<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Burning mouth syndrome and explain in detail? [/INST] Burning mouth syndrome (BMS) is a burning, tingling or scalding sensation in the mouth, lasting for at least four to six months, with no underlying known dental or medical cause. No related signs of disease are found in the mouth.  People with burning mouth syndrome may also have a subjective xerostomia (dry mouth sensation where no cause can be found such as reduced salivary flow), paraesthesia (altered sensation such as tingling in the mouth), or an altered sense of taste or smell.A burning sensation in the mouth can be a symptom of another disease when local or systemic factors are found to be implicated; this is not considered to be burning mouth syndrome,  which is a syndrome of medically unexplained symptoms.  The International Association for the Study of Pain defines burning mouth syndrome as "a distinctive nosological entity characterized by unremitting oral burning or similar pain in the absence of detectable mucosal changes" and "burning pain in the tongue or other oral mucous membranes", and the International Headache Society defines it as "an intra-oral burning sensation for which no medical or dental cause can be found". To ensure the correct diagnosis of burning mouth syndrome, Research Diagnostic Criteria (RDC/BMS) have been developed.Insufficient evidence leaves it unclear if effective treatments exist.

Signs and symptoms
By definition, BMS has no signs. Sometimes affected persons will attribute the symptoms to sores in the mouth, but these are in fact normal anatomic structures (e.g. lingual papillae, varices). Symptoms of BMS are variable, but the typical clinical picture is given below, considered according to the Socrates pain assessment method (see table). If clinical signs are visible, then another explanation for the burning sensation may be present. Erythema (redness) and edema (swelling) of papillae on the tip of the tongue may be a sign that the tongue is being habitually pressed against the teeth. The number and size of filiform papillae may be reduced. If the tongue is very red and smooth, then there is likely a local or systemic cause (e.g. eythematous candidiasis, anemia).

Causes
Theories
In about 50% of cases of burning mouth sensation  no identifiable cause is apparent; these cases are termed (primary) BMS. Several theories of what causes BMS have been proposed, and these are supported by varying degrees of evidence, but none is proven.
As most people with BMS are postmenopausal women, one theory of the cause of BMS is of estrogen or progesterone deficit, but a strong statistical correlation has not been demonstrated. Another theory is that BMS is related to autoimmunity, as abnormal antinuclear antibody and rheumatoid factor can be found in the serum of more than 50% of persons with BMS, but these levels may also be seen in elderly people who do not have any of the symptoms of this condition. Whilst salivary flow rates are normal and there are no clinical signs of a dry mouth to explain a complaint of dry mouth, levels of salivary proteins and phosphate may be elevated and salivary pH or buffering capacity may be reduced.Depression and anxiety are strongly associated with BMS. It is not known if depression is a cause or result of BMS, as depression may develop in any setting of constant unrelieved irritation, pain, and sleep disturbance. It is estimated that about 20% of BMS cases involve psychogenic factors, and some consider BMS a psychosomatic illness, caused by cancerophobia, concern about sexually transmitted infections, or hypochondriasis.Chronic low-grade trauma due to parafunctional habits (e.g. rubbing the tongue against the teeth or pressing it against the palate), may be involved. BMS is more common in persons with Parkinsons disease, so it has been suggested that it is a disorder of reduced pain threshold and increased sensitivity. Often people with BMS have unusually raised taste sensitivity, termed hypergeusia ("super tasters"). Dysgeusia (usually a bitter or metallic taste) is present in about 60% of people with BMS, a factor which led to the concept of a defect in sensory peripheral neural mechanisms. Changes in the oral environment, such as changes in the composition of saliva, may induce neuropathy or interruption of nerve transduction. The onset of BMS is often spontaneous, although it may be gradual. There is sometimes a correlation with a major life event or stressful period in life. In women, the onset of BMS is most likely three to twelve years following menopause.

Other causes of an oral burning sensation
Several local and systemic factors can give a burning sensation in the mouth without any clinical signs, and therefore may be misdiagnosed as BMS. Some sources state that where there is an identifiable cause for a burning sensation, this can be termed "secondary BMS" to distinguish it from primary BMS. However, the accepted definitions of BMS hold that there are no identifiable causes for BMS, and where there are identifiable causes, the term BMS should not be used.Some causes of a burning mouth sensation may be accompanied by clinical signs in the mouth or elsewhere on the body. For example, burning mouth pain may be a symptom of allergic contact stomatitis. This is a contact sensitivity (type IV hypersensitivity reaction) in the oral tissues to common substances such as sodium lauryl sulfate, cinnamaldehyde or dental materials. However, allergic contact stomatitis is accompanied by visible lesions and gives positive response with patch testing. Acute (short term) exposure to the allergen (the substance triggering the allergic response) causes non-specific inflammation and possibly mucosal ulceration. Chronic (long term) exposure to the allergen may appear as chronic inflammatory, lichenoid (lesions resembling oral lichen planus), or plasma cell gingivitis, which may be accompanied by glossitis and cheilitis. Apart from BMS itself, a full list of causes of an oral burning sensation is given below:

Deficiency of iron, folic acid or various B vitamins (glossitis e.g. due to anemia), or zinc
Neuropathy, e.g. following damage to the chorda tympani nerve.
Hypothyroidism.
Medications ("scalded mouth syndrome", unrelated to BMS) - protease inhibitors and angiotensin-converting-enzyme inhibitors (e.g. captopril).
Type 2 diabetes
True xerostomia, caused by hyposalivation e.g. Sjögrens syndrome
Parafunctional activity, e.g. nocturnal bruxism or a tongue thrusting habit.
Restriction of the tongue by poorly constructed dentures.
Geographic tongue.
Oral candidiasis.
Herpetic infection (herpes simplex virus).
Fissured tongue.
Lichen planus.
Allergies and contact sensitivities to foods, metals, and other substances (see table).
Hiatal hernia.
Human immunodeficiency virus.
Multiple myeloma

Diagnosis
BMS is a diagnosis of exclusion, i.e. all other explanations for the symptoms are ruled out before the diagnosis is made. There are no clinically useful investigations that would help to support a diagnosis of BMS (by definition all tests would have normal results), but blood tests and / or urinalysis may be useful to rule out anemia, deficiency states, hypothyroidism and diabetes. Investigation of a dry mouth symptom may involve sialometry, which objectively determines if there is any reduction of the salivary flow rate (hyposalivation). Oral candidiasis can be tested for with use of a swabs, smears, an oral rinse or saliva samples.  It has been suggested that allergy testing (e.g., patch test) is inappropriate in the absence of a clear history and clinical signs in people with a burning sensation in the mouth. The diagnosis of a people with a burning symptom may also involve psychologic screening e.g. depression questionnaires.The second edition of the International Classification of Headache Disorders lists diagnostic criteria for "Glossodynia and Sore Mouth":

A. Pain in the mouth present daily and persisting for most of the day,
B. Oral mucosa is of normal appearance,
C. Local and systemic diseases have been excluded.

Classification
A burning sensation in the mouth may be primary (i.e. burning mouth syndrome) or secondary to systemic or local factors. Other sources refer to a "secondary BMS" with a similar definition, i.e. a burning sensation which is caused by local or systemic factors, or "where oral burning is explained by a clinical abnormality". However this contradicts the accepted definition of BMS which specifies that no cause can be identified. "Secondary BMS" could therefore be considered a misnomer. BMS is an example of dysesthesia, or a distortion of sensation.Some consider BMS to be a variant of atypical facial pain. More recently, BMS has been described as one of the 4 recognizable symptom complexes of chronic facial pain, along with atypical facial pain, temporomandibular joint dysfunction and atypical odontalgia. BMS has been subdivided into three general types, with type two being the most common and type three being the least common. Types one and two have unremitting symptoms, whereas type three may show remitting symptoms.
Type 1 - Symptoms not present upon waking, and then increase throughout the day
Type 2 - Symptoms upon waking and through the day
Type 3 - No regular pattern of symptomsSometimes those terms specific to the tongue (e.g. glossodynia) are reserved for when the burning sensation is located only on the tongue.

Treatment
If a cause can be identified for a burning sensation in the mouth, then treatment of this underlying factor is recommended. If symptom persist despite treatment a diagnosis of BMS is confirmed. BMS has been traditionally treated by reassurance and with antidepressants, anxiolytics or anticonvulsants. A 2016 Cochrane review of treatment for burning mouth syndrome concluded that strong evidence of an effective treatment was not available, however,  a systematic review in 2018 found that the use of antidepressants and alpha-lipoic acids gave promising results.Other treatments which have been used include atypical antipsychotics, histamine receptor antagonists, and dopamine agonists. Supplementation with vitamin complexes and cognitive behavioral therapy may be helpful in the management of burning mouth syndrome.

Prognosis
BMS is benign (importantly, it is not a symptom of oral cancer), but as a cause of chronic pain which is poorly controlled, it can detriment quality of life, and may become a fixation which cannot be ignored, thus interfering with work and other daily activities. Two thirds of people with BMS have a spontaneous partial recovery six to seven years after the initial onset, but in others the condition is permanent. Recovery is often preceded by a change in the character of the symptom from constant to intermittent </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Bursitis and explain in detail? [/INST] Bursitis is the inflammation of one or more bursae (fluid filled sacs) of synovial fluid in the body. They are lined with a synovial membrane that secretes a lubricating synovial fluid. There are more than 150 bursae in the human body. The bursae rest at the points where internal functionaries, such as muscles and tendons, slide across bone. Healthy bursae create a smooth, almost frictionless functional gliding surface making normal movement painless. When bursitis occurs, however, movement relying on the inflamed bursa becomes difficult and painful. Moreover, movement of tendons and muscles over the inflamed bursa aggravates its inflammation, perpetuating the problem. Muscle can also be stiffened.

Signs and symptoms
Bursitis commonly affects superficial bursae. These include the subacromial, prepatellar, retrocalcaneal, and pes anserinus bursae of the shoulder, knee, heel and shin, etc. (see below). Symptoms vary from localized warmth and erythema to joint pain and stiffness, to stinging pain that surrounds the joint around the inflamed bursa. In this condition, the pain usually is worse during and after activity, and then the bursa and the surrounding joint becomes stiff the next morning.Bursitis could possibly also cause a snapping, grinding or popping sound – known as snapping scapula syndrome – when it occurs in the shoulder joint. This is not necessarily painful.

Cause
There can be several concurrent causes. Trauma, auto-immune disorders, infection and iatrogenic (medicine-related) factors can all cause bursitis. Bursitis is commonly caused by repetitive movement and excessive pressure. Shoulders, elbows and knees are the most commonly affected. Inflammation of the bursae may also be caused by other inflammatory conditions such as rheumatoid arthritis, scleroderma, systemic lupus erythematosus, and gout. Immune deficiencies, including HIV and diabetes, can also cause bursitis. Infrequently, scoliosis can cause bursitis of the shoulders; however, shoulder bursitis is more commonly caused by overuse of the shoulder joint and related muscles.Traumatic injury is another cause of bursitis. The inflammation irritates because the bursa no longer fits in the original small area between the bone and the functionary muscle or tendon. When the bone increases pressure upon the bursa, bursitis results. Sometimes the cause is unknown </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Clostridioides difficile infection and explain in detail? [/INST] Clostridioides difficile infection
  (CDI or C-diff), also known as Clostridium difficile infection, is a symptomatic infection due to the spore-forming bacterium Clostridioides difficile. Symptoms include watery diarrhea, fever, nausea, and abdominal pain. It makes up about 20% of cases of antibiotic-associated diarrhea.  Antibiotics can contribute to detrimental changes in gut microbiota; specifically, they decrease short-chain fatty acid absorption which results in osmotic, or watery, diarrhea. Complications may include pseudomembranous colitis, toxic megacolon, perforation of the colon, and sepsis.Clostridioides difficile infection is spread by bacterial spores found within feces. Surfaces may become contaminated with the spores with further spread occurring via the hands of healthcare workers. Risk factors for infection include antibiotic or proton pump inhibitor use, hospitalization, other health problems, and older age. Diagnosis is by stool culture or testing for the bacterias DNA or toxins. If a person tests positive but has no symptoms, the condition is known as C. difficile colonization rather than an infection.Prevention efforts include terminal room cleaning in hospitals, limiting antibiotic use, and handwashing campaigns in hospitals. Alcohol based hand sanitizer does not appear effective. Discontinuation of antibiotics may result in resolution of symptoms within three days in about 20% of those infected. The antibiotics metronidazole, vancomycin or fidaxomicin, will cure the infection. Retesting after treatment, as long as the symptoms have resolved, is not recommended, as a person may often remain colonized. Recurrences have been reported in up to 25% of people. Some tentative evidence indicates fecal microbiota transplantation and probiotics may decrease the risk of recurrence.C. difficile infections occur in all areas of the world. About 453,000 cases occurred in the United States in 2011, resulting in 29,000 deaths. Global rates of disease increased between 2001 and 2016. C. difficile infections occur more often in women than men. The bacterium was discovered in 1935 and found to be disease-causing in 1978. In the United States, healthcare-associated infections increase the cost of care by US$1.5 billion each year. Although C. difficile is a common healthcare-associated infection, at most 30% of infections are transmitted within hospitals. The majority of infections are acquired outside of hospitals, where medications and a recent history of diarrheal illnesses (e.g. laxative abuse or food poisoning due to Salmonellosis) are thought to drive the risk of colonization.

Signs and symptoms
Signs and symptoms of CDI range from mild diarrhea to severe life-threatening inflammation of the colon.In adults, a clinical prediction rule found the best signs to be significant diarrhea ("new onset of more than three partially formed or watery stools per 24-hour period"), recent antibiotic exposure, abdominal pain, fever (up to 40.5 °C or 105 °F), and a distinctive foul odor to the stool resembling horse manure. In a hospital population, prior antibiotic treatment plus diarrhea or abdominal pain had a sensitivity of 86% and a specificity of 45%. In this study with a prevalence of positive cytotoxin assays of 14%, the positive predictive value was 18% and the negative predictive value was 94%.In children, the most prevalent symptom of a CDI is watery diarrhea with at least three bowel movements a day for two or more days, which may be accompanied by fever, loss of appetite, nausea, and/or abdominal pain. Those with a severe infection also may develop serious inflammation of the colon and have little or no diarrhea.

Cause
Infection with C. difficile bacteria is responsible for C. difficile diarrhea.

C. difficile
Clostridia are anaerobic motile bacteria, ubiquitous in nature, and especially prevalent in soil. Under the microscope, they appear as long, irregular (often drumstick- or spindle-shaped) cells with a bulge at their terminal ends. Under Gram staining, C. difficile cells are Gram-positive and show optimum growth on blood agar at human body temperatures in the absence of oxygen. When stressed, the bacteria produce spores that are able to tolerate extreme conditions that the active bacteria cannot tolerate.C. difficile may colonize the human colon without symptom; approximately 2–5% of the adult population are carriers, although it varies considerably with demographics. The risk of colonization has been linked to a history of unrelated diarrheal illnesses (e.g. laxative abuse and food poisoning due to Salmonellosis or Vibrio cholerae infection).Pathogenic C. difficile strains produce multiple toxins. The most well-characterized are enterotoxin (Clostridium difficile toxin A) and cytotoxin (Clostridium difficile toxin B), both of which may produce diarrhea and inflammation in infected people, although their relative contributions have been debated. Toxins A and B are glucosyltransferases that target and inactivate the Rho family of GTPases. Toxin B (cytotoxin) induces actin depolymerization by a mechanism correlated with a decrease in the ADP-ribosylation of the low molecular mass GTP-binding Rho proteins. Another toxin, binary toxin, also has been described, but its role in disease is not fully understood.Antibiotic treatment of CDIs may be difficult, due both to antibiotic resistance and physiological factors of the bacteria (spore formation, protective effects of the pseudomembrane). The emergence of a new and highly toxic strain of C. difficile that is resistant to fluoroquinolone antibiotics such as ciprofloxacin and levofloxacin, said to be causing geographically dispersed outbreaks in North America, was reported in 2005. The U.S. Centers for Disease Control and Prevention  in Atlanta warned of the emergence of an epidemic strain with increased virulence, antibiotic resistance, or both.C. difficile is transmitted from person to person by the fecal-oral route. The organism forms heat-resistant spores that are not killed by alcohol-based hand cleansers or routine surface cleaning. Thus, these spores survive in clinical environments for long periods. Because of this, the bacteria may be cultured from almost any surface. Once spores are ingested, their acid-resistance allows them to pass through the stomach unscathed. Upon exposure to bile acids, they germinate and multiply into vegetative cells in the colon. People without a history of gastrointestinal disturbances due to antibiotic use or diarrheal illness are less likely to become colonized by C. difficile.In 2005, molecular analysis led to the identification of the C. difficile strain type characterized as group BI by restriction endonuclease analysis, as North American pulse-field-type NAP1 by pulsed-field gel electrophoresis  and as ribotype 027; the differing terminology reflects the predominant techniques used for epidemiological typing. This strain is referred to as C. difficile BI/NAP1/027.

Risk factors
Antibiotics
C. difficile colitis is associated most strongly with the use of these antibiotics: fluoroquinolones, cephalosporins, and clindamycin.Some research suggests the routine use of antibiotics in the raising of livestock is contributing to outbreaks of bacterial infections such as C. difficile.

Healthcare environment
People are most often infected in hospitals, nursing homes, or other medical institutions, although infection outside medical settings is increasing. Individuals can develop the infection if they touch objects or surfaces that are contaminated with feces and then touch their mouth or mucous membranes. Healthcare workers could possibly spread the bacteria or contaminate surfaces through hand contact. The rate of C. difficile acquisition is estimated to be 13% in those with hospital stays of up to two weeks, and 50% with stays longer than four weeks.Long-term hospitalization or residence in a nursing home within the previous year are independent risk factors for increased colonization.

Acid suppression medication
Increasing rates of community-acquired CDI are associated with the use of medication to suppress gastric acid production: H2-receptor antagonists increased the risk 1.5-fold, and proton pump inhibitors by 1.7 with once-daily use and 2.4 with more than once-daily use.

Diarrheal illnesses
People with a recent history of diarrheal illness are at increased risk of becoming colonized by C. difficile when exposed to spores, including laxative abuse and gastrointestinal pathogens.  Disturbances that increase intestinal motility are thought to transiently elevate the concentration of available dietary sugars, allowing C. difficile to proliferate and gain a foothold in the gut. Although not all colonization events lead to disease, asymptomatic carriers remain colonized for years at a time. During this time, the abundance of C. difficile varies considerably day-to-day, causing periods of increased shedding that could substantially contribute to community-acquired infection rates.

Other
As a result of suppression of healthy bacteria, via a loss of bacterial food source, prolonged use of an elemental diet increases the risk of developing C. difficile infection. Low serum albumin levels is a risk factor for the development of C. difficile infection and when infected for severe disease. The protective effects of serum albumin may be related to the capability of this protein to bind C. difficile toxin A and toxin B, thus impairing entry into enterocytes.

Pathophysiology
The use of systemic antibiotics, including broad-spectrum penicillins/cephalosporins, fluoroquinolones, and clindamycin, causes the normal microbiota of the bowel to be altered. In particular, when the antibiotic kills off other competing bacteria in the intestine, any bacteria remaining will have less competition for space and nutrients. The net effect is to permit more extensive growth than normal of certain bacteria. C. difficile is one such type of bacterium. In addition to proliferating in the bowel, C. difficile also produces toxins. Without either toxin A or toxin B, C. difficile may colonize the gut, but is unlikely to cause pseudomembranous colitis. The colitis associated with severe infection is part of an inflammatory reaction, with the "pseudomembrane" formed by a viscous collection of inflammatory cells, fibrin, and necrotic cells.

Diagnosis
Prior to the advent of tests to detect C. difficile toxins, the diagnosis most often was made by colonoscopy or sigmoidoscopy. The appearance of "pseudomembranes" on the mucosa of the colon or rectum is highly suggestive, but not diagnostic of the condition. The pseudomembranes are composed of an exudate made of inflammatory debris, white blood cells. Although colonoscopy and sigmoidoscopy are still employed, now stool testing for the presence of C. difficile toxins is frequently the first-line diagnostic approach. Usually, only two toxins are tested for—toxin A and toxin B—but the organism produces several others. This test is not 100% accurate, with a considerable false-negative rate even with repeat testing.

Classification
CDI may be classified in non-severe CDI, severe CDI and fulminant CDI depending on creatinine and white blood count parameters.

Cytotoxicity assay
C. difficile toxins have a cytopathic effect in cell culture, and neutralization of any effect observed with specific antisera is the practical gold standard for studies investigating new CDI diagnostic techniques. Toxigenic culture, in which organisms are cultured on selective media and tested for toxin production, remains the gold standard and is the most sensitive and specific test, although it is slow and labor-intensive.

Toxin ELISA
Assessment of the A and B toxins by enzyme-linked immunosorbent assay (ELISA) for toxin A or B (or both) has a sensitivity of 63–99% and a specificity of 93–100%.Previously, experts recommended sending as many as three stool samples to rule out disease if initial tests are negative, but evidence suggests repeated testing during the same episode of diarrhea is of limited value and should be discouraged. C. difficile toxin should clear from the stool of somebody previously infected if treatment is effective. Many hospitals only test for the prevalent toxin A. Strains that express only the B toxin are now present in many hospitals, however, so testing for both toxins should occur. Not testing for both may contribute to a delay in obtaining laboratory results, which is often the cause of prolonged illness and poor outcomes.

Other stool tests
Stool leukocyte measurements and stool lactoferrin levels also have been proposed as diagnostic tests, but may have limited diagnostic accuracy.

PCR
Testing of stool samples by real-time polymerase chain reaction is able to detect C. difficile about 93% of the time and when positive is incorrectly positive about 3% of the time. This is more accurate than cytotoxigenic culture or cell cytotoxicity assay. Another benefit is that the result can be achieved within three hours. Drawbacks include a higher cost and the fact that the test only looks for the gene for the toxin and not the toxin itself. The latter means that if the test is used without confirmation, overdiagnosis may occur. Repeat testing may be misleading, and testing specimens more than once every seven days in people without new symptoms is highly unlikely to yield useful information.

Prevention
Self containment by housing people in private rooms is important to prevent the spread of C. difficile. Contact precautions are an important part of preventing the spread of  C. difficile. C. difficile does not often occur in people who are not taking antibiotics so limiting use of antibiotics decreases the risk.

Antibiotics
The most effective method for preventing CDI is proper antibiotic prescribing. In the hospital setting, where CDI is most common, most people who develop CDI are exposed to antibiotics. Although proper antibiotic prescribing is highly recommended, about 50% is considered inappropriate. This is consistent whether in the hospital, clinic, community, or academic setting. A decrease in CDI by limiting antibiotics or by limiting unnecessary prescriptions in general, both in an outbreak and nonoutbreak setting has been demonstrated to be most strongly associated with reduced CDI. Further, reactions to medication may be severe: CDI infections were the most common contributor to adverse drug events seen in U.S. hospitals in 2011. In some regions of the UK, reduced used of fluoroquinolone antibiotics seems to lead to reduced rates of CDI.

Probiotics
Some evidence indicates probiotics may be useful to prevent infection and recurrence. Treatment with Saccharomyces boulardii in those who are not immunocompromised with C. difficile also may be useful. Initially, in 2010, the Infectious Diseases Society of America recommended against their use due to the risk of complications. Subsequent reviews, however, did not find an increase in adverse effects with treatment, and overall treatment appears safe and moderately effective in preventing Clostridium difficile-associated diarrhea.One study in particular found that there does appear to be a "protective effect" of probiotics, specifically reducing the risk of antibiotic-associated diarrhea (AAD) by 51% in 3,631 outpatients, but it is important to note that the types of infections in the subjects were not specified. Yogurt, tablets, dietary supplements are just a few examples of probiotics available for people.

Infection control
Rigorous infection protocols are required to minimize this risk of transmission. Infection control measures, such as wearing gloves and noncritical medical devices used for a single person with CDI, are effective at prevention. This works by limiting the spread of C. difficile in the hospital setting. In addition, washing with soap and water will wash away the spores from contaminated hands, but alcohol-based hand rubs are ineffective. These precautions should remain in place among those in hospital for at least 2 days after the diarrhea has stopped.Bleach wipes containing 0.55% sodium hypochlorite have been shown to kill the spores and prevent transmission. Installing lidded toilets and closing the lid prior to flushing also reduces the risk of contamination.Those who have CDIs should be in rooms with other people with CDIs or by themselves when in hospital.Common hospital disinfectants are ineffective against C. difficile spores, and may promote spore formation, but various oxidants   (e.g 1% sodium hypochlorite solution) rapidly destroy spores. Hydrogen peroxide vapor (HPV) systems used to sterilize a room after treatment is completed have been shown to reduce infection rates and to reduce risk of infection to others. The incidence of CDI was reduced by 53% or 42% through use of HPV. Ultraviolet cleaning devices, and housekeeping staff especially dedicated to disinfecting the rooms of people with C. difficile after discharge may be effective.

Treatment
Carrying C. difficile without symptoms is common. Treatment in those without symptoms is controversial. In general, mild cases do not require specific treatment. Oral rehydration therapy is useful in treating dehydration associated with the diarrhea.

Medications
Several different antibiotics are used for C. difficile, with the available agents being more or less equally effective.Vancomycin or fidaxomicin by mouth are the typically recommended for mild, moderate, and severe infections. They are also the first-line treatment for pregnant women, especially since metronidazole may cause birth defects. Typical vancomycin 125mg is taken four times a day by mouth for 10 days. Fidaxomicin is taken at 200 mg twice daily for 10 days. It may also be given rectally if the person develops an ileus.Fidaxomicin is tolerated as well as vancomycin, and may have a lower risk of recurrence. Fidaxomicin has been found to be as effective as vancomycin in those with mild to moderate disease, and it may be better than vancomycin in those with severe disease. Fidaxomicin may be used in those who have recurrent infections and have not responded to other antibiotics. Metronidazole (500 mg 3 times daily for 10 days) by mouth is recommended as an alternative treatment only for C. difficile infections when the affected person is allergic to first-line treatments, is unable to tolerate them, or has financial difficulties preventing them from accessing them. In fulminant disease vancomycin by mouth and intravenous metronidazole are commonly used together.Medications used to slow or stop diarrhea, such as loperamide, may only be used after initiating the treatment.Cholestyramine, an ion-exchange resin, is effective in binding both toxin A and B, slowing bowel motility, and helping prevent dehydration. Cholestyramine is recommended with vancomycin. A last-resort treatment in those who are immunosuppressed is intravenous immunoglobulin. Monoclonal antibodies against C. difficile toxin A and C. difficile toxin B are approved to prevent recurrence of C. difficile infection including bezlotoxumab.

Probiotics
Evidence to support the use of probiotics in the treatment of active disease is insufficient. Researchers have recently begun taking a mechanical approach to fecal-derived products. It is known that certain microbes with 7α-dehydroxylase activity can metabolize primary to secondary bile acids, which inhibit C. difficile. Thus, incorporating such microbes into therapeutic products such as probiotics may be protective, although more pre-clinical investigations are needed.

Fecal microbiota transplantation
Fecal microbiota transplant, also known as a stool transplant, is roughly 85% to 90% effective in those for whom antibiotics have not worked. It involves infusion of the microbiota acquired from the feces of a healthy donor to reverse the bacterial imbalance responsible for the recurring nature of the infection. The procedure replenishes the normal colonic microbiota that had been wiped out by antibiotics, and re-establishes resistance to colonization by Clostridioides difficile. Side effects, at least initially, are few.Some evidence looks hopeful that fecal transplant can be delivered in the form of a pill. They are available in the United States, but are not FDA-approved as of 2015.

Surgery
In those with severe C. difficile colitis, colectomy may improve the outcomes. Specific criteria may be used to determine who will benefit most from surgery.

Recurrent infection
Recurrent CDI occurs in 20 to 30% of the patients, with increasing rates of recurrence with each subsequent episode. In clinical settings, it is virtually impossible to distinguish a recurrence that develops as a relapse of CDI with the same strain of C. difficile versus reinfection that is the result of a new strain.
Several treatment options exist for recurrent C difficile infection. For the first episode of recurrent C difficile infection, the 2017 IDSA guidelines recommend oral vancomycin at a dose of 125 mg four times daily for 10 days if metronidazole was used for the initial episode. If oral vancomycin was used for the initial episode, then a prolonged oral vancomycin pulse dose of 125 mg four times daily for 10-14 days followed by a taper (twice daily for one week, then every two to three days for 2-8 weeks) or fidaxomicin 200 mg twice daily for 10 days. For a second recurrent episode, the IDSA recommends options including the aforementioned oral vancomycin pulse dose followed by the prolonged taper; oral vancomycin 125 mg four times daily for 10 days followed by rifaximin 400 mg three times daily for 20 days; fidaxomicin 200 mg twice daily for 10 days, or a fecal microbiota transplant.For patients with C. diff infections that fail to be resolved with traditional antibiotic regimens, fecal microbiome transplants boasts an average cure rate of >90%. In a review of 317 patients, it was shown to lead to resolution in 92% of the persistent and recurrent disease cases. It is clear that restoration of gut flora is paramount in the struggle against recurrent CDI. With effective antibiotic therapy, C. difficile can be reduced and natural colonization resistance can develop over time as the natural microbial community recovers. Reinfection or recurrence may occur before this process is complete. Fecal microbiota transplant may expedite this recovery by directly replacing the missing microbial community members. However, human-derived fecal matter is difficult to standardize and has multiple potential risks, including the transfer of infectious material and long-term consequences of inoculating the gut with a foreign fecal material. As a result, further research is necessary to study the long term effective outcomes of FMT.

Prognosis
After a first treatment with metronidazole or vancomycin, C. difficile recurs in about 20% of people. This increases to 40% and 60% with subsequent recurrences.

Epidemiology
C. difficile diarrhea is estimated to occur in eight of 100,000 people each year. Among those who are admitted to hospital, it occurs in between four and eight people per 1,000. In 2011, it resulted in about half a million infections and 29,000 deaths in the United States.Due in part to the emergence of a fluoroquinolone-resistant strain, C. difficile-related deaths increased 400% between 2000 and 2007 in the United States. According to the CDC, "C. difficile has become the most common microbial cause of healthcare-associated infections in U.S. hospitals and costs up to $4.8 billion each year in excess health care costs for acute care facilities alone."

History
Ivan C. Hall and Elizabeth OToole first named the bacterium Bacillus difficilis in 1935, choosing its specific epithet because it was resistant to early attempts at isolation and grew very slowly in culture. André Romain Prévot subsequently transferred it to the genus Clostridium, which made its binomen Clostridium difficile. Its combination was later changed to Clostridiodes difficile after being transferred to the new genus Clostridioides.Pseudomembranous colitis first was described as a complication of C. difficile infection in 1978, when a toxin was isolated from people with pseudomembranous colitis and Kochs postulates were met.

Notable outbreaks
On 4 June 2003, two outbreaks of a highly virulent strain of this bacterium were reported in Montreal, Quebec, and Calgary, Alberta. Sources put the death count to as low as 36 and as high as 89, with around 1,400 cases in 2003 and within the first few months of 2004. CDIs continued to be a problem in the Quebec healthcare system in late 2004. As of March 2005, it had spread into the Toronto area, hospitalizing 10 people. One died while the others were being discharged.
A similar outbreak took place at Stoke Mandeville Hospital in the United Kingdom between 2003 and 2005. The local epidemiology of C. difficile may offer clues on how its spread may relate to the time a patient spends in hospital and/or a rehabilitation center. It also samples the ability of institutions to detect increased rates, and their capacity to respond with more aggressive hand-washing campaigns, quarantine methods, and the availability of yogurt containing live cultures to patients at risk for infection.
Both the Canadian and English outbreaks possibly were related to the seemingly more virulent strain NAP1/027 of the bacterium.  Known as Quebec strain, it has been implicated in an epidemic at two Dutch hospitals (Harderwijk and Amersfoort, both 2005). A theory for explaining the increased virulence of 027 is that it is a hyperproducer of both toxins A and B and that certain antibiotics may stimulate the bacteria to hyperproduce.
On 1 October 2006, C. difficile was said to have killed at least 49 people at hospitals in Leicester, England, over eight months, according to a National Health Service investigation. Another 29 similar cases were investigated by coroners. A UK Department of Health memo leaked shortly afterward revealed significant concern in government about the bacterium, described as being "endemic throughout the health service"
On 27 October 2006, nine deaths were attributed to the bacterium in Quebec.
On 18 November 2006, the bacterium was reported to have been responsible for 12 deaths in Quebec. This 12th reported death was only two days after the St. Hyacinthes Honoré Mercier announced the outbreak was under control. Thirty-one people were diagnosed with CDIs. Cleaning crews took measures in an attempt to clear the outbreak.
C. difficile was mentioned on 6,480 death certificates in 2006 in UK.
On 27 February 2007, a new outbreak was identified at Trillium Health Centre in Mississauga, Ontario, where 14 people were diagnosed with CDIs. The bacteria were of the same strain as the one in Quebec. Officials have not been able to determine whether C. difficile was responsible for the deaths of four people over the prior two months.
Between February and June 2007, three people at Loughlinstown Hospital in Dublin, Ireland, were found by the coroner to have died as a result of C. difficile infection. In an inquest, the Coroners Court found the hospital had no designated infection control team or consultant microbiologist on staff.
Between June 2007 and August 2008, Northern Health and Social Care Trust Northern Ireland, Antrim Area, Braid Valley, Mid Ulster Hospitals were the subject of inquiry. During the inquiry, expert reviewers concluded that C. difficile was implicated in 31 of these deaths, as the underlying cause in 15, and as a contributory cause in 16. During that time, the review also noted 375 instances of CDIs in those being treated at the hospital.
In October 2007, Maidstone and Tunbridge Wells NHS Trust was heavily criticized by the Healthcare Commission regarding its handling of a major outbreak of C. difficile in its hospitals in Kent from April 2004 to September 2006. In its report, the Commission estimated approximately 90 people "definitely or probably" died as a result of the infection.
In November 2007, the 027 strain spread into several hospitals in southern Finland, with 10 deaths out of 115 infected people reported on 2007-12-14.
In November 2009, four deaths at Our Lady of Lourdes Hospital in Ireland have possible links to CDI. A further 12 people tested positive for infection, and another 20 showed signs of infection.
From February 2009 to February 2010, 199 people at Herlev hospital in Denmark were suspected of being infected with the 027 strain. In the first half of 2009, 29 died in hospitals in Copenhagen after they were infected with the bacterium.
In May 2010, a total of 138 people at four different hospitals in Denmark were infected with the 027 strain  plus there were some isolated occurrences at other hospitals.
In May 2010,  14 fatalities were related to the bacterium in the Australian state of Victoria. Two years later, the same strain of the bacterium was detected in New Zealand.
On 28 May 2011, an outbreak in Ontario had been reported, with 26 fatalities as of 24 July 2011.
In 2012/2013, a total of 27 people at one hospital in the south of Sweden (Ystad) were infected with 10 deaths. Five died of the strain 017.

Etymology and pronunciation
The genus name is from the Greek klōstēr (κλωστήρ), "spindle", and the specific name is from Latin difficile, neuter singular form of difficilis "difficult, obstinate", chosen in reference to fastidiousness upon culturing.
Regarding the pronunciation of the current and former genus assignments, Clostridioides is  and Clostridium is . Both genera still have species assigned to them, but this species is now classified in the former. Via the norms of binomial nomenclature, it is understood that the former binomial name of this species is now an alias.
Regarding the specific name,  is the traditional norm, reflecting how medical English usually pronounces naturalized New Latin words (which in turns largely reflects traditional English pronunciation of Latin), although a restored pronunciation of  is also sometimes used (the classical Latin pronunciation is reconstructed as [kloːsˈtrɪdɪ.ũː dɪfˈfɪkɪlɛ]). The specific name is also commonly pronounced , as though it were French, which from a prescriptive viewpoint is a "mispronunciation" but from a linguistically descriptive viewpoint cannot be described as erroneous because it is so widely used among health care professionals; it can be described as "the non-preferred variant" from the viewpoint of sticking most regularly to New Latin in binomial nomenclature, which is also a valid viewpoint, although New Latin specific names contain such a wide array of extra-Latin roots (including surnames and jocular references) that extra-Latin pronunciation is involved anyway (as seen, for example, with Ba humbugi, Spongiforma squarepantsii, and hundreds of others).

Research
As of 2019, vaccine candidates providing immunity against C. difficile toxin A and C. difficile toxin B have advanced the most in clinical research, but do not prevent bacterial colonization. A vaccine candidate by Pfizer is in a phase 3 clinical trial that is estimated to be completed in September 2021 and a vaccine candidate by GlaxoSmithKline is in a phase 1 clinical trial that is estimated to be completed in July 2021.
CDA-1 and CDB-1 (also known as MDX-066/MDX-1388 and MBL-CDA1/MBL-CDB1) is an investigational, monoclonal antibody combination co-developed by Medarex and Massachusetts Biologic Laboratories (MBL) to target and neutralize C. difficile toxins A and B, for the treatment of CDI. Merck & Co., Inc. gained worldwide rights to develop and commercialize CDA-1 and CDB-1 through an exclusive license agreement signed in April 2009. It is intended as an add-on therapy to one of the existing antibiotics to treat CDI.
Nitazoxanide is a synthetic nitrothiazolyl-salicylamide derivative indicated as an antiprotozoal agent (FDA-approved for the treatment of infectious diarrhea caused by Cryptosporidium parvum and Giardia lamblia) and also is currently being studied in C </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Cachexia and explain in detail? [/INST] Cachexia () is a complex syndrome associated with an underlying illness, causing ongoing muscle loss that is not entirely reversed with nutritional supplementation. A range of diseases can cause cachexia, most commonly cancer, congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease, and AIDS. Systemic inflammation from these conditions can cause detrimental changes to metabolism and body composition. In contrast to weight loss from inadequate caloric intake, cachexia causes mostly muscle loss instead of fat loss. Diagnosis of cachexia can be difficult due to the lack of well-established diagnostic criteria. Cachexia can improve with treatment of the underlying illness but other treatment approaches have limited benefit. Cachexia is associated with increased mortality and poor quality of life.
The term is from Greek κακός kakos, "bad", and ἕξις hexis, "condition".

Causes
Cachexia can be caused by diverse medical conditions, but is most often associated with end-stage cancer, known as cancer cachexia. About 50% of all cancer patients develop cachexia. Those with upper gastrointestinal and pancreatic cancers have the highest frequency of developing a cachexic symptom. Prevalence of cachexia rises in more advanced stages and is estimated to affect 80% of terminal cancer patients.Congestive heart failure, AIDS, chronic obstructive pulmonary disease, and chronic kidney disease are other conditions that often cause cachexia. Cachexia can also be the result of advanced stages of cystic fibrosis, multiple sclerosis, motor neuron disease, Parkinsons disease, dementia, tuberculosis, multiple system atrophy, mercury poisoning, Crohns disease, trypanosomiasis, rheumatoid arthritis, and celiac disease as well as other systemic diseases.

Mechanism
The exact mechanism in which these diseases cause cachexia is poorly understood, and likely is multifactorial with multiple disease pathways involved. Inflammatory cytokines appear to play a central role including tumor necrosis factor (TNF) (which is also nicknamed cachexin or cachectin), interferon gamma and interleukin 6. TNF has been shown to have a direct catabolic effect on skeletal muscle and adipose tissue through the ubiquitin proteasome pathway. This mechanism involves the formation of reactive oxygen species leading to upregulation of the transcription factor NF-κB. NF-κB is a known regulator of the genes that encode cytokines and cytokine receptors. The increased production of cytokines induces proteolysis and breakdown of myofibrillar proteins. Systemic inflammation also causes reduced protein synthesis through inhibition of the Akt/mTOR pathway.Although many different tissues and cell types may be responsible for the increase in circulating cytokines, evidence indicates tumors themselves are an important source of factors that may promote cachexia in cancer. Tumor-derived molecules such as lipid mobilizing factor, proteolysis-inducing factor, and mitochondrial uncoupling proteins may induce protein degradation and contribute to cachexia. Uncontrolled inflammation in cachexia can lead to an elevated resting metabolic rate, further increasing the demands for protein and energy sources.There is also evidence of alteration in feeding control loops in cachexia. High levels of leptin, a hormone secreted by adipocytes, block the release of neuropeptide Y, which is the most potent feeding-stimulatory peptide in the hypothalamic orexigenic network, leading to decreased energy intake despite the high metabolic demand for nutrients.

Diagnosis
Diagnostic guidelines and criteria have only recently been proposed despite the prevalence of cachexia and varying criteria, the primary features of cachexia include progressive depletion of muscle and fat mass, reduced food intake, abnormal metabolism of carbohydrate, protein, and fat, reduced quality of life, and increased physical impairment.Historically, body weight changes were used as the primary metrics of cachexia, including low body mass index and involuntary weight loss of more than 10%. Using weight alone is limited by the presence of edema, tumor mass and the high prevalence of obesity in the general population. Weight-based criteria do not take into account changes in body composition, especially loss of lean body mass.
In the attempt to include a broader evaluation of the burden of cachexia, diagnostic criteria using assessments of laboratory metrics and symptoms in addition to weight have been proposed. The criteria included weight loss of at least 5% in 12 months or low body mass index (less than 22  kg/m2) with at least three of the following features: decreased muscle strength, fatigue, anorexia, low fat‐free mass index, or abnormal biochemistry (increased inflammatory markers, anemia, low serum albumin). In cancer patients, cachexia is diagnosed from unintended weight loss of more than 5%. For cancer patients with a body mass index of less than 20  kg/m2, cachexia is diagnosed after the unintended weight loss of more than 2%. Additionally, it can be diagnosed through sarcopenia, or loss of skeletal muscle mass.Laboratory markers are used in evaluation of people with cachexia, including albumin, prealbumin, C-reactive protein, or hemoglobin. However, laboratory metrics and cut-off values are not standardized across different diagnostic criteria. Acute phase reactants (IL-6, IL-1b, tumor necrosis factor-a, IL-8, interferon-g) are sometimes measured but correlate poorly with outcomes. There are no biomarkers to identify people with cancer who may develop cachexia.In the effort to better classify cachexia severity, several scoring systems have been proposed including the Cachexia Staging Score (CSS) and Cachexia Score (CASCO). The CSS takes into account weight loss, subjective reporting of muscle function, performance status, appetite loss, and laboratory changes to categorize patients into non-cachexia, pre-cachexia, cachexia, and refractory cachexia. The Cachexia SCOre (CASCO) is another validated score that includes evaluation of body weight loss and composition, inflammation, metabolic disturbances, immunosuppression, physical performance, anorexia, and quality of life.Evaluation of changes in body composition is limited by the difficulty in measuring muscle mass and health in a non-invasive and cost-effective way. Imaging with quantification of muscle mass has been investigated including bioelectrical impedance analysis, computed tomography, dual-energy X-ray absorptiometry (DEXA), and magnetic resonance imaging but are not widely used.

Definition
Identification, treatment, and research of cachexia have historically been limited by the lack of a widely accepted definition of cachexia. In 2011, an international consensus group adopted a definition of cachexia as "a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that can be partially but not entirely reversed by conventional nutritional support."Cachexia differs from weight loss due to malnutrition from malabsorption, anorexia nervosa, or anorexia due to major depressive disorder. Weight loss from inadequate caloric intake generally causes fat loss before muscle loss, whereas cachexia causes predominantly muscle wasting. Cachexia is also distinct from sarcopenia, or age-related muscle loss, although they often co-exist.

Treatment
The management of cachexia depends on the underlying cause, the general prognosis, and the needs of the person affected. The most effective approach to cachexia is treating the underlying disease process. An example is the reduction in cachexia from AIDS by highly active antiretroviral therapy. However this is often not possible or maybe inadequate to reverse the cachexia syndrome in other diseases. Approaches to mitigate muscle loss include exercise, nutritional therapies, and medications.

Exercise
Therapy that includes regular physical exercise can be recommended for the treatment of cachexia due to the positive effects of exercise on skeletal muscle but current evidence remains uncertain as to its effectiveness, acceptability and safety for cancer patients.  Individuals with cachexia generally report low levels of physical activity and few engage in an exercise routine, owing to low motivation to exercise and a belief that exercising may worsen their symptoms or cause harm.

Medications
Appetite stimulant medications are used to treat cachexia to increase food intake, but are not effective in stopping muscle wasting and may have detrimental side effects. Appetite stimulants include glucocorticoids, cannabinoids, or progestins such as megestrol acetate. Anti-emetics such as 5-HT3 antagonists are also commonly used in cancer cachexia if nausea is a prominent symptom.Anabolic-androgenic steroids like oxandrolone may be beneficial in cachexia but their use is recommended for a maximum of two weeks since a longer duration of treatment increases side effects. Whilst preliminary studies have suggested thalidomide may be useful, a Cochrane review found no evidence to make an informed decision about the use of this drug in cancer patients with cachexia.

Nutrition
The increased metabolic rate and appetite suppression common in cachexia can compound muscle loss. Studies using a calorie-dense protein supplementation have suggested at least weight stabilization can be achieved, although improvements in lean body mass have not been observed in these studies.

Supplements
Administration of exogenous amino acids have been investigated to serve as a protein-sparing metabolic fuel by providing substrates for both muscle metabolism and gluconeogenesis. The branched-chain amino acids leucine and valine may have potential in inhibiting overexpression of protein breakdown pathways. The amino acid glutamine has been used as a component of oral supplementation to reverse cachexia in people with advanced cancer or HIV/AIDS.β-hydroxy β-methylbutyrate (HMB) is a metabolite of leucine that acts as a signaling molecule to stimulate protein synthesis. Studies showed positive results for chronic pulmonary disease, hip fracture, and in AIDS‐related and cancer‐related cachexia. However, many of these clinical studies used HMB as a component of combination treatment with glutamine, arginine, leucine, higher dietary protein and/or vitamins, which limits the assessment of the efficacy of HMB alone.

Epidemiology
Accurate epidemiological data on the prevalence of cachexia is lacking due to changing diagnostic criteria and under-identification of people with the disorder. It is estimated that cachexia from any disease is estimated to affect more than 5 million people in the United States. The prevalence of cachexia is growing and estimated at 1% of the population. The prevalence is lower in Asia but due to the larger population, represents a similar burden. Cachexia is also a significant problem in South America and Africa.The most frequent causes of cachexia in the United States by population prevalence are: 1) chronic obstructive pulmonary disease (COPD), 2) heart failure, 3) cancer cachexia, 4) chronic kidney disease. The prevalence of cachexia ranges from 15 to 60% among people with cancer, increasing to an estimated 80% in terminal cancer </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Calcium channel blocker toxicity and explain in detail? [/INST] Calcium channel blocker toxicity is the taking of too much of the medications known as calcium channel blockers (CCBs), either by accident or on purpose. This often causes a slow heart rate and low blood pressure. This can progress to the heart stopping altogether. Some CCBs can also cause a fast heart rate as a result of the low blood pressure. Other symptoms may include nausea, vomiting, sleepiness, and shortness of breath. Symptoms usually occur in the first six hours but with some forms of the medication may not start until 24 after hours.There are a number of treatments that may be useful. These include efforts to reduce absorption of the drug including: activated charcoal taken by mouth if given shortly after the ingestion or whole bowel irrigation if an extended release formula was taken. Efforts to bring about vomiting are not recommended. Medications to treat the toxic effects include: intravenous fluids, calcium gluconate, glucagon, high dose insulin, vasopressors and lipid emulsion. Extracorporeal membrane oxygenation may also be an option.More than ten thousand cases of calcium channel blocker toxicity were reported in the United States in 2010. Along with beta blockers and digoxin calcium channel blockers have one of the highest rates of death in overdose. These medications first became available in the 1970s and 1980s. They are one of the few types of medication in which one pill can result in the death of a child.

Signs and symptoms
Most people who have taken too much of a calcium channel blocker, especially diltiazem, get slow heart rate and low blood pressure (vasodilatory shock). This can progress to the heart stopping altogether. CCBs of the dihydropyridine group, as well as flunarizine, predominantly cause reflex tachycardia as a reaction to the low blood pressure.Other potential symptoms include: nausea and vomiting, a decreased level of consciousness, and breathing difficulties. Symptoms usually begin within 6 hours of taking the medication by mouth. With extended release formulations symptoms may not occur for up to a day. Seizures are rare in adults but in children occur more often. Hypocalcaemia may also occur.

Cause
Calcium channel blockers, also known as calcium channel antagonists, are widely used for a number of health conditions. Thus they are commonly present in many peoples homes. In young children one pill may cause serious health problems and potentially death. The calcium channel blocker that caused the greatest number of deaths in 2010 in the United States was verapamil. This agent is believed to cause more heart problems than many of the others.

Diagnosis
A blood or urine test to diagnose overdose is not generally available. CCB overdose may cause high blood sugar levels, and this is often a sign of how severe the problem will become.

Electrocardiogram
CCB toxicity can cause a number of electrocardiogram abnormalities with a low sinus rhythm being the most common. Others include: QT prolongation, bundle branch block, first-degree atrioventricular block, and even sinus tachycardia.

Differential
It may not be possible to tell the difference between beta blocker toxicity and calcium channel blocker overdose based on signs and symptoms.

Management
The medical management of CCB toxicity may be difficult. It may not improve with the usual treatments used for a low blood pressure and a slow heart rate. In those who have no symptoms or signs six hours following taking an immediate release formulation and 24 hours after taking an extended release formulation need no further medical treatment.

Detoxification
Activated charcoal is recommended if it can be given within an hour or two of taking the calcium channel blockers. In those who have taken an extended release formulation of a CCB but are otherwise doing fine, whole bowel irrigation with polyethylene glycol may be useful. Causing vomiting by the use of medications such as ipecac is not recommended.

Insulin
High doses of intravenous insulin with glucose may be useful and are a first line treatment in overdoses. As this treatment may cause a drop in blood sugar and blood potassium levels, these should be monitored closely.

Other
Intravenous calcium gluconate or calcium chloride is considered a specific antidotes. Slow heart rate can be treated with atropine and sympathomimetics </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Campylobacteriosis and explain in detail? [/INST] Campylobacteriosis is an infection by the Campylobacter bacterium, most commonly C. jejuni. It is among the most common bacterial infections of humans, often a foodborne illness. It produces an inflammatory, sometimes bloody, diarrhea or dysentery syndrome, mostly including cramps, fever and pain.

Symptoms and signs
The prodromal symptoms are fever, headache, and myalgia, which can be severe, lasting as long as 24 hours. After 1–5 days, typically, these are followed by diarrhea (as many as 10 watery, frequently bloody, bowel movements per day) or dysentery, cramps, abdominal pain, and fever as high as 40 °C (104 °F). In most people, the illness lasts for 2–10 days. It is classified as invasive/inflammatory diarrhea, also described as bloody diarrhea or dysentery.There are other diseases showing similar symptoms. For instance, abdominal pain and tenderness may be very localized, mimicking acute appendicitis. Furthermore, Helicobacter pylori is closely related to Campylobacter and causes peptic ulcer disease.

Complications
Complications include toxic megacolon, dehydration and sepsis. Such complications generally occur in young children (< 1 year of age) and immunocompromised people. A chronic course of the disease is possible; this disease process is likely to develop without a distinct acute phase. Chronic campylobacteriosis features a long period of sub-febrile temperature and asthenia; eye damage, arthritis, endocarditis may develop if infection is untreated. Occasional deaths occur in young, previously healthy individuals because of blood volume depletion (due to dehydration), and in people who are elderly or immunocompromised.Some individuals (1–2 in 100,000 cases) develop Guillain–Barré syndrome, in which the nerves that join the spinal cord and brain to the rest of the body are damaged, sometimes permanently. This occurs only with infection of C. jejuni and C. upsaliensis.

Other factors
In patients with HIV, infections may be more frequent, may cause prolonged bouts of dirty brown diarrhea, and may be more commonly associated with bacteremia and antibiotic resistance. In participants of unprotected anal intercourse, campylobacteriosis is more localized to the distal end of the colon and may be termed a proctocolitis. The severity and persistence of infection in patients with AIDS and hypogammaglobulinemia indicates that both cell-mediated and humoral immunity are important in preventing and terminating infection.

Cause
Campylobacteriosis is caused by Campylobacter bacteria (curved or spiral, motile, non–spore-forming, Gram-negative rods). The disease is usually caused by C. jejuni, a spiral and comma-shaped bacterium normally found in cattle, swine, and birds, where it is nonpathogenic, but the illness can also be caused by C. coli (also found in cattle, swine, and birds), C. upsaliensis (found in cats and dogs) and C. lari (present in seabirds in particular).One effect of campylobacteriosis is tissue injury in the gut. The sites of tissue injury include the jejunum, the ileum, and the colon. C jejuni appears to achieve this by invading and destroying epithelial cells.C. jejuni can also cause a latent autoimmune effect on the nerves of the legs, which is usually seen several weeks after a surgical procedure of the abdomen. The effect is known as an acute idiopathic demyelinating polyneuropathy (AIDP), i.e. Guillain–Barré syndrome, in which one sees symptoms of ascending paralysis, dysaesthesias usually below the waist, and, in the later stages, respiratory failure.Some strains of C jejuni produce a cholera-like enterotoxin, which is important in watery diarrhea observed in infections. The organism produces diffuse, bloody, edematous, and exudative enteritis. In a small number of cases, the infection may be associated with hemolytic uremic syndrome and thrombotic thrombocytopenic purpura through a poorly understood mechanism.

Transmission
The common routes of transmission for the disease-causing bacteria are fecal-oral, person-to-person sexual contact, ingestion of contaminated food (generally unpasteurized (raw) milk and undercooked or poorly handled poultry), and waterborne (i.e., through contaminated drinking water). Contact with contaminated poultry, livestock, or household pets, especially puppies, can also cause disease.Animals farmed for meat are the main source of campylobacteriosis. A study published in PLoS Genetics (26 September 2008) by researchers from Lancashire, England, and Chicago, Illinois, found that 97 percent of campylobacteriosis cases sampled in Lancashire were caused by bacteria typically found in chicken and livestock. In 57 percent of cases, the bacteria could be traced to chicken, and in 35 percent to cattle. Wild animal and environmental sources were accountable for just three percent of disease.The infectious dose is 1000–10,000 bacteria (although ten to five hundred bacteria can be enough to infect humans). Campylobacter species are sensitive to hydrochloric acid in the stomach, and acid reduction treatment can reduce the amount of inoculum needed to cause disease.Exposure to bacteria is often more common during travelling, and therefore campylobacteriosis is a common form of travelers diarrhea.

Diagnosis
Campylobacter organisms can be detected by performing a Gram stain of a stool sample with high specificity and a sensitivity of ~60%, but are most often diagnosed by stool culture. Fecal leukocytes should be present and indicate the diarrhea to be inflammatory in nature. Methods currently being developed to detect the presence of campylobacter organisms include antigen testing via an EIA or PCR.

Prevention
Pasteurization of milk and chlorination of drinking water destroys the organisms.
Treatment with antibiotics can reduce fecal excretion.
Infected health care workers should not provide direct patient care.
Separate cutting boards should be used for foods of animal origin and other foods. After preparing raw food of animal origin, all cutting boards and countertops should be carefully cleaned with soap and hot water.
Contact with pet saliva and feces should be avoided.The World Health Organization recommends the following:
Food should be properly cooked and hot when served.
Consume only pasteurized or boiled milk and milk products, never raw milk products.
Make sure that ice is from safe water.
If you are not sure of the safety of drinking water, boil it, or disinfect it with chemical disinfectant.
Wash hands thoroughly and frequently with soap, especially after using the toilet and after contact with pets and farm animals.
Wash fruits and vegetables thoroughly, especially if they are to be eaten raw. Peel fruits and vegetables whenever possible.
Food handlers, professionals and at home, should observe hygienic rules during food preparation.
Professional food handlers should immediately report to their employer any fever, diarrhea, vomiting or visible infected skin lesions.

Treatment
The infection is usually self-limiting, and in most cases, symptomatic treatment by liquid and electrolyte replacement is enough in human infections.

Antibiotics
Antibiotic treatment only has a marginal effect on the duration of symptoms, and its use is not recommended except in high-risk patients with clinical complications.Erythromycin can be used in children, and tetracycline in adults. Some studies show, however, that erythromycin rapidly eliminates Campylobacter from the stool without affecting the duration of illness. Nevertheless, children with dysentery due to C. jejuni benefit from early treatment with erythromycin. Treatment with antibiotics, therefore, depends on the severity of symptoms. Quinolones are effective if the organism is sensitive, but high rates of quinolone use in livestock mean that quinolones are now largely ineffective.Antimotility agents, such as loperamide, can lead to prolonged illness or intestinal perforation in any invasive diarrhea, and should be avoided.  Trimethoprim/sulfamethoxazole and ampicillin are ineffective against Campylobacter.

In animals
In the past, poultry infections were often treated by mass administration of enrofloxacin and sarafloxacin for single instances of infection. The FDA banned this practice, as it promoted the development of fluoroquinolone-resistant populations.
A major broad-spectrum fluoroquinolone used in humans is ciprofloxacin.Currently growing resistance of the Campylobacter to fluoroquinolones and macrolides is of a major concern.

Prognosis
Campylobacteriosis is usually self-limited without any mortality (assuming proper hydration is maintained). However, there are several possible complications.

Epidemiology
Campylobacter is one of the most common causes of human bacterial gastroenteritis. For instance, an estimated 2 million cases of Campylobacter enteritis occur annually in the U.S., accounting for 5–7% of cases of gastroenteritis. Furthermore, in the United Kingdom during 2000, Campylobacter jejuni was involved in 77.3% in all cases of laboratory confirmed foodborne illness. About 15 of every 100,000 people are diagnosed with campylobacteriosis every year, and with many cases going unreported, up to 0.5% of the general population may unknowingly harbor Campylobacter in their gut.Unfortunately, the true incidence of campylobacteriosis is unknown in most countries, especially developing countries. The reasons are among others underreporting, difficulties with diagnosis and differences in reporting systems in different countries.A large animal reservoir is present as well, with up to 100% of poultry, including chickens, turkeys, and waterfowl, having asymptomatic infections in their intestinal tracts. Infected chicken feces may contain up to 109 bacteria per 25 grams, and due to the animals close proximity, the bacteria are rapidly spread to other chickens. This vastly exceeds the infectious dose of 1000–10,000 bacteria for humans.In January 2013, the UKs Food Standards Agency warned that two-thirds of all raw chicken bought from UK shops was contaminated with campylobacter, affecting an estimated half a million people annually and killing approximately 100.

Outbreak
In August–September 2016, 5,200 people fell ill with campylobacteriosis in Hastings, New Zealand after the local water supply in Havelock North tested positive for the pathogen Campylobacter jejuni. Four deaths were suspected to be due to the outbreak. It is suspected that after heavy rain fell on 5–6 August, water contamination from flooding caused the outbreak, although this is the subject of a government Inquiry </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Fungemia and explain in detail? [/INST] Fungemia is the presence of fungi or yeasts in the blood. The most common type, also known as candidemia, candedemia, or systemic candidiasis, is caused by Candida species; candidemia is also among the most common bloodstream infections of any kind.  Infections by other fungi, including Saccharomyces, Aspergillus and Cryptococcus, are also called fungemia. It is most commonly seen in immunosuppressed or immunocompromised patients with severe neutropenia, cancer patients, or in patients with intravenous catheters.  It has been suggested the otherwise immunocompetent patients taking infliximab may be at a higher risk for fungemia.
Diagnosis is difficult, as routine blood cultures have poor sensitivity.

Signs and symptoms
Symptoms can range from mild to extreme—often described as extreme flu-like symptoms. Many symptoms may be associated with fungemia, including pain, acute confusion, chronic fatigue, and infections. Skin infections can include persistent or non-healing wounds and lesions, sweating, itching, and unusual discharge or drainage.

Risk factors
Pathogens
The most commonly known pathogen is Candida albicans, causing roughly 70% of fungemias, followed by Candida glabrata with 10%, Aspergillus with 1% and Saccharomyces as the fourth most common. However, the frequency of infection by C. glabrata, Saccharomyces boulardii, Candida tropicalis, C. krusei and C. parapsilosis is increasing, perhaps because significant use of fluconazole is common or due to increase in antibiotic use.Candida auris is an emerging multidrug-resistant (MDR) yeast that can cause invasive infections and is associated with high mortality.  It was first described in 2009 after being isolated from external ear discharge of a patient in Japan.  Since the 2009 report, C </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Capillariasis and explain in detail? [/INST]  </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Cardiac stress test and explain in detail? [/INST] A cardiac stress test (also referred to as a cardiac diagnostic test, cardiopulmonary exercise test, or abbreviated CPX test) is a cardiological test that measures the hearts ability to respond to external stress in a controlled clinical environment. The stress response is induced by exercise or by intravenous pharmacological stimulation.
Cardiac stress tests compare the coronary circulation while the patient is at rest with the same patients circulation during maximum cardiac exertion, showing any abnormal blood flow to the myocardium (heart muscle tissue). The results can be interpreted as a reflection on the general physical condition of the test patient. This test can be used to diagnose coronary artery disease (also known as ischemic heart disease) and assess patient prognosis after a myocardial infarction (heart attack).
Exercise-induced stressors are most commonly either exercise on a treadmill or pedalling a stationary exercise bicycle ergometer. The level of stress is progressively increased by raising the difficulty (steepness of the slope on a treadmill or resistance on an ergometer) and speed. People who cannot use their legs may exercise with a bicycle-like crank that they turn with their arms, or may be given a medication to induce cardiac stress. Once the stress test is completed, the patient generally is advised to not suddenly stop activity but to slowly decrease the intensity of the exercise over the course of several minutes.
The test administrator or attending physician examines the symptoms and blood pressure response. To measure the hearts response to the stress the patient may be connected to an electrocardiogram (ECG); in this case the test is most commonly called a cardiac stress test but is known by other names, such as exercise testing, stress testing treadmills, exercise tolerance test, stress test or stress test ECG. Alternatively a stress test may use an echocardiogram for ultrasonic imaging of the heart (in which case the test is called an echocardiography stress test or stress echo), or a gamma camera to image radioisotopes injected into the bloodstream (called a nuclear stress test).

Stress echocardiography
A stress test may be accompanied by echocardiography. The echocardiography is performed both before and after the exercise so that structural differences can be compared.
A resting echocardiogram is obtained prior to stress. The images obtained are similar to the ones obtained during a full surface echocardiogram, commonly referred to as transthoracic echocardiogram. The patient is subjected to stress in the form of exercise or chemically (usually dobutamine). After the target heart rate is achieved, stress echocardiogram images are obtained. The two echocardiogram images are then compared to assess for any abnormalities in wall motion of the heart. This is used to detect obstructive coronary artery disease.

Cardiopulmonary exercise test
While also measuring breathing gases (e.g. O2, VO2), the test is often referred to as a cardiopulmonary exercise test (CPET).
Common indications for a cardiopulmonary exercise test is:
Evaluation of dyspnea.
Work up before heart transplantation.
Prognosis and risk assessment of heart failure patients.
The test is also common in sport science for measuring athletes VO2 max.

Nuclear stress test
The best known example of a nuclear stress test is myocardial perfusion imaging. Typically, a radiotracer (Tc-99 sestamibi, Myoview or thallous chloride 201) may be injected during the test. After a suitable waiting period to ensure proper distribution of the radiotracer, scans are acquired with a gamma camera to capture images of the blood flow. Scans acquired before and after exercise are examined to assess the state of the coronary arteries of the patient.Showing the relative amounts of radioisotope within the heart muscle, the nuclear stress tests more accurately identify regional areas of reduced blood flow.Stress and potential cardiac damage from exercise during the test is a problem in patients with ECG abnormalities at rest or in patients with severe motor disability. Pharmacological stimulation from vasodilators such as dipyridamole or adenosine, or positive chronotropic agents such as dobutamine can be used. Testing personnel can include a cardiac radiologist, a nuclear medicine physician, a nuclear medicine technologist, a cardiology technologist, a cardiologist, and/or a nurse.The typical dose of radiation received during this procedure can range from 9.4 millisieverts to 40.7 millisieverts.

Function
The American Heart Association recommends ECG treadmill testing as the first choice for patients with medium risk of coronary heart disease according to risk factors of smoking, family history of coronary artery stenosis, hypertension, diabetes and high cholesterol. In 2013, in its "Exercise Standards for Testing and Training", the AHA indicated that high frequency QRS analysis during ECG treadmill test have useful test performance for detection of coronary heart disease.
Perfusion stress test (with 99mTc labelled sestamibi) is appropriate for select patients, especially those with an abnormal resting electrocardiogram.
Intracoronary ultrasound or angiogram can provide more information at the risk of complications associated with cardiac catheterization.

Diagnostic value
The common approach for stress testing by American College of Cardiology and American Heart Association indicates the following:
Treadmill test: sensitivity 73-90%, specificity 50-74% (modified Bruce protocol)
Nuclear test: sensitivity 81%, specificity 85-95%(Sensitivity is the percentage of people with the condition who are correctly identified by the test as having the condition; specificity is the percentage of people without the condition are correctly identified by the test as not having the condition).
To arrive at the patients posttest likelihood of disease, interpretation of the stress test result requires integration of the patients pretest likelihood with the tests sensitivity and specificity. This approach, first described by Diamond and Forrester in the 1970s, results in an estimate of the patients post-test likelihood of disease.
The value of stress tests has always been recognized as limited in assessing heart disease such as atherosclerosis, a condition which mainly produces wall thickening and enlargement of the arteries. This is because the stress test compares the patients coronary flow status before and after exercise and is suitable to detecting specific areas of ischemia and lumen narrowing, not a generalized arterial thickening.According to American Heart Association data, about 65% of men and 47% of women present with a heart attack or sudden cardiac arrest as their first symptom of cardiovascular disease. Stress tests, carried out shortly before these events, are not relevant to the prediction of infarction in the majority of individuals tested. Over the past two decades, better methods have been developed to identify atherosclerotic disease before it becomes symptomatic. These detection methods include anatomical and physiological methods.

Examples of anatomical methodsCT coronary calcium score
Coronary CT angiography
Intima-media thickness (IMT)
Intravascular ultrasound (IVUS)Examples of physiological methodsLipoprotein analysis
HbA1c
Hs-CRP
HomocysteineThe anatomic methods directly measure some aspects of the actual process of atherosclerosis itself and therefore offer the possibility of early diagnosis but are often more expensive and may be invasive (in the case of IVUS, for example). The physiological methods are often less expensive and safer but are not able to quantify the current status of the disease or directly track progression.

Contraindications and termination conditions
Stress cardiac imaging is not recommended for asymptomatic, low-risk patients as part of their routine care. Some estimates show that such screening accounts for 45% of cardiac stress imaging, and evidence does not show that this results in better outcomes for patients. Unless high-risk markers are present, such as diabetes in patients aged over 40, peripheral arterial disease; or a risk of coronary heart disease greater than 2 percent yearly, most health societies do not recommend the test as a routine procedure.Absolute contraindications to cardiac stress test include:

Acute myocardial infarction within 48 hours
Unstable angina not yet stabilized with medical therapy
Uncontrolled cardiac arrhythmia, which may have significant hemodynamic responses (e.g. ventricular tachycardia)
Severe symptomatic aortic stenosis, aortic dissection, pulmonary embolism, and pericarditis
Multivessel coronary artery diseases that have a high risk of producing an acute myocardial infarction
Decompensated or inadequately controlled congestive heart failure
Uncontrolled hypertension (blood pressure>200/110mm Hg)
Severe pulmonary hypertension
Acute aortic dissection
Acutely ill for any reasonIndications for termination:
A cardiac stress test should be terminated before completion under the following circumstances:Absolute indications for termination include:

Systolic blood pressure decreases by more than 10 mmHg with increase in work rate, or drops below baseline in the same position, with other evidence of ischemia.
Increase in nervous system symptoms: Dizziness, ataxia or near syncope
Moderate to severe anginal pain (above 3 on standard 4-point scale)
Signs of poor perfusion, e.g. cyanosis or pallor
Request of the test subject
Technical difficulties (e.g. difficulties in measuring blood pressure or EGC)
ST Segment elevation of more than 1 mm in aVR, V1 or non-Q wave leads
Sustained ventricular tachycardiaRelative indications for termination include:

Systolic blood pressure decreases by more than 10 mmHg with increase in work rate, or drops below baseline in the same position, without other evidence of ischemia.
ST or QRS segment changes, e.g. more than 2 mm horizontal or downsloping ST segment depression in non-Q wave leads, or marked axis shift
Arrhythmias other than sustained ventricular tachycardia e.g. Premature ventricular contractions, both multifocal or triplet; heart block; supraventricular tachycardia or bradyarrhythmias
Intraventricular conduction delay or bundle branch block or that cannot be distinguished from ventricular tachycardia
Increasing chest pain
Fatigue, shortness of breath, wheezing, claudication or leg cramps
Hypertensive response (systolic blood pressure > 250 mmHg or diastolic blood pressure > 115 mmHg)

Adverse effects
Side effects from cardiac stress testing may include
Palpitations, chest pain, myocardial infarction, shortness of breath, headache, nausea or fatigue.
Adenosine and dipyridamole can cause mild hypotension.
As the tracers used for this test are carcinogenic, frequent use of these tests carries a small risk of cancer.

Pharmacological agents
Pharmacologic stress testing relies on coronary steal. Vasodilators are used to dilate coronary vessels, which causes increased blood velocity and flow rate in normal vessels and less of a response in stenotic vessels </s>


<s> [INST] <<SYS>> You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information. <</SYS>> What is Systemic primary carnitine deficiency and explain in detail? [/INST] Systemic primary carnitine deficiency (SPCD)  is an inborn error of fatty acid transport caused by a defect in the transporter responsible for moving carnitine across the plasma membrane. Carnitine is an important amino acid for fatty acid metabolism. When carnitine cannot be transported into tissues, fatty acid oxidation is impaired, leading to a variety of symptoms such as chronic muscle weakness, cardiomyopathy, hypoglycemia and liver dysfunction.  The specific transporter involved with SPCD is OCTN2, coded for by the SLC22A5 gene located on chromosome 5.  SPCD is inherited in an autosomal recessive manner, with mutated alleles coming from both parents.
Acute episodes due to SPCD are often preceded by metabolic stress such as extended fasting, infections or vomiting.  Cardiomyopathy can develop in the absence of an acute episode, and can result in death.  SPCD leads to increased carnitine excretion in the urine and low levels in plasma.  In most locations with expanded newborn screening, SPCD can be identified and treated shortly after birth.  Treatment with high doses of carnitine supplementation is effective, but needs to be rigorously maintained for life.

Signs and symptoms
The presentation of patient with SPCD can be incredibly varied, from asymptomatic to lethal cardiac manifestations.  Early cases were reported with liver dysfunction, muscular findings (weakness and underdevelopment), hypoketotic hypoglycemia, cardiomegaly, cardiomyopathy and marked carnitine deficiency in plasma and tissues, combined with increased excretion in urine.  Patients who present clinically with SPCD fall into two categories, a metabolic presentation with hypoglycemia and a cardiac presentation characterized by cardiomyopathy.  Muscle weakness can be found with either presentation.In countries with expanded newborn screening, SPCD can be identified shortly after birth.  Affected infants show low levels of free carnitine and all other acylcarnitine species by tandem mass spectrometry.  Not all infants with low free carnitine are affected with SPCD.  Some may have carnitine deficiency secondary to another metabolic condition or due to maternal carnitine deficiency.  Proper follow-up of newborn screening results for low free carnitine includes studies of the mother to determine whether her carnitine deficiency is due to SPCD or secondary to a metabolic disease or diet.  Maternal cases of SPCD have been identified at a higher than expected rate, often in women who are asymptomatic.  Some mothers have also been identified through newborn screening with cardiomyopathy that had not been previously diagnosed.  The identification and treatment of these asymptomatic individuals is still developing, as it is not clear whether they require the same levels of intervention as patients identified with SPCD early in life based on clinical presentation.

Genetics
SPCD is an autosomal recessive condition, meaning a mutated allele must be inherited from each parent for an individual to be affected.  The gene responsible for the OCTN2 carnitine transporter is SLC22A5, located at 5q31.1-32.  SLC22A5 is regulated by peroxisome proliferator-activated receptor alpha.  The transporter, OCTN2, is located in the apical membrane of the renal tubular cells, where it plays a role in tubular reabsorption.The defective OCTN2 is unable to recapture carnitine prior to its excretion in urine, leading to the characteristic biochemical findings of massively increased urine carnitine levels and significantly decreased plasma carnitine levels.  Decreased levels of plasma carnitine inhibit fatty acid oxidation during times of excessive energy demand.  Carnitine is needed to transport long chain fatty acids into the mitochondria, where they can be broken down to produce acetyl-CoA.  Individuals with SPCD cannot produce ketone bodies as energy due to the interruption of fatty acid oxidation.  Although SPCD is an autosomal recessive condition, heterozygotes have been shown to be at an increased risk for developing benign cardiomyopathy compared to wild type individuals.

Diagnosis
The first suspicion of SPCD in a patient with a non-specific presentation is an extremely low plasma carnitine level.  When combined with an increased concentration of carnitine in urine, the suspicion of SPCD can often be confirmed by either molecular testing or functional studies assessing the uptake of carnitine in cultured fibroblasts.

Treatment
Identification of patients presymptomatically via newborn screening has allowed early intervention and treatment.  Treatment for SPCD involves high dose carnitine supplementation, which must be continued for life.  Individuals who are identified and treated at birth have very good outcomes, including the prevention of cardiomyopathy.  Mothers who are identified after a positive newborn screen but are otherwise asymptomatic are typically offered carnitine supplementation as well </s>