70-430: A placebo ( / p l ə ˈ s iː b oʊ / plə- SEE -boh ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like saline ), sham surgery , and other procedures. Placebos are used in randomized clinical trials to test the efficacy of medical treatments . In a placebo-controlled clinical trial , any change in
140-559: A central venous catheter , also known as a 'central line'. Such hypertonic saline is normally available in two strengths, the former of which is more commonly administered: Hypertonic NaCl solutions that are less commonly used are 7% (1200 mEq/L) and 23.4% (approx 4000 mEq/L), both of which are used (also via central line), often in conjunction with supplementary diuretics, in the treatment of traumatic brain injury . Other concentrations commonly used include: In medicine, common types of salines include: And in cell biology, in addition to
210-501: A sterile 9 g of salt per litre (0.9%) solution, known as normal saline . Higher and lower concentrations may also occasionally be used. Saline is acidic, with a pH of 5.5 (due mainly to dissolved carbon dioxide). The medical use of saline began around 1831. It is on the World Health Organization's List of Essential Medicines . In 2022, sodium salts was the 216th most commonly prescribed medication in
280-438: A stimulant may trigger an effect on heart rhythm and blood pressure , but when administered as a depressant , the opposite effect. In psychology, the two main hypotheses of the placebo effect are expectancy theory and classical conditioning . In 1985, Irving Kirsch hypothesized that placebo effects are produced by the self-fulfilling effects of response expectancies, in which the belief that one will feel different leads
350-449: A treatment process is a placebo when none of the characteristic treatment factors are effective (remedial or harmful) in the patient for a given disease . In a clinical trial, a placebo response is the measured response of subjects to a placebo; the placebo effect is the difference between that response and no treatment. The placebo response may include improvements due to natural healing, declines due to natural disease progression,
420-473: A great reputation; it was taken as a powder, as an extract, as an elixir, even in baths. It was good for the nerves, the chest, the stomach—what can I say?— it was a true panacea. At the peak of the fad, one of Bouvard's [ sic ] patients asked him if it might not be a good idea to take some: "Take it, Madame", he replied, "and hurry up while it [still] cures." [dépêchez-vous pendant qu'elle guérit] Placebos have featured in medical use until well into
490-441: A group of subjects that receives a sham treatment. The subjects in such trials are blinded as to whether they receive the treatment or a placebo. If a person is given a placebo under one name, and they respond, they will respond in the same way on a later occasion to that placebo under that name but not if under another. Clinical trials are often double-blinded so that the researchers also do not know which test subjects are receiving
560-422: A lowered perception of pain). Placebos can improve patient-reported outcomes such as pain and nausea . A 2001 meta-analysis of the placebo effect looked at trials in 40 different medical conditions, and concluded the only one where it had been shown to have a significant effect was for pain. Another Cochrane review in 2010 suggested that placebo effects are apparent only in subjective, continuous measures, and in
630-456: A neutral stimulus saccharin is paired in a drink with an agent that produces an unconditioned response. For example, that agent might be cyclophosphamide , which causes immunosuppression . After learning this pairing, the taste of saccharin by itself is able to cause immunosuppression, as a new conditioned response via neural top-down control. Such conditioning has been found to affect a diverse variety of not just basic physiological processes in
700-501: A person a placebo when there is an effective treatment available is a bioethically complex issue. While placebo-controlled trials might provide information about the effectiveness of a treatment, it denies some patients what could be the best available (if unproven) treatment. Informed consent is usually required for a study to be considered ethical, including the disclosure that some test subjects will receive placebo treatments. The ethics of placebo-controlled studies have been debated in
770-451: A person to actually feel different. According to this theory, the belief that one has received an active treatment can produce the subjective changes thought to be produced by the real treatment. Similarly, the appearance of effect can result from classical conditioning, wherein a placebo and an actual stimulus are used simultaneously until the placebo is associated with the effect from the actual stimulus. Both conditioning and expectations play
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#1732791908219840-483: A person's perception of pain. According to the American Cancer Society, "A person might reinterpret a sharp pain as uncomfortable tingling." Measuring the extent of the placebo effect is difficult due to confounding factors. For example, a patient may feel better after taking a placebo due to regression to the mean (i.e. a natural recovery or change in symptoms), but this can be ruled out by comparing
910-543: A placebo can also be due to unrelated factors, such as regression to the mean (a statistical effect where an unusually high or low measurement is likely to be followed by a less extreme one). The use of placebos in clinical medicine raises ethical concerns, especially if they are disguised as an active treatment, as this introduces dishonesty into the doctor–patient relationship and bypasses informed consent . Placebos are also popular because they can sometimes produce relief through psychological mechanisms (a phenomenon known as
980-555: A quote from the Vulgate 's Psalm 116:9 ( Psalm 114 :9 in modern bibles), placēbō Dominō in regiōne vīvōrum , "[I] shall please the Lord in the land of the living". From that, a singer of placebo became associated with someone who falsely claimed a connection to the deceased to get a share of the funeral meal, and hence a flatterer, and so a deceptive act to please. The definition of placebo has been debated. One definition states that
1050-448: A role in placebo effect, and make different kinds of contributions. Conditioning has a longer-lasting effect, and can affect earlier stages of information processing. Those who think a treatment will work display a stronger placebo effect than those who do not, as evidenced by a study of acupuncture. Additionally, motivation may contribute to the placebo effect. The active goals of an individual changes their somatic experience by altering
1120-407: A safe osmolality while providing less sodium chloride. The amount of normal saline infused depends largely on the needs of the person (e.g. ongoing diarrhea or heart failure ). Saline is also often used for nasal washes to relieve some of the symptoms of rhinitis and the common cold . The solution exerts a softening and loosening influence on the mucus to make it easier to wash out and clear
1190-432: A significant, albeit slightly smaller overall effect of open-label placebos, while noting that "research on OLPs is still in its infancy". If the person dispensing the placebo shows their care towards the patient, is friendly and sympathetic, or has a high expectation of a treatment's success, then the placebo is more effectual. In the 2022 book Epigenetics and Anticipation published by Springer , Goli integrates many of
1260-403: A vein , it is used to treat hypovolemia such as that from gastroenteritis and diabetic ketoacidosis . Large amounts may result in fluid overload , swelling , acidosis , and high blood sodium . In those with long-standing low blood sodium , excessive use may result in osmotic demyelination syndrome . Saline is in the crystalloid family of medications. It is most commonly used as
1330-399: Is 1.0046 grams at 22 °C. The molecular weight of sodium chloride is approximately 58.4 grams per mole, so 58.4 grams of sodium chloride equals 1 mole. Since normal saline contains 9 grams of NaCl, the concentration is 9 grams per litre divided by 58.4 grams per mole, or 0.154 mole per litre. Since NaCl dissociates into two ions – sodium and chloride – 1 molar NaCl
1400-404: Is 2 osmolar. Thus, NS contains 154 mEq /L of Na and the same amount of Cl . This points to an osmolarity of 154 + 154 = 308, which is higher (i.e. more solute per litre) than that of blood (approximately 285). However, if the osmotic coefficient (a correction for non-ideal solutions) is taken into account, then the saline solution is much closer to isotonic. The osmotic coefficient of NaCl
1470-705: Is Professor of Evidence-Based Medicine and Clinical Research Methodology at the University of Southern Denmark , as well as head of research at Odense University Hospital 's Center for Evidence-Based Medicine. He is the former editor-in-chief of the Danish journal Bibliotek for Læger . He is also affiliated with the Nordic Cochrane Centre in Copenhagen . He received his Ph.D. in June 2001 from
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#17327919082191540-403: Is about 0.93, which yields an osmolarity of 0.154 × 1000 × 2 × 0.93 = 286.44. Therefore, the osmolarity of normal saline is a close approximation to the osmolarity of blood. For medical purposes, saline is often used to flush wounds and skin abrasions . However, research indicates that it is no more effective than potable tap water. Normal saline will not burn or sting when applied. Saline
1610-420: Is also used in I.V. therapy , intravenously supplying extra water to rehydrate people or supplying the daily water and salt needs ("maintenance" needs) of a person who is unable to take them by mouth. Because infusing a solution of low osmolality can cause problems such as hemolysis , intravenous solutions with reduced saline concentrations (less than 0.9%) typically have dextrose ( glucose ) added to maintain
1680-587: Is currently recommended by the Cystic Fibrosis Foundation as a primary part of a cystic fibrosis treatment regimen. An 11% solution of xylitol with 0.65% saline stimulates the washing of the nasopharynx and has an effect on the nasal pathogenic bacteria. This has been used in complementary and alternative medicine. Hypertonic saline may be used in perioperative fluid management protocols to reduce excessive intravenous fluid infusions and lessen pulmonary complications. Hypertonic saline
1750-481: Is getting the placebo and who is getting the treatment under test, as patients' and clinicians' expectations of efficacy can influence results. The idea of a placebo effect was discussed in 18th century psychology, but became more prominent in the 20th century. Modern studies find that placebos can affect some outcomes such as pain and nausea , but otherwise do not generally have important clinical effects. Improvements that patients experience after being treated with
1820-629: Is real is misguided." A survey in the United States of more than 10,000 physicians came to the result that while 24% of physicians would prescribe a treatment that is a placebo simply because the patient wanted treatment, 58% would not, and for the remaining 18%, it would depend on the circumstances. Referring specifically to homeopathy , the House of Commons of the United Kingdom Science and Technology Committee has stated: In
1890-406: Is technically accurate because normal saline is not exactly like blood serum , they convey the practical effect usually seen: good fluid balance with minimal hypotonicity or hypertonicity. NS is used frequently in intravenous drips (IVs) for people who cannot take fluids orally and have developed or are in danger of developing dehydration or hypovolemia . NS is also used for aseptic purpose. NS
1960-991: Is tentative evidence that saline nasal irrigation may help with long term cases of rhinosinusitis . Evidence for use in cases of rhinosinusitis of short duration is unclear. Saline is used in scleral tattooing , coloring the white part of the human eye. Saline is used to lighten tattoos (including microblading tattoos) through the process of osmosis . Concentrations lower and higher than normal also exist. High concentrations are used rarely in medicine but frequently in molecular biology . Hypertonic saline—7% NaCl solutions are considered mucoactive agents and thus are used to hydrate thick secretions ( mucus ) in order to make it easier to cough up and out ( expectorate ). 3% hypertonic saline solutions are also used in critical care settings, acutely increased intracranial pressure , or severe hyponatremia . Inhalation of hypertonic saline has also been shown to help in other respiratory problems, specifically bronchiolitis . Hypertonic saline
2030-456: Is typically the first fluid used when hypovolemia is severe enough to threaten the adequacy of blood circulation, and has long been believed to be the safest fluid to give quickly in large volumes. However, it is now known that rapid infusion of NS can cause metabolic acidosis . The solution is 9 grams of sodium chloride (NaCl) dissolved in water, to a total volume of 1000 ml (weight per unit volume). The mass of 1 millilitre of normal saline
2100-719: Is used in treating hyponatremia and cerebral edema . Rapid correction of hyponatremia via hypertonic saline, or via any saline infusion > 40 mmol/L (Na+ having a valence of 1, 40 mmol/L = 40 mEq/L) greatly increases risk of central pontine myelinolysis (CPM), and so requires constant monitoring of the person's response. Water privation combined with diuretic block does not produce as much risk of CPM as saline administration does; however, it does not correct hyponatremia as rapidly as administration of hypertonic saline does. Due to hypertonicity, administration may result in phlebitis and tissue necrosis . As such, concentrations greater than 3% NaCl should normally be administered via
2170-402: The University of Copenhagen , with a thesis entitled Are placebo interventions associated with clinically important effects? He is best-known for a 2001 article he co-authored with Peter C. Gotzsche on the placebo effect . The article reviewed 114 studies comparing placebo treatment to no treatment, and concluded that placebos did not have clinically important effects for any condition, with
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2240-404: The control group is known as the placebo response , and the difference between this and the result of no treatment is the placebo effect . Placebos in clinical trials should ideally be indistinguishable from so-called verum treatments under investigation, except for the latter's particular hypothesized medicinal effect. This is to shield test participants (with their consent ) from knowing who
2310-416: The eye . Depending on the condition being treated, they may contain steroids , antihistamines , sympathomimetics , beta receptor blockers , parasympathomimetics , parasympatholytics , prostaglandins , non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics or topical anesthetics . Eye drops sometimes do not have medications in them and are only lubricating and tear -replacing solutions. There
2380-563: The "placebo effect"). They can affect how patients perceive their condition and encourage the body's chemical processes for relieving pain and a few other symptoms, but have no impact on the disease itself. The Latin term placebo (pronounced /plaˈkebo/ or /plaˈt͡ʃebo) means [I] shall be pleasing . It was used as a name for the Vespers in the Office of the Dead , taken from its incipit ,
2450-555: The Committee's view, homeopathy is a placebo treatment and the Government should have a policy on prescribing placebos. The Government is reluctant to address the appropriateness and ethics of prescribing placebos to patients, which usually relies on some degree of patient deception. Prescribing of placebos is not consistent with informed patient choice—which the Government claims is very important—as it means patients do not have all
2520-521: The United States from 1990 to 2013. The researchers suggested that this may be because such trials have "increased in study size and length" during this time period. Children seem to have a greater response than adults to placebos. The administration of the placebos can determine the placebo effect strength. Studies have found that taking more pills would strengthen the effect. Capsules appear to be more influential than pills, and injections are even stronger than capsules. Some studies have investigated
2590-446: The United States, with more than 1 million prescriptions. Normal saline ( NSS, NS or N/S ) is the commonly used phrase for a solution of 0.90% w/v of NaCl , 308 mOsm /L or 9.0 g per liter. Less commonly, this solution is referred to as physiological saline or isotonic saline (because it is approximately isotonic to blood serum, which makes it a physiologically normal solution). Although neither of those names
2660-513: The above the following are used: Saline was believed to have originated during the Indian Blue cholera pandemic that swept across Europe in 1831. William Brooke O'Shaughnessy , a recent graduate of Edinburgh Medical School , proposed in an article to medical journal The Lancet to inject people infected with cholera with highly oxygenated salts to treat the "universal stagnation of the venous system and rapid cessation of arterialisation of
2730-424: The abovementioned issues, 60% of surveyed physicians and head nurses reported using placebos in an Israeli study, with only 5% of respondents stating that placebo use should be strictly prohibited. A British Medical Journal editorial said, "that a patient gets pain relief from a placebo does not imply that the pain is not real or organic in origin ...the use of the placebo for 'diagnosis' of whether or not pain
2800-450: The activation, and increased functional correlation between this activation, in the anterior cingulate , prefrontal , orbitofrontal and insular cortices, nucleus accumbens , amygdala , the brainstem 's periaqueductal gray matter , and the spinal cord . Since 1978, it has been known that placebo analgesia depends upon the release of endogenous opioids in the brain. Such analgesic placebos activation changes processing lower down in
2870-470: The active or placebo treatment. The placebo effect in such clinical trials is weaker than in normal therapy since the subjects are not sure whether the treatment they are receiving is active. Saline (medicine) Saline (also known as saline solution ) is a mixture of sodium chloride (salt) and water . It has a number of uses in medicine including cleaning wounds, removal and storage of contact lenses , and help with dry eyes . By injection into
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2940-529: The blood" seen in people with severely dehydrated cholera. He found his treatment harmless in dogs, and his proposal was soon adopted by the physician Thomas Latta in treating people with cholera to beneficial effect. In the following decades, variations and alternatives to Latta's solution were tested and used in treating people with cholera. These solutions contained a range of concentrations of sodium, chloride, potassium, carbonate, phosphate, and hydroxide. The breakthrough in achieving physiological concentrations
3010-629: The brain by enhancing the descending inhibition through the periaqueductal gray on spinal nociceptive reflexes , while the expectations of anti-analgesic nocebos acts in the opposite way to block this. Functional imaging upon placebo analgesia has been summarized as showing that the placebo response is "mediated by 'top-down' processes dependent on frontal cortical areas that generate and maintain cognitive expectancies. Dopaminergic reward pathways may underlie these expectancies". "Diseases lacking major 'top-down' or cortically based regulation may be less prone to placebo-related improvement". In conditioning,
3080-475: The change in response to receiving a placebo had increased significantly between 1960 and 2013. The review's authors identified several factors that could be responsible for this change, including inflation of baseline scores and enrollment of fewer severely ill patients. Another analysis published in Pain in 2015 found that placebo responses had increased considerably in neuropathic pain clinical trials conducted in
3150-427: The combined risk of mortality, need for additional dialysis, or persistent kidney problems from 15% to 14%, which given the large number of patients is a significant reduction. Coconut water has been used in place of normal saline in areas without access to normal saline. Its use, however, has not been well studied. Asbj%C3%B8rn Hr%C3%B3bjartsson Asbjørn Hróbjartsson is a Danish medical researcher. He
3220-547: The compassion you show your patients." In an opinion piece about homeopathy, Ernst argues that it is wrong to support alternative medicine on the basis that it can make patients feel better through the placebo effect. His concerns are that it is deceitful and that the placebo effect is unreliable. Goldacre also concludes that the placebo effect does not justify alternative medicine, arguing that unscientific medicine could lead to patients not receiving prevention advice. Placebo researcher Fabrizio Benedetti also expresses concern over
3290-428: The detection and interpretation of expectation-congruent symptoms, and by changing the behavioral strategies a person pursues. Motivation may link to the meaning through which people experience illness and treatment. Such meaning is derived from the culture in which they live and which informs them about the nature of illness and how it responds to treatment. Functional imaging upon placebo analgesia suggests links to
3360-414: The drug effect was not related to depression severity. Another meta-analysis found that 79% of depressed patients receiving placebo remained well (for 12 weeks after an initial 6–8 weeks of successful therapy) compared to 93% of those receiving antidepressants. In the continuation phase however, patients on placebo relapsed significantly more often than patients on antidepressants. A phenomenon opposite to
3430-411: The existence of placebo effects seems undeniable. For example, recent research has linked placebo interventions to improved motor functions in patients with Parkinson's disease . Other objective outcomes affected by placebos include immune and endocrine parameters, end-organ functions regulated by the autonomic nervous system , and sport performance. Placebos are believed to be capable of altering
3500-674: The immune system but ones such as serum iron levels , oxidative DNA damage levels, and insulin secretion. Recent reviews have argued that the placebo effect is due to top-down control by the brain for immunity and pain. Pacheco-López and colleagues have raised the possibility of "neocortical-sympathetic-immune axis providing neuroanatomical substrates that might explain the link between placebo/conditioned and placebo/expectation responses". There has also been research aiming to understand underlying neurobiological mechanisms of action in pain relief, immunosuppression , Parkinson's disease and depression . Dopaminergic pathways have been implicated in
3570-417: The information needed to make choice meaningful. A further issue is that the placebo effect is unreliable and unpredictable. In his 2008 book Bad Science , Ben Goldacre argues that instead of deceiving patients with placebos, doctors should use the placebo effect to enhance effective medicines. Edzard Ernst has argued similarly that "As a good doctor you should be able to transmit a placebo effect through
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#17327919082193640-548: The magnitude of placebo analgesia can be measured is by conducting "open/hidden" studies, in which some patients receive an analgesic and are informed that they will be receiving it (open), while others are administered the same drug without their knowledge (hidden). Such studies have found that analgesics are considerably more effective when the patient knows they are receiving them. A review published in JAMA Psychiatry found that, in trials of antipsychotic medications,
3710-423: The name of the drug they are receiving, its side effects, and other treatment options. This view is shared by some on the grounds of patient autonomy . There are also concerns that legitimate doctors and pharmacists could open themselves up to charges of fraud or malpractice by using a placebo. Critics also argued that using placebos can delay the proper diagnosis and treatment of serious medical conditions. Despite
3780-683: The nasal passages for both babies and adults. In very rare instances, fatal infection by the amoeba Naegleria fowleri can occur if it enters the body through the nose; therefore tap water must not be used for nasal irrigation. Water is only appropriate for this purpose if it is sterile, distilled, boiled, filtered, or disinfected. Sterile isotonic saline is also used to fill breast implants for use in breast augmentation surgery, to correct congenital abnormalities such as tuberous breast deformity, and to correct breast asymmetry. Saline breast implants are also used in reconstructive surgery post-mastectomy. Eye drops are saline-containing drops used on
3850-469: The patient". Although this definition contained a derogatory implication it did not necessarily imply that the remedy had no effect. It was recognized in the 18th and 19th centuries that drugs or remedies often were perceived to work best while they were still novel: We know that, in Paris, fashion imposes its dictates on medicine just as it does with everything else. Well, at one time, pyramidal elm bark had
3920-407: The placebo effect has also been observed. When an inactive substance or treatment is administered to a recipient who has an expectation of it having a negative impact, this intervention is known as a nocebo ( Latin nocebo = "I shall harm"). A nocebo effect occurs when the recipient of an inert substance reports a negative effect or a worsening of symptoms, with the outcome resulting not from
3990-627: The placebo group with a no treatment group (as all the placebo research does). It is harder still to tell the difference between the placebo effect and the effects of response bias , observer bias and other flaws in trial methodology, as a trial comparing placebo treatment and no treatment will not be a blinded experiment . In their 2010 meta-analysis of the placebo effect, Asbjørn Hróbjartsson and Peter C. Gøtzsche argue that "even if there were no true effect of placebo, one would expect to record differences between placebo and no-treatment groups due to bias associated with lack of blinding". One way in which
4060-459: The placebo response in pain and depression. Placebo-controlled studies, as well as studies of the placebo effect itself, often fail to adequately identify confounding factors. False impressions of placebo effects are caused by many factors including: The word placebo was used in a medicinal context in the late 18th century to describe a "commonplace method or medicine" and in 1811 it was defined as "any medicine adapted more to please than to benefit
4130-427: The potential for placebos to be used unethically, warning that there is an increase in "quackery" and that an "alternative industry that preys on the vulnerable" is developing. The mechanism for how placebos could have effects is uncertain. From a sociocognitive perspective, intentional placebo response is attributed to the “ritual effect” that induces anticipation for transition to a better state. A placebo presented as
4200-567: The revision process of the Declaration of Helsinki . Of particular concern has been the difference between trials comparing inert placebos with experimental treatments, versus comparing the best available treatment with an experimental treatment; and differences between trials in the sponsor's developed countries versus the trial's targeted developing countries. Some suggest that existing medical treatments should be used instead of placebos, to avoid having some patients not receive medicine during
4270-467: The specific and non-specific factors influencing the placebo effect in the perceived healing response formula, developed based on main placebo studies. In 2008, a meta-analysis led by psychologist Irving Kirsch , analyzing data from the Food and Drug Administration (FDA), concluded that 82% of the response to antidepressants was accounted for by placebos. However, other authors expressed serious doubts about
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#17327919082194340-645: The substance itself, but from negative expectations about the treatment. Another negative consequence is that placebos can cause side-effects associated with real treatment. Withdrawal symptoms can also occur after placebo treatment. This was found, for example, after the discontinuation of the Women's Health Initiative study of hormone replacement therapy for menopause . Women had been on placebo for an average of 5.7 years. Moderate or severe withdrawal symptoms were reported by 4.8% of those on placebo compared to 21.3% of those on hormone replacement. Knowingly giving
4410-462: The tendency for people who were temporarily feeling either better or worse than usual to return to their average situations ( regression toward the mean ), and errors in the clinical trial records, which can make it appear that a change has happened when nothing has changed. It is also part of the recorded response to any active medical intervention. Measurable placebo effects may be either objective (e.g. lowered blood pressure ) or subjective (e.g.
4480-411: The treatment of pain and related conditions. The review found that placebos do not appear to affect the actual diseases, or outcomes that are not dependent on a patient's perception. The authors, Asbjørn Hróbjartsson and Peter C. Gøtzsche , concluded that their study "did not find that placebo interventions have important clinical effects in general". This interpretation has been subject to criticism, as
4550-419: The trial. The practice of doctors prescribing placebos that are disguised as real medication is controversial. A chief concern is that it is deceptive and could harm the doctor–patient relationship in the long run. While some say that blanket consent, or the general consent to unspecified treatment given by patients beforehand, is ethical, others argue that patients should always obtain specific information about
4620-483: The twentieth century. An influential 1955 study entitled The Powerful Placebo firmly established the idea that placebo effects were clinically important, and were a result of the brain's role in physical health . A 1997 reassessment found no evidence of any placebo effect in the source data, as the study had not accounted for regression to the mean . The placebo effect makes it more difficult to evaluate new treatments. Clinical trials control for this effect by including
4690-539: The use of placebos where the patient is fully aware that the treatment is inert, known as an open-label placebo . Clinical trials found that open-label placebos may have positive effects in comparison to no treatment, which may open new avenues for treatments, but a review of such trials noted that they were done with a small number of participants and hence should be interpreted with "caution" until further, better-controlled trials are conducted. An updated 2021 systematic review and meta-analysis based on 11 studies also found
4760-512: The used methods and the interpretation of the results, especially the use of 0.5 as the cut-off point for the effect size . A complete reanalysis and recalculation based on the same FDA data found that the Kirsch study had "important flaws in the calculations". The authors concluded that although a large percentage of the placebo response was due to expectancy, this was not true for the active drug. Besides confirming drug effectiveness, they found that
4830-540: Was accomplished by Sydney Ringer in the early 1880s, when he determined the optimal salt concentrations to maintain the contractility of frog heart muscle tissue. Normal saline is considered a descendant of the pre-Ringer solutions, as Ringer's findings were not adopted and widely used until decades later. The term "normal saline" itself appears to have little historical basis, except for studies done in 1882–83 by Dutch physiologist Hartog Jacob Hamburger ; these in vitro studies of red cell lysis suggested incorrectly that 0.9%
4900-401: Was the concentration of salt in human blood (rather than 0.6%, the true concentration). Normal saline has become widely used in modern medicine, but due to the mismatch with real blood, other solutions have proved better. The 2018 publication of a randomized, controlled trial with 15,000 people in intensive care units showed that compared to normal saline, lactated Ringer's solution reduced
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