case reports or case series that reported information about the outcomes of pregnancy in women who used LAI antipsychotics at any point in pregnancy,with available full texts,were included.Descriptive statistics,narrative summation,and tabulation of the extracted data were performed.RESULTS A total of 19 publications satisfied the inclusion criteria:3 case series,15 case reports,and 1 conference abstract.They reported the outcomes of LAI antipsychotic use in 74 women and 77 pregnancies.The use of secondgeneration LAI antipsychotics was reported in the majority(n=47;61.0%)of pregnancies.First-generation LAI antipsychotics were administered during 30 pregnancies(39.0%).Most of the women(approximately 64%)had either satisfactory control of symptoms or no information about relapse,while approximately 12%of them had developed gestational diabetes mellitus.A minority of cases reported adverse outcomes such as stillbirth,spontaneous abortion,preterm birth,low birth weight,congenital anomalies,and neurological manifestations in newborns.However,there were no reports of negative long-term developmental outcomes.CONCLUSION Currently available data seem reassuring,but further well-designed studies are required to properly evaluate the risks and benefits of LAI antipsychotic use during pregnancy.

Impacts and Demonstration Effects of Applying Long-acting Slow-release Fertilizer on Economic Yield of Peanut

[Objectives]To study the impacts and demonstration effects of long-acting slow-release fertilizer application on economic yield of peanut.[Methods]The 25,30,35,40,45,50 kg of long-acting slow-release fertilizers were applied to 667 m 2 of peanuts,and different amounts of urea were applied together.[Results]Applying 40 kg of long-acting slow-release fertilizer and 10.45 kg of urea had the best effect.Compared with the application of ordinary compound fertilizers,the plants did not age prematurely,the leaf diseases were mild,the stems and leaves remained dark green when harvested,and the stems and leaves had a longer functional period.Bearing shoots increased by 1.7,single-plant full pods increased by 2.4,double-seed peanuts increased by 3.2,empty pods decreased by 0.5,and single-seed peanuts decreased by 0.7.The experimental demonstration results show that the spring-sowed peanuts had an average yield increase of 29.0-67.2 kg/667 m 2,and the yield increase rate was 7.35%-16.89%,and the difference was extremely significant.[Conclusions]In the high-yield cultivation of peanuts,the application of long-acting slow-release fertilizer can be promoted to improve peanut production.

Factors Influencing the Choice between IUD and Implant among Long-Acting Reversible Contraceptive (LARCs) Users in Burkina Faso

Background: Long-acting and reversible contraceptive methods hold great potential as solutions to address the unmet need for contraception and the significant discontinuation rates, especially in sub-Saharan Africa. Among these methods, the Implant has gained popularity in sub-Saharan Africa, whereas the utilization of Intrauterine Devices (IUDs) has remained comparatively low, particularly in Burkina Faso. This study aims to evaluate the shifts in IUD and Implant usage from 2010 to 2020 and to pinpoint the factors influencing the choice of IUDs among LARCs users in Burkina Faso. Data and Methods: We conducted an analysis using data from Burkina Faso, drawn from the 2010 Demographic and Health Survey (DHS) and the 2020 PMA Phase 1 data. The 2010 DHS garnered responses from 17,087 women aged 15 - 49, achieving a response rate of 98.4%. The 2020 PMA data collected responses from 6590 women aged 15 - 49, with a response rate of 95.8%. The final sample of Long-Acting Reversible Contraceptives (LARCs) users consisted of 1502 women, including 576 women from the 2010 survey and 926 women from the 2020 survey. Results: The study demonstrates an expansion of IUD usage to include socioeconomically disadvantaged segments among LARC users. However, higher levels of education, older age, and decisions influenced by healthcare providers are correlated with the preference for IUDs over Implants. The choice of IUDs is also connected to a comprehensive understanding of contraceptive methods, suggesting potential biases in the counseling process. Conclusion: Facilitating the broader adoption of IUDs among disadvantaged groups could be achieved by improving the accessibility of IUD products and services in rural areas. Nevertheless, there should be focused initiatives to enhance access to removal services, as this factor could dissuade specific users. Further efforts are required to train healthcare providers, aiming to mitigate biases in delivering Long-Acting Reversible Contraceptives (LARCs). Providers should provide impartial counseling, irrespective of the selected type of LARC.

Clinical Efficacy and Incidence of Adverse Reactions of Entecavir Combined with Long-Acting Interferon in Treating Hepatitis B

Objective:To explore and analyze the clinical efficacy and incidence of adverse reactions of entecavir combined with long-acting interferon in treating hepatitis B.Methods:The study was conducted from January 2020 to December 2022,and the research subjects were 69 hepatitis B patients admitted to our hospital.The patients were divided into a research group(n=35)and a control group(n=34).Patients in the control group were treated with entecavir,while patients in the study group were treated with entecavir combined with long-acting interferon.The antiviral efficacy,liver function indicators,clinical effectiveness,and incidence of adverse reactions were compared between the two groups.Results:The HBV-DNA negative conversion rate and HBeAg seroconversion rate of the patients in the study group were higher than those of the control group,and the virological breakthrough rate was lower than that of the control group(P<0.05);the alanine transaminase(ALT),aspartate aminotransferase(AST),and total bilirubin(TBIL)levels of the patients in the study group were all lower after treatment.In the control group,the albumin(ALB)level was higher than that in the control group(P<0.05).The clinical effective rate of patients in the study group was higher than that in the control group(P<0.05);there was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion:The treatment effect of entecavir combined with long-acting interferon in patients with hepatitis B is significant.It can effectively antiviral and improve the liver function of patients.The incidence of adverse reactions is low and can be promoted and applied.

Intra-Articular injection of acid-sensitive stearoxyl-ketal-dexamethasone microcrystals for long-acting arthritis therapy

Despite advances in treatment of chronic arthritis,there is still a strong need for the development of long-acting formulations that can enable local and sustained drug release at the inflamed tissues.In this work,we fabricated microcrystals of an acid-sensitive stearoxyl-ketal-dexamethasone prodrug for treatment of arthritis.Microcrystals of the prodrug with two sizes were successfully engineered and showed pH-dependent hydrolysis kinetics in vitro.In a collagen-induced arthritis rat model,we evaluated the influence of particle size and injection dose on anti-inflammatory effect after intra-articular injection.Such prodrug demonstrated long-acting anti-arthritis effects with good safety.Our results indicate ketal-based prodrugs are promising for the development of long-acting injectables and may stimulate the development of new treatments for chronic diseases.

Thermal stability and long-acting antibacterial activity of phosphonium montmorillonites

Na-montruorillonite （Na-MMT） was exchanged with three quaternary atkylphosphonium salts： decyl tributylphosphonium bromide （DTBPBr）, dodecyl tributylphosphonium bromide （DDTBPBr） and hexadecyl tributylphosphonium bromide （HDTBPBr）, to investigate the effects of phosphonium salts species and relative molecular mass on the characteristics, morphology, thermal stability and long-acting antibacterial property of phosphonium montmorillonites. The resulting modified montmorillonites were characterized by the FTIR, XRD, TEM, and TG/DTG techniques. And minimum inhibitory concentration （MIC） was used to investigate antibacterial activity. The results show that the phosphonium salts are intercalated into Na-MMT, and the basal spacing of P-MMTs is enlarged with the increase of phosphonium salt content or the growth of alkyl chain length. DDTBP-MMT-3 with 19.83% （mass fraction of dodecyl tributylphosphonium salts, displays excellent thermal stability and long-acting antibacterial activity.

Efficacy and Tolerability of Long-Acting Injectable Formulation of Nalmefene (Nalmefene Consta 393.1 mg) for Opioid Relapse Prevention: A Multicentre, Open-Label, Randomised Controlled Trial

Objective: To determine the efficacy and tolerability of a long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) for the treatment of opioid-dependent patients. Design, Setting, and Participants: A 12 weeks, open-label, randomised controlled trial conducted between June 2009-July 2011, at 14 Hospital-based drug clinics, in the 12 countries. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder. Of the 3200 individuals screened, 3000 (93.7%) adults were randomized 1500 participants to receive injections of Long-acting depot formulations ofNalmefene (Nalmefene Consta 393.1 mg) given intramuscularly once in 12 weeks and 1500participants to receive extended-release Naltrexone (Vivitrol 380 mg), administered intramuscularly every fourth week for 12 weeks. Main Outcomes and Measures: The primary endpoints (protocol) were: Confirmed Opioid abstinence (percentage i.e. the number of patients who achieved complete abstinence during week 12). Confirmed abstinence or “opioid-free” was defined as a negative urine drug test for opioids and no self-reported opioid use. Weeks 1 - 4 were omitted from this endpoint to allow for stabilization of abstinence. Secondary end points included a number of days in treatment, treatment retention and craving. The study also investigated, on 275 participants, degree and time course of mu-opioid receptor occupancy following single doses of Nalmefene extended-release injection (Nalmefene Consta 393.1 mg) as well as the plasma concentration of Nalmefene and Nalmefene-3-O-glucuronide. Safety was assessed by adverse event reporting. Results: Of 3000 participants, mean (SD) age was 27.1 (±4.8) years and 831 (27.7%) were women. 1500 individuals were randomized to receive injections of Long-acting depot formulations of Nalmefene (Nalmefene Consta 393.1 mg) and 1500 to receive injections of extended-release Naltrexone (Vivitrol 380 mg);2088 participants (69.6.0%) completed the trial. Primary endpoints: Confirmed Opioid Abstinence: Complete abstinence was sustained by 86% (n = 1290) of Nalmefene patients (patients treated with Nalmefene Consta 393.1 mg, long-acting depot formulations) compared with 43% (n = 645) of patients treated with extended-release Naltrexone 380 mg (Vivitrol), during weeks 5 - 12 (χ2 = 672.34, P Secondary Endpoint: Craving: A statistically and clinically significant reduction in opioid craving was observed with Nalmefene (Nalmefene Consta 393.1 mg, long-acting depot formulations) vs. Naltrexone (extended-release Naltrexone, Vivitrol 380 mg) by week 4 (P =0.0048), which persisted every week through 12 (P < 0.0001). Patients given Nalmefene (Nalmefene Consta 393.1 mg, long-acting depot formulations) had a 75% decrease in craving from baseline to week 12. Patients given a Naltrexone (extended-release Naltrexone, Vivitrol 380 mg) had a 3% increase in craving from baseline to week 12 (Mean change in self-reporting craving). Secondary Endpoint: Treatment Retention: Long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) helped significantly more patients complete 12 weeks treatment (n = 1245, 83%) compared with extended-release Naltrexone (Vivitrol 380 mg) (n = 570, 38%) (χ2 = 635.53, P < 0.0001). Patients on long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) had longer treatment retention than patients on extended-release Naltrexone (Vivitrol 380 mg). Concentrations of Nalmefene and Nalmefene-3-O-Glucuronide in Plasma: Analyses were made of 275 study sample. There was no statistically significant difference for plasma nalmefene concentrations between days 2 and 84 (p = 0.416). The plasma concentration of Nalmefene were 20.3 and 28.5 ng/ml and concentrations of nalmefene-3-O-glucuronide were 2.1 and 4.1 ng/ml, respectively. Plasma levels of Nalmefene remained above 20 ng/ml for approximately 12 weeks after administration of Nalmefene, long-acting depot formulations (Nalmefene Consta 393.1 mg). PET Assessments: Very high mu-opioid receptor occupancy by Nalmefene was detected 1 day after treatments at which time point the occupancy was 100.0% after Nalmefene injection (Nalmefene Consta 393.1 mg). Nalmefene Consta 393.1 mg injection (long-acting intramuscular formulation of Nalmefene) led to a very high occupancy ofmu-opioid receptors in all brain areas examined;the thalamus, caudate nucleus, and frontal cortex. Depending on the brain area mu-opioid receptor occupancy varied between 83.0% and 85.8% 84 days after dosing. Adverse Reactions: Adverse events were similar in opioid-dependent patients treated with long-acting intramuscular formulation of Nalmefene (Nalmefene Consta 393.1 mg) vs. patients treated with extended-release Naltrexone (Vivitrol 380 mg). Conclusions and Relevance: Long-acting depot formulations of Nalmefene (Nalmefene Consta 393.1 mg) was more effective then extended-release Naltrexone (Vivitrol 380 mg) in maintaining short-term abstinence from heroin and should be considered as a treatment option for opioid-dependent individuals.

Control Effect of Slow-release, Long-acting and Multi-functional New Pesticides on Sugarcane Borders and Woolly Aphids

In order to select the long-acting,low toxic,low-risk and multi-functional new pesticides for the control of sugarcane borders and woolly aphids and precise and efficient application technology,the control effect of 10% monosultap · thiamethoxam granular formulation and 1% Bt · clothianidin granular formulation on sugarcane borders and woolly aphids were studied.The results showed that 10% monosultap·thiamethoxam GR and 1% Bt·clothianidin GR had good control effects on sugarcane borders and woolly aphids.They were ideal slow-release,long-acting,low toxic and multi-functional new pesticides used to control sugarcane borders and woolly aphids.They could be used alternately with other pesticides to delay the emergence and development of pest resistance to pesticides.The best dosage of the two pesticides in the field was 45 kg/hm^2.They could be mixed with fertilizer( 1200-1800 kg/hm^2),scattered in sugarcane ditches or at the base of sugarcane plants,and covered with soil or film from January to July.The control effect on dead heart seedlings damaged by borers could be up to above 79.2%,and the control effect on sugarcane woolly aphids could reach more than 98.8%.In comparison with the control group,the actual yield and sugar content of sugarcane increased by above 41 555 kg/hm^2 and 6.5% respectively.The application of slow-release,long-acting,strong systemic and multi-functional new agents with fertilizer around roots is convenient,precise and efficient,labor-saving,time-saving and environmentally friendly,and is worthy of being widely applied in sugarcane areas.

Hypercalcemia Appeared in a Patient with Glucagonoma Treated with Octreotide Acetate Long-acting Release

PABCREATIC neuroendocrine tumours are uncommon neoplasms of the pancreas.They may cause a clinical syndrome due to hormone overproduction.Glucagonoma is a rare kind of pancreatic tumors. Here we report a case of glucagonoma. Hypercalcemia occurred when the patient underwent octreotide acetate long-acting release.

Study on Organic Long-acting Fertilizer of Trichosanthes kirilowii Maxim. and Preliminary Report on its Application Effect

This paper studied the fertilizer requirement and soil fertility supply capacity of Trichosanthes kirilowii Maxim.,discussed the application effects of organic fertilizer in Trichosanthes kirilowii Maxim.The results showed that the yield of Trichodanthes kirilowii Maxim.at Jinjing site by applying special organic longacting fertilizer increased by 11.3%and earnings by 3.6%,the yield at Ansha site increased by 17.4%,and earnings by 9.2%.It was pointed out that high-yielding fertilization of Trichosanthes kirilowii Maxim.was achieved by first applying organic fertilizer to ensure good soil structure,and then by ensuring an effective supply of nitrogen,potassium,boron,molybdenum and zinc fertilizers.

Optimal needle insertion length for intramuscular injection of risperidone long-acting injectable (RLAI)

Risperidone long-acting injectable (RLAI) is approved for the treatment of schizophrenia in many countries. The suggested site is the gluteal muscle with a needle length of two inches (50 mm) in Japan, which is longer than the ordinarily used needle for intramuscular injections. The aim of this study was to determine the optimal needle insertion length for accurate delivery of RLAI procedure among subjects who have normal body mass index (BMI: 18 to 25) and high BMI (>25). Thirty-seven patients with schizophrenia were administered RLAI intramuscularly into the dorsogluteal muscle. The standard procedure required inserting 80% of the two inch needle. By using data collected by ultrasonography, the findings confirmed that the median needle insertion lengths for subjects with normal and high BMI were 39.0 and 45.5 mm, respectively. To deliver RLAI effectively and safely, the authors strongly recommend that a specialized needle be used that is “marked” at the 40 mm point from the tip of the needle to the base. In this way regardless of subcutaneous fat content, the RLAI can be safely delivered into the muscle without causing untoward or side effects.

Effects of Depth of Needle Insertion with Risperidone Long-Acting Injectable in Persons with Schizophrenia: A Randomized Double-Blind Study

In some cases, if the insertion depth is shallower than expected, intramuscular (IM) injection of risperidone long-acting injectable (RLAI) may not penetrate the muscle fascia. However, if needle insertion depth is deeper than anticipated, needle penetration may cause damage to nerves, arteries and veins. Few clinical studies were done to evaluate the depth of needle length insertion reaching the intended gluteal muscle. The aim of this study was to evaluate the suitable depth of injecting RLAI. Twenty-six patients with schizophrenia were treated with RLAI, and randomly divided into two groups: 50 mm needle inserted group (Group-D, deep insertion, n = 13) and 20 mm needle insertion group (Group-S, shallow insertion, n = 13). For Group-S, the needle length was marked with a spacer at exactly 20 mm. Injections were performed by the psychiatrist or nurse, alternating between the two gluteal sites by double-cross method every two weeks. Clinical psychotic symptoms and injection site reactions were recorded throughout the study period. Experienced psychologists who were blinded from the needle-length experimental variable evaluated patients’ psychotic symptoms using the Positive and Negative Syndrome Scale (PANSS) every two weeks. The plasma 9-hydroxyrisperidone (9-OH-RIS) concentrations were measured every two weeks;comparison data were determined on the 8th week and the 14th week. No significant difference was observed in 9-OH-RIS concentrations, psychotic symptoms, injection site skin reactions of subjects in both groups. However, in Group-D, injection site adverse reactions were confirmed in two subjects (15%). In Group-S, injection site reactions were confirmed in six subjects (46%). Although effective 9-OH-RIS concentrations were obtained with the insertion using both depth, it was concluded that the 50 mm insertion length was more suitable for dorsogluteal IM injections in adult patients with schizophrenia as demonstrated by the incidence of local adverse skin reactions.

A Multicenter, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Long-Acting Injectable Formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) for Cocaine Relapse Prevention

Objective: To determine the efficacy and tolerability of a long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) for treatment of cocaine-dependent patients. Design, Setting, and Participants: A 12-week, A multicenter, randomized, placebo-controlled trial conducted between June 2009-July 2011, at 17 Hospital-based drug clinics, in the 15 countries. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 cocaine use disorder. Of the 2800 patients who were assessed between March 10, 2009 to August 10, 2010, 2600 (93%) were eligible and willing to take part in the trial and were enrolled: 1300 were randomly assigned to receive injections of Long-acting depot formulations of Vanoxerine (Vanoxerine Consta 394.2 mg) given intramuscularly once in 12 weeks and 1300 to receive Placebo injections, given intramuscularly once in 12 weeks. Only 100 of 2800 patients (3.6%) did not meet the inclusion criteria. Main Outcomes and Measures: The primary endpoints (protocol) were: Confirmed Cocaine abstinence (percentage i.e. the number of patients who achieved complete abstinence during 12 weeks). Confirmed abstinence or “cocaine-free” was defined as a negative urine drug test for cocaines and no self-reported cocaine use. Secondary end points included a number of days in treatment, treatment retention and craving. The study also investigated, on 275 participants, degree and time course of Central Dopamine transporter receptor occupancy following single doses of long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) as well as the plasma concentration of Vanoxerine and 17-hydroxyl Vanoxerine. Safety was assessed by adverse event reporting. Results: Of 2600 participants, mean (SD) age was 28.5 (±5.5) years and 598 (23%) were women. 1300 individuals were randomized to receive injections of Long-acting depot formulations of Vanoxerine (Vanoxerine Consta 394.2 mg) and 1300 to receive injections of Placebo. 1417 participants (54.5.0%) completed the trial. Primary Endpoints: Confirmed Cocaine Abstinence: Complete abstinence was sustained by 72% (n = 936) of Vanoxerine patients (patients treated with Vanoxerine Consta 394.2 mg, long-acting depot formulations) compared with 37% (n = 481) of patients treated with Placebo, during weeks 5 - 12. The difference was significant as evaluated using a Chi-square test (χ2 = 672.34, P < 0.0001). Secondary Endpoint: Craving: A statistically and clinically significant reduction in cocaine craving was observed with Vanoxerine (Vanoxerine Consta 394.2 mg, long-acting depot formulations) vs. Placeboby week 4 (P = 0.0048), which persisted every week through 12 (P < 0.0001). Patients given Vanoxerine (Vanoxerine Consta 394.2 mg, long-acting depot formulations) had a 87% decrease in craving from baseline to 12th week. Patients given a Placebo had a 2% increase in craving from baseline to 12th week. Secondary Endpoint: Treatment Retention: Long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) helped significantly more patients complete 12 weeks treatment (n = 936, 72%) compared with Placebo (n = 481, 37%) (χ2 = 635.53, P < 0.0001). Patients on the long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) had longer treatment retention than patients on Placebo. Concentrations of Vanoxerine and 17-Hydroxyl Vanoxerinein Plasma: Analyses were made of 275 study samples. There was no statistically significant difference for plasma Vanoxerine concentrations between days 2 and 84 (p = 0.416). The plasma concentration of Vanoxerine were 70.4 and 94.3 ng/ml and concentrations of 17-hydroxyl Vanoxerine were 10.5 and 13.2 ng/ml, respectively. Plasma levels of Vanoxerine remained above 70 ng/ml for approximately 12 weeks after administration of Vanoxerine, long-acting depot formulations (Vanoxerine Consta 394.2 mg). PET Assessments: Very high central dopamine transporter receptor occupancy by Vanoxerine was detected 1 day after treatments, at which time point the occupancy was 100.0% after Vanoxerine injection (Vanoxerine Consta 394.2 mg). At days 7, 28, 56 and 84 post-Vanoxerine Consta 394.2 mg administration, occupancies were 95% to 79%. Vanoxerine Consta 394.2 mg injection (long-acting intramuscular formulation of Vanoxerine) led to very high occupancy of Central Dopamine transporter receptors in all brain areas examined;nucleus accumbens, caudate nucleus and putamen. Depending on the brain area Central Dopamine transporter receptor occupancy varied between 95.0% and 79% at days 7, 28, 56 and 84 after dosing. High Vanoxerine occupancy (77%) persisted at 12 weeks after the dosings. Adverse Reactions: Adverse events were similar in cocaine-dependent patients treated with the long-acting intramuscular formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) vs. patients treated with Placebo. Conclusions and Relevance: Long-acting depot formulations of Vanoxerine (Vanoxerine Consta 394.2 mg) were more effective than Placebo injection in maintaining short-term abstinence from cocaine and should be considered as a treatment option for cocaine-dependent individuals.

Countermeasures on improving the charge rules and long-acting operation mechanism for the treating residential domestic sewage and household garbage in rural Yunnan

Improving the rural living environment in rural China is one of the key tasks for the country to accomplish its goal of building a moderately prosperous society by 2020. Yunnan has highly focused on the task of the treatment of residential domestic sewage and household garbage in rural area. Many efforts and resources have been put into this field in Yunnan since 2016. Progress has been made to increase the coverage rate of the sewage and household garbage treatment facilities. Seventy-five percent of total administrative villages have built up garbage transportation system and treatment facilities. Sixty-three percent of towns have collected and treated the residential domestic sewage by constructing various scale sewage treatment stations. However, the lack of the long-acting operation mechanism and the imperfection of the charge rules for the sewage and garbage treatment facilities have become problems that would hinder the achieving of the environmental goals in Yunnan. The reasons were elaborated on the basis of the local actual situations. Therefore, it is significant to improve the charge rules and frame the long-acting operation mechanism by strengthening the governance capacity, frame an overall mechanism and encourage the mass to be involved in the improvements of the living environment in rural Yunnan.

Long-Term Clinical Outcome of Patients Using Risperidone Long-Acting Injectable: The Romanian e-STAR Database

The objectives of e-STAR Romania (NCT00283517) were to collect clinical outcome data of Romania schizophrenia or schizo-affective disorder patients;prospectively to assess the reasons of treatment initiation, medication usage patterns;to document (long-term) clinical efficacy;and to collect safety data, as well as recording 2-year corresponding retrospective data. In total, 378 eligible subjects were enrolled who were initiated either on risperidone long-acting injectable (RLAI) (290) or on an oral antipsychotic (OA) (88) at baseline as required by the local Summary of the Product Characteristics. Data were collected from per patient both retrospectively and prospectively over a 24-month period at 3-month intervals after starting treatment. The results indicated that subjects suffering from schizophrenia or schizo-affective disorder initiated on RLAI were less likely to be hospitalized within the first 24 months after the initiation of treatment. Moreover, subjects treated with RLAI experienced significant improvements in their illness severity and functioning. Discontinuation rates for RLAI were low and doses were stable throughout the 24 months following the initiation of treatment. In addition, the necessity for supplementary concomitant medication was reduced. Adverse events were reported in 20.3% (RLAI) and 11.4% (OA) of the subjects. In general, patients initiated on RLAI and OA at baseline both clinically improved on all assessed parameters but a larger improvement was observed for patients on RLAI. Incidences of reported AEs during the use of RLAI in a naturalistic setting are comparable with those described in clinical studies;however, the incidence of extrapyramidal signs and weight gain was lower than expected.

Accelerated infected wound healing by probiotic-based living microneedles with long-acting antibacterial effect

Delays in infected wound healing are usually a result of bacterial infection and local inflammation,which imposes a significant and often underappreciated burden on patients and society.Current therapies for chronic wound infection generally suffer from limited drug permeability and frequent drug administration,owing to the existence of a wound biofilm that acts as a barrier restricting the entry of various antibacterial drugs.Here,we report the design of a biocompatible probiotic-based microneedle(MN)patch that can rapidly deliver beneficial bacteria to wound tissues with improved delivery efficiency.The probiotic is capable of continuously producing antimicrobial substances by metabolizing introduced glycerol,thereby facilitating infected wound healing through long-acting antibacterial and anti-inflammatory effects.Additionally,the beneficial bacteria can remain highly viable(>80%)inside MNs for as long as 60 days at 4℃.In a mouse model of Staphylococcus aureus-infected wounds,a single administration of the MN patch exhibited superior antimicrobial efficiency and wound healing performance in comparison with the control groups,indicating great potential for accelerating infected wound closure.Further development of live probiotic-based MN patches may enable patients to better manage chronically infected wounds.

Fixed-ratio combinations of basal insulin and glucagon-like peptide-1 receptor agonists as a promising strategy for treating diabetes

The maintenance of appropriate glycemic control is important for the prevention of diabetic complications in people with type 2 diabetes(T2D). Numerous oral antidiabetic drugs are now clinically available, but in particular, the introduction of injection regimens using insulin and/or glucagon-like peptide-1 receptor agonist(GLP-1RA)s represents promising step-up options for oral antidiabetic drug treatment. The recently licensed fixed-ratio combination(FRC) products,which comprise basal insulin and a GLP-1RA, have potent anti-hyperglycemic effects and reduce the undesirable side-effects of each component, such as body weight gain, hypoglycemia, and gastrointestinal symptoms. Two FRCs-insulin degludec/Liraglutide and insulin glargine/Lixisenatide-are now clinically available and, to date, several phase Ⅱ/Ⅲ trials have been conducted in particular groups of subjects with T2D. However, their utility in real-world clinical settings is of interest for most clinicians. Recently reported real-world clinical trials of these two FRCs in various situations have demonstrated their efficacy regarding glycemic control and the quality of life of people with T2D. Their long-term safety and efficacy require confirmation, but a treatment strategy that includes an FRC may be compatible with the concept of “well-balanced” therapy in certain groups of patients with T2D who have inadequate glycemic control.

Long-acting growth hormone in 2022

After the isolation of pituitary growth hormone(GH)in 1957,this form of GH,always in limited supply,was the only drug available for the treatment of GH deficiency.In 1985,recombinant GH became available,and the modalities of GH therapies changed dramatically as the supply was unlimited.New indications for GH in pediatrics and adult medicine were developed.Treatment was daily.Now in 2021 long-acting GH(LAGH)became available the world over making GH therapy more patient-friendly and even showing slightly greater efficacy than daily GH therapy.We are now entering a new era of LAGH therapy for pediatric and adult use with new formulations of GH,which will predictably be the preferred form of GH therapy for years to come increasing adherence to GH therapy and possibly even efficacy,that is,better growth rate.The continued availability of new safety data will further solidify the use of LAGH in clinical medicine.

皮下埋植缬沙坦缓释制剂对自发性高血压大鼠血压及血药浓度的影响

目的:探讨皮下埋植缬沙坦缓释制剂对自发性高血压大鼠(spontaneously hypertensive rat,SHR)血压及血药浓度的影响。方法:将缬沙坦原药装入药用硅胶管并密封制作成可皮下埋植的缓释制剂;将SHR随机分为空白对照组、埋植组、灌胃组,每组5只。空白组、埋植组大鼠分别于皮下植入空白硅胶管、缬沙坦缓释制剂(100 mg/s),灌胃组用缬沙坦每天灌胃(16 mg/kg),另以5只Wistar大鼠作为正常对照组行假手术。各组均干预15 d。定期测量大鼠尾动脉血压,并采集静脉血,采用超高相液相色谱串联质谱法检测缬沙坦血药浓度。结果:干预7 d后,埋植组、灌胃组SHR收缩压均明显低于空白组SHR(P<0.05),与正常对照组SHR无统计学差别(P>0.05),埋植组与灌胃组SHR收缩压间差异无统计学意义(P>0.05);这种趋势一直维持至干预结束。用药2 h后,埋植组SHR缬沙坦血药浓度达到稳定水平,灌胃组SHR血药浓度在服药2 h达峰值,为埋植组SHR血药浓度的4.8倍;此后,灌胃组血药浓度逐渐下降,于第24小时低于埋植组;48 h后至干预结束,灌胃组SHR血药浓度与埋植组SHR无统计学差别。结论:与口服途径相比,皮下埋植缬沙坦缓释制剂,仅用药1次,即可达到与每天口服药物一样的目标血压长达2周,并能维持更为稳定的血药浓度。

Influence of Different Gonadotropin-releasing Hormone Agonist Administration Methods on Pregnancy Outcomes of Patients Undergoing In-vitro Fertilization-embryo Transfer

This study aimed to investigate the effect of different gonadotropin-releasing hormone agonist (GnRH-a) administration methods on pregnancy outcomes of patients undergoing in-vitro fertilization-embryo transfer (IVF-ET). Clinical data of 5217 patients who underwent IVF-ET were retrospectively analyzed. Patients were divided into the long-acting GnRH-a group (n=1330) and the short-acting GnRH-a group (w=3887) based on their various treatment plans. The clinical and laboratory embryo data and clinical pregnancy outcomes were compared between the two groups. The results showed that there were no significant differences in the age, infertility, primary/secondary infertility rate, IVF rate, body mass index (BMI), antral follicle counting (AFC), folliclestimulating hormone (FSH) level, and the number of transplanted embryos between the two groups (P>0.05). There were no significant differences in the oocyte numbers, M II rate, fertilization rate, cleavage rate and blastocyst formation rate (P>0.05) between the two groups. The gonadotropin (Gn) using days, Gn dose and endometrial thickness were significantly greater in the long-acting GnRH-a group than those in the short-acting GnRH-a group (P<0.01). Additionally, the estradiol (E2) levels, blastocyst freezing rate, embryo utilization rate, transplant cancellation rate and abortion rate were significantly lower in the long-acting GnRH-a group than those in the shortacting GnRH-a group (P<0.01). The clinical pregnancy rate and embryo implantation rate were significantly higher in the long-acting GnRH-a group than in the short-acting GnRH-a group (P<O.Ol). It was concluded that use of long-acting GnRH-a can effectively reduce the transplant cancellation rate and improve the clinical pregnancy rate of the fresh cycle.