KEAMANAN PENGGUNAAN OBAT PADA KEHAMILAN DI RUMAH SAKIT SWASTA YOGYAKARTA

“Black box” 101: How the Food and Drug Administration evaluates, communicates, and manages drug benefit/risk

DRUG labeling is of vital importance in guiding the safe and effective use of approved drugs. Drug labels represent the most visible expression of months or years of scientific review by physicians and scientists at the U.S. Food and Drug Administration (FDA), and they are also fundamental to the purpose and mission of the FDA. Creation of the FDA dates to the 1906 passage of the Food and Drugs Act, which prohibited the manufacture and interstate shipment of adulterated and misbranded foods and drugs.†A 1937 disaster, in which more than 100 people died after ingestion of Elixir Sulfanilamide, precipitated the Federal Food, Drug, and Cosmetic Act of 1938, which, for the first time in U.S. history, required demonstration of safety before marketing new drugs. Elixir Sulfanilamide contained diethylene glycol and had never been tested for safety. In 1960, a marketing application for the drug thalidomide was submitted to the FDA. Withstanding enormous pressure from the applicant, FDA reviewers, including Frances Kelsey, M.D., Ph.D., a medical officer at the Center for Drug Evaluation and Research at the FDA (Washington D.C.),‡determined that inadequate data were available to support the safety of the drug product despite its already widespread use throughout the rest of the world. The application was not approved. After thousands of children in 46 countries were born with deformities as a consequence of thalidomide use, leaving the United States relatively unscathed, a political movement for tighter drug controls in the United States gained popular support. The Drug Amendments of 1962 were the first to require demonstration of effectiveness before marketing, recognizing that the assessment of safety must also consider benefit. Since 1962, more than a thousand prescription drugs have had their labeling changed or have been taken off the market to reflect the scientific evidence (or lack thereof) documenting their safety and/or effectiveness.§Section 505 of the Federal Food, Drug, and Cosmetic Act (21 USC 355)∥currently specifies that approved drugs must be safe and effective for use under the conditions prescribed, recommended, or suggested in the labeling.Current regulations stipulate the following labeling requirements1:The Code of Federal Regulations provides the basic skeleton for drug labels,#specifying the section headings and content, as well as the order in which these sections should appear. Regulations have been proposed to improve on the current system of labeling by changing the format of drug labeling to make the information more useful and accessible to practitioners.2This proposal would partition the label into three parts: a Highlights section, an Index, and Comprehensive Prescribing Information.Most typically, the drug manufacturer drafts proposed labeling based on relevant available data. This includes data acquired during drug development, as well as publicly available data on the drug and other related drugs. FDA reviewers carefully scrutinize every phrase in the proposed label for completeness and fair balance and also to ensure that all statements are adequately supported by data.**Scientific experts outside of the FDA and the general public may also be consulted for advice on labeling, particularly in the case of difficult or controversial issues. Commonly, labels undergo one or more rounds of revisions before final approval.Generally, new indications for a drug require evidence of effectiveness based on data submitted from adequate and well-controlled studies (i.e. , generally more than one) conducted in humans under an Investigational New Drug application, under defined standards for data quality and integrity and the reporting of adverse events.††All relevant data must be submitted to a new drug application (NDA), including data from failed trials, along with complete protocols and protocol revisions. Supporting chemistry, pharmacokinetic, and preclinical (in vitro and animal) data are usually required as well. FDA grants indications only after its own internal review and analyses of these data by physicians, statisticians, chemists, clinical pharmacologists, toxicologists, and other relevant scientific and regulatory disciplines within the FDA. In addition, experts external to the FDA, including members of FDA advisory committees, may be consulted as needed. Medical literature, on which much off-label use is based, is usually not accepted as the sole basis for approval of a new drug indication. There are several reasons for this. First, the raw data, along with complete protocols and revisions, are usually unavailable for review. Second, the standards for data quality, integrity, monitoring, and adverse events reporting are often unknown. Last, the study sites are unavailable for inspection. The FDA must also consider the possibility that published literature may present a skewed or incomplete profile of the efficacy and safety of a drug for human use.This regulatory process can be illustrated using the examples of levobupivacaine (Chirocaine; Purdue Pharma LP, Stamford, CT) and of dexmedetomidine hydrochloride (Precedex; Hospira, Lake Forest, IL).‡‡Levobupivacaine (Chirocaine) was approved in 1999 for adult patients for the production of local or regional anesthesia for surgery and obstetrics, and for postoperative pain management. The NDA applicant studied more than 1,400 patients in a total of 27 clinical studies in the United States and Europe. These included 2 pharmacokinetic studies, 4 phase I pharmacodynamic studies examining neurologic and cardiovascular endpoints, 2 studies of epidural administration for cesarean delivery, 2 studies of epidural administration for labor analgesia, 2 studies of epidural infusion for operative procedures, 1 study of intrathecal injection for lower limb surgery, 4 studies of epidural infusion for postoperative pain, 7 studies of peripheral nerve blocks, and 3 pediatric studies, 2 of which were still ongoing at the time of NDA submission. Much of the preclinical support for this application was in the form of animal studies of levobupivacaine and bupivacaine (approved in 1972) that were available in the published literature. Before its approval, the FDA consulted the Anesthetic and Life Support Drugs Advisory Committee, which included a guest cardiac electrophysiology consultant, to discuss the relative safety of levobupivacaine compared with bupivacaine and how the product should be labeled with respect to cardiotoxicity. In addition, FDA chemists and microbiologists reviewed data and information related to the product chemistry, manufacturing, and quality before approval.Dexmedetomidine hydrochloride (Precedex), an α2-adrenoceptor agonist, was approved in 1999 for sedation of initially intubated and mechanically ventilated patients during treatment in an intensive care setting. It is to be administered by continuous infusion for not more than 24 h. The NDA applicant submitted full reports of animal pharmacokinetic, toxicology, and teratogenicity studies; two placebo-controlled human studies demonstrating the efficacy of dexmedetomidine; and a total human safety database of more than 3,038 subjects, of whom 1,473 were intensive care unit patients who received the drug by continuous infusion. Only 78 patients received dexmedetomidine for longer than 24 h, and no patient received the drug for longer than 40 h. No safety data in pediatric patients were submitted, and more than 500 patients older than 65 yr were studied, 129 of whom were aged 75 yr or older. Human pharmacokinetic data included evaluation in patients with renal failure after single administration and evaluation of pharmacokinetics with hepatic impairment, as well as analysis of the effects of age on pharmacokinetics in adults. In addition, the FDA inspected clinical trial sites and reviewed information related to the product chemistry, manufacturing, and quality before approval. The NDA applicant also agreed to seven phase IV commitments to address areas in which the FDA desired additional information that might be used to inform future labeling. These included (1) dog studies to evaluate general toxicology, effects on the hypothalamic-pituitary axis, and changes in drug metabolism after 2 weeks of drug infusion; (2) an animal study to evaluate the effects of the three major human metabolites of dexmedetomidine that are absent in rats and dogs; (3) preclinical mutagenicity studies to elucidate findings from studies submitted before approval; and (4) long-term continuous infusion studies in patients to evaluate the pharmacokinetics, safety, and extended effectiveness of dexmedetomidine in the intensive care unit setting and to evaluate the use of long-term infusions in patients with renal failure. To date, these commitments have not been deemed fulfilled in their entirety, and there have not been any labeling changes for dexmedetomidine (Precedex) that are based on these postmarketing commitments.After a drug has been approved for marketing, a supplemental application to the FDA is required to change the labeling to reflect a new indication. The supplemental application must present data to support the safety and effectiveness of the new indication. The data requirements for a supplemental application might not be as extensive as would be expected for a novel NDA application, depending on the nature of the supplement and the indication sought.For example, a supplemental application for ropivacaine (Naropin; AstraZeneca, Wilmington, DE) was approved in 2000 for changes in the labeling, including (1) use of the 0.75% concentration for major nerve block and for epidural administration for cesarean delivery (previously approved concentrations for these indications were 0.2% and 0.5%, respectively); (2) use of 0.2% ropivacaine (Naropin) for up to 72 h for postoperative pain (previously approved for up to 24 h only); and (3) a change in the recommended infusion range for thoracic epidural administration for postoperative pain from 4–8 ml/h of 0.2% ropivacaine (Naropin) to 6–14 ml/h. To support the new labeling recommendations, the NDA sponsor submitted the results of clinical trials in which 324 women received 0.75% ropivacaine by the lumbar epidural route for cesarean delivery, 119 patients received 0.75% ropivacaine for brachial plexus block, and 441 patients received epidural infusions of 0.2% ropivacaine for postoperative pain. Pharmacokinetic data were obtained in 8 of the 20 submitted clinical studies. The FDA also reviewed preclinical (in vitro and animal) studies investigating acute, subchronic, and chronic toxicity; pharmacokinetics; cardiovascular toxicity; reproductive toxicology; and genotoxicology before approval of the supplement.Generally, the FDA requires that indications reflect the likely clinical use of a drug to ensure that a drug is not approved for unrealistically narrow indications. For example, drug company XYZ might propose to develop a novel general anesthetic agent only for "general anesthesia for left foot bunionectomies" and submit data supporting only this indication. In such a case, the company might be asked for more data to support a broader indication that would realistically reflect the likely clinical use, or they would be asked to provide adequate justification that such a limited indication is appropriate. As a corollary, a very broad indication for "maintenance of general anesthesia" would not be supportable by submission of data only from healthy patients undergoing bunionectomy procedures.Food and Drug Administration guidance to industry states that "in general, drugs should be studied prior to approval in subjects representing a full range of patients likely to receive the drug once it is marketed. …"3Therefore, to the extent possible, sponsors are expected to study the full range of patients likely to receive drug for the desired indications. Further, recent legislation stipulates that new drug applications are specifically required to contain an assessment of the safety and effectiveness of the product in pediatric patients unless this requirement is waived or deferred.4In addition, drug product sponsors are generally expected to study elderly patients, and to investigate the effects of metabolic and renal impairment and drug–drug interactions when relevant.5–7In a new drug application, sponsors are also required to present effectiveness and safety data for important demographic subgroups, specifically sex, age, and racial subgroups.Current regulations also require specific labeling in the following subpopulations as applicable: pregnant women (including use during labor and delivery), nursing mothers, pediatric patients, and elderly patients.8However, with the exception of those few special populations defined by regulation or guidance, unless there are data to indicate a need for special study or labeling, it is generally not required, feasible, or even scientifically meaningful, to discuss all potential subpopulations in the label.Therefore, industry is encouraged to study drugs in the range of settings and populations reflecting their likely clinical use, including the range of likely comedications and comorbidities. Labels, in turn, are written to reflect the clinical trials that were performed to support them. However, these clinical trials cannot anticipate or thoroughly study all of the ways that a drug may be used after it is approved. Because every patient and clinical situation is unique in some way, this would truly be an impossible task. In spite of the best efforts of the FDA and the drug industry, neither labels nor the supporting clinical trials can comprehensively describe all potential labeled or off-label uses.What exactly is off-label use, and what are the implications for the anesthesia practitioner? Any use of a drug for a condition or in a manner not appearing in the drug's approved label is considered off-label. This lack of approval is most commonly because data have not been submitted to the FDA to support the safety and efficacy of that use, not necessarily because there has been an adverse finding with respect to safety or efficacy. Off-label use most often describes a deviation from the labeled indication, dosage form, dose regimen, or patient population. However, any significant departure from the approved labeling or any use that is not described in the approved label may be considered to be off-label. When off-label uses are associated with a particular safety hazard, they may be described in the Contraindications, Warnings, or Precautions sections of the label. However, although all contraindicated uses are off-label uses, the Warnings and Precautions sections may discuss both labeled and off-label uses.For example, dexmedetomidine (Precedex) is indicated for sedation of initially intubated and mechanically ventilated patients during treatment in an intensive care setting. It is to be administered by continuous infusion for not more than 24 h. In this case, the use of dexmedetomidine outside an intensive care setting or in non–mechanically ventilated patients, such as for monitored anesthesia care sedation in the operating room, would be considered off-label. Similarly, infusions of dexmedetomidine lasting longer than 24 h are also off-label, as noted in the Indications and Usage, Precautions, and Dosage and Administration sections of the label. Data have not been submitted to the FDA to support the safe and effective use of dexmedetomidine outside the labeled indications, and for monitored anesthesia care sedation or long-term infusions to be reflected in the FDA-approved labeling, an application would need to be submitted to the FDA with adequate supporting data.The following are additional examples of off-label uses in anesthesiology:Where does that leave the individual anesthesiologist who, based on his or her own knowledge of the medical literature, medical judgment, and experience, believes that a particular off-label use would be safe and effective for the patient at hand? Anesthesiology is unique among medical specialties in the methods by which practitioners administer drugs that they prescribe. Anesthesiologists administer drugs with their own hands and often do not conform to a fixed algorithm. Instead, drug use is tailored to effect and to the individual needs of the patient, as well as to surgical and medical conditions. Anesthesiology is a specialty that prides itself on innovation and resourcefulness. New routes and modes of administration, mixes, doses, and applications for medications are commonly used to solve complex problems.The FDA does not restrict a physician's discretionary use of an approved drug, which is considered the practice of medicine. In fact, it is recognized that off-label use can be essential to medical care, that it is not always investigational or experimental, and that there is no legal or ethical obligation for physicians to discuss FDA regulatory status issues with their patients.9For example, many drugs used in anesthesia have never been approved for use in children. Restricting anesthesiologists only to labeled uses would have a devastating effect on the practice of pediatric anesthesia, and indeed, practitioners restricting their practice in such a way might well be accused of engaging in poor medical practice. It is the physician's prerogative to use legally marketed drugs in a way that he or she believes is best for the individual patient, according to his or her medical judgment (outside of medical research).However, in this context, perhaps understandably, physicians are often unfamiliar with information available in drug labels and even are unaware of basic information the labeling for drugs that they use, such as indications, dosage and administration and are many other reasons that physicians might not have many on their medical practice is and labels may be as to and often cannot the information they are in the label. practitioners may the information contained in the label with and of the for use in drug labeling and practice is illustrated by the drug In 2 yr after it was approved for marketing, a was to the label because of the of related to The label contraindicated use in patients drugs that and the labeling change was by the of a After the of these contraindicated use of in a of practice sites was to in of In the was to other patient at This change was by the of a and of these the of contraindicated use recent history, several effective drugs such as have been from the market because labeling has been in and adverse are very reasons for anesthesiologists to and the of drug labels and to carefully off-label The label much important information that can inform such are the and should what these are and the for in order to inform on when a particular patient may despite an is as important to the label is a particular use is not because data demonstrating safety and effectiveness do not or have never been submitted to the there is no of in the label of a general anesthetic drug, is use in this For the individual who is not to or a drug, the of use in is off-label may be The more relevant is can the drug be used and in and use a of for which the FDA has a that the the in the labeled populations and for individual patients within that the range of and may be even to the extent that some individual patients within the indicated may adverse events that are not by individual benefit. Off-label uses represent a of and unless as would be reflected in a specific labeled or the FDA has not been with adequate data to make a of safety and efficacy for the indication. The label is a to present those conditions in which safety and efficacy have been and to the trials and data that were used to support these As required by regulation and as labeling describes specific and that may for special use is contraindicated in this might be considered a of the adult that was studied to support the drug's indication. However, are not in the it is also likely that they not represent a of the total clinical database to make use of the drug in this should from the adult population. The label describes the important clinical trials and available information on pharmacokinetic, and safety and special this the is expected to clinical judgment in the best use of the drug in the individual patient at may require of dose based on from the general in and of renal and of older drugs for which are available have limited to develop new drug indications. as the clinical use of these drugs clinical use may from the approved labeling, and clinical judgment and ongoing medical may on an important in guiding their of this is the NDA for which was submitted to the FDA in the is approved only for and injection in patients aged 2 yr and older. the widespread use of by intrathecal and epidural and the use of this drug in pediatric patients than 2 data demonstrating the safety and efficacy of these uses have never been submitted to the FDA to support the of these indications to the anesthesiologist should consider several other when off-label use of a data and pharmacokinetic data usually inform labeled Off-label populations and indications have data to indications for new routes of administration and new populations are generally supported by studies in animal In these it is to more the potential profile for drugs in ways that are not in such as by of at the proposed human and data are often unavailable to support the safety of off-label routes of administration or of of or longer than approved and routes of who to administer a drug that is labeled only for use by the or intrathecal route should that the potential for local may not have been thoroughly in those for that Drugs that are used by routes may also have very of than by the approved a situation that may in very drug efficacy and safety for of are often defined by the clinical and preclinical trials from which safety and efficacy data are available only for a limited of may also be limited by specific related to safety or in which case these are usually in the label. may also into For example, assessment of safety for labeling into the potential to drug, and drugs that are approved only for use may in to patients For example, is approved only for of general anesthesia and for of anesthesia during operative infusion of is off-label and has been associated with In addition, many drugs used by pain and or with use of these drugs is not in clinical trials, the may not have adequate information to with use and may not even be of the efficacy of the are also a of and issues of particular to anesthesia For example, drugs approved for epidural or intrathecal use may be to standards than medications with respect to potential to and (including This is a Anesthesiologists commonly use drugs by routes that are not approved for such The and concentrations of and are generally not in the product labeling may the drug is anesthesiologists may to for epidural or intrathecal use, they may not always which drug contain For example, the labels to some of not the of these The had to the to that In addition, drugs can from the product in the of and that the applicant and the and provides information that the do not the safety or efficacy of the drug product for the labeled although the product may contain a or no a of that product may or may not contain that and it may or may not contain a are often in the ways that they and drugs for these are not specifically in the these may be considered off-label The Dosage and Administration section of the label information and administration of the dosage These are supported by data demonstrating and of the drug in the final In addition, drugs are tested for and with with which they into Anesthesiologists and drugs off-label should be of the of and After the FDA received reports of of with FDA a label to Before this the label was on of these drugs. drug labels do not anticipate the range of clinical is the practice of to that contain is a that has been associated with adverse events in particularly to reproductive in in have concentrations under use and conditions. However, is to in into that contain The extent and time for the of of into which is and the potential for to humans related to such have not been Anesthesiologists should be and of drugs outside their not described in the label. When or drugs off-label, practitioners should be in for and for drug When these events do practitioners should are the best of for an individual However, information from trials, the individual may be at a in this Drug effects from patient to patient and from situation to situation in the In addition, relatively adverse events may not be as potential events in clinical practice. This potential is particularly in the and surgical an in which adverse events are and in which there are usually potential for adverse is on individual physicians to be of off-label use and to adverse events when they in the of both labeled and use of adverse reporting is a major by which the FDA can and safety information off-label use of drugs. information the patient, the clinical and the clinical supporting data the are to the effective analysis and of these adverse data. on how to adverse product or can be on the FDA may be submitted or by or after which they are into a database they undergo FDA labeling has implications for and marketing of drugs. Drug generally must conform to labeling and contain information and effectiveness as in the drug label. Drug sponsors are not to off-label uses of although they may medical literature relevant to such uses under some usually submission or a to submit an application for the off-label that the use is not FDA along with the approved labeling for the drug, must also such FDA itself has that a product has been approved for marketing, a may it for uses or in treatment or patient populations that are not included in approved labeling. new uses for drugs already on the market are often first and regulatory with respect to off-label uses of medications may be a of in the literature and in the However, it is that (1) the associated with off-label use represent a broad (2) the of off-label uses may the associated in patients, and (3) off-label use a vital in the practice and of have the to be well the drugs they are and to off-label use on scientific or on medical To best and consider the potential implications and of off-label use, it is that anesthesia practitioners be with the labels for the drugs that they use and the and of these

Labeling refers to the label on the drug container and all printed materials, including the package insert, that accompanies the product. Labeling of a drug indicates that there is substantial evidence from adequate and well controlled clinical trials for the safe and effective use of that drug. Labeling provides important information on clinical pharmacology, indications and usage, contraindications, precautions, adverse effects, dosage, and administration. Unfortunately for children, most drug labeling contains the precautionary disclaimer, because safety and efficacy in children have not been established. The availability of safe and effective drugs has been directly responsible for the improvement in health over the past 50 years. Children essentially have been excluded from the benefit of the many therapeutic advances that have marked pharmaceutic drug development. The failure to include children in clinical trials during drug development leads to delay in implementing potentially effective treatment. Most US food and Drug Administration-approved drugs lack approval for use in all children or are restricted to certain pediatric age groups, primarily older children.1 Only a few of the new drugs released in this country each year are approved for use in children. This lack of information on the safe and effective use of drugs in the most vulnerable patients, infants and neonates, is of greatest concern. Only five of the 80 most frequently used drugs have been approved for use in this population. Another problem is that most drugs are not available in suitable pediatric dosage forms. They are not available in appropriate dosage sizes, lack liquid formulation, and taste peculiar to the child, making compliance difficult. Pharmacies extemporaneously prepare many drugs in liquid dosage forms for use in children. These dosage forms are not sufficiently tested to determine stability, efficacy, or expiration dating. For solid dosage forms, parents often must divide adult tablets …

This study aims to analyze the relationship between the compliance with the implementation of clinical pathways to therapeutic outcomes (ILO events, length of stay, pain intensity) and the total real cost of cesarean section patients. The study was conducted at a type C private hospital in Yogyakarta. This study is a non-experimental analytical study (observational analytic) with a cross sectional design using a retrospective data collection method and analyzed using Chi square test and non parametric regression test. Descriptive analysis for compliance with the implementation of clinical pathways was carried out by assessing the compliance of each care point contained in the clinical pathway section of the cesarean consisting of 12 points of care and will be grouped into two categories namely low compliance category with the average compliance value for clinical pathway <85% and good compliance with the average compliance value for clinical pathway ≥85%. Descriptions of adherence to the implementation of clinical pathway cesarean section each patient showed that as many as 686 patients (98%) had a good average compliance score and 14 patients (2%) had a low average compliance score. Outcome description 700 patients with cesarean section were found 1 patient experienced ILO, LOS according to clinical pathway (≤3 days) as many as 620 patients and 700 patients with pain scale ≤3. The results of the analysis of the relationship between the compliance and the implementation of the clinical pathway to the outcome of therapy (ILO events, length of stay, and pain intensity) showed the existence of a compliance relationship to the implementation of the clinical pathway with a value of p<0.05. The analysis of the relationship between the compliance to the implementation of the clinical pathway and the total real costs shows the relationship between the compliance with the implementation of the caesarean section clinical pathway at a type C private hospitals in Yogyakarta with the total real costs with p value of 0,000 and r value of 0.014.

Background: Job satisfaction is a manifestation of the success of employees in carrying out their responsibilities at work. Self-management is self-regulation in the use of time, choices, interests, activities, and physical and mental balance. The results of measuring nurse job satisfaction amid the COVID-19 pandemic decreased and affected the quality of hospital services. Objective: This research aims to determine the effect of self-management interventions on nurse job satisfaction at type C private hospital in Yogyakarta. Methods: Pre-experimental research design, one group pre-posttest. The research population is nurses at type C private hospital in Yogyakarta. The sample in this study was 45 respondents using a total population technique as the sample. This study used the Minnesota Satisfaction Questionnaire and the intervention was carried out online meeting. Results: The majority was female with a percentage (86.7%), the ages of nurses were 31-38 years with the most (42.2%), Diploma III education dominated (82.3%). Wilcoxon obtained Asymp.Sig (2-tailed) worth 0.001. The value of 0.001 is less than 0.05, so H0 is rejected and Hα is accepted. Conclusion: There is an effect of self-management interventions on the job satisfaction of nurses at type C private hospital in Yogyakarta.

Background: Stress because of stressors. One source of stress for the patient's family is when one of the members is treated in the ICU. Various changes when a family member is being treated can trigger prolonged stress. Lack of patient information during treatment is one of the causes of stress in the family. Objective: To determine the description of stress in patient families in the Intensive Care Unit of a Private Hospital in Yogyakarta. Methodology: This type of research is quantitative descriptive with cross-sectional approach and total of 51 respondents using consecutive sampling techniques. The research instrument used Perceived Stress Scale 10 (PSS-10). Univariate analysis to find out and describe description of each variable consisting of age, gender, and stress. The research location was carried out in the Intensive Care Unit (ICU) room at a private hospital in Yogyakarta City. Results: The results of the study showed that the characteristics of the respondents were 37 people or 72.5% female, the ages of the respondents were mostly in the 46 -55 years age group, totaling 24 people or 47.1%. Description of the stress level of the families of Intensive Care Unit patients: 39 people or 76.5% of respondents were in a state of moderate stress and 10 people or 19.6% were in a state of severe stress. Conclusion: The stress level of the families of Intensive Care Unit patients in one of the private hospitals in Yogyakarta is mostly moderate to severe stress. So the importance of information from medical staff in helping reduce the stress level of families of critical patients in the ICU.

ABSTRACTIntroduction:Chronic obstruction pulmonary disease (COPD) is a chronic airflow disorder along with decreasing health status. COPD assessment test (CAT) is commonly used to assess the health status of patients and their medical results. The aim of this study was to assess the therapeutic outcomes in patients with COPD using CAT in private hospitals in Yogyakarta.Materials and Methods:This was a cross-sectional study involving 156 patients, aged >40 years who had completed the CAT questionnaire. CAT scores were categorized into four groups and consisted of eight items: cough, phlegm, chest tightness, breathlessness going up hills/stairs, activity limitations at home, confidence leaving home, sleep, and energy. The four categories were successful therapy (CAT scores <10), moderately successful CAT 10–19), less successful (CAT scores 20–30), and unsuccessful (CAT score >30). The study was conducted from April to August 2018 at two Private Hospitals in Yogyakarta followed by descriptive-analytical data processing and chi-square analysis.Results:The therapeutic outcomes of COPD were 30.13% successful (CAT score: <10), 60.26% moderately successful (CAT score: 10–19), 9.62% less successful (CAT score: 20–30), and there were no patients with unsuccessful therapy. The majority of patients had moderate airflow severity. Exacerbation condition, severity level, and type of therapy showed a significant result (P < 0.05) toward therapy results with COPD measurement, and from eight CAT items, it was identified that 37.8% of respondents had breathlessness going up hills/stairs.Conclusion:CAT can assess the therapeutic outcomes and COPD patient’s health status with moderately successful therapy (CAT score 10–19) in more than sixty percent of respondents.

Prophylactic antibiotics are used before, during, and up to 24 hours after surgery, and can be administered to patients 30-60 minutes before surgery, must adhere to the principle of “Right Antibiotics”. This study aims to assess the application of prophylactic antibiotics in surgical patients in a private hospital in Yogyakarta to promote rational antibiotic use. This study is quantitative and non-experimental. Data were collected prospectively over a period of 30 days from August 4 to September 4, 2024. The study sample consisted of all surgical patients who received prophylactic antibiotics. Prophylactic antibiotic data were analyzed using the Gyssens method. Out of the data collected, 110 patients received preventive antibiotics, and 97 of these patients met the inclusion criteria. Patient characteristics predominantly included a 46% incidence of cesarean sections. Prophylaxis employed three antibiotics, viz. ceftriaxone in 78 patients (79.38%), cefazolin in 19 patients (19.59%), and cefotaxime in 1 patient (1.03%). The assessment utilizing the Gyssens approach revealed that 31 patients were classified into category V (no indication), 49 patients into category IVA (more effective antibiotics available), and one patient into category I (not suitable during prophylaxis). Sixteen patients in category 0 were included in the reasonable antibiotic regimen. This study states that most antibiotics are not in accordance with the Guidelines for Antibiotic Use established by the Ministry of Health of the Republic of Indonesia in 2021.

In their editorial entitled “Pediatric Research and Scholarship,” Tobin et al. (1) question whether the Food and Drug Administration (FDA) has taken an acceptably proactive role in efforts to encourage high quality clinical trials of drugs in the pediatric patient population when those studies are performed by individual academic investigators. In particular, they question the obligation of academic investigators to abide by federal regulations when conducting small clinical trials with drugs not yet approved for the pediatric population. In response, we will review the role of the FDA in clinical research conducted by individual academic investigators, summarize recent progress in pediatric drug development, and offer suggestions to academic investigators who wish to perform these types of drug trials. FDA: THE INVESTIGATIONAL NEW DRUG (IND) APPLICATION Most investigational use of drugs is subject to the IND regulations. While these clearly apply to unapproved new drugs, in certain circumstances, federal regulations require that a protocol utilizing an approved drug product must be reviewed by the FDA before a clinical drug trial may proceed. The FDA Web site offers guidance to investigators to help them determine when their proposed study will require FDA review (http://www.fda.gov/cder/guidance/phase1.pdf). When FDA review of a protocol is required, the investigator must submit an IND application. FDA review is always required when the intent of an investigation is to change a product’s label, such as to permit the product’s use in a new, potentially more vulnerable population. For example, the novel use of a product in pediatric patients would require a pharmaceutical company to perform all clinical research under an IND. However, even in the setting of a small-scale academic investigation, an IND would likely be required in a vulnerable population such as pediatric patients, whether or not there is common off-label use of this drug in the pediatric population. If an investigator is uncertain whether an IND application is necessary, he or she should contact the FDA for advice prior to initiating subject recruitment. When an IND application is required, the FDA review process can benefit the investigator and reduce the risk to subjects participating in the clinical study. For example, if there is preliminary evidence that a particular drug is associated with organ toxicity in an animal model of growth and development, the FDA may be able to advise the IND applicant how to safely monitor patients, and provide this information without compromising proprietary work by other investigators. Furthermore, because the FDA is often aware of trials that have failed, the agency can advise an IND applicant when the risk of planned research exceeds the putative benefit. Academic investigators who are not expert in conducting clinical drug research can also receive assistance in developing an appropriate trial design based on FDA experience in the evaluation of previously completed trials (2–4). In contradistinction to statements by Tobin et al. (1), the FDA clearly recognizes the utility of alternative designs to placebo-controlled trials (CFR 314.126) when appropriate. The review of an IND application is conducted by a team consisting of chemists, nonclinical pharmacologists/toxicologists, clinical pharmacologists, statisticians, and physicians, concluding with a determination of whether or not the trial is considered safe to proceed. This process is typically completed within 30 days. When a clinical trial that required an IND review has been conducted without FDA approval, the FDA Division of Scientific Investigations may perform an evaluation at the research site to assess the potential risk that was incurred by subjects during that study. In such cases, the FDA evaluation of the trial and any subsequent regulatory action do not depend on whether the trial data have been or will be published in the medical literature. The magnitude of the risk to research subjects is incorporated into the assessment and can result in a legal action when appropriate. PROGRESS IN PEDIATRIC DRUG DEVELOPMENT Most medications are initially studied and approved in the adult population, which is appropriate given the unknowns of safety and efficacy during initial development. However, this means that children are often treated off-label with these medications prior to the development of well-controlled clinical trials in the pediatric population. Consequently, physicians rely on extrapolating adult experience and on anecdotal information to determine safety and effectiveness of many medications for the treatment of pediatric patients. Congress has enacted several laws intended to directly promote drug development for the pediatric population. These measures have increased the amount of information on the safe and efficacious use of drugs for pediatric patients. The first law, passed in 1997, was the Food and Drug Administration Modernization Act (FDAMA). FDAMA offered pharmaceutical companies a 6-month period of marketing exclusivity if they performed studies in pediatric patients in response to a Written Request (WR) issued by the FDA. Marketing exclusivity incentives attach to a period of existing patent protection or exclusivity and were effective in prompting industry to conduct needed pediatric trials for drugs with existing patent protection or exclusivity. This program did not provide an incentive for the study of off-patent, mostly generic, drugs. The Best Pharmaceuticals for Children Act (BPCA) was signed into law on January 4, 2002, shortly after the pediatric exclusivity provision of FDAMA expired on January 1, 2002. The BPCA reauthorizes the exclusivity incentive enacted originally in FDAMA. Further, section 409I(a)(2) of the BPCA provides a process for the study of off-patent drugs (approved drugs that have no remaining patent protection or exclusivity). This law directs the National Institute of Health (NIH), in consultation with the FDA and experts in pediatric research, to develop and prioritize a list of “off-patent” drugs for which pediatric studies are most urgently needed. The list was originally published in January 2003 and is updated at least annually. WRs for pediatric studies will be issued by the FDA for drugs on the priority list requiring studies to develop adequate pediatric labeling. In turn, the NIH will issue contracts for the studies. Once the trials are performed and the results are analyzed, the data become publicly available for dissemination and incorporation into the label (http://www.fda.gov/cder/pediatric/70FR3937.txt). Since the inception of FDAMA and BPCA, over 450 proposed pediatric study requests from industrial sponsors have been received and more than 300 pediatric WRs have been issued. This has resulted in revisions to more than 100 drug labels to include new pediatric information. The Pediatric Rule, which became effective on April 1, 1999, required that manufacturers of certain new and marketed drugs and biological products conduct studies to provide adequate labeling for the use of these products in children. A District of Columbia federal district court invalidated the Pediatric Rule on October 17, 2002. In December 2003, Congress enacted the Pediatric Research Equity Act (PREA), which requires (retroactively to April 1, 1999) all applications for new active ingredients, new dosage forms, new indications, new routes of administration, and new dosing regimens to contain an assessment of the safety and effectiveness of the product in pediatric patients. PREA is complimentary to BPCA and allows the FDA to obtain pediatric information when applications are submitted. This requirement may be waived or deferred depending on existing labeling, public health benefit, and usefulness of the drug in different pediatric populations. With passage of the BPCA and the PREA, there have been gains in the information available in labeling for the appropriate use of medications in children. While much has been achieved, there are still many drugs that need to be studied for the pediatric population. The anesthesia community can become involved by alerting the leadership of their specialty societies regarding drugs when they feel additional information would benefit the pediatric population. Academic investigators can compete for NIH funding to support pediatric clinical trials. SUGGESTIONS FOR FURTHER RESEARCH IN PEDIATRIC DRUG DEVELOPMENT The editorial by Tobin et al. (1) suggests that a consensus statement by children’s advocacy groups, increased commitment by pharmaceutical companies, and additional resources at FDA are needed to improve pediatric drug development. We concur that all stakeholders should work together to find new ways to advance the development of pediatric drug development. The FDA continues to be active in organizing an increased commitment to this vital area of research. For example, the Newborn Drug Development Initiative: Improving Neonatal Therapeutics workshop, sponsored by the NIH and FDA, included summary recommendations for pain control by members of the academic anesthesia community (5,6). Full-length articles on procedural pain, sedation and analgesia, perioperative pain, and study designs resulting from this effort have also been published (7–10). High-caliber academic investigations, when conducted under an approved IND application, can continue to make valuable contributions to improve the spectrum and quality of therapeutics available to pediatric patients.

Background: Lipid modifying agents have an important role in the primary and secondary prevention of cardiovascular diseases such as coronary heart disease and stroke. The use of lipid-modifying agents tends to increase along with the increasing prevalence of these diseases. Objectives: To determine the utilization of lipid modifying agents for hospitalized patients in a private hospital in Yogyakarta during the period of 2013 - 2019 in regard to the agents used and their quantity. Methods: The main data for this study were aggregate data on the use of lipid modifying agents for hospitalized patients during 2013-2019 obtained from the hospital pharmacy department. After identification of the names of lipid modifying agents, the quantities of these drugs were then calculated in units of defined daily dose (DDD) and the final quantity was expressed in DDD/100 bed days (BD). The R2 value from linear regression was used to determine the trend of use of individual agents over the period. Results: There were two pharmacological subgroups of lipid modifying agents used during the period of 2013 – 2019 with an average of total quantity of 14.81 DDD/100 BD. Utilization of statins was approximately 90% of the total use, and utilization of fibrates tended to decrease over the period. Individually, simvastatin use decreased significantly over the period (R2 = 0.885), but atorvastatin use continued to increase (R2 = 0.908) with 10-fold increase from 2013 to 2019. Conclusion: The lipid modifying agents used during the period 2013 - 2019 were predominantly statins, and the utilization of atorvastatin increased significantly during this period. Keywords: lipid modifying agents, ATC/DDD, fibrates, statins

Background: Hypertension is a chronic disease that requires long-term treatment and has an impact on the cost of treatment. The costs will be greater given the loss of productivity, family burden, and social life impacted by hypertension based on patient’s perspective. Objective: The purpose of the study was to determine the costs and clinical outcome of antihypertensive therapy from the patient's perspective and to identify the discrepancies between the costs and the INA-CBGs (Indonesia Case Based Groups) tariff. Methods: The research was an observational study with a cross-sectional design. The targeted population was outpatients who had received antihypertensive therapy for at least 1 month at a private hospital in Yogyakarta. The costs included direct medical costs, direct non-medical costs, and indirect costs, while the clinical outcomes were patient’s blood pressure. The descriptive analysis was carried out to describe the characteristics of the research subjects, the clinical outcome, and the cost. Analysis of the discrepancies between the costs and the INA-CBGs tariff used the Mann-Whitney test and One-Sample t-test. Results: The results showed that the average direct medical costs, direct non-medical costs, and indirect costs from the patient’s perspective were IDR359,408.00, IDR24,617.00, and IDR 40,583.00, respectively. There was a significant difference between the real costs and the rate of INA-CBGs based on the results of statistical tests, while the cost discrepancy was IDR5,287,045.00. Conclusion: The direct non-medical costs and indirect costs of hypertensive outpatients were less than the direct medical costs. A significant difference occurred between the real costs and INA CBG’s tariff. Keywords: hypertension, cost consequences, pharmacoeconomics, patient’s perspective

Clinical pharmacist in Indonesian hospitals has begun to be recognized as an essential part of the healthcare team along with physicians, nurses and other healthcare professionals. While recognition is still on the way, the implementation of clinical pharmacy services is still limited. This could occur because of various factors, one of which is the lack of interprofessional collaboration. Interprofessional collaborations with other healthcare provider are necessary for a pharmacist to implement their clinical services. Hence, health professionals' perception of clinical pharmacy services would give a contribution to developing strategies for the service in the hospital. This study aims to determine perceptions of health professionals in a private hospital in Yogyakarta, Indonesia, on clinical pharmacy services. A total of 96 nurses and 17 physicians were given a questionnaire with items related to clinical pharmacy services. The result showed that health professionals had a positive perception of the role of the pharmacist in clinical pharmacy service with a total mean score of 0.83. Relationship between respondents' characteristic and their perceptions showed that nurses' workplace (ward) had a significant effect on their perceptions (p&lt;0.05). In contrast, characteristics of age, gender, profession, length of work experience, and interaction intensity with the pharmacist did not reveal significant effect.

Breastfeeding is essential for infant nutrition, survival, and development. Identifying factors associated with breastfeeding success is important for improving early postpartum care and breastfeeding support in hospital settings. This study aimed to identify determinants of successful breastfeeding among postpartum mothers in a private hospital in Yogyakarta, Indonesia. A cross-sectional study was conducted among 124 postpartum mothers who had delivered vaginally and had healthy infants. Participants were recruited using convenience sampling. Data were collected using a structured questionnaire during the postpartum hospital stay. Variables included maternal education, occupation, knowledge, early initiation of breastfeeding (EIBF), supplementary feeding, rooming-in, breastfeeding frequency, breastfeeding experience, health worker support, and family support. Data were analyzed using univariate analysis, Pearson's chi-square test for bivariate analysis, and binary logistic regression for multivariable analysis. Multivariable analysis results were presented as adjusted odds ratios (AORs) with 95% confidence intervals (CIs), with p < 0.05 considered statistically significant. Bivariate analysis showed that maternal occupation (p = 0.040), EIBF (p = 0.024), supplementary feeding (p = 0.017), and breastfeeding experience (p = 0.002) were significantly associated with breastfeeding success. In multivariable analysis, only breastfeeding experience remained significantly associated with breastfeeding success. Mothers with previous breastfeeding experience were 3.66 times more likely to achieve breastfeeding success than those without prior experience (AOR = 3.66; 95% CI [1.47, 9.12]; p = 0.005). Breastfeeding experience emerged as the most consistent factor associated with breastfeeding success. Early postpartum breastfeeding support, especially for first-time mothers, should be strengthened to improve breastfeeding success.

Smoking behavior is known to be a significant factor that has adverse effects on people with type 2 diabetes (T2DM). Nicotine in cigarettes stimulate adrenoreceptors and promotes lipolysis, leading to the synthesis of free fatty acids, which in turn increase the susceptibility to dyslipidemia and the development of cardiovascular disorders. This study aimed to examine the relationship between smoking status and the occurrence of dyslipidemia in patients with T2DM in a private hospital in Yogyakarta. A total of 107 T2DM patients participated in this cross-sectional observational study. Through live interviews, we collected smoking status conducted using the Fagerström Test for Nicotine Dependence (FTND) questionnaire. The fasting blood samples taken from participants were used to analyze the lipid profiles, including triglycerides (TG), total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). The chi-square test revealed a significant association between smoking status and the risk of dyslipidemia among the participants, with χ²(2) = 13.463, p = 0.001. The findings suggest that smoking increases the risk of dyslipidemia among T2DM patients. These results highlight the importance of smoking cessation as a preventive measure to reduce metabolic complications in individuals with T2DM.

Introduction: The high workload of nurses can cause burnout. Burnout can occur if the number of patients admitted does not match the number of available nurses and facilities, and occurs for a long time. Burnout in nurses causes a lack of attention to the application of patient safety culture. This study aims to find out the correlation between burnout and patient safety culture among nurses at Private Hospital in Yogyakarta. Methods: Research design was descriptive cross-sectional method. There were 58 nurses, acquired by total sampling technique. We used the MBI-questionnaire to measure burnout levels and the HSOPSC questionnaire to measure patient safety culture. Results: The results of this study indicate that the burnout level is low as many as 58 people (100.0%), patient safety culture is fairly good as many as 41 people (70,7%) and burnout has a negative effect on patient safety culture, but has no significant relationship (p 0,200 and r -0,171). Conclusion: The burnout level of nurses is in low category, the patient safety culture of most nurses is fairly good and burnout has a negative effect on patient safety culture, this is because when burnout is felt by an individual, it will affect all individual activities both physically and mentally. Nurses are expected to be able to manage the workload so that they can avoid burnout and cooperate with hospital management to improve patient safety culture.