Evidence-based expert consensus on clinical management of safety of Bruton’s tyrosine kinase inhibitors(2024)

Bruton’s tyrosine kinase inhibitors(BTKis)have revolutionized the treatment of B-cell lymphomas.However,safety issues related to the use of BTKis may hinder treatment continuity and further affect clinical efficacy.A comprehensive and systematic expert consensus from a pharmacological perspective is lacking for safety issues associated with BTKi treatment.A multidisciplinary consensus working group was established,comprising 35 members from the fields of hematology,cardiovascular disease,cardio-oncology,clinical pharmacy,and evidencebased medicine.This evidence-based expert consensus was formulated using an evidence-based approach and the Delphi method.The Joanna Briggs Institute Critical Appraisal(JBI)tool and Grading of Recommendations Assessment,Development,and Evaluation(GRADE)approach were used to rate the quality of evidence and grade the strength of recommendations,respectively.This consensus provides practical recommendations for BTKis medication based on nine aspects within three domains,including the management of common adverse drug events such as bleeding,cardiovascular events,and hematological toxicity,as well as the management of drug-drug interactions and guidance for special populations.This multidisciplinary expert consensus could contribute to promoting a multi-dimensional,comprehensive and standardized management of BTKis.

Pregabalin induced balance disorder,asthenia,edema,and constipation in an elderly adult:A case report

BACKGROUND Pregabalin is widely used to treat neuropathic pain associated with postherpetic neuralgia.To our knowledge,this is the first report on simultaneously occurring dose-related adverse drug reactions(ADRs)of balance disorder,asthenia,peripheral edema,and constipation in an elderly patient after pregabalin.CASE SUMMARY A 76-year-old female with a history of postherpetic neuralgia was prescribed pregabalin(300 mg daily).After taking pregabalin for 7 d,the patient developed balance disorder,weakness,peripheral pitting edema(2+),and constipation.On days 8-14,the pregabalin dose was reduced to 150 mg/d based on creatinine clearance.The patient’s peripheral edema improved significantly with the disappearance of all other adverse symptoms.On day 15,the pregabalin dose was increased to 225 mg/d to relieve pain.Unfortunately,the symptoms mentioned earlier gradually reappeared after 1 wk of pregabalin treatment.However,the complaints were not as severe as when taking 300 mg/d pregabalin.The patient consulted her pharmacist by telephone and was advised to reduce the dose of pregabalin to 150 mg/d and add acetaminophen(0.5 g,q6h)to relieve pain.The patient’s ADRs gradually improved over the following week.CONCLUSION Older patients should be prescribed a lower initial dose of pregabalin.The dose should be titrated to the maximum tolerable dose to avoid dose-limiting ADR.Dose reduction and the addition of acetaminophen may help limit ADR and improve pain control.

Treatment and Maintenance of Interstitial Cystitis/Bladder Pain Syndrome in Female Patients with Cetirizine-Famotidine: A Case Series

Purpose: Interstitial cystitis/Bladder pain syndrome is an inflammatory disorder of the bladder, for which histamine has been implicated in the pathogenesis of the disease. The condition is often refractory to standard-of-care medical treatments, including the antihistamines hydroxyzine or cimetidine, and procedures. Herein we report a physician-sponsored proof-of-principle case series of four adult female patients with chronic painful bladder and frequent urination, who were treated once daily with a low dose H1 + H2 histamine receptor antagonist combination. Materials and Methods: Four adult females with Interstitial cystitis/Bladder pain syndrome were treated once daily with a compounded oral dosage form containing the H1 receptor antagonist-cetirizine 8 mg in combination with the H2 receptor antagonist-famotidine 22 mg. The case series consists of a retrospective review of the symptom severity prior to versus following H1 + H2 treatment. Results and Conclusions: The once daily dual histamine receptor antagonist therapy substantially reduced the pain and urination frequency, and prophylactically maintained all four patients long-term with substantially reduced disease severity. The reduction in symptom severity was achieved at amounts that do not exceed the US FDA approved and exceptionally safe daily doses for the two over-the-counter monotherapies. This case series provides proof-of-principle evidence that a dual antihistamine combination of cetirizine plus famotidine effectively treated and maintained female patients, who were previously refractory to standard-of-care medications and/or procedures.

Evaluation of directly observed treatment short courses at a secondary health institution in Ibadan,Oyo State,Southwestern Nigeria

Objective:To evaluate the success rate of tuberculosis intervention programme at a specialist hospital in(?)badan,Nigeria through a retrospective study as well as carry out physicochemical evaluation of anti-tuberculous agents as a way of eliminating drug-related failure.Methods:The retrospective study involved the use of quarterly tuberculosis central register at the Government Chest Hospital,(?)badan between 1st quarter(2003)to 4th quarter(2009).Relevant data were extracted from these register with the aid of data collection forms.The basic physicochemical analyses of the drugs given to the patients were also carried out using the International Pharmacopoeia methods.Results:All the drugs examined for their physicochemical properties passed the International Pharmacopeia recommended tests.A total number of 1 260 patients enrolled at the hospital were assessed through case notes.This comprises of 59.4%males of which69.23%new cases were also males.There was a significant(P<0.05)patient enrollment across the quarters for the seven years.An overall 80.24%cure rate over the 7-period was obtained which is less than the WHO target of 85%.Cure rates were better in females than males.Failure treatment outcomes such as positive(1.51%),deaths(8.73%),defaulted(3.33%)and transferred out(5.95%)were recorded though not statistically significant(P>0.05).Failure rates in all categories were higher in males than females(P>0.05).Conclusions:More enlightenment and counseling is still required to meet up with the target for TB control.

Optimize the combination regimen of Trastuzumab and Nab-paclitaxel in HER2-positive tumors via modulating Caveolin-1 expression by lovastatin

The combination regimen of trastuzumab(Tras)plus Nab-paclitaxel(Nab)is recommended to treat HER2-positive(HER2+)cancers.However,they exert effects in different mechanisms:Tras need to stay on cell membranes,while Nab need to be endocytosed,therefore the concurrent combination regimen may not be the best one in HER2+tumors treatment.Caveolin-1(Cav-1)is a key player in mediating their endocytosis and is associated with their efficacy,but few researches noticed the opposite effect of Cav-1 expression on the combination efficacy.Herein,we systematically studied the Cav-1 expression level on the combination efficacy and proposed an optimized and clinically feasible combination regimen for HER2+Cav-1 High tumor treatment.In the regimen,lovastatin(Lova)was introduced to modulate the Cav-1 expression and the results indicated that Lova could downregulate Cav-1 expression,increase Tras retention on cell membrane and enhance the in vitro cytotoxicity of Tras in HER2+Cav-1 High cells but not in HER2+Cav-1 Low cells.Therefore,by exchanging the dosing sequence of Nab and Tras,and by adding Lova at appropriate time points,the precise three-drug-sequential regimen(PTDS,Nab(D1)-Lova(D2)-Lova&Tras(D2+12 h))was established.Compared with the concurrent regimen,the PTDS regimen exhibited a higher in vitro cytotoxicity and a stronger tumor growth inhibition in HER2+Cav-1 High tumors,which might be a promising combination regimen for these patients in clinics.

Healthcare waste management in selected government and private hospitals in Southeast Nigeria

Objective:To assess healthcare workers' involvement in healthcare waste management in public and private hospitals.Methods:Validated questionnaires(n = 660) were administered to randomly selected healthcare workers from selected private hospitals between April and July 2013.Results:Among the healthcare workers that participated in the study,187(28.33%) were medical doctors,44(6.67%) were pharmacists,77(11.67%) were medical laboratory scientist,35(5.30%) were waste handlers and 317(48.03%) were nurses.Generally,the number of workers that have heard about healthcare waste disposal system was above average 424(69.5%).More health-workers in the government(81.5%) than in private(57.3%) hospitals were aware of healthcare waste disposal system and more in government hospitals attended training on it.The level of waste generated by the two hospitals differed significantly(P=0.0086) with the generation level higher in government than private hospitals.The materials for healthcare waste disposal were significantly more available(P=0.001) in government than private hospitals.There was no significant difference(P = 0.285) in syringes and needles disposal practices in the two hospitals and they were exposed to equal risks(P =0.8510).Fifty-six(18.5%) and 140(45.5%) of the study participants in private and government hospitals respectively were aware of the existence of healthcare waste management committee with 134(44.4%) and 19(6.2%) workers confirming that it did not exist in their institutions.The existence of the committee was very low in the private hospitals.Conclusions:The availability of material for waste segregation at point of generation,compliance of healthcare workers to healthcare waste management guidelines and the existence of infection control committee in both hospitals is generally low and unsatisfactory.

A Protocol for Developing a Clinical Practice Guideline for Therapeutic Drug Monitoring of Vancomycin

This study aimed to develop a guideline for therapeutic drug monitoring（TDM） of vancomycin. We adopted the new guideline definition from the Institute of Medicine（IOM）, adhered closely to the six domains of the Appraisal of Guidelines for Research ＆ Evaluation Ⅱ（AGREE Ⅱ）, and made recommendations based on systematic reviews. We established a Guideline Steering Group and a Guideline Development Group, formulated 12 questions in the form of Population, Intervention, Comparison, Outcome（PICO） and completed a literature search. As far as we know, we will develop the first evidenced-based guideline for vancomycin TDM under the framework of the Grade of Recommendations Assessment, Development and Evaluation（GRADE）.

Health-seeking behaviour and student perception of health care services in a university community in Nigeria

Objectives: Examining consumers’ healthcare behavior can help in the design of ways to ensure better access to health and the quality of care. Health-seeking behavior is viewed as the varied response of individuals to states of ill-health, depending on their knowledge and perceptions of health, socioeconomic constraints, adequacy of available health services and attitude of healthcare providers. This study examines health-seeking behavior of university students, their use of healthcare services in the community and barriers to seeking help at the university health centre. Method: Structured questionnaires were validated and administered on a random sample of university students spread over different academic disciplines in a large institution. The sample consisted of 1608 undergraduate students attending the public university in southwesternNigeria. The demographic profile reflects the national university student population. Relevant information was collected on preferred health services consulted by the undergraduates such as barriers to seeking adequate medical attention and their experiences with salient aspects of service delivery. Responses were weighted and the average was taken to be representative. Results: Students consulted their peers (37.5%) in health related academic disciplines rather than seek treatment at the university health centre. Some students (24.7%) preferred community pharmacies while others took personal responsibilities for their health or abstained from medical care for religious reasons (16.8%). Significant barriers to seeking medical attention at the health centre were cost of care, protracted waiting time, inadequate health information, unfriendly attitude of healthcare workers and drug shortage. Conclusions: Students sought help from community pharmacies (ease of access) and from peers in health related academic programmes rather than from physicians at the health centre. Health-seeking behavior of the students was influenced, essentially, by the nature of ailment, waiting time in the health facility and attitude of healthcare professionals. Implications for policy, practice or delivery: The findings of this research identified the relative use of available health services within the university. Initiatives to improve student access to the university health centre should address significant barriers of patient delays, the need for attitudinal change and continuing professional development of relevant workers in the health facility. Promotional activities may be necessary to inform and educate students on rational use of medicines and access to treatment at the health centre.

International collaboration to promote global health:The 2017 Belt and Road Initiative Global Health International Congress&2017 Chinese Preventive Medicine Association--Chinese Society on Global Health Annual Meeting

With the rapid development of new technologies and global trade and increasing collaboration am ong countries worldwide,public health has become a global issue.Global health,as a new discipline,has been drawing more attention from both academ ia and governments.The Belt and Road Initiative(BRI),proposed by China in 2013,aimed to prom ote trade and resource exchange,including education,research,and health issues,with over 60 countries in Asia,Africa,and Europe.The BRI provides good opportunities for involved countries to address health problems jointly as well.In response to the BRI and to promote international collaboration on global health issues,"The 2017 Belt and Road Initiative Global Health International Congress&2017 Chinese Preventive M edicine Association-Chinese Society on Global Health Annual Meeting"was held on Septem ber 24-27,2017 in Xi’an,China.Thus far,this is the largest high-quality international conference held in China that focused on the BRI global health issues.This article summarized the background,key sessions and topics covered during the congress,and important events,and highlights different perspectives of the BRI and global health by invited experts from China and abroad.The conference included 14 sessions(three keynote speech forums and ten scientific sessions and a research poster session)and about 100 speakers,around 40 of which were leading experts outside of China.All the major sessions were held in English.More than 40 leaders and experts of health sectors from 13 countries presented their work in the congress.Approximately 400 delegates from 29 countries attended the congress.Delegates had extensive discussions about global health related issues,future cooperation and development in global health.The congress fostered international exchange and collaboration.

Correlation of docking energies with spectroscopic kinetic assays of potential xanthine oxidase substrates

Here we present a docking model that ranks compounds according to their potential effectiveness as a potential substrate or inhibitor. We utilize xanthine oxidase (XO), a multi-cofactor oxido-reductase which converts hypoxanthine to xanthine and xanthine to uric acid. During the reductive half reaction, electrons flow from the molybdopterin, to each of two Fe/S centers, and finally to FAD. During the oxidative half reaction, electrons are passed from the FAD to O2. Under ideal physiological conditions, this reduction of oxygen generates H2O2 and, under multiple turnover conditions, superoxide in amounts which is regulated by catalase and superoxide dismutase. Utilizing computer modeling predictions of the docking orientations and energies of a group of purine based structures was selected. Correlating computer estimations with steady state kinetic data, a rapid screening process for inhibittor prediction was highlighted. This method allows educated selection of likely inhibitors, thereby decreasing the time and supplies required to complete a traditional kinetic analysis screening. Results demonstrate the functionality and reliability of this method and have proven particularly useful in understanding binding orienttations or poses of each compound.

Research on Hospital Medical Crisis Management Based on 4R Theory: A Case Study of the Crisis Event in the Second Affiliated Hospital of Harbin Medical University

The hospital medical crisis management is the strategy adopted by hospitals for medical crisis.It aims to minimize the loss brought about by medical crisis to the hospital through management.By using 4R theory of crisis management and taking the incident of"sky-high medical expenses"happened in Second Affiliated Hospital of Harbin Medical University as an example,we study how to improve and perfect the medical crisis management strategy of hospitals in our country.As a result,we think hospitals can improve the crisis management strategy from four aspects of curtailment,preparation,reaction and resilience,so as to solve this issue appropriately,protect the legitimate rights and interests of patients to the greatest extent and promote the sustainable development of the hospital.

A retrospective Evaluation of Antibacterials Used in theManagement of Diabetics in a Tertiary Hospital inSouth-western Nigeria

Objective： Co-medication with antibacterials is often necessary in the management of diabetic patients. There is a constantneed to evaluate the use of these antibacterials to improve therapeutic outcomes and to avoid practices that could possibly increase theemergence of antimicrobial resistance. The aim of this study was to evaluate the utilization of antibacterials in the diabetic clinic of aNigerian tertiary hospital. Methods： A retrospective evaluation and analysis of patients＇ case notes written by physicians in the diabeticclinic over a three-year period （January, 2008-December, 2010） was conducted. The case notes were the individual medical records for150 different hospitalized diabetic patients with infection as co-indication. Data was collected using a WHO instrument for studies ofrational drug use. Results： Descriptive statistics such as mean, frequency, percentages and standard deviation were used to analyzecategorical data obtained from the demographic variables. Fisher exact test and chi square test were employed to determine whetherthere were statistically significant differences or associations between mean values of antibacterial prescription pattern and attendantdosage errors. （P =/〈 0.05 was accepted as significant）. Comparing the mean number of antibacterial drugs in each prescription yearlyyielded a mean of 1.32 in 2008, 1.37 in 2009 and 1.67 in 2010, indicating that there was no statistically significant difference.Antibacterials were used to manage complications often seen in the diabetic patient, including; diabetic foot gangrene, injection abscess,septiceamia, diabetic foot ulcer, vaginal yeast infection, amongst others. Conclusions： The majority of prescriptions met the criteria forcompliance with the hospital＇s drug use protocol. The few instances of non-compliance with the hospital＇s antibiotic drug use protocolmay indicate the need for continuing education, especially for the less experienced prescribers.

Construction of an intelligent patient satisfaction assessment system and its application in emergency management

Hospital emergency management work is of great importance which not only related to the life and health of the people but also related to social stability.It is necessary to construct and improve the patient satisfaction assessment system so that doctors and patients can interact in a timely and effective manner,and the hospital can alert or respond promptly.This study constructs a closed-loop emergency management system consisting of patient-end,data center and decision-making-end,and apply the feedback information to hospital emergency management.In the preliminary applications,the system has a significant effect on the hospital emergency management mechanism.The researchers will improve the system in the follow-up study。

Going-out Behaviors of Patients with Chronic Diseases When Purchasing Drugs During Covid-19

Objective:This study sheds light on the going-out behaviors of patients with chronic diseases when purchasing drugs during COVID-19,explores what factors influence these behaviors,and makes recommendations to guarantee the pharmaceutical treatment of patients with chronic diseases.Methods:A questionnaire based on the health belief model(HBM)was designed and convenience sampling was employed to administer the online questionnaires.The influence of the respondents’demographic information on their going-out behaviors was analyzed by means of multiple linear regression.A structural equation model(SEM)was constructed to explore how health beliefs related to chronic diseases and COVID-19 influenced patients’going-out behaviors.Results:A total of 869 questionnaires were analyzed.The structural equation model revealed that while the severity of the chronic disease had a direct positive effect on going-out behaviors(l=0.106),chronic disease behavior barriers had a direct negative effect on their going-out behaviors(l=-0.204).Conclusion:Educational background,co-living situation,and income could influence patients’going-out behaviors.The severity of the chronic disease and chronic disease behavior barriers directly affected patients’going-out behaviors.Furthermore,patients’health beliefs about COVID-19 ultimately affected their going-out behaviors by influencing their health beliefs related to chronic disease.

中国非儿童癌症患者脓毒血症流行情况及地域分布:一项全国横断面研究

Cancer poses a major public health burden worldwide,with approximately 18,094,716 newly diagnosed cases and 9,894,402 cancer-related deaths in 2020[1].Infections such as sepsis are among the leading causes of death in this population after cancer itself[2].

Liuwei Dihuang Pills(六味地黄丸) Enhance the Effect of Western Medicine in Treating Type 2 Diabetes:A Meta-Analysis of Randomized Controlled Trials

Objective： To perform meta-analyses evaluating the efficacy of adding Liuwei Dihuang Pills （六味地黄丸 LDP） to Western medicine in improving treatment outcomes for type 2 diabetes. Methods： Medline, PubMed, Cochrane Library, and Chinese databases, including the Chinese National Knowledge Infrastructure were searched to identify eligible studies; i.e., if the study involved a randomized clinical trial in which the experimental group combined LDP with Western drugs and the control group used the corresponding Western drugs alone to treat type 2 diabetes. Outcomes were measured in terms of fasting blood glucose （FBG）, postprandial blood glucose （2hPG） and HbAlc level. Efficacy was also measured by using control and response rates. The combined odds ratio （OR）, mean difference （MD）, and 95% confidence intervals （95% CI） were calculated. Results： Studies included in the analysis were less adequate than expected in terms of methodological qualify. A total of 1,609 patients from 18 studies were included. We found that adding LDP can lower patients＇ FBG （MD=0.54 mmol/L, 95% CI [0.15, 0.93], P=0.007）, 2hPG （MD=1.05 mmol/L, 95% CI [0.29, 1.81], P〈0.01） and HbAlc （MD=0.23, 95% CI [0.02, 0.45], P=0.008）. There were also improvements in treatment response rates （OR=3.41, 95% CI [2.38, 4.90], P〈0.01） and control rates （OR=2.47, 95% CI [1.91, 3.20], P〈0.01）. Conclusion： Adding LDP to Western medicine might improve treatment outcomes of diabetes, including FBG, 2hPG, response rates and control rates.

Prevalence and influence factors of self-medication in Chinese middle-aged and elderly people: evidence from 2011, 2013 and 2015 CHARLS panel data

Self-medication is an increasingly frequent phenomenon worldwide and has an important influence on health.In this study,we analyzed the self-medication prevalence rate in Chinese middle-aged and elderly people,and explored the influence factors.The data from China Health and Retirement Longitudinal Study(CHARLS)in 2011,2013 and 2015 were used.Self-medication prevalence was calculated as the number of whole people divided by the number of people taking self-medication.The influence factors of self-medication were analyzed by panel data random effect model.We excluded observations with missing values in our analysis,leaving 16 962,17 876 and 19 572 observations in 2011,2013 and 2015,respectively.The average 3-year self-medication prevalence was 45.52%.Moreover,11.70%of respondents practiced self-medication with prescription medicine in 2011,2013 and 2015.Respondents living in non-rural areas(P=0.009)and western region(P=0.000)took more self-medication.Self-medication was a common phenomenon among middle-aged and elderly population in China.The government should strengthen the guidance for the middle-aged and elderly people who took more self-medication,such as those living in urban and western region.

Research and development of Chinese anti-COVID-19 drugs

The outbreak and spread of coronavirus disease 2019(COVID-19)highlighted the importance and urgency of the research and development of therapeutic drugs.Very early into the COVID-19 pandemic,China has begun developing drugs,with some notable progress.Herein,we summarizes the anti-COVID-19 drugs and promising drug candidates originally developed and researched in China.Furthermore,we discussed the developmental prospects,mechanisms of action,and advantages and disadvantages of the anti-COVID-19 drugs in development,with the aim to contribute to the rational use of drugs in COVID-19 treatment and more effective development of new drugs against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and the variants.Neutralizing antibody is an effective approach to overcome COVID-19.However,drug resistance induced by rapid virus mutation will likely to challenge neutralizing antibodies.Taking into account current epidemic trends,small molecule drugs have a crucial role in fighting COVID-19 due to their significant advantage of convenient administration and affordable and broad-spectrum.Traditional Chinese medicines,including natural products and traditional Chinese medicine prescriptions,contribute to the treatment of COVID-19 due to their unique mechanism of action.Currently,the research and development of Chinese anti-COVID-19 drugs have led to some promising achievements,thus prompting us to expect even more rapidly available solutions.

The role of caveolin-1 in the biofate and efficacy of anti-tumor drugs and their nano-drug delivery systems

As one of the most important components of caveolae,caveolin-1 is involved in caveolaemediated endocytosis and transcytosis pathways,and also plays a role in regulating the cell membrane cholesterol homeostasis and mediating signal transduction.In recent years,the relationship between the expression level of caveolin-1 in the tumor microenvironment and the prognostic effect of tumor treatment and drug treatment resistance has also been widely explored.In addition,the interplay between caveolin-1 and nano-drugs is bidirectional.Caveolin-1 could determine the intracellular biofate of specifc nano-drugs,preventing from lysosomal degradation,and facilitate them penetrate into deeper site of tumors by transcytosis;while some nanocarriers could also affect caveolin-1 levels in tumor cells,thereby changing certain biophysical function of cells.This article reviews the role of caveolin-1 in tumor prognosis,chemotherapeutic drug resistance,antibody drug sensitivity,and nano-drug delivery,providing a reference for the further application of caveolin-1 in nano-drug delivery systems.

Trends of consumption and expenditure of antibacterial traditional Chinese medicine in secondary and tertiary hospitals in China:an analysis of pharmaceutical sales data,2011–2015

Traditional Chinese medicines(TCMs)are commonly used in China,and some of them have been proved to be effective against infection caused by certain pathogenic bacteria.In the present study,we aimed to describe the trends of antibacterial-effect traditional Chinese medicine(AeTCM)consumption and expenditure in secondary and tertiary hospitals in China using pharmaceutical sales data from January 2011 to December 2015.Aggregated monthly surveillance data on AeTCM sales in China’s hospitals were retrospectively analyzed.Population weighted daily define doses,which are the recommended daily amounts based on dosage regimen recommended in the manufacturers’instructions,were adopted.The AeTCM consumption was expressed in DDD per 1000 inhabitants per day(DID).The AeTCM expenditure was expressed in US dollars.A compound annual growth rate(CAGR)was used to describe the growth of AeTCM consumption and expenditure.A total of 1293 AeTCMs were matched and analyzed from 468 tertiary hospitals and 114 secondary hospitals from 28 provinces.The total AeTCM consumption and expenditure demonstrated a significant upward trend during the study period from 4.07 DID to 6.82 DID with a CAGR of 13.75%,and 839.75 million US dollars to 1276.82 million US dollars with a CAGR of 11.04%,respectively.Compared with eastern provinces,the consumption of AeTCMs was higher in the central and western provinces.Parenteral AeTCMs accounted for 7.20%of the total Ae TCM consumption,but nearly 45%of the total AeTCM expenditure.The AeTCM use in China demonstrated a rapid growth,which could be the result of the substitutional effect from antimicrobial stewardship and brought a potential risk of overuse.More studies are needed to further explore the potential efficacy of AeTCMs as an alternative approach towards infection treatment and to help confine antimicrobial resistance.