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.

Effects of Direct Switching Dual Bronchodilators between Dry Powder and Soft Mist Inhalers in COPD Patients

Objective: Dual bronchodilation with long-acting muscarinic antagonist and long-acting β2-agonist combinations are available worldwide in COPD patients. However, the choice of agents remains under debate. We hypothesized that switching devices between dry powder and soft mist inhalers without a wash-out period to mimic clinical practice would improve clinical symptoms and lung function. The aim of this study was to examine the effects of switching between once-daily glycopyrronium/indacaterol (GLY/IND) or umeclidinium/vilanterol (UMEC/VI), dry powder inhalers, and tiotropium/olodaterol (TIO/OLO), a soft mist inhaler, in COPD patients. Methods: This was a prospective, open-label, 8-week, observational study with follow-up. Subjects included 57 COPD patients, who attended outpatient clinics at Shizuoka General Hospital for routine check-ups between February and December 2015, receiving GLY/IND (50/110 μg) or UMEC/VI (62.5/25 μg). After an 8-week run-in period, medications were switched to TIO/OLO (5/5 μg). Study outcomes included patient’s global rating (PGR), modified MRC (mMRC), COPD assessment test (CAT), and spirometric and forced oscillatory parameters after 8 weeks. PGR used in this study was a 7-point scale ranging from 1 to 7, with 4 in the middle. Patients who consented to switch from TIO/OLO to GLY/IND or UMEC/VI were followed-up thereafter. Results: In total, 53 patients completed the study (mean age, 75 years;48 males and 5 females;GOLD 1/2/3/4 = 19/27/6/1;mMRC 0/1/2/3/4 = 14/22/12/4/1;UMEC/VI 26, GLY/IND 27). PGR, mMRC, and CAT improved in 20 (38%), 9 (17%), and 15 patients (28%), respectively. Respiratory system resistance at 5 Hz (R5), 20 Hz (R20), and the difference between R5 and R20 (R5 - R20) significantly improved. In a follow-up of 16 patients after switching from TIO/OLO to UMEC/VI (9) or GLY/IND (7), PGR, mMRC, and CAT improved in 5 (31%), 3 (12%), and 4 patients (25%), respectively, and R20 significantly improved (p = 0.011). Conclusions: Switching dual bronchodilators between dry powder and soft mist inhalers improves symptoms and airway narrowing in some COPD patients.

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.

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.

Benefit of prophylactic bronchodilator withβ2 adrenergic agonist in ischemia-reperfusion-induced lung injury

Primary lung graft dysfunction could significantly attribute to ischemia-reperfusion lung injury(IRLI)during transplantation surgery.β2-adrenergic agonists were one of the bronchodilators that had been well-established in the management of asthma and chronic obstructive pulmonary disease(COPD)with anti-inflammatory potency.By applying the model of isolated rat lung,we evaluated the efficacy of short-actingβ2-agonist inhalation to ameliorate ischemia-reperfusion damage.The experiment protocol was 180 min of global ischemia and then reperfusion for 60 min.In theβ2-agonist inhalation group,aerosolized albuterol was administrated prior ischemia procedure.Increased weight ratios of wet to dry lung and microvascular permeability were characterized in the IRLI group.In contrast,pre-inhaledβ2-agonist significantly mitigated the severity of pulmonary edema.Bronchoalveolar lavage from theβ2-agonist group presented decreased leukocyte counts and cytokines production,including interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and macrophage inflammatory protein 2(MIP-2).Devastating oxidative stress was widely recognized during the ischemia-reperfusion process,whileβ2-agonist pretreatment revealed subsided H2O2,myeloperoxidase(MPO),and the cleavage of caspase-3.Western blotting from lung homogenates identified the blockade of NF-κB and MAPK activation in theβ2-agonist inhalation group.Currently,there was no specific pharmacotherapy in IRLI management.Our results elucidated the protective effect ofβ2-agonist bronchodilator against ischemia-reperfusion induced oxidative stress,inflammation reaction,and pulmonary edema.

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.

The Clinical Role of Changes of Maximum Expiratory Flow at 25%and 50%of Vital Capacity before and after Bronchodilator Reversibility Test in Diagnosing Asthma

Summary:Changes of maximum expiratory flow at 25%and 50%of vital capacity(MEF2s and MEFso,respectively),and predominant parameters indicating small airways function in asthmatics before and after bronchodilator(BD)reversibility test have been less interpreted.Our study aimed to investigate the clinical role of changes of MEF2s and MEFso before and after BD reversibility test in diagnosing asthma.Forced expiratory volume in the first second(FEV),MEF2s,and MEFso were measured before and after BD reversibility test in 207 asthmatic patients using standard process.Forty healthy individuals were enrolled as controls.Receiver operating characteristic(ROC)curve was used to assess the diagnostic accuracy of reversibility of MEF2s and MEFgo before and after BD reversibility test(OMEF 2s%and AMEF so%,respectively)in diagnosing asthma.Among these functional criteria,AMEF2;%and 0MEFs%≥25%performed the best diagnostic performance.The sensitivity,specificity,and accuracy of AMEF 25%≥25%as an objcctive diagnostic test for asthma were 63.29%,87.50%,and 67.21%,and of AMEFs0%≥25%were 79.23%,85.00%,and 80.16%,respectively.The area under the ROC curve of the indicators was 0.8203 and 0.9104,respectively.By contrast,an increase in FEV≥12%and 200 mL demonstrated a sensitivity of 62.32%,specificity of 82.50%,and accuracy of 65.59%in diagnosing asthma.The changes of MEF2s and MEFso before and after BD reversibility test may be of additional value in the clinical diagnosis of asthma,with cutoff values of 25%being the most.

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.

双长效支气管扩张剂治疗支气管扩张症合并慢性阻塞性肺疾病的临床效果及肺功能改善效果研究

目的分析双长效支气管扩张剂治疗支气管扩张症合并慢性阻塞性肺疾病(COPD)的临床效果及肺功能改善效果。方法通过盲法、便利抽样、对照原则回顾性研究河北省胸科医院呼吸三科2019年9月至2021年9月接诊的100例支气管扩张症合并COPD患者,根据治疗方法的不同分为观察组和对照组,每组50例。对照组给予噻托溴铵吸入粉雾剂治疗,观察组给予噻托溴铵奥达特罗吸入喷雾剂治疗,治疗6个月。比较2组临床疗效、肺功能、圣乔治呼吸问卷(SGRQ)评分、改良呼吸困难指数(mMRC)评分、动脉血气指标、不良反应总发生率和1年再入院率。结果观察组总有效率高于对照组[96.0%(48/50)比78.0%(39/50)](P=0.007)。观察组治疗2、4、6个月后用力肺活量(FVC)、第1秒用力呼气容积(FEV_(1))、FEV_(1)/FVC均高于对照组,SGRQ评分、mMRC评分均低于对照组,动脉血二氧化碳分压低于对照组,动脉血氧分压高于对照组(均P<0.05)。2组不良反应总发生率比较差异无统计学意义(P=1.000)。观察组1年再入院率低于对照组[2.0%(1/50)比16.0%(8/50)](P=0.036)。结论双长效支气管扩张剂噻托溴铵奥达特罗吸入喷雾剂在改善支气管扩张症合并COPD患者肺功能以及动脉血氧状态方面效果显著,可有效缓解患者呼吸困难等症状,降低再入院率,且安全性较好。

2型炎症对慢阻肺大、小气道支气管舒张反应性的不同影响

目的探讨2型炎症指标血嗜酸性粒细胞(EOS)和呼出气一氧化氮(FeNO)对慢性阻塞性肺疾病(慢阻肺)患者支气管舒张反应性(BDR)的影响。方法纳入我院2019年10月~2023年10月临床确诊的389例慢阻肺患者,根据大气道的支气管舒张试验(BDT)分为BDT阳性组(n=197)和BDT阴性组(n=192)、以及小气道舒张试验阳性与否分为最大呼气中期流量(MMEF)阳性组(n=118)和MMEF阴性组(n=271)。再根据吸烟史、血EOS和FeNO水平将慢阻肺患者分为4组:A组:血EOS<300个/μL+FeNO<35ppb+吸烟史<20包年;B组:血EOS<300个/μL+FeNO<35ppb+吸烟史≥20包年;C组:血EOS≥300个/μL或FeNO≥35ppb+吸烟史≥20包年;D组:血EOS≥300个/μL或FeNO≥35ppb+吸烟史<20包年,分析临床相关指标与BDR的关系。结果以第1秒用力呼气容积(FEV1)、用力肺活量(FVC)和MMEF评估的BDR所得的结果一致,均表现为舒张阳性组的平均年龄更小、FeNO水平以及血EOS计数和百分比都更高(P<0.05)。A组患者的FEV1改善值(P=0.005)和FEV1改善率(P=0.024)均显著低于D组。B组患者的FEV1改善值(P=0.001)、FEV1改善率(P=0.035)和MMEF改善率(P=0.025)也显著低于D组。在所有患者中,年龄和FeNO水平与FEV1改善值、FEV1改善率、MMEF改善率有显著关联(P<0.05)。结论2型炎症指标对慢阻肺大、小气道BDR具有不同的影响,其临床意义值得进一步探讨。

利用支气管舒张试验结果辅助评估哮喘患者吸入性糖皮质激素治疗的有效性和规范性

1例贲门腺癌初诊拟手术患者,术前肺功能提示重度混合性通气功能障碍,且有长期慢性咳嗽病史,予吸入ICS/LABA/LAMA联合口服复方甲氧那明改善肺功能。治疗半月后,肺功能有所改善,但支气管舒张试验阳性,提示患者诊断为哮喘(未控制)。临床药师对其使用控制药物后哮喘依然控制不佳常见原因进行分析,最后发现患者吸入装置使用中吸气步骤错误,测吸气峰流速小于最低吸气流速要求30 L/min。通过药师指导,患者掌握吸入技术,测吸气峰流速为58 L/min,达理想范围。该病例提示通过支气管舒张试验也能发现哮喘治疗是否规范,可作为ICS有效性和规范性的潜在预测因子。

一种治疗慢性阻塞性气道疾病的新药:那伐芬特罗

那伐芬特罗(navafenterol)是一单分子且同时具备毒蕈碱受体拮抗和β_(2)受体激动效应的新型化合物,正开发用于治疗慢性阻塞性肺疾病和哮喘等慢性阻塞气道疾病。该药可显著改善肺功能,且安全性和耐受性良好,常见治疗后不良事件包括头痛、鼻咽炎、头晕等,有可能成为慢性阻塞性气道疾病下一代支气管扩张剂。本文就那伐芬特罗的基础和临床研究现状等进行介绍。

脉冲振荡肺功能检测在儿童支气管舒张试验中诊断阈值探讨

目的探讨脉冲振荡(impulse oscillometry,IOS)肺功能检测在儿童支气管舒张试验中的诊断价值,确定脉冲振荡肺功能各指标舒张试验的阳性标准。方法本研究选取2021年1月—2022年8月在四川大学华西第二医院就诊的86例儿童为研究对象,年龄在4~14岁。其中,哮喘门诊就诊患儿为哮喘组(51例),健康体检儿童为对照组(35例)。两组患者均在吸入沙丁胺醇前后进行常规肺通气功能测定和IOS肺功能检测,以第一秒用力呼气容积(forced expiratory volume in one second,FEV1)≥12%作为标准,比较两组受试者在支气管舒张试验前后IOS各参数的差异,确定IOS舒张试验的阳性标准。结果舒张试验前,哮喘组肺通气功能测定指标FEV1/FVC、FEV1为(82.64±7.53)和(78.64±16.49),对照组为(99.27±6.16)和(98.19±9.02),吸入沙丁胺醇后哮喘组FEV1改善率≥12%,而对照组<12%。支气管舒张试验后,哮喘组和对照组IOS肺功能各参数均有不同程度改善。ROC结果显示,IOS各指标中,振荡频率为5Hz时的呼吸总阻抗(Z5)、周边弹性阻力(X5)、气道黏性阻力(R5)等指标对于支气管舒张试验阳性有较好的诊断价值。以Z5下降≥13.91%、X5下降≥14.78%、R5下降≥14.96%为脉冲振荡肺功能支气管舒张试验阳性的分界点,敏感性和特异性较高。结论支气管舒张试验后,Z5下降≥13.91%、X5下降≥14.78%、R5下降≥14.96%可以判断支气管舒张试验阳性。