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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
For a diagnosis of benzodiazepine dependence to be made, the ICD-10 requires that at least 3 of the below criteria are met and that they have been present for at least a month, or, if less than a month, that they appeared repeatedly during a 12-month period.
- Behavioral, cognitive, and physiological phenomena that are associated with the repeated use and that typically include a strong desire to take the drug.
- Difficulty controlling use
- Continued use despite harmful consequences
- Preference given to drug use rather than to other activities and obligations
- Increased tolerance to effects of the drug and sometimes a physical withdrawal state.
These diagnostic criteria are good for research purposes, but, in everyday clinical practice, they should be interpreted according to clinical judgement. In clinical practice, benzodiazepine dependence should be suspected in those having used benzodiazepines for longer than a month, in particular, if they are from a high-risk group. The main factors associated with an increased incidence of benzodiazepine dependence include:
- Dose
- Duration
- Concomitant use of antidepressants
Benzodiazepine dependence should be suspected also in individuals having substance use disorders including alcohol, and should be suspected in individuals obtaining their own supplies of benzodiazepines. Benzodiazepine dependence is almost certain in individuals who are members of a tranquilizer self-help group.
Research has found that about 40 percent of people with a diagnosis of benzodiazepine dependence are not aware that they are dependent on benzodiazepines, whereas about 11 percent of people judged not to be dependent believe that they are.
When assessing a person for benzodiazepine dependence, asking specific questions rather than questions based on concepts is recommended by experts as the best approach of getting a more accurate diagnosis. For example, asking persons if they "think about the medication at times of the day other than when they take the drug" would provide a more meaningful answer than asking "do you think you are psychologically dependent?". The Benzodiazepine Dependence Self Report Questionnaire is one questionnaire used to assess and diagnose benzodiazepine dependence.
Causality assessment is used to determine the likelihood that a drug caused a suspected ADR. There are a number of different methods used to judge causation, including the Naranjo algorithm, the Venulet algorithm and the WHO causality term assessment criteria. Each have pros and cons associated with their use and most require some level of expert judgement to apply.
An ADR should not be labeled as 'certain' unless the ADR abates with a challenge-dechallenge-rechallenge protocol (stopping and starting the agent in question). The chronology of the onset of the suspected ADR is important, as another substance or factor may be implicated as a cause; co-prescribed medications and underlying psychiatric conditions may be factors in the ADR.
Assigning causality to a specific agent often proves difficult, unless the event is found during a clinical study or large databases are used. Both methods have difficulties and can be fraught with error. Even in clinical studies some ADRs may be missed as large numbers of test individuals are required to find that adverse drug reaction. Psychiatric ADRs are often missed as they are grouped together in the questionnaires used to assess the population.
Many hospitals use the Clinical Institute Withdrawal Assessment for Alcohol (CIWA) protocol in order to assess the level of withdrawal present and therefore the amount of medication needed. When overuse of alcohol is suspected but drinking history is unclear, testing for elevated values of carbohydrate-deficient transferrin or gammaglutamyl transferase can help make the diagnosis of alcohol overuse and dependence more clear. The CIWA has also been shortened (now called the CIWA-Ar), while retaining its validity and reliability, to help assess patients more efficiently due to the life-threatening nature of alcohol withdrawal.
Other conditions that may present similarly include benzodiazepine withdrawal syndrome (a condition also mainly caused by GABA receptor adaptation).
Sending a letter to patients warning of the adverse effects of long-term use of benzodiazepines and recommending dosage reduction has been found to be successful and a cost-effective strategy in reducing benzodiazepine consumption in general practice. Within a year of the letter's going out, there was found to be a 17% fall in the number of benzodiazepines being prescribed, with 5% of patients having totally discontinued benzodiazepines. A study in the Netherlands reported a higher success rate by sending a letter to patients who are benzodiazepine-dependent. The results of the Dutch study reported 11.3% of patients discontinuing benzodiazepines completely within a year.
Many countries have official bodies that monitor drug safety and reactions. On an international level, the WHO runs the Uppsala Monitoring Centre, and the European Union runs the European Medicines Agency (EMEA). In the United States, the Food and Drug Administration (FDA) is responsible for monitoring post-marketing studies.
In Canada, the Marketed Health Products Directorate of Health Canada is responsible for the surveillance of marketed health products. In Australia, the Therapeutic Goods Administration (TGA) conducts postmarket monitoring of therapeutic products.
The overmedication of children has dramatically risen with those between the ages of 2 and 5 years old who are being prescribed atypical antipsychotics for bipolar disorders, developmental disabilities, ADHD, and behavior disorders. Drug companies have benefited considerably with profits made in sales for drugs such as stimulants for hyperactive children, with half a million children in the United States receiving medication. Children have become more involved with technology resulting in less play time outside and less time spent with parents. The long hours children spend with technology has impacted their attachment development, sensory and motor development, along with socialization skills, in return causing behavioral and psychological disorders and learning disabilities being diagnosed by psychotropic medication.
According to recent data from IMS health one of the leading services for data distribution in health care, 274,000 infants (0 to 1) are on anti-anxiety drugs, and 26,000 under a year old are on antidepressants. This is only a fraction of the millions of children 5 to 12 being prescribed these same drugs.
While these drugs can provide relief from some symptoms the children may suffer, psychiatric drugs have been shown in some instances to worsen the symptoms of mental illness and can cause adverse physical effects such as liver damage, weight gain, decreased cognitive function and dependency on the drug. (1) Antidepressants have side effects that can include suicidal thoughts and worsening depression. These medications can have long lasting effects on the children and these risks need to be taken into consideration.
It's important for parents to monitor their child's behavior and regulate their environment in order to help prevent any future affective disorders. Medication is often prescribed to these children however, it alone will not teach a child to create more valuable relationships at home or in the community. Other forms of intervention can be applied to supplement the effects of medication therapy and teach the child self-regulatory behaviors and healthy coping skills. The increase of psychiatric medication of children may be a result of the declining support for caregiving, leading to psychopathology in which drugs are oftentimes the go to method of treatment. Families do not always have knowledge regarding or the means to pursue other methods of intervention such as one-on-one therapy with the child, family therapy and parenting counseling that can teach effective parenting strategies to meet their child's specific needs. There is debate that healthcare professionals have been put under pressure to perform proficiently causing the influence of piecemeal polypharmacy.
The diagnosis of benzodiazepine overdose may be difficult, but is usually made based on the clinical presentation of the patient along with a history of overdose. Obtaining a laboratory test for benzodiazepine blood concentrations can be useful in patients presenting with CNS depression or coma of unknown origin. Techniques available to measure blood concentrations include thin layer chromatography, gas liquid chromatography with or without a mass spectrometer, and radioimmunoassay. Blood benzodiazepine concentrations, however, do not appear to be related to any toxicological effect or predictive of clinical outcome. Blood concentrations are, therefore, used mainly to confirm the diagnosis rather than being useful for the clinical management of the patient.
The DSM-5 guidelines for diagnosis of opioid use disorder require that the individual has significant impairment or distress related to opioid uses. In order to make the diagnosed two or more of eleven criteria must be present in a given year:
1. More opioids are taken than intended
2. The individual is unable to decrease the amount of opioids used
3. Large amounts of time are spent trying to obtain opioids, use opioids, or recover from taking them
4. The individual has cravings for opioids
5. Difficulty fulfilling professional duties at work or school
6. Continued use of opioids leading to social and interpersonal consequences
7. Decreased social or recreational activities
8. Using opioids despite it being physically dangerous settings
9. Continued use despite opioids worsening physical or psychological health (i.e. depression, constipation)
10. Tolerance
11. Withdrawal
Benzodiazepines are effective for the management of symptoms as well as the prevention of seizures. Certain vitamins are also an important part of the management of alcohol withdrawal syndrome. In those with severe symptoms inpatient care is often required. In those with lesser symptoms treatment at home may be possible with daily visits with a health care provider.
A related issue is overprescription, which occurs when doctors give prescription drugs to patients who do not need them. Antibiotics are a common example, as are narcotic painkillers. Aggressive marketing by drug companies is sometimes cited as a reason for overprescription.
Heroin-assisted treatment (HAT, the medical prescription of heroin) has been available in Switzerland since 1994. A 2001 study found a high rate of treatment retention and significant improvement in health, social situation and likelihood to leave the illegal drug scene in enrolled participants. The study found that the most common reason for discharge was the start of abstinence treatment or methadone treatment. The study also found that heroin-assisted treatment is cost-beneficial on a society level due to reduced criminality and improved overall health of participants.
The heroin-assisted treatment program was introduced in Switzerland to combat the increase in heroin use in the 1980s and 1990s and written into law 2010 as one pillar of a four-pillar strategy using repression, prevention, treatment and risk reduction. Usually, only a small percentage of patients receives heroin and have to fulfil a number of criteria. Since then, HAT programs have been adopted in the Netherlands, United Kingdom, Germany, Spain, Denmark, Belgium, Canada, and Luxembourg.
Drug tolerance is a pharmacological concept describing subjects' reduced reaction to a drug following its repeated use. Increasing its dosage may re-amplify the drug's effects, however this may accelerate tolerance, further reducing the drug's effects. Drug tolerance is indicative of drug use but is not necessarily associated with drug dependence or addiction. The process of tolerance development is reversible (e.g., through a drug holiday) and can involve both physiological factors and psychological factors.
One may also develop drug tolerance to side effects, in which case tolerance is a desirable characteristic. A medical intervention that has for objective to increase tolerance (e.g., allergen immunotherapy, in which one is exposed to larger and larger amounts of allergen to decrease one's allergic reactions) is called drug desensitization.
The opposite concept to drug tolerance is drug reverse tolerance (or drug sensitization), in which case the subject's reaction or effect will increase following its repeated use. The two notions are not incompatible and tolerance may sometimes lead to reverse tolerance. For example, heavy drinkers initially develop tolerance to alcohol (requiring them to drink larger amounts to achieve a similar effect) but excessive drinking can cause liver damage, which then puts them at risk of intoxication when drinking even very small amounts of alcohol.
Drug tolerance should not be confused with drug tolerability, which refers to the degree to which overt adverse effects of a drug can be tolerated by a patient.
Little attention has focused on the degree that benzodiazepines are abused as a primary drug of choice, but they are frequently abused alongside other drugs of abuse, especially alcohol, stimulants and opiates. The benzodiazepine most commonly abused can vary from country to country and depends on factors including local popularity as well as which benzodiazepines are available. Nitrazepam for example is commonly abused in Nepal and the United Kingdom, whereas in the United States of America where nitrazepam is not available on prescription other benzodiazepines are more commonly abused. In the United Kingdom and Australia there have been epidemics of temazepam abuse. Particular problems with abuse of temazepam are often related to gel capsules being melted and injected and drug-related deaths. Injecting most benzodiazepines is dangerous because of their relative insolubility in water (with the exception of midazolam), leading to potentially serious adverse health consequences for users.
Benzodiazepines are a commonly misused class of drug. A study in Sweden found that benzodiazepines are the most common drug class of forged prescriptions in Sweden. Concentrations of benzodiazepines detected in impaired motor vehicle drivers often exceeding therapeutic doses have been reported in Sweden and in Northern Ireland. One of the hallmarks of problematic benzodiazepine drug misuse is escalation of dose. Most licit prescribed users of benzodiazepines do not escalate their dose of benzodiazepines.
Problem benzodiazepine use can be associated with various deviant behaviors, including drug-related crime. In a survey of police detainees carried out by the Australian Government, both legal and illegal users of benzodiazepines were found to be more likely to have lived on the streets, less likely to have been in full-time work and more likely to have used heroin or methamphetamines in the past 30 days from the date of taking part in the survey. Benzodiazepine users were also more likely to be receiving illegal incomes and more likely to have been arrested or imprisoned in the previous year. Benzodiazepines were sometimes reported to be used alone, but most often formed part of a poly drug-using problem. Female users were more likely than men to be using heroin, whereas male users were more likely to report amphetamine use. Benzodiazepine users were more likely than non-users to claim government financial benefits and benzodiazepine users who were also poly-drug users were the most likely to be claiming government financial benefits. Those who reported using benzodiazepines alone were found to be in the mid-range when compared to other drug using patterns in terms of property crimes and criminal breaches. Of the detainees reporting benzodiazepine use, one in five reported injection use, mostly of illicit temazepam, with some who reported injecting prescribed benzodiazepines. The injection was a concern in this survey due to increased health risks. The main problems highlighted in this survey were concerns of dependence, the potential for overdose of benzodiazepines in combination with opiates and the health problems associated with injection of benzodiazepines.
Benzodiazepines are also sometimes used for drug facilitated sexual assaults and robbery, however, alcohol remains the most common drug involved in drug facilitated assaults. The muscle relaxant, disinhibiting and amnesia producing effects of benzodiazepines are the pharmacological properties which make these drugs effective in drug-facilitated crimes. Serial killer Jeffrey Dahmer admitted to using triazolam (Halcion), and occasionally temazepam (Restoril), in order to sedate his victims prior to murdering them.
In a 2017 publication, an analysis of the blood samples of 22 victims of drug-facilitated robberies in Bangladesh revealed that criminals use different mixtures of Benzodiazepines including Lorazepam, Midazolam, Diazepam and Nordiazepam to immobilize and then rob their victims.
Medical observation and supportive care are the mainstay of treatment of benzodiazepine overdose. Although benzodiazepines are absorbed by activated charcoal, gastric decontamination with activated charcoal is not beneficial in pure benzodiazepine overdose as the risk of adverse effects would outweigh any potential benefit from the procedure. It is recommended only if benzodiazepines have been taken in combination with other drugs that may benefit from decontamination. Gastric lavage (stomach pumping) or whole bowel irrigation are also not recommended. Enhancing elimination of the drug with hemodialysis, hemoperfusion, or forced diuresis is unlikely to be beneficial as these procedures have little effect on the clearance of benzodiazepines due to their large volume of distribution and lipid solubility.
Behavioral tolerance occurs with the use of certain psychoactive drugs, where tolerance to a behavioral effect of a drug, such as increased motor activity by methamphetamine, occurs with repeated use; it may occur through drug-independent learning or as a form of pharmacodynamic tolerance in the brain; the latter mechanism of behavioral tolerance occurs when one learns how to actively overcome drug-induced impairment through practice. Behavioral tolerance is often context-dependent, meaning tolerance depends on the environment in which the drug is administered, and not on the drug itself. Behavioral sensitization describes the opposite phenomenon.
Medication phobia, also known as pharmacophobia, is a fear of the use of pharmacological treatments. In severe, excessive and irrational, cases it may be a type of specific phobia.
While lack of awareness by patient or doctor of adverse drug reactions can have serious consequences, having a phobia of medications can also have serious detrimental effects on patient health, for example refusal of necessary pharmacological interventions. Medication phobia can also lead to problems with medication compliance. Medication phobia can also present in parents who are concerned about giving medications to their children, fearing that the medications will do more harm than good. Medication phobia can be triggered by unpleasant adverse reactions to medications which are sometimes prescribed inappropriately or at excessive doses. Lack of awareness of the patient's predisposition to adverse effects (e.g. anxious patients and the elderly) and failure to attribute the adverse effects to the drug serves to compound the phobia. Starting at low doses and slowly increasing the medication dosage can avoid medication phobia secondary to adverse effects from developing.
Fears of medication use is also prevalent in people who have experienced unpleasant withdrawal effects from psychotropic drugs. Sometimes patients wrongly associate symptoms of an acute disease or illness with medications used to treat the disease or illness. This form of pharmacophobia can be treated by attempting to convince the patient to take test doses of the drug or another drug in the same drug class to prove to the patient that the symptoms were not due to the drug but due to the illness the drug was taken to treat.
A drug interaction is a situation in which a substance (usually another drug) affects the activity of a drug when both are administered together. This action can be synergistic (when the drug's effect is increased) or antagonistic (when the drug's effect is decreased) or a new effect can be produced that neither produces on its own. Typically, interactions between drugs come to mind (drug-drug interaction). However, interactions may also exist between drugs and foods (drug-food interactions), as well as drugs and medicinal plants or herbs (drug-plant interactions). People taking antidepressant drugs such as monoamine oxidase inhibitors should not take food containing tyramine as hypertensive crisis may occur (an example of a drug-food interaction). These interactions may occur out of accidental misuse or due to lack of knowledge about the active ingredients involved in the relevant substances.
It is therefore easy to see the importance of these pharmacological interactions in the practice of medicine. If a patient is taking two drugs and one of them increases the effect of the other it is possible that an overdose may occur. The interaction of the two drugs may also increase the risk that side effects will occur. On the other hand, if the action of a drug is reduced it may cease to have any therapeutic use because of under dosage. Notwithstanding the above, on occasion these interactions may be sought in order to obtain an improved therapeutic effect. Examples of this include the use of codeine with paracetamol to increase its analgesic effect. Or the combination of clavulanic acid with amoxicillin in order to overcome bacterial resistance to the antibiotic. It should also be remembered that there are interactions that, from a theoretical standpoint, may occur but in clinical practice have no important repercussions.
The pharmaceutical interactions that are of special interest to the practice of medicine are primarily those that have negative effects for an organism. The risk that a pharmacological interaction will appear increases as a function of the number of drugs administered to a patient at the same time. Over a third (36%) of older adults in the U.S. regularly use 5 or more medications or supplements and 15% are potentially at risk for a major drug-drug interaction. Both the use of medications and subsequent adverse drug interactions have increased significantly between 2005-2011.
It is possible that an interaction will occur between a drug and another substance present in the organism (i.e. foods or alcohol). Or in certain specific situations a drug may even react with itself, such as occurs with dehydration. In other situations, the interaction does not involve any effect on the drug. In certain cases, the presence of a drug in an individual's blood may affect certain types of laboratory analysis (analytical interference).
It is also possible for interactions to occur outside an organism before administration of the drugs has taken place. This can occur when two drugs are mixed, for example, in a saline solution prior to intravenous injection. Some classic examples of this type of interaction include that thiopentone and suxamethonium should not be placed in the same syringe and same is true for benzylpenicillin and heparin. These situations will all be discussed under the same heading due to their conceptual similarity.
Drug interactions may be the result of various processes. These processes may include alterations in the pharmacokinetics of the drug, such as alterations in the absorption, distribution, metabolism, and excretion (ADME) of a drug. Alternatively, drug interactions may be the result of the pharmacodynamic properties of the drug, e.g. the co-administration of a receptor antagonist and an agonist for the same receptor.
Among US adults older than 55, 4% are taking medication and or supplements that put them at risk of a major drug interaction. Potential drug-drug interactions have increased over time and are more common in the low educated elderly even after controlling for age, sex, place of residence, and comorbidity.
Increased nicotine or cotinine (the nicotine metabolite) is detected in urine or blood, or serum nicotine concentrations increase.
Over the counter medications are those medications that do not require a prescription to purchase in the US. Medications that require a prescription to purchase in the US may be available in other countries without a prescription. The following guidelines are recommended:
- taking oral medications after breastfeeding rather than before will allow some of the medication to leave the mother's body through her kidneys between nursings.
- in most women without kidney disease, nonsteroidal anti-inflammatory drugs and paracetamol (acetaminophen) are used safely.
- aspirin can cause rashes and even cause bleeding in infants.
- limit the use of antihistamines for long periods of time. These anti-allergy medications can cause crying, sleep problems, fussiness, exsessive sleepiness in babies. Antihistamines have an effect on the amount of milk the body produces and decrease the supply.
- carefully observe the infant for changes or side effects when first taking a medication to watch for side effects. Side effects indicating that the medication is having an affect on the baby is difficulty breathing, rash and other questionable changes that occurred after the medication was started by the mother.
- many times other young children are in the home and keeping these over the counter medications out of their reach is a safe practice.
Other substances or chemicals have been evaluated regarding their safe use during pregnancy. Hair dye or solutions used for a 'permanent' do not pass to breastmilk. No adverse reports of using oral antihastamines and breastfeeding are found. Some of the older antihistamines used by a nursing mother can cause drowsiness in the infant. This may be a concern if the infant misses feedings by sleeping instead of nursing.
Drug intolerance or drug sensitivity refers to an inability to tolerate the adverse effects of a medication, generally at therapeutic or subtherapeutic doses. Conversely, a patient is said to be "tolerating" a drug when they can tolerate its adverse effects. It is not to be confused with a drug allergy, which is a form of drug intolerance, but requires an immune-mediated component. It is also not to be confused with drug tolerance ("drug resistance," or tachyphylaxis) which refers to a "lack" of adverse effects even at higher than average doses. Some instances of drug intolerance are known to result from genetic variations in drug metabolism.
The prognosis is typically good when medical care is provided and patients adequately treated are unlikely to have any long-term sequelae. However, severely affected patients with prolonged seizures or respiratory failure may have ongoing impairments secondary to the hypoxia. It has been stated that if a patient survives nicotine poisoning during the first 4 hours, they usually recover completely. At least at "normal" levels, as nicotine in the human body is broken down, it has an approximate biological half-life of 1–2 hours. Cotinine is an active metabolite of nicotine that remains in the blood for 18–20 hours, making it easier to analyze due to its longer half-life.
Intolerance to analgesics, particularly NSAIDs, is relatively common. It is thought that a variation in the metabolism of arachidonic acid is responsible for the intolerance. Symptoms include chronic rhinosinusitis with nasal polyps, asthma, gastrointestinal ulcers, angioedema, and urticaria.
Generally, a person experiencing a psychedelic crisis can be helped either to resolve the impasse, to bypass it, or, failing that, to terminate the experience. A person's thoughts before taking or while under the influence of the psychedelic, often greatly influence the trip.
Medical treatment consists of supportive therapy and minimization of external stimuli. In some cases, sedation is used when necessary to control self-destructive behavior, or when hyperthermia occurs. Diazepam is the most frequently used sedative for such treatment, but other benzodiazepines such as lorazepam are also effective. Such sedatives will only decrease fear and anxiety, but will not subdue hallucinations. In severe cases, antipsychotics such as haloperidol can reduce or stop hallucinations. Haloperidol is effective against drug-induced psychosis caused by LSD and other tryptamines, amphetamines, ketamine and phencyclidine.