Clinical Pharmacology Studies in Critically Ill Children

Developmental and physiological changes in children contribute to variation in drug disposition with age. Additionally, critically ill children suffer from various life-threatening conditions that can lead to pathophysiological alterations that further affect pharmacokinetics (PK). Some factors that can alter PK in this patient population include variability in tissue distribution caused by protein binding changes and fluid shifts, altered drug elimination due to organ dysfunction, and use of medical interventions that can affect drug disposition (e.g., extracorporeal membrane oxygenation and continuous renal replacement therapy). Performing clinical studies in critically ill children is challenging because there is large inter-subject variability in the severity and time course of organ dysfunction; some critical illnesses are rare, which can affect subject enrollment; and critically ill children usually have multiple organ failure, necessitating careful selection of a study design. As a result, drug dosing in critically ill children is often based on extrapolations from adults or non-critically ill children. Dedicated clinical studies in critically ill children are urgently needed to identify optimal dosing of drugs in this vulnerable population. This review will summarize the effect of critical illness on pediatric PK, the challenges associated with performing studies in this vulnerable subpopulation, and the clinical PK studies performed to date for commonly used drugs.     

福建省福州地区哮喘儿童知信行问卷调查结果分析

目的了解患儿家长对哮喘知识的掌握情况及哮喘患儿日常生活管理和用药情况。方法 2010年7~12月,采用首都儿科研究所提供的哮喘患儿家长知信行问卷,对就诊于福建省福州儿童医院哮喘专科门诊确诊支气管哮喘的患儿的家长进行调查。结果共调查100份问卷,有效问卷86份。问卷中,84.88%家长在孩子的哮喘不发作时,会带孩子复诊;55.81%家长平均1~3个月带孩子去医院复诊一次。63.95%家长认为哮喘的本质是气道慢性炎症性疾病;89.53%家长认为哮喘是能够控制的,但需要规律用药;33.72%家长认为遵从医嘱规律地使用吸入型激素,对孩子的生长发育无影响。27.91%家长认为在孩子哮喘急性发作时,自我紧急处理的首选措施是吸入速效β2受体激动剂;80.23%家长在孩子哮喘没有症状时,会让他/她坚持用药;65.12%家长不愿意给孩子长期用哮喘控制药物的原因是,认为会对孩子的生长发育产生严重的影响。结论福建省福州地区多数哮喘患儿家长对哮喘疾病有较好的认识,但仍需进一步完善哮喘健康知识,提高治疗依从性,改善患儿生活质量。     

Public awareness and views on unlicensed use of medicines in children

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• There is increasing concern about the use of those medicines in children which have not been fully studied and licensed for childhood use. Such use is not uncommon, due in large part to a lack of availability of fully licensed products and formulations that are suitable for children.
• There is little published information on the views of the public on this important area of paediatric care.

WHAT THIS STUDY ADDS

• A survey of 1000 members of the public in Northern Ireland indicated that such use of medicines in children is not well known.
• However, when informed about this practice, the majority believed that it would compromise safety and increase the likelihood of adverse effects. They also believed that parents/guardians should be told if their child was prescribed a medicine that had not been fully tested in children.
• Participants in the survey indicated that they would be reluctant to involve their child in a clinical trial to help with the licensing process unless the child was suffering from a life-threatening illness.

AIMS

To explore awareness and views of the general public on unlicensed use of medicines in children and on the participation of children in clinical trials.

METHODS

Members of the public completed a questionnaire survey administered by face-to-face interview in public areas in N. Ireland. The main outcome measures were the views on unlicensed use of medicines in children and on clinical trials in children.

RESULTS

One thousand participants (59.2% female) took part; 610 were parents. Most participants (86%) had no previous knowledge about unlicensed use of medicines in children. Being a parent did not influence this nor did being a parent of a child who suffered from a health problem (P > 0.05). Most participants (92%) felt that parents should be told about unlicensed use of medicines, with the doctor most frequently selected as the person who should inform parents. At the outset, only 1.8% of participants felt that the use of medicines in children was unsafe. However, having been informed about unlicensed use of medicines, this proportion increased dramatically (62.4%; P < 0.001). Views on whether participants would enter a child of their own into a clinical trial varied according to the health status of the child (P < 0.05) i.e. a child in good health (3.9%) vs a child with a life-threatening condition (41.9%).

CONCLUSIONS

There is limited public knowledge of unlicensed use of medicines in children and a general reluctance to involve children in clinical trials unless the child to be involved has a life-threatening condition.     

An exploration of parents’ knowledge,attitudes and practices towards the use of antibiotics in childhood upper respiratory tract infections in a tertiary Jordanian Hospital

Objectives

The present study aimed to evaluate the parents' knowledge, attitudes and practices (KAP) towards the use of antibiotics for childhood upper respiratory tract infections (URTIs), at the Jordanian University Hospital.

1596例吸毒者家长的心理调查和分析

目的··:了解吸毒者父母在其子女吸毒前对毒品危害的认识和子女吸毒后的心理状态以及在禁毒戒毒中所起的作用。方法··:采用自行设计的《吸毒者家长心理调查表》 ,对1596例吸毒者家长进行调查。结果··:有99.62%的家长在子女吸毒前对毒品危害认识不足 ,98.81 %的家长从子女开始吸毒到出事前未能觉察 ,98.80%以上的家长一旦知道子女吸毒后对外严守秘密 ,不能断然采取措施。因此在1596例强制戒毒者中由公安部门经侦查抓获送来强制戒毒的占99 %以上。有些家长虽将其子女多次送自愿戒毒部门戒毒 ,但总是戒而复吸 ,家长痛心疾首 ,又无可奈何 ,就是不敢公开求助公安部门给予必要的强制戒毒和求助于社会监督 ,不敢与毒品违法犯罪作坚决斗争。结论··:由于家长存在众多错综复杂的心理 ,导致多数家长在禁毒戒毒中起了不利的作用。     

Paying the Price for their Parents' Addiction: meeting the needs of the children of drug-using parents

This paper reports on the impact of parental drug use on children and considers the possible responses that may be needed to reduce the risks being faced by the children of drug-using parents. The paper is based on interviews with 30 recovering heroin addict parents who provided detailed information on the impact of their drug use on their children. According to these parents, their children experienced material neglect associated with their parents' drug use, they were exposed to drug use and drug dealing and they were at risk of violence and physical abuse, criminal behaviour and family break-up. The paper concludes by identifying a number of policy changes and changes in service delivery that will be required to meet the needs of children in drug-using households and outlines the case for the creation of safe havens for the children of drug-using parents.     

Drug utilization in paediatrics: Non-medical factors affecting decision making by prescribers

Summary The study was done to show that in certain areas of paediatric pharmacotherapy unexpected discrepancies may arise between accepted therapeutic principles and the actual behaviour of a prescribing doctor. The first example was of a great reduction in penicillin use in a university teaching hospital after certain therapeutic accidents: in one year, there were 2 fatal cases of rhabdomyolysis due to use of procaine benzyl-penicillin. Other antimicrobial drugs inferior to penicillin, such as lincomycin and sulphonamides, replaced penicillins. The second example showed the inverse relationship between the use of antitussives and other drugs in symptomatic treatment of respiratory diseases in outpatients and inpatients; the pressure of unduly optimistic expectations of therapy imposes a high prescribing rate of these drugs in the outpatient population, in contrast to hospitalized patients, whose doctors, being spared such pressure, prescribe antitussives far less often. The third example demonstrates the possibility of inadequate education in the use of antimicrobial drugs. Although doctors from regional hospitals receive their training at an university hospital, they tend to prescribe chloramphenicol ten times more per bed-day than their colleagues in an university hospital. In terms of the cost/effectiveness ratio, a high prescribing rate of cephalosporins is not economically favourable in a university teaching hospital. It is also shown that studies of drug utilization in children are feasible if age — appropriate adaptation of the statistical value expressed as the defined daily dose is performed. The adaptation was evaluated by comparing pharmacy-based drug consumption data expressed in paediatric defined daily doses, with actual days of treatment with particular drugs, i.e. data from patient records for 244 beds in the University Teaching Hospital.     

Path of socialization and cognitive factors' effects on adolescents' alcohol use in Taiwan

Objectives

The purpose of this study was to explore the direct and indirect effects of alcohol-related socialization factors and cognitive factors on adolescent alcohol use in a country with a low prevalence of drinking.

Methods

Data were obtained from the 2006 phase of the Child and Adolescent Behaviors in Long-term Evolution (CABLE) project, at which time the study participants were in grade nine (aged 14–15 years). Data from 1940 participants were analyzed. The main study variables included the current alcohol use of each adolescent, alcohol expectations, alcohol refusal efficacy, alcohol use among parents and peers, attitudes of the parents toward underage drinking, and peer encouragement of drinking. Path analysis was conducted to examine whether parental and peer socialization factors had direct effects on adolescent alcohol use, or whether they acted indirectly via cognitive factors.

Results

Among the participants, 19.54% had used alcohol in the previous month. Path analysis demonstrated that father, mother and peer alcohol use directly influenced alcohol use in adolescents. Attitudes of mothers toward underage drinking, peer drinking and peer encouragement of drinking had indirect effects on adolescent alcohol use that were mediated by cognitive factors.

Conclusions

This study demonstrated that alcohol-related socialization factors could directly influence adolescent drinking behavior and had indirect effects on alcohol use that were mediated by cognitive factors partially. Parents and peers play important roles in preventing adolescent alcohol use. Establishing appropriate alcohol expectations and strengthening alcohol refusal skills could aid in decreasing alcohol use in adolescents.     

Economic constraint and modes of consumption of addictive goods

Background

To see how economic recession, or, more generally, how increased economic constraint amongst drug users may impact their behaviour regarding the mode of drug consumption.

Methods

The theoretical framework is the theory of rational addiction – drug users are considered to be rational and well-informed about the way they use drugs and the consequences of using them. Surveys in the specialist literature dealing with the potential changes in the economic context of drugs users, and with the mechanisms of the bioavailability of psychoactive substances are examined in order to highlight one of the strategies drug users can implement to circumvent economic problems – namely a change in the mode of administration. An examination of ethnographic studies and French data are also used to test our assumptions.

Results

Changes in the mode of drug consumption can be the result of a maximization behaviour. Injection is the most effective way to reach a maximum bioavailability of substances. There is evidence in favour of the hypothesis that in times of economic recession, when the economic resources of drug users can decrease, they may prefer injection to other modes of administration in order to maximize the effect of what they have purchased.

Conclusion

In times of economic recession, harm reduction policy has to be reinforced as injection behaviour can increase. As a result, economic and social policies should be an integral consideration for health policy issues.     

Relationship between adolescents’ and their parents’ attitudes toward medicines and awareness of the risk of medicines

Background When they reach adolescence, children begin to independently use medicine without their parents’ supervision, but parents usually still want to be involved in their drug therapy. Objective The aim of this study was to investigate how parental attitudes and awareness toward medicine relate to adolescents’ attitudes and awareness. Setting Twelve secondary schools in different regions of the Slovak Republic. Method Adolescents and parents responded to a questionnaire, and the answers were paired and analysed. Parental and adolescents’ attitudes toward medicines and awareness of the risk of medicines were measured using a five-point Likert scale. Main outcome measure The strength of the relationship between parents’ and their adolescent children’s level of agreement with statements about medicines. Results There were significant differences between parents? and adolescents’ mean Likert scores for statements about their attitudes toward medicines and their awareness of the risk of medicines (p?<?0.05). Parents and adolescents were not fully aware of the risks of cough medicine (73.5% and 76.1%), antihistamines (32.7% and 52.1%), painkillers (33.6% and 47%) and combining medicines (25.2% and 40.4%). More than half of the parents and adolescents had a positive perception of the effectiveness of medication and believed that taking medicine would not hurt adolescents. Parents’ and adolescents’ responses to the statements were directly proportional (r?=?0.94, p?<?0.001). Conclusion The analysis revealed a relationship between Slovakian adolescents’ and their parents’ attitudes and awareness toward medicine; it highlighted areas of adolescents’ and parents’ education about the proper use of medications.     

Alcohol-specific socialization, parenting behaviors and alcohol use by children.

OBJECTIVE: This panel study examined the relations between alcohol-specific socialization by parents (monitoring of alcohol use by children, allowing alcohol use by children at home, communicating against alcohol use and setting rules against alcohol use), general dimensions of parenting behavior (responsiveness and demandingness) and alcohol use by children. METHOD: A sample of 488 fifth-grade children reported their perceptions of alcohol-specific socialization by parents, parental responsiveness and parental demandingness. These variables were used to predict alcohol use when children in the panel were in seventh grade. RESULTS: Nineteen percent of seventh-grade children reported alcohol use in the past 30 days. Logistic regression analyses indicated that, after accounting for children's age, sex, single parent status, prior use of alcohol and exposure to parental modeling of alcohol use, the odds of alcohol use were significantly greater among children who perceived no parental monitoring of alcohol use, who had been allowed by parents to have a drink with alcohol at home and who perceived relatively low levels of parental demandingness. Rules against alcohol use, parental communication against alcohol use and parental responsiveness were unrelated to the study outcome. CONCLUSIONS: Parental monitoring of alcohol use by children, family norms regarding alcohol use by children at home and parental ability to set and enforce behavioral rules merit consideration as factors that should be modified by prevention programs. There is a need, however, for additional research that further examines the relations between exposure to such parenting behaviors during childhood and alcohol use during adolescence.     

Parental social support as a moderator of self-medication in adolescents

Objective

We examined the moderating effects of parenting on the temporal relationship between negative affect and subsequent alcohol use in adolescents as an indicator of self-medication. Specifically, we tested whether youth are more likely to self-medicate if they receive less parental social support.

Method

We used a multi-method, multi-reporter strategy and an experience sampling paradigm to examine these mechanisms in an elevated-risk sample preparing for the transition to high school. Seventy-one adolescents and their parents completed home-based interviews and adolescents completed a 21-day experience sampling protocol in which they reported their alcohol use daily and their affect thrice daily.

Results

Parent-reported family communication, though no other parental support indicators, moderated the relation between daily negative affect and alcohol use. Plotting of interactions showed a greater likelihood of drinking on days characterized by greater negative affect only in adolescents with higher levels of parent-reported family communication.

Conclusions

This study offers tentative support for parental support as a moderator of the relation between daily negative affect and alcohol use. Parental support may be a response to alcohol use and self-medication in teens such that parents become more involved and open in talking with their teens when they notice these patterns of behavior.     

The reasons why children in their pre and early teenage years do or do not use illegal drugs

This paper examines the drug-related decisions of a previously under researched group of children; those in their pre-teen and early teenage years. Based on a prospective study of 92 ‘at risk’ children, it explores the reasons which they gave for their use or non-use of illegal drugs. The accounts of those who used drugs on a regular or occasional basis are strongly supportive of the importance of personal choice, emphasising the role of enjoyment and boredom as the main motivating factors. The reasons given for not using drugs included a lack of interest in the activity, fear of the effects of the drug and a concern that drug taking would compromise other valued activities or pursuits. The anticipated reaction of parents, and the extent to which they had internalised parental values on drugs, also appeared to act as an important restraint for some of the children. While there is a vital role for drug education in seeking to influence children's drug-related decisions, the study's conclusions also emphasise the significance of parents in this regard. The fact that the overwhelming majority of the children reported using drugs because they enjoyed them or because they were bored also suggests that the provision of alternative activities should be central to any preventive strategy.     

Training of medical staff positively influences postoperative pain management at home in children

The aim of this study was to describe how parents manage their child's postoperative pain at home following daycase surgery. The incidence of pain, different analgesics used and problems related to administering medications were the main interests of the study. A postal questionnaire was sent to the parents of 275 children who were under 8 years of age and had undergone an ear, nose and throat (ENT) daycase operation. The questionnaire was sent to the parents a week after discharge from hospital. Altogether, the parents of 227 children answered the questionnaire (response rate 83%). The study was divided into two phases (preintervention and postintervention), and incorporated a training program for doctors and nurses between these two phases. The training program aimed to improve the treatment practices of postoperative pain in children. Seventyeight per cent of the children in the preintervention study and 75% in the postintervention study experienced at least mild pain after discharge. The training program for doctors and nurses affected the home treatment practices of postoperative pain. The proportion of parents treating their children increased from 68% to 80% after the training program (p=0.028). Many parents faced problems while treating their children; for example, 19% (n=30) of the children refused to take their medicine, and suppositories were regarded to be an especially unpleasant dosage form. However, no serious adverse effects were reported. We conclude that due to the pain experienced at home by the great majority of children following daycase ENT operations, parents need information on how to manage their child's pain. A training program for doctors and nurses can improve the treatment of children's pain even at home. Since some children dislike suppositories, it would be worth considering the use of small tablets or mixtures instead.     

Cytotoxic Effects of Topotecan Combined with Various Active G2/M-Phase Anticancer Drugs in Human Tumor-Derived Cell Lines

Topotecan (TPT) is a DNA-Topoisomerase I poison that exhibitsantitumor activity. TPT, like other DNA-damaging agents, arrests ordelays cell cycle progression during S- and G2-phase in a widevariety of tumor-derived cell lines. Particularly, the G2-arrest gives time for the cell to repair its DNA lesions prior tostarting a new cell cycle. Based on these observations, we assessedthe interaction between TPT and G2/M-active agents in p53–mutatedcell lines of diverse origin in order to achieve cell toxicity. Two short-term sequential schedules were administered(TPT G2/M-active drug at the interval of greatest TPT-inducedG2/M-phase cell arrest, and G2/M-active drug TPT), in threehuman tumor-derived cell lines with proven sensitivity to the following drugs: Bleomycin in HEp-2 (squamous larynx carcinoma);Docetaxel in SKBr-3 (breast adenocarcinoma); Etoposide in NCI-H23(non-small-cell lung cancer). Our results show that: 1) SequentialTPT G2/M-active drugs are synergistic when administrationoverlapped the maximum percentage of TPT-induced G2/M–phase cellarrest interval in all three mutated p53 cell lines; 2) the reversesequential schedule (G2/M-active drug TPT) was antagonistic,and being only additive for Etoposide TPT association. Inconclusion, our findings further support the potential cytotoxicrole of TPT in combination with other active drugs when the correctschedule of administration is applied. In addition, they provide arationale for new applications in clinical trials using short-termsequential TPT G2/M-active drugs.     

Pharmacology of antihypertensive agents with multiple actions

Compounds with two or more different pharmacodynamic activities in a single molecule are designated as hybrid drugs. If several stereoisomers with different pharmacodynamic activities exist in one molecule, the term pseudo-hybrid drug is applied. In the treatment of hypertension, the use of hybrid drugs enables a considerable reduction in the number of tablets to be taken per day. Conversely, the dose of each individual component cannot be tritrated. Most hybrid drugs used in antihypertensive treatment are -blockers with an additional vasodilator component, caused by different mechanisms such as -adrenoceptor blockade, ₂-adrenoceptor agonism, ACE inhibition or direct relaxation of vascular smooth muscle. Examples include labetalol (in fact, a mixture of four stereoisomers), carvedilol, celiprolol, dilevalol, tertatolol and BWA-575 C. A combination of -receptor blockade and vasodilatation may be beneficial from a hemodynamic point of view. More recently it has been recognized that urapidil and ketanserin are hybrid drugs, each containing at least two pharmacodynamic activities in their molecules.