<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 Hidradenitis suppurativa and explain in detail? [/INST] Hidradenitis suppurativa (HS), sometimes known as acne inversa or Verneuils disease, is a long-term dermatological condition characterized by the occurrence of inflamed and swollen lumps. These are typically painful and break open, releasing fluid or pus. The areas most commonly affected are the underarms, under the breasts, and the groin. Scar tissue remains after healing. HS may significantly limit many everyday activities, for instance, walking, hugging, moving, and sitting down. Sitting disability may occur in patients with lesions in sacral, gluteal, perineal, femoral, groin or genital regions; and prolonged periods of sitting down itself can also worsen the condition of the skin of these patients.The exact cause is usually unclear, but believed to involve a combination of genetic and environmental factors. About a third of people with the disease have an affected family member. Other risk factors include obesity and smoking. The condition is not caused by an infection, poor hygiene, or the use of deodorant. Instead, it is believed to be caused by hair follicles being obstructed, with the nearby apocrine sweat glands being strongly implicated in this obstruction. The sweat glands themselves may or may not be inflamed. Diagnosis is based on the symptoms.No cure is known. Warm baths may be tried in those with mild disease. Cutting open the lesions to allow them to drain does not result in significant benefit. While antibiotics are commonly used, evidence for their use is poor. Immunosuppressive medication may also be tried. In those with more severe disease, laser therapy or surgery to remove the affected skin may be viable. Rarely, a skin lesion may develop into skin cancer.If mild cases of HS are included, then the estimate of its frequency is from 1–4% of the population. Women are three times more likely to be diagnosed with it than men. Onset is typically in young adulthood and may become less common after 50 years old. It was first described between 1833 and 1839 by French anatomist Alfred Velpeau.

Causes
The exact cause of hidradenitis suppurativa remains unknown, and there has, in the recent past, been notable disagreement among experts in this regard. The condition, however, likely stems from both genetic and environmental causes. Specifically, an immune-mediated pathology has been proposed, although there have been sources that have already contradicted the probable likelihood of such an idea.Lesions will occur in any body areas with hair follicles, although areas such as the axilla, groin, and perineal region are more commonly involved. This theory includes most of these potential indicators:
Post-pubescent individuals
Blocked hair follicles or blocked apocrine sweat glands
Excessive sweating
Androgen dysfunction
Genetic disorders that alter cell structure
Patients with more advanced cases may find exercise intolerably painful, which may increase their rate of obesity.The historical understanding of the disease suggests dysfunctional apocrine glands or dysfunctional hair follicles, possibly triggered by a blocked gland, which creates inflammation, pain, and a swollen lesion.

Triggering factors
Several triggering factors should be taken into consideration:

Obesity is an exacerbating rather than a triggering factor, through mechanical irritation, occlusion, and skin maceration.
Tight clothing, and clothing made of heavy, nonbreathable materials
Deodorants, depilation products, shaving of the affected area – their association with HS is still an ongoing debate among researchers.
Drugs, in particular oral contraceptive pills and lithium.
Hot and especially humid climates.

Predisposing factors
Genetic factors: an autosomal dominant inheritance pattern has been proposed.
Endocrine factors: sex hormones, especially an excess of androgens, are thought to be involved, although the apocrine glands are not sensitive to these hormones. Women often have outbreaks before their menstrual period and after pregnancy; HS severity usually decreases during pregnancy and after menopause.Some cases have been found to result from mutations in the NCSTN, PSEN1, or PSENEN genes. The genes produce proteins that are all components of a complex called gamma- (γ-) secretase. This complex cuts apart (cleaves) many different proteins, which is an important step in several chemical signaling pathways. One of these pathways, known as notch signaling, is essential for the normal maturation and division of hair follicle cells and other types of skin cells. Notch signaling is also involved in normal immune system function. Studies suggest that mutations in the NCSTN, PSEN1, or PSENEN gene impair notch signaling in hair follicles. Although little is known about the mechanism, abnormal notch signaling appears to promote the development of nodules and to lead to inflammation in the skin. In addition,  the composition of the intestinal microflora and as a consequence dietary patterns appear to play a role. Although dysbiosis of the cutaneous microbiome apparent in HS is not observed, the concurrent existence of inflammatory gut and skin diseases has led to the postulation of a gut-skin axis in which gut microbiota is implicated. Indeed, analysis of bacterial taxa in fecal samples from HS patients support the possibility of a role for intestinal microbial alterations in this chronic inflammatory skin disease.

Diagnosis
Stages
Hidradenitis suppurativa presents itself in three stages. Due to the large spectrum of clinical severity and the severe impact on quality of life, a reliable method for evaluating HS severity is needed.

Hurleys staging system
Hurleys staging system was the first classification system proposed, and is still in use for the classification of patients with skin diseases (i.e., psoriasis, HS, acne). Hurley separated patients into three groups based largely on the presence and extent of cicatrization and sinuses. It has been used as a basis for clinical trials in the past and is a useful basis to approach therapy for patients. These three stages are based on Hurleys staging system, which is simple and relies on the subjective extent of the diseased tissue the patient has. Hurleys three stages of hidradenitis suppurativa are:

Sartorius staging system
The Sartorius staging system is more sophisticated than Hurleys. Sartorius et al. suggested that the Hurley system is not sophisticated enough to assess treatment effects in clinical trials during research. This classification allows for better dynamic monitoring of the disease severity in individual patients. The elements of this staging system are:
Anatomic regions involved (axilla, groin gluteal, or other region or inframammary region left or right)
Number and types of lesions involved (abscesses, nodules, fistulas or sinuses, scars, points for lesions of all regions involved)
The distance between lesions, in particular the longest distance between two relevant lesions (i.e., nodules and fistulas in each region or size if only one lesion present)
The presence of normal skin in between lesions (i.e., if all lesions are clearly separated by normal skin)Points are accumulated in each of the above categories, and added to give both a regional and total score. In addition, the authors recommend adding a visual analog scale for pain or using the dermatology life quality index (DLQI, or the skindex) when assessing HS.

Treatment
Treatment depends upon presentation and severity of the disease. Due to the poorly studied nature of the disease, the effectiveness of the drugs and therapies listed below is unclear. Possible treatments include the following:

Lifestyle
Warm baths may be tried in those with mild disease. Weight loss and the cessation of smoking are also recommended.

Medication
Antibiotics: taken by mouth, these are used for their anti-inflammatory properties rather than to treat infection. Most effective is a combination of rifampicin and clindamycin given concurrently for 2–3 months. Popular antibiotics also include tetracycline and minocycline. Topical clindamycin has been shown to have an effect in double-blind placebo controlled studies.
Corticosteroid injections, also known as intralesional steroids, can be particularly useful for localized disease, if the drug can be prevented from escaping via the sinuses.
Antiandrogen therapy, hormonal therapy with antiandrogenic medications such as spironolactone, flutamide, cyproterone acetate, ethinylestradiol, finasteride, dutasteride, and metformin, have been found to be effective in clinical studies. However, the quality of available evidence is low and does not presently allow for robust evidence-based recommendations.
Intravenous infusion or subcutaneous injection of anti-inflammatory (TNF inhibitors; anti-TNF-alpha) drugs such as infliximab, and etanercept This use of these drugs is not currently Food and Drug Administration (FDA) approved and is somewhat controversial, so may not be covered by insurance.
TNF inhibitor: Studies have supported that various TNF inhibitors have a positive effect on HS lesions. Specifically adalimumab at weekly intervals is useful. Adalimumab is the only medication approved by the FDA for the treatment of HS as of 2021.
Topical isotretinoin is usually ineffective in people with HS, and is more commonly known as a medication for the treatment of acne vulgaris. Individuals affected by HS who responded to isotretinoin treatment tended to have milder cases of the condition.

Surgery
When the process becomes chronic, wide surgical excision is the procedure of choice. Wounds in the affected area do not heal by secondary intention, and immediate or delayed application of a split-thickness skin graft is an option.
Another option is covering the defect with a perforator flap. With this technique, the (mostly totally excised) defect is covered with tissue from an area nearby. For example, the axilla with a fully excised defect of 15 × 7 cm can be covered with a thoracodorsal artery perforator flap.

Laser hair removal
The 1064-nm wavelength laser for hair removal may aid in the treatment of HS. A randomized control study has shown improvement in HS lesions with the use of an Nd:YAG laser.

Prognosis
In stage III disease, as classified by the Hurleys staging system, fistulae left undiscovered, undiagnosed, or untreated, can rarely lead to the development of squamous cell carcinoma in the anus or other affected areas. Other stage III chronic sequelae may also include anemia, multilocalized infections, amyloidosis, and arthropathy. Stage III complications have been known to lead to sepsis, but clinical data are still uncertain.

Potential complications
Contractures and reduced mobility of the lower limbs and axillae due to fibrosis and scarring occur. Severe lymphedema may develop in the lower limbs.
Local and systemic infections (meningitis, bronchitis, pneumonia, etc.), are seen, which may even progress to sepsis.
Interstitial keratitis
Anal, rectal, or urethral fistulae
Normochromic or hypochromic anemia
People with HS may be at increased risk for autoimmune disorders including ankylosing spondylitis, rheumatoid arthritis, and psoriatic arthritis.
Squamous cell carcinoma has been found on rare occasions in chronic hidradenitis suppurativa of the anogenital region. The mean time to the onset of this type of lesion is 10 years or more and the tumors are usually highly aggressive.
Tumors of the lung and oral cavity, and liver cancer
Hypoproteinemia and amyloidosis, which can lead to kidney failure and death
Seronegative and usually asymmetric arthropathy: pauciarticular arthritis, polyarthritis/polyarthralgia syndrome

History
From 1833 to 1839, in a series of three publications, Velpeau identified and described a disease now known as hidradenitis suppurativa.
In 1854, Verneuil described hidradenitis suppurativa as hidrosadénite Phlegmoneuse. This is how HS obtained its alternate name "Verneuils disease".
In 1922, Schiefferdecker hypothesized a pathogenic link between "acne inversa" and human sweat glands.
In 1956, Pillsbury et al. coined the term follicular occlusion triad for the common association of hidradenitis suppurativa, acne conglobata and dissecting cellulitis of the scalp. Modern clinical research still employs Pillsburys terminology for these conditions descriptions.
In 1975, Plewig and Kligman, following Pillsburys research path, modified the "acne triad", replacing it with the "acne tetrad: acne triad, plus pilonidal sinus". Plewig and Kligmans research follows in Pillsburys footsteps, offering explanations of the symptoms associated with hidradenitis suppurativa.
In 1989, Plewig and Stegers research led them to rename hidradenitis suppurativa, calling it "acne inversa" – which is not still used today in medical terminology, although some individuals still use this outdated term.A surgeon from Paris, Velpeau described an unusual inflammatory process with formation of superficial axillary, submammary, and perianal abscesses, in a series of three publications from 1833 to 1839 </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 Urinary incontinence and explain in detail? [/INST] Urinary incontinence (UI), also known as involuntary urination, is any uncontrolled leakage of urine. It is a common and distressing problem, which may have a large impact on quality of life. It has been identified as an important issue in geriatric health care. The term enuresis is often used to refer to urinary incontinence primarily in children, such as nocturnal enuresis (bed wetting). UI is an example of a stigmatized medical condition, which creates barriers to successful management and makes the problem worse. People may be too embarrassed to seek medical help, and attempt to self-manage the symptom in secrecy from others.
Pelvic surgery, pregnancy, childbirth, and menopause are major risk factors. Urinary incontinence is often a result of an underlying medical condition but is under-reported to medical practitioners. There are four main types of incontinence:
Urge incontinence due to an overactive bladder
Stress incontinence due to "a poorly functioning urethral sphincter muscle (intrinsic sphincter deficiency) or to hypermobility of the bladder neck or urethra"
Overflow incontinence due to either poor bladder contraction or blockage of the urethra
Mixed incontinence involving features of different other typesTreatments include pelvic floor muscle training, bladder training, surgery, and electrical stimulation. Behavioral therapy generally works better than medication for stress and urge incontinence. The benefit of medications is small and long term safety is unclear. Urinary incontinence is more common in older women.

Causes
Urinary incontinence can result from both urologic and non-urologic causes. Urologic causes can be classified as either bladder dysfunction or urethral sphincter incompetence and may include detrusor overactivity, poor bladder compliance, urethral hypermobility, or intrinsic sphincter deficiency. Non-urologic causes may include infection, medication or drugs, psychological factors, polyuria, hydrocephalus, stool impaction, and restricted mobility. The causes leading to urinary incontinence are usually specific to each sex, however, some causes are common to both men and women.

Women
The most common types of urinary incontinence in women are stress urinary incontinence and urge urinary incontinence. Women that have symptoms of both types are said to have "mixed" urinary incontinence. After menopause, estrogen production decreases and, in some women, urethral tissue will demonstrate atrophy, becoming weaker and thinner, possibly playing a role in the development of urinary incontinence.Stress urinary incontinence in women is most commonly caused by loss of support of the urethra, which is usually a consequence of damage to pelvic support structures as a result of pregnancy, childbirth, obesity, age, among others. About 33% of all women experience urinary incontinence after giving birth, and women who deliver vaginally are about twice as likely to have urinary incontinence as women who give birth via a Caesarean section. Stress incontinence is characterized by leaking of small amounts of urine with activities that increase abdominal pressure such as coughing, sneezing, laughing and lifting. This happens when the urethral sphincter cannot close completely due to the damage in the sphincter itself, or the surrounding tissue.  Additionally, frequent exercise in high-impact activities can cause athletic incontinence to develop. Urge urinary incontinence, is caused by uninhibited contractions of the detrusor muscle, a condition known as overactive bladder syndrome. It is characterized by leaking of large amounts of urine in association with insufficient warning to get to the bathroom in time.

Men
Urge incontinence is the most common type of incontinence in men. Similar to women, urine leakage happens following a very intense feeling of urination, not allowing enough time to reach the bathroom, a condition called overactive bladder syndrome. In men, the condition is commonly associated with benign prostatic hyperplasia (an enlarged prostate), which causes bladder outlet obstruction, a dysfunction of the detrusor muscle (muscle of the bladder), eventually causing overactive bladder syndrome, and the associated incontinence.Stress urinary incontinence is the other common type of incontinence in men, and it most commonly happens after prostate surgery. Prostatectomy, transurethral resection of the prostate, prostate brachytherapy, and radiotherapy can all damage the urethral sphincter and surrounding tissue, causing it to be incompetent. An incompetent urethral sphincter cannot prevent the urine from leaking out of the urinary bladder during activities that increase the intraabdominal pressure, such as coughing, sneezing, or laughing. Continence usually improves within 6 to 12 months after prostate surgery without any specific interventions, and only 5 to 10% of people report persistent symptoms.

Both
Age is a risk factor that increases both the severity and prevalence of UI
Polyuria (excessive urine production) of which, in turn, the most frequent causes are: uncontrolled diabetes mellitus, primary polydipsia (excessive fluid drinking), central diabetes insipidus and nephrogenic diabetes insipidus. Polyuria generally causes urinary urgency and frequency, but does not necessarily lead to incontinence.
Neurogenic disorders like multiple sclerosis, spina bifida, Parkinsons disease, strokes and spinal cord injury can all interfere with nerve function of the bladder. This can lead to neurogenic bladder dysfunction
Overactive bladder syndrome. However, the etiology behind this is usually different between men and women, as mentioned above.
Other suggested risk factors include smoking, caffeine intake and depression

Mechanism
Adults
The body stores urine — water and wastes removed by the kidneys — in the urinary bladder, a balloon-like organ. The bladder connects to the urethra, the tube through which urine leaves the body.Continence and micturition involve a balance between urethral closure and detrusor muscle activity (the muscle of the bladder). During urination, detrusor muscles in the wall of the bladder contract, forcing urine out of the bladder and into the urethra. At the same time, sphincter muscles surrounding the urethra relax, letting urine pass out of the body.  The urethral sphincter is the muscular ring that closes the outlet of the urinary bladder preventing urine to pass outside the body. Urethral pressure normally exceeds bladder pressure, resulting in urine remaining in the bladder, and maintaining continence. The urethra is supported by pelvic floor muscles and tissue, allowing it to close firmly. Any damage to this balance between the detrusor muscle, urethral sphincter, supportive tissue and nerves can lead to some type of incontinence .For example, stress urinary incontinence is usually a result of the incompetent closure of the urethral sphincter. This can be caused by damage to the sphincter itself, the muscles that support it, or nerves that supply it. In men, the damage usually happens after prostate surgery or radiation, and in women, its usually caused by childbirth and pregnancy. The pressure inside the abdomen (from coughing and sneezing) is normally transmitted to both urethra and bladder equally, leaving the pressure difference unchanged, resulting in continence. When the sphincter is incompetent, this increase in pressure will push the urine against it, leading to incontinence.Another example is urge incontinence. This incontinence is associated with sudden forceful contractions of the detrusor muscle (bladder muscle), leading to an intense feeling of urination, and incontinence if the person does not reach the bathroom on time. The syndrome is known as overactive bladder syndrome, and its related to dysfunction of the detrusor muscle.

Children
Urination, or voiding, is a complex activity. The bladder is a balloon-like muscle that lies in the lowest part of the abdomen. The bladder stores urine then releases it through the urethra, the canal that carries urine to the outside of the body. Controlling this activity involves nerves, muscles, the spinal cord and the brain.The bladder is made of two types of muscles: the detrusor, a muscular sac that stores urine and squeezes to empty, and the sphincter, a circular group of muscles at the bottom or neck of the bladder that automatically stays contracted to hold the urine in and automatically relax when the detrusor contracts to let the urine into the urethra. A third group of muscles below the bladder (pelvic floor muscles) can contract to keep urine back.A babys bladder fills to a set point, then automatically contracts and empties. As the child gets older, the nervous system develops. The childs brain begins to get messages from the filling bladder and begins to send messages to the bladder to keep it from automatically emptying until the child decides it is the time and place to void.Failures in this control mechanism result in incontinence. Reasons for this failure range from the simple to the complex.

Diagnosis
The pattern of voiding and urine leakage is important as it suggests the type of incontinence. Other points include straining and discomfort, use of drugs, recent surgery, and illness.The physical examination looks for signs of medical conditions causing incontinence, such as tumors that block the urinary tract, stool impaction, and poor reflexes or sensations, which may be evidence of a nerve-related cause.Other tests include:
Stress test – the patient relaxes, then coughs vigorously as the doctor watches for loss of urine.
Urinalysis – urine is tested for evidence of infection, urinary stones, or other contributing causes.
Blood tests – blood is taken, sent to a laboratory, and examined for substances related to causes of incontinence.
Ultrasound – sound waves are used to visualize the kidneys and urinary bladder, assess the capacity of the bladder before voiding, and the remaining amount of urine after voiding. This helps know if theres a problem in emptying.
Cystoscopy – a thin tube with a tiny camera is inserted in the urethra and used to see the inside of the urethra and bladder.
Urodynamics – various techniques measure pressure in the bladder and the flow of urine.People are often asked to keep a diary for a day or more, up to a week, to record the pattern of voiding, noting times and the amounts of urine produced.
Research projects that assess the efficacy of anti-incontinence therapies often quantify the extent of urinary incontinence. The methods include the 1-h pad test, measuring leakage volume; using a voiding diary, counting the number of incontinence episodes (leakage episodes) per day; and assessing of the strength of pelvic floor muscles, measuring the maximum vaginal squeeze pressure.

Main types
There are 4 main types of urinary incontinence:

Stress incontinence, also known as effort incontinence, is essentially due to incomplete closure of the urinary sphincter, due to problems in the sphincter itself or insufficient strength of the pelvic floor muscles supporting it. This type of incontinence is when urine leaks during activities that increase intra-abdominal pressure, such as coughing, sneezing or bearing down.
Urge incontinence is an involuntary loss of urine occurring while suddenly feeling the need or urge to urinate, usually secondary to overactive bladder syndrome.
Overflow incontinence is the incontinence that happens suddenly without feeling an urge to urinate and without necessarily doing any physical activities. It is also known as under-active bladder syndrome. This usually happens with chronic obstruction of the bladder outlet or with diseases damaging the nerves supplying the urinary bladder. The urine stretches the bladder without the person feeling the pressure, and eventually, it overwhelms the ability of the urethral sphincter to hold it back.
Mixed incontinence contains symptoms of multiple other types of incontinence. It is not uncommon in the elderly female population and can sometimes be complicated by urinary retention.

Other types
Functional incontinence occurs when a person recognizes the need to urinate but cannot make it to the bathroom. The loss of urine may be large. There are several causes of functional incontinence including confusion, dementia, poor eyesight, mobility or dexterity, unwillingness to the toilet because of depression or anxiety or inebriation due to alcohol.  Functional incontinence can also occur in certain circumstances where no biological or medical problem is present. For example, a person may recognize the need to urinate but may be in a situation where there is no toilet nearby or access to a toilet is restricted.
Structural incontinence: Rarely, structural problems can cause incontinence, usually diagnosed in childhood (for example, an ectopic ureter). Fistulas caused by obstetric and gynecologic trauma or injury are commonly known as obstetric fistulas and can lead to incontinence. These types of vaginal fistulas include, most commonly, vesicovaginal fistula and, more rarely, ureterovaginal fistula. These may be difficult to diagnose. The use of standard techniques along with a vaginogram or radiologically viewing the vaginal vault with instillation of contrast media.
Nocturnal enuresis is episodic UI while asleep. It is normal in young children.
Transient incontinence is temporary incontinence most often seen in pregnant women when it subsequently resolves after the birth of the child.
Giggle incontinence is an involuntary response to laughter. It usually affects children.
Double incontinence. There is also a related condition for defecation known as fecal incontinence. Due to involvement of the same muscle group (levator ani) in bladder and bowel continence, patients with urinary incontinence are more likely to have fecal incontinence in addition.  This is sometimes termed "double incontinence".
Post-void dribbling is the phenomenon where urine remaining in the urethra after voiding the bladder slowly leaks out after urination.
Coital incontinence (CI) is urinary leakage that occurs during either penetration or orgasm and can occur with a sexual partner or with masturbation. It has been reported to occur in 10% to 24% of sexually active women with pelvic floor disorders.
Climacturia is urinary incontinence at the moment of orgasm. It can be a result of radical prostatectomy.

Screening
Yearly screening is recommended for women by the Womens Preventive Services Initiative. Screening questions should inquire about what symptoms they have experienced, how severe the symptoms are, and if the symptoms affect their daily lives. As of 2018, studies have not shown a change in outcomes with urinary incontinence screenings in women.

Management
Treatment options range from conservative treatment, behavioral therapy, bladder retraining, pelvic floor therapy, collecting devices (for men), fixer-occluder devices for incontinence (in men), medications and surgery. A 2018 systematic review update showed that both nonpharmacological and pharmacological treatments are effective for treating UI in non-pregnant women. All treatments, except hormones and periurethral bulking agents, are more effective than no treatment in improving or curing UI symptoms or achieving patient satisfaction. The success of treatment depends on the correct diagnoses.

Behavioral therapy
Behavioral therapy involves the use of both suppressive techniques (distraction, relaxation) and learning to avoid foods that may worsen urinary incontinence. This may involve avoiding or limiting consumption of caffeine and alcohol. Behavioral therapies, including bladder training, biofeedback, and pelvic floor muscle training, are most effective for improving urinary incontinence in women, with a low risk of adverse events. Behavioral therapy is not curative for urinary incontinence, but it can improve a persons quality of life. Behavioral therapy has benefits as both a monotherapy and as an adjunct to medications for symptom reduction.Avoiding heavy lifting and preventing constipation may help with uncontrollable urine leakage. Stopping smoking is also recommended as it is associated with improvements in urinary incontinence in men and women. Weight loss is recommended in those who are obese.

Physical therapy and exercise
Physical therapy can be effective for women in reducing urinary incontinence.Pelvic floor physical therapists work with patients to identify and treat underlying pelvic muscle dysfunction that can cease urinary incontinence. They may recommend exercises to strengthen the muscles, electrostimulation, or biofeedback treatments. Exercising the muscles of the pelvis such as with Kegel exercises are a first line treatment for women with stress incontinence. Efforts to increase the time between urination, known as bladder training, is recommended in those with urge incontinence. Both these may be used in those with mixed incontinence.Small vaginal cones of increasing weight may be used to help with exercise. They seem to be better than no active treatment in women with stress urinary incontinence, and have similar effects to training of pelvic floor muscles or electrostimulation.Biofeedback uses measuring devices to help the patient become aware of his or her bodys functioning. By using electronic devices or diaries to track when the bladder and urethral muscles contract, the patient can gain control over these muscles. Biofeedback can be used with pelvic muscle exercises and electrical stimulation to relieve stress and urge incontinence.Time voiding while urinating and bladder training are techniques that use biofeedback. In time voiding, the patient fills in a chart of voiding and leaking. From the patterns that appear in the chart, the patient can plan to empty his or her bladder before he or she would otherwise leak. Biofeedback and muscle conditioning, known as bladder training, can alter the bladders schedule for storing and emptying urine. These techniques are effective for urge and overflow incontinenceA 2013 randomized controlled trial found no benefit of adding biofeedback to pelvic floor muscle exercise in stress urinary incontinence, but observing improvements in both groups. In another randomized controlled trial the addition of biofeedback to the training of pelvic floor muscles for the treatment of stress incontinence, improved pelvic floor muscle function, reduced urinary symptoms, and improved the quality of life.Preoperative pelvic floor muscle training (PFMT) in men undergoing radical prostatectomy was not effective in reducing urinary incontinence.Alternative exercises have been studied for stress urinary incontinence in women. Evidence was insufficient to support the use of Paula method, abdominal muscle training, Pilates, Tai Chi, breathing exercises, postural training, and generalized fitness.

Devices
Individuals who continue to experience urinary incontinence need to find a management solution that matches their individual situation. The use of mechanical devices has not been well studied in women, as of 2014.
Collecting systems (for men) – consists of a sheath worn over the penis funneling the urine into a urine bag worn on the leg. These products come in a variety of materials and sizes for individual fit. Studies show that urisheaths and urine bags are preferred over absorbent products – in particular when it comes to ‘limitations to daily activities’. Solutions exist for all levels of incontinence. Advantages with collecting systems are that they are discreet, the skin stays dry all the time, and they are convenient to use both day and night.  Disadvantages are that it is necessary to get measured to ensure proper fit, and in some countries, a prescription is needed.
Absorbent products (include shields, incontinence pads, undergarments, protective underwear, briefs, diapers, adult diapers and underpants) are the best-known product types to manage incontinence. They are widely available in pharmacies and supermarkets. The advantages of using these are that they barely need any fitting or introduction by a healthcare specialist. The disadvantages with absorbent products are that they can be bulky, leak, have odors and can cause skin breakdown due to the constant dampness.
Intermittent catheters are single-use catheters that are inserted into the bladder to empty it, and once the bladder is empty they are removed and discarded. Intermittent catheters are primarily used for urinary retention (inability to empty the bladder), but for some people they can be used to reduce or avoid incontinence.  These are prescription-only medical devices.
Indwelling catheters (also known as foleys) are often used in hospital settings, or if the user is not able to handle any of the above solutions himself/herself (e.g. severe neurologic injury or neurodegenerative disease). These are also prescription-only medical devices. The indwelling catheter is typically connected to a urine bag that can be worn on the leg or hung on the side of the bed. Indwelling catheters need to be monitored and changed on a regular basis by a healthcare professional. The advantage of indwelling catheters is that because the urine is funneled away from the body, the skin remains dry. However, the disadvantage is that it is very common to incur urinary tract infections when using indwelling catheters.  Bladder spasms and other problems can also occur with long-term use of indwelling catheters.
Penis clamp (or penis compression device), which is applied to compress the urethra to compensate for the malfunctioning of the natural urinary sphincter, preventing leakage from the bladder. This management solution is only suitable for light or moderate incontinence.
Vaginal pessaries for women are devices inserted into the vagina. This device provides support to the urethra which passes right in front of it, allowing it to close more firmly.

Medications
A number of medications exist to treat urinary incontinence including: fesoterodine, tolterodine and oxybutynin. These medications work by relaxing smooth muscle in the bladder. While some of these medications appear to have a small benefit, the risk of side effects are a concern. Medications are effective for about one in ten people, and all medications have similar efficacy.Medications are not recommended for those with stress incontinence and are only recommended in those with urge incontinence who do not improve with bladder training.Injectable bulking agents may be used to enhance urethral support, however, they are of unclear benefit.

Surgery
Women and men that have persistent incontinence despite optimal conservative therapy may be candidates for surgery. Surgery may be used to help stress or overflow incontinence. Common surgical techniques for stress incontinence include slings, tension-free vaginal tape, bladder suspension, artificial urinary sphincters, among others.The use of transvaginal mesh implants and bladder slings is controversial due to the risk of debilitating painful side effects such as vaginal erosion. In 2012 transvaginal mesh implants were classified as a high risk device by the US Food and Drug Administration. Urodynamic testing seems to confirm that surgical restoration of vault prolapse can cure motor urge incontinence.
Traditional suburethral sling operations are probably slightly better than open abdominal retropubic colposuspension and are probably slightly less effective than mid-urethral sling operations in reducing urinary incontinence in women, but it is still uncertain if any of the different types of traditional suburethral sling operations are better than others. Similarly, there is insufficient evidence to be certain about the effectiveness or safety of single-incision sling operations for urinary incontinence in women. Traditional suburethral slings may have a higher risk of surgical complications than minimally invasive slings but the risk of complications compared with other types of operation is still uncertain.Laparoscopic colposuspension (keyhole surgery through the abdomen) with sutures is as effective as open colposuspension for curing incontinence in women up to 18 months after surgery, but it is unclear whether there are fewer risk of complications during or after surgery. There is probably a higher risk of complications with traditional suburethral slings than with open abdominal retropubic suspension.

The artificial urinary sphincter is an implantable device used to treat stress incontinence, mostly in men. The device is made of 2 or 3 parts: The pump, cuff, and balloon reservoir connected to each other by specialized tubes.  The cuff wraps around the urethra and closes it. When the person wants to urinate, he presses the pump (implanted in the scrotum), to deflate the cuff, and allow the urine to pass. The cuff regains pressure within a few minutes to regain continence. The European Association of Urology considers the artificial urinary sphincter as the gold standard in surgical management of stress urinary incontinence in men after prostatectomy.

Epidemiology
Globally, up to 35% of the population over the age of 60 years is estimated to be incontinent.
In 2014, urinary leakage affected between 30% and 40% of people over 65 years of age living in their own homes or apartments in the U.S. Twenty-four percent of older adults in the U.S. have moderate or severe urinary incontinence that should be treated medically. People with dementia are three times more likely to have urinary incontinence compared to people of similar ages.Bladder control problems have been found to be associated with higher incidence of many other health problems such as obesity and diabetes. Difficulty with bladder control results in higher rates of depression and limited activity levels.Incontinence is expensive both to individuals in the form of bladder control products and to the health care system and nursing home industry. Injury-related to incontinence is a leading cause of admission to assisted living and nursing care facilities. In 1997 more than 50% of nursing facility admissions were related to incontinence.

Women
Bladder symptoms affect women of all ages. However, bladder problems are most prevalent among older women. Women over the age of 60 years are twice as likely as men to experience incontinence; one in three women over the age of 60 years are estimated to have bladder control problems </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 Hypovolemia and explain in detail? [/INST] Hypovolemia, also known as volume depletion or volume contraction, is a state of abnormally low extracellular fluid in the body. This may be due to either a loss of both salt and water or a decrease in blood volume. Hypovolemia refers to the loss of extracellular fluid and should not be confused with dehydration.Hypovolemia is caused by a variety of events, but these can be simplified into two categories: those that are associated with kidney function and those that are not. The signs and symptoms of hypovolemia worsen as the amount of fluid lost increases. Immediately or shortly after mild fluid loss (from blood donation, diarrhea, vomiting, bleeding from trauma, etc.), one may experience headache, fatigue, weakness, dizziness, or thirst. Untreated hypovolemia or excessive and rapid losses of volume may lead to hypovolemic shock. Signs and symptoms of hypovolemic shock include increased heart rate, low blood pressure, pale or cold skin, and altered mental status. When these signs are seen, immediate action should be taken to restore the lost volume.

Signs and symptoms
Signs and symptoms of hypovolemia progress with increased loss of fluid volume.Early symptoms of hypovolemia include headache, fatigue, weakness, thirst, and dizziness. The more severe signs and symptoms are often associated with hypovolemic shock. These include oliguria, cyanosis, abdominal and chest pain, hypotension, tachycardia, cold hands and feet, and progressively altering mental status.

Causes
The causes of hypovolemia can be characterized into two categories:

Kidney
Loss of body sodium and consequent intravascular water (due to impaired reabsorption of salt and water in the tubules of the kidneys)
Osmotic diuresis: the increase in urine production due to an excess of osmotic (namely glucose and urea) load in the tubules of the kidneys
Overuse of pharmacologic diuretics
Impaired response to hormones controlling salt and water balance (see mineralocorticoids)
Impaired kidney function due to tubular injury or other diseases

Other
Loss of bodily fluids due to:Gastrointestinal losses; e.g. vomiting and diarrhea
Skin losses; e.g. excessive sweating and burns
Respiratory losses; e.g. hyperventilation (breathing fast)
Build up of fluid in empty spaces (third spaces) of the body due to:Acute pancreatitis
Intestinal obstruction
Increase in vascular permeability
Hypoalbuminemia
Loss of blood (external or internal bleeding or blood donation)

Pathophysiology
The signs and symptoms of hypovolemia are primarily due to the consequences of decreased circulating volume and a subsequent reduction in the amount of blood reaching the tissues of the body. In order to properly perform their functions, tissues require the oxygen transported in the blood. A decrease in circulating volume can lead to a decrease in bloodflow to the brain, resulting in headache and dizziness.Baroreceptors in the body (primarily those located in the carotid sinuses and aortic arch) sense the reduction of circulating fluid and send signals to the brain to increase sympathetic response (see also: baroreflex). This sympathetic response is to release epinephrine and norepinephrine, which results in peripheral vasoconstriction (reducing size of blood vessels) in order to conserve the circulating fluids for organs vital to survival (i.e. brain and heart). Peripheral vasoconstriction accounts for the cold extremities (hands and feet), increased heart rate, increased cardiac output (and associated chest pain). Eventually, there will be less perfusion to the kidneys, resulting in decreased urine output.

Diagnosis
Hypovolemia can be recognized by a fast heart rate, low blood pressure, and the absence of perfusion as assessed by skin signs (skin turning pale) and/or capillary refill on forehead, lips and nail beds.  The patient may feel dizzy, faint, nauseated, or very thirsty.  These signs are also characteristic of most types of shock.In children, compensation can result in an artificially high blood pressure despite hypovolemia (a decrease in blood volume). Children typically are able to compensate (maintain blood pressure despite hypovolemia) for a longer period than adults, but deteriorate rapidly and severely once they are unable to compensate (decompensate) </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 Slipping and explain in detail? [/INST] Slipping is a technique used in boxing that is similar to bobbing. It is considered one of the four basic defensive strategies, along with blocking, holding, and clinching. It is performed by moving the head to either side so that the opponents punches "slip" by the boxer.Slipping punches allows the fighter to recover quicker and counter punches faster than the opponent can reset into proper fighting stance. In boxing, timing is known to be a key factor in the outcome. Timing your slips correctly is essential in protecting yourself and saving energy. Slipping, if done incorrectly, can be dangerous as it exposes you to a counter-punch and an unbalanced stance. Which can lead to an opening for the opponent. Muhammad Ali is considered to be, pound for pound, one of the greatest fighters of all time. But what made him so lethal? Was it his power, speed, or technique of slipping punches? Many fighters and analysts will say it was his slipping capability.

How to slip punches
There are multiple ways to slip punches in boxing, but the most basic types are slipping the inside jab, and outside jab. When slipping an outside jab, your body weight needs to be centered. And as your opponent throws the jab, rotate your body clockwise and lean slightly to your right. Which would then shift weight to the rear of your leg. Pivot both your feet in the same direction </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 Maxillary hypoplasia and explain in detail? [/INST] Maxillary hypoplasia, or maxillary deficiency, is an underdevelopment of the bones of the upper jaw. It is associated with Crouzon syndrome, Angelman syndrome, as well as Fetal alcohol syndrome. It can also be associated with Cleft lip and cleft palate. Some people could develop it due to poor dental extractions.

Signs and symptoms
The underdevelopment of the bones in the upper jaw, which gives the middle of the face a sunken look. This same underdevelopment can make it difficult to eat and can lead to complications such as Nasopharyngeal airway restriction. This restriction causes forward head posture which can then lead to back pain, neck pain, and numbness in the hands and arms. The nasopharyngeal airway restriction can also lead to Sleep apnea and snoring. Sleep apnea can lead to heart problems, endocrine problems, increased weight, and cognition problems, among other issues.

Cause
Although the exact genetic link for isolated maxillary hypoplasia has not been identified, the structure of the facial bones as a whole relies on genetic inheritance and therefore there is likely an inheritance pattern. Maxillary hypoplasia can be present as part of genetic syndromes such as Angelman syndrome.Fetal alcohol syndrome is associated with maxillary hypoplasia. Injury to facial bones during childhood can lead to atypical growth. Exposure to Phenytoin in the first trimester of pregnancy has also been associated with the development of maxillary hypoplasia.

Pathophysiology
Abnormal development of the bones of the upper face which is usually a secondary effect of a different developmental abnormality. When associated with cleft lip and palate, the abnormal development can be due to deficiency in the ability to grow because of the cleft lip or palate. The underdevelopment can also be caused by scarring from surgical repair of a cleft lip or palate.

Diagnosis
Diagnosed mainly on visual inspection. The cheekbones and nose appear flat with thin lips and the lower jaw appears to be protruding even though it is normal in size. Computed tomography scan CT scan can be performed to compare the size of the Maxilla and Mandible. Computed tomography scan.

Treatment
Corrective surgery is the most common treatment to correct this disorder. It involves the repositioning of the upper jaw to align with the lower jaw, to provide symmetry </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 Non-celiac gluten sensitivity and explain in detail? [/INST] Non-celiac gluten sensitivity (NCGS) or gluten sensitivity is "a clinical entity induced by the ingestion of gluten leading to intestinal and/or extraintestinal symptoms that improve once the gluten-containing foodstuff is removed from the diet, and celiac disease and wheat allergy have been excluded".NCGS is included in the spectrum of gluten-related disorders. The definition and diagnostic criteria of non-celiac gluten sensitivity were debated and established by three consensus conferences. However, as of 2019, there remained much debate in the scientific community as to whether or not NCGS was a distinct clinical disorder.The pathogenesis of NCGS is not well understood, but the activation of the innate immune system, the direct cytotoxic effects of gluten and probably other wheat components, are implicated. There is evidence that not only gliadin (the main cytotoxic antigen of gluten), but also other proteins named ATIs which are present in gluten-containing cereals (wheat, rye, barley, and their derivatives) may have a role in the development of symptoms. ATIs are potent activators of the innate immune system. FODMAPs, especially fructans, are present in small amounts in gluten-containing grains and have been identified as a possible cause of some gastrointestinal symptoms in NCGS patients. As of 2019, reviews have concluded that although FODMAPs may play a role in NCGS, they explain only certain gastrointestinal symptoms, such as bloating, but not the extra-digestive symptoms that people with NCGS may develop, such as neurological disorders, fibromyalgia, psychological disturbances, and dermatitis.For these reasons, NCGS is a controversial clinical condition and some authors still question it.  It has been suggested that "non-celiac wheat sensitivity" is a more appropriate term, without forgetting  that other gluten-containing cereals are implicated in the development of symptoms.NCGS is the most common syndrome of gluten-related disorders with prevalence rates between 0.5%–13% in the general population. As no biomarker for diagnosing this condition is available, its diagnosis is made by exclusion of other gluten-related disorders such as celiac disease and wheat allergy. Many people have not been diagnosed following strict criteria, and there is a "fad component" to the recent rise in popularity of the gluten-free diet, leading to debate surrounding the evidence for this condition and its relationship to celiac disease and irritable bowel syndrome. People with NCGS are often unrecognized by specialists and lack adequate medical care and treatment. They often have a long history of health complaints and unsuccessful consultations with physicians, and thus many resort to a gluten-free diet and a self-diagnosis of gluten sensitivity.

Signs and symptoms
Reported symptoms of NCGS are similar to those of celiac disease, with most patients reporting both gastrointestinal and non-gastrointestinal symptoms. In the "classical" presentation of NCGS, gastrointestinal symptoms are similar to those of irritable bowel syndrome, and are also not distinguishable from those of wheat allergy, but there is a different interval between exposure to wheat and onset of symptoms. Wheat allergy has a fast onset (from minutes to hours) after the consumption of food containing wheat and can be anaphylaxic.

Gastrointestinal
Gastrointestinal symptoms may include any of the following: abdominal pain, bloating, bowel habit abnormalities (either diarrhea or constipation), nausea, aerophagia, flatulence, gastroesophageal reflux disease, and aphthous stomatitis.

Extraintestinal
NCGS can cause a wide range of extraintestinal symptoms, which can be the only manifestation of NCGS in absence of gastrointestinal symptoms. These include any of the following: headache, migraine, "foggy mind", fatigue, fibromyalgia, joint and muscle pain, leg or arm numbness, tingling of the extremities, dermatitis (eczema or skin rash), atopic disorders such as asthma, rhinitis, other allergies, depression, anxiety, iron-deficiency anemia, folate deficiency, or autoimmune diseases.

NCGS is also linked to a wide spectrum of neurological and psychiatric disorders, including  ataxia, schizophrenia, epilepsy, peripheral neuropathy, encephalopathy, vascular dementia, eating disorders, autism, attention deficit hyperactivity disorder (ADHD), hallucinations (so-called "gluten psychosis"),  and various movement disorders (restless legs syndrome, chorea, parkinsonism, Tourette syndrome, palatal tremor,  myoclonus, dystonia, opsoclonus myoclonus syndrome, paroxysms, dyskinesia, myorhythmia, myokymia).Above 20% of people with NCGS have IgE-mediated allergy to one or more inhalants, foods, or metals, among which most common are mites, graminaceae, parietaria, cat or dog hair, shellfish, and nickel.  Approximately 35% of patients suffer other food intolerances, mainly lactose intolerance.

Causes
The pathogenesis of NCGS is not yet well understood, but the activation of the innate immune system, the direct cytotoxic effects of gluten, and probably the cytotoxicity of other wheat molecules are implicated. Besides gluten, other components in wheat, rye, barley, and their derivatives, including amylasetrypsin inhibitors (ATIs) and FODMAPs, may  cause symptoms.

Gluten
It was hypothesized that gluten, as occurs in celiac disease, is the cause of NCGS. In addition to its ability to elicit abnormal responses of the immune system, in vitro studies on cell cultures showed that gluten is cytotoxic and causes direct intestinal damage. Gluten and gliadin promote cell apoptosis (a form of programmed cell death) and reduce the synthesis of nucleic acids (DNA and RNA) and proteins, leading to a reduction in the viability of cells. Gluten alters cellular morphology and motility, cytoskeleton organization, oxidative balance and intercellular contact (tight junction proteins).

Other proteins
Some people may have a reaction to other proteins (α-amylase/trypsin inhibitors [ATIs]) present in gluten-containing cereals that are able to inhibit amylase and trypsin. They have been identified as the possible activator of the innate immune system in celiac disease and NCGS.ATIs are part of the plants natural defence against insects and may  cause toll-like receptor 4 (TLR4)-mediated intestinal inflammation in humans. These TLR4-stimulating activities of ATIs are limited to gluten-containing cereals (wheat, rye, barley, and derivatives) and may induce innate immunity in people with celiac disease or NCGS. ATIs resist proteolytic digestion. ATIs are about 2%–4% of the total protein in modern wheat and are present in commercial gluten. A 2017 study in mice demonstrated that ATIs exacerbate preexisting inflammation and may also worsen it at extraintestinal sites. This may explain why there is an increase of inflammation in people with preexisting diseases upon ingestion of ATI-containing grains.Modern wheat cultivation, by breeding for high ATI content, may play a role in the onset and course of disorders such as celiac disease and gluten sensitivity. However, it has been questioned whether there is sufficient empirical evidence to support this claim, because as of 2018 we lack studies that directly compare modern wheat versus ancient cultivars with low ATI content (such as einkorn wheat) in people with NCGS.Wheat germ agglutinin is also considered to be a possible trigger of NCGS-like symptoms.

FODMAPs
FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) that are present in gluten-containing grains (mainly fructans) have been identified as a possible cause of gastrointestinal symptoms in people with NCGS, in place of, or in addition to, gluten.The amount of fructans in gluten-containing cereals is relatively small and their role has been controversial. In rye they account for 3.6%–6.6% of dry matter, 0.7%–2.9% in wheat, and barley contains only trace amounts. They are only minor sources of FODMAPs when eaten in the usual standard amounts in the daily diet. Wheat and rye may comprise a major source of fructans when consumed in large amounts. They may cause mild wheat intolerance at most, limited to certain gastrointestinal symptoms, such as bloating, but do not justify the NCGS extradigestive symptoms. A 2018 review concluded that although fructan intolerance may play a role in NCGS, it only explains some gastrointestinal symptoms, but not the extradigestive symptoms that people with NCGS may develop, such as neurological disorders, fibromyalgia, psychological disturbances, and dermatitis. FODMAPs cause digestive symptoms when the person is hypersensitive to luminal distension. A 2019 review concluded that wheat fructans can cause certain IBS-like symptoms, such as bloating, but are unlikely to cause immune activation or extra-digestive symptoms. Many people with NCGS report resolution of their symptoms after removing gluten-containing cereals while continue to eat fruits and vegetables with high FODMAPs content.

Diagnosis
Absence of reliable biomarkers and the fact that some people do not have digestive symptoms make the recognition and diagnosis of non-celiac gluten sensitivity (NCGS) difficult.Diagnosis is generally performed only by exclusion criteria. NCGS diagnostic recommendations have been established by several consensus conferences. Exclusion of celiac disease and wheat allergy is important because these two conditions also appear in people who experience symptoms similar to those of NCGS, which improve with a gluten withdrawal and worsen after gluten consumption.The onset of NCGS symptoms may be delayed hours to a few days after gluten ingestion, whereas in celiac disease it can take days to weeks. Wheat allergy has a fast onset (from minutes to hours) after the consumption of food containing wheat and can lead to anaphylaxis.The presence of related extraintestinal manifestations has been suggested to be a feature of NCGS. When symptoms are limited to gastrointestinal effects, there may be an overlap with wheat allergy, irritable bowel syndrome (IBS), and (less likely) intolerance to FODMAPs.Proposed criteria for a diagnosis of NCGS suggest an improvement of gastrointestinal symptoms and extra-intestinal manifestations higher than 30% with a gluten-free diet (GFD), assessed through a rating scale, is needed to make a clinical diagnosis of NCGS. To exclude a placebo effect, a double-blind placebo-controlled gluten challenge is a useful tool, although it is expensive and complicated for routine clinical use, and so is usually performed in research studies.These suggestions were incorporated in the Salerno expert consensus on diagnostic criteria for NCGS. These recommend assessment of the response to a 6-week trial of a gluten-free diet using a defined rating scale (Step 1), followed by a double-blind, placebo-controlled challenge of gluten (or placebo) for a week of each (Step 2).  A variation of greater than 30% in the main symptoms when challenged by gluten or placebo is needed for a positive result. Further research on possible biomarkers was also identified.

Differential diagnosis
Examinations evaluating celiac disease and wheat allergy should be performed before patients remove gluten from their diet. It is critical to make a clear distinction between celiac disease and NCGS.

Celiac disease
The main goal in diagnosing NCGS is to exclude celiac disease. NCGS and celiac disease cannot be separated in diagnosis because many gastrointestinal and non-gastrointestinal symptoms are similar in both diseases, and there are people with celiac disease having negative serology (absence of specific celiac disease antibodies in serum) or without villus atrophy. There is no test capable of eliminating a diagnosis of a celiac disease, but such a diagnosis is unlikely without confirming HLA-DQ2 and/or HLA-DQ8 haplotypes.The prevalence of undiagnosed celiac disease has increased fourfold during the past half-century, with most cases remaining unrecognized, undiagnosed and untreated, leaving celiac patients with the risk of long-term complications. Some people with NCGS may indeed have celiac disease. A 2015 systematic review found that 20% of people with NCGS presenting with HLA-DQ2 and/or HLA-DQ8 haplotypes, negative serology, and normal histology or duodenal lymphocytosis had celiac disease.The presence of autoimmune symptoms in people with NCGS suggests the possibility of undiagnosed celiac disease. Autoimmune diseases typically associated with celiac disease are diabetes mellitus type 1, thyroiditis, gluten ataxia, psoriasis, vitiligo, autoimmune hepatitis, dermatitis herpetiformis, primary sclerosing cholangitis, and others.To evaluate the possible presence of celiac disease, specific serology and duodenal biopsies are required while the person is still on a diet that includes gluten.

Serological markers
Serological CD markers (IgA tissue transglutaminase [tTGA], IgA endomysial [EmA] and IgG deamidated gliadin peptide [DGP] antibodies) are always negative in those with NCGS; in addition to specific IgA autoantibody levels, it is necessary to determine total IgA levels. IgG tTGA antibodies should be checked in selective IgA deficiency, which can be associated with celiac disease and occurs in as many as one in 40 celiac patients.Nevertheless, the absence of serological markers does not certainly exclude celiac disease. In those with celiac disease before diagnosis (on a gluten-containing diet), celiac disease serological markers are not always present. As the age of diagnosis increases, these antibody titers decrease, and may be low or even negative in older children and adults. The absence of celiac disease-specific antibodies is more common in patients without villous atrophy who only have duodenal lymphocytosis (Marsh 1 lesions) and who respond to a gluten-free diet with histological and symptomatic improvement.

Duodenal biopsies
According to the diagnostic criteria established by the consensus conferences (2011 and 2013), it is necessary to perform duodenal biopsies to exclude celiac disease in symptomatic people with negative specific celiac disease antibodies. Because of the patchiness of the celiac disease lesions, four or more biopsies are taken from the second and third parts of the duodenum, and at least one from the duodenal bulb. Even in the same biopsy fragments, different degrees of pathology may exist.Duodenal biopsies in people with NCGS are always almost normal – an essential parameter for diagnosis of NCGS, although is generally accepted that a subgroup of people with NGCS may have an increased number of duodenal intraepithelial lymphocytes (IELs) ( ≥25/100 enterocytes), which represent Marsh I lesions. Nevertheless, Marsh I is considered compatible with celiac disease and the most frequent cause of these findings, especially in people positive for HLA DQ2 and/or DQ8 haplotypes, is celiac disease, with a prevalence of 16-43%.In people with duodenal lymphocytosis – following guidelines from the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) – a high count of celiac disease cells (or CD/CD3 ratio) in immunohistochemical assessment of biopsies, or the presence of IgA anti-TG2 and/or anti-endomysial intestinal deposits, might be specific markers for celiac disease. Catassi and Fasano proposed in 2010 that in patients without celiac disease antibodies, either lymphocytic infiltration associated with IgA subepithelial deposits or a histological response to a gluten-free diet, could support a diagnosis of celiac disease.

Wheat allergy
The clinical presentation may be sufficient in most cases to distinguish a wheat allergy from other entities. It is excluded when there are normal levels of serum IgE antibodies to gluten proteins and wheat fractions, and no skin reaction to prick tests for wheat allergy. Nevertheless, these tests are not always completely reliable.If an allergic reaction can not be clearly identified, the diagnosis should be confirmed by food provocation tests, ideally performed in a double-blinded and placebo-controlled manner. Delayed allergic reactions may occur with these type of tests, which have to be negative over time, but there are no international consensus statements on diagnosing delayed wheat/food-related symptoms. Usually, reactions that appear between two hours and five days after the oral challenge are considered delayed. Mucosal challenge followed by confocal endomicroscopy is a complementary diagnostic technique, but this technology is not yet generally available and remains experimental.

Other tests
Evaluating the presence of antigliadin antibodies (AGA) can be a useful complementary diagnostic test. Up to 50% NCGS patients may have elevated AGA IgG antibodies, but rarely AGA IgA antibodies (only 7% of the cases). In these patients, unlike in those with celiac disease, the IgG AGA became undetectable within six months of following a gluten-free diet.

People already on a gluten-free diet
Many people remove gluten from their diet after a long history of health complaints and unsuccessful consultations with numerous physicians, who simply consider them to be suffering from irritable bowel syndrome, and some may eliminate gluten before seeking medical attention. This fact can diminish the CD serological markers titers and may attenuate the inflammatory changes found in the duodenal biopsies. In these cases, patients should be tested for the presence of HLA-DQ2/DQ8 genetic markers because a negative HLA-DQ2 and HLA-DQ8 result has a high negative predictive value for celiac disease. If these markers are positive, it is advisable to undertake a gluten challenge under medical supervision, followed by serology and duodenal biopsies. However, gluten challenge protocols have significant limitations, because a symptomatic relapse generally precedes the onset of a serological and histological relapse, and therefore becomes unacceptable for many patients. Gluten challenge is also discouraged before the age of five and during pubertal growth.It remains unclear what daily intake of gluten is adequate and how long the gluten challenge should last. Some protocols recommend eating a maximum of 10 g of gluten per day for six weeks. Nevertheless, recent studies have shown that a two-week challenge of 3 g of gluten per day may induce histological and serological abnormalities in most adults with proven celiac disease. This new proposed protocol has shown higher tolerability and compliance. It has been calculated that its application in secondary-care gastrointestinal practice would identify celiac disease in 7% of patients referred for suspected NCGS, while the remaining 93% would be confirmed as NCGS; this is not yet universally adopted.For people on a gluten-free diet who are unable to perform an oral gluten challenge, an alternative to identify possible celiac disease is an in vitro gliadin challenge of small bowel biopsies, but this test is only available at selected specialized tertiary-care centers.

Treatment
After exclusion of celiac disease and wheat allergy, the subsequent step for diagnosis and treatment of NCGS is to start a strict gluten-free diet (GFD) to assess if symptoms improve or resolve completely. This may occur within days to weeks of starting a GFD, but improvement may also be due to a non-specific, placebo response. The recovery of the nervous system is slow and sometimes incomplete.Recommendations may resemble those for celiac disease, for the diet to be strict and maintained, with no transgression. The degree of gluten cross contamination tolerated by people with NCGS is not clear but there is some evidence that they can present with symptoms even after consumption of small amounts. Sporadic accidental contaminations with gluten can reactivate movement disorders. A part of people with gluten-related neuropathy or ataxia appears not to be able to tolerate even the traces of gluten allowed in most foods labeled as "gluten-free".Whereas celiac disease requires adherence to a strict lifelong gluten-free diet, it is not yet known whether NCGS is a permanent or a transient condition. The results of a 2017 study suggest that NCGS may be a chronic disorder, as is the case with celiac disease. A trial of gluten reintroduction to observe any reaction after one to two years of strict gluten-free diet might be performed.A strict gluten-free diet is effective in most of the neurological disorders associated with NCGS, ameliorating or even resolving the symptoms. It should be started as soon as possible to improve the prognosis. The death of neurons in the cerebellum in ataxia is the result of gluten exposure and is irreversible. Early treatment with a strict gluten-free diet can improve ataxia symptoms and prevent its progression. When dementia has progressed to an advanced degree, the diet has no beneficial effect. Cortical myoclonus appears to be treatment-resistant on both gluten-free diet and immunosuppression.

Persistent symptoms
Approximately one third of presumed NCGS patients continue to have symptoms, despite gluten withdrawal. Apart from a possible diagnostic error, there are multiple possible explanations.One reason is poor compliance with gluten withdrawal, whether voluntary and/or involuntary.  There may be ingestion of gluten, in the form of cross contamination or food containing hidden sources.  In some cases, the amelioration of gastrointestinal symptoms with a gluten-free diet is only partial, and these patients could significantly improve with the addition of a low-FODMAP diet.A subgroup may not improve when eating commercially available gluten-free products, as these can be rich in preservatives and additives such as sulfites, glutamates, nitrates and benzoates, which can also have a role in triggering functional gastrointestinal symptoms.  Furthermore, people with NCGS may often present with IgE-mediated allergies to one or more foods. It has been estimated that around 35% suffer other food intolerances, mainly lactose intolerance.

History
The subject of "food intolerance", including gluten sensitivity and elimination diets, was discussed in 1976.Patients with symptoms including abdominal pain and diarrhea, which improved on gluten withdrawal, and who did not have celiac disease were initially described in 1976 and 1978 with the first series in 1980.  Debate regarding the existence of a specific condition has continued since then, but the three consensus conferences held since 2010 produced consistent definitions of NCGS and its diagnostic criteria.

Society and culture
NCGS has been a topic of popular interest. Gluten has been named "the new diet villain". The gluten-free diet has become popular in the United States and other countries. Clinicians worldwide have been challenged by an increasing number of people who do not have celiac disease nor wheat allergy, with digestive or extra-digestive symptoms which improved after removing wheat / gluten from the diet. Many of these persons began a gluten-free diet on their own, without having been previously evaluated. Another reason that contributed to this trend was the publication of several books that demonize gluten and point to it as a cause of type 2 diabetes, weight gain and obesity, and a broad list of conditions ranging from depression and anxiety to arthritis and autism. The book that has had the most impact is Grain Brain: The Surprising Truth about Wheat, Carbs, and Sugar – Your Brains Silent Killers, by the American neurologist David Perlmutter, published in September 2013. Another book that has had great impact is Wheat Belly: Lose the Wheat, Lose the Weight, and Find Your Path Back to Health, by cardiologist William Davis. The gluten-free diet has been advocated and followed by many celebrities to lose weight, such as Miley Cyrus and Gwyneth Paltrow, and some elite athletes to improve performance.Estimates suggest that in 2014, 30% of people in the US and Australia were consuming gluten-free foods, with estimates that by 2016 approximately 100 million Americans would consume gluten-free products. Data from a 2015 Nielsen survey of 30,000 adults in 60 countries around the world showed that 21% of people prefer to buy gluten-free foods, with interest highest among younger generations. Another school of thought suggests that many people may be unnecessarily avoiding gluten when they do not need to.Debate around NCGS as a genuine clinical condition can be heightened because often patients are self diagnosed, or a diagnosis is made by alternative health practitioners. Many people who are making a gluten-free diet did not previously exclude celiac disease or, when they are fully evaluated, other alternative diagnoses can be found such as fructose intolerance or small intestinal bacterial overgrowth, or a better response to a low-FODMAP diet obtained.

Research
There are many open questions on gluten sensitivity, emphasized in one review that "it is still to be clarified whether this disorder is permanent or transient and whether it is linked to autoimmunity" </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 Omphalocele and explain in detail? [/INST] Omphalocele or omphalocoele also called exomphalos, is a rare abdominal wall defect. Beginning at the 6th week of development, rapid elongation of the gut and increased liver size reduces intra abdominal space, which pushes intestinal loops out of the abdominal cavity. Around 10th week, the intestine returns to the abdominal cavity and the process is completed by the 12th week. Persistence of intestine or the presence of other abdominal viscera (e.g. stomach, liver) in the umbilical cord results in an omphalocele.
Omphalocele occurs in 1 in 4,000 births and is associated with a high rate of mortality (25%) and severe malformations, such as cardiac anomalies (50%), neural tube defect (40%), exstrophy of the bladder and Beckwith–Wiedemann syndrome. Approximately 15% of live-born infants with omphalocele have chromosomal abnormalities. About 30% of infants with an omphalocele have other congenital abnormalities.

Signs and symptoms
The sac, which is formed from an outpouching of the peritoneum, protrudes in the midline, through the umbilicus (navel).It is normal for the intestines to protrude from the abdomen, into the umbilical cord, until about the tenth week of pregnancy, after which they return to inside the fetal abdomen. The omphalocele can be mild, with only a small loop of intestines present outside the abdomen, or severe, containing most of the abdominal organs. In severe cases surgical treatment is made more difficult because the infants abdomen is abnormally small, having had no need to expand to accommodate the developing organs.
Larger omphaloceles are associated with a higher risk of cardiac defects.

Complications
Complications may occur prenatally, during birth, management, treatment or after surgery. Both prenatally and during birth, the exomphalos can rupture. During birth there may be trauma to the liver for giant omphaloceles. During management exomphalos can act as a metabolic drain affecting nitrogen balance which can lead to failure to thrive, as well as hypothermia. Use of a non-absorbent patch during surgery can lead to wound sepsis post-surgery. Herniation from the patch is also a possibility. Intestinal dysfunction for a few weeks after the surgery is common, therefore parenteral feeding is continued post-surgery, however prolonged use of this may lead to hepatomegaly and cholestasis. If intestinal dysfunction persists it can lead to intestinal necrosis. Intestinal atresia can occur, which is where the mucosa and submucosa of the intestine form a web that obstructs the lumen which leads to malabsorption. Obstruction of the bowel can occur which results in short bowel syndrome. For the first few years of life there is a high incidence of gastroesophageal reflux which can be complicated by oesophagitis.Post-surgery the umbilicus (navel) is deficient or abnormally placed that causes dislike amongst many patients. Umbilical reconstruction can be difficult due to scar tissue and lack of extra skin for surgical use, though this can be overcome by using tissue expanders below the skin and umbilicoplasty.Ultimately, prognosis depends on the size of the defect and whether associated abnormalities are present or complications develop. Mortalities and morbidities still occur, with the mortality rate for large omphaloceles with associated abnormalities being higher. Most surviving omphalocele infants have no-long-term problems and grow up to be normal individuals.

Causes
Omphalocele is caused by malrotation of the bowels while returning to the abdomen during development. Some cases of omphalocele are believed to be due to an underlying genetic disorder, such as Edwards syndrome (trisomy 18) or Patau syndrome (trisomy 13).
Beckwith–Wiedemann syndrome is also associated with omphaloceles.

Pathophysiology
Exomphalos is caused by a failure of the ventral body wall to form and close the naturally occurring umbilical hernia that occurs during embryonic folding which is a process of embryogenesis. The normal process of embryogenesis is that at 2 weeks gestation the human embryo is a flat disc that consists of three layers, the outer ectoderm and inner endoderm separated by a middle layer called the mesoderm. The ectoderm gives rise to skin and the CNS, the mesoderm gives rise to muscle and the endoderm gives rise to organs. The focus areas for exomphalos are that the ectoderm will form the umbilical ring, the mesoderm will form the abdominal muscles and the endoderm will form the gut. After the disc becomes tri-layered, it undergoes growth and folding to transform it from disc to cylinder shaped. The layer of ectoderm and mesoderm in the dorsal axis grow ventrally to meet at the midline. Simultaneously, the cephalic (head) and caudal (tail) ends of these layers of the disc fold ventrally to meet the lateral folds in the center. The meeting of both axis at the center form the umbilical ring. Meanwhile, the endoderm migrates to the center of this cylinder.By the fourth week of gestation the umbilical ring is formed. During the 6th week the midgut rapidly grows from the endoderm which causes a herniation of the gut through the umbilical ring. The gut rotates as it re-enters the abdominal cavity which allows for the small intestine and colon to migrate to their correct anatomical position by the end of the 10th week of development. This process fails to occur normally in cases of exomphalos, resulting in abdominal contents protruding from the umbilical ring.Gut contents fail to return to the abdomen due to a fault in myogenesis (muscle formation and migration during embryogenesis). During embryogenesis the mesoderm that forms muscle divides into several somites that migrate dorso-ventrally towards the midline. The somites develop three parts that are sclerotome which will form bone, dermatome which will form skin of the back and myotome which will form muscle. The somites that remain close to the neural tube at the back of the body have epaxial myotome, whilst the somites that migrate to the midline have hypaxial myotome. The hypaxial myotome forms the abdominal muscles. The myotome cells will give rise to myoblasts (embryonic progenitor cells) which will align to form myotubules and then muscle fibers. Consequently, the myotome will become three muscle sheets that form the layers of abdominal wall muscles. The muscle of concern for exomphalos is the rectus abdominis. In the disease the muscle undergoes normal differentiation but fails to expand ventro-medially and narrow the umbilical ring which causes the natural umbilical hernia that occurs at 6 weeks of gestation to remain external to the body.The location of the folding defect in the embryo determines the ultimate position of the exomphalos. A cephalic folding defect results in an epigastric exomphalos that is positioned high up on the abdomen which can be seen in the chromosomal defect pentalogy of Cantrell. Lateral folding defects result in a typical exomphalos that is positioned in the middle of the abdomen. A caudal folding defect results in a hypogastric exomphalos that is positioned on the lower abdomen.

Genetics
The genes that cause exomphalos are controversial and subject to research. Exomphalos is greatly associated with chromosomal defects and thus these are being explored to pinpoint the genetic cause of the disease. Studies in mice have indicated that mutations in the fibroblast growth factor receptors 1 and 2 (Fgfr1, Fgfr2) cause exomphalos. Fibroblast growth factor (FBGF) encourages the migration of myotubules during myogenesis. When FBGF runs out myoblasts stop migrating, cease division and differentiate into myotubules that form muscle fibers. Mutations in homeobox genes such as Alx4, that direct the formation of body structures during early embryonic development cause exomphalos in mice. Mutations in the Insulin like growth factor-2 gene (IGF2) and its associated receptor gene IGF2R cause high levels of IGF-2 protein in humans which leads to exomphalos in the associated disease Beckwith Wiedemann syndrome (BWS).  IFG2R is responsible for degradation of excess IGF-2 protein. BWS disease is caused by a mutation in chromosome 11 at the locus where the IGF2 gene resides. Observance of the inheritance patterns of the associated anomalies through pedigrees show that exomphalos can be the result of autosomal dominant, autosomal recessive and X-linked inheritance.

Environmental factors
It is not well known if actions of the mother could predispose or cause the disease. Alcohol use during the first trimester, heavy smoking, use of certain medications like the selective serotonin-reuptake inhibitors and methimazole (anti-thyroid drug) during pregnancy, maternal febrile illness, IVF, parental consanguinity and obesity elevate the risk of a woman giving birth to a baby with exomphalos. Preventive methods that could be utilised by mothers include ingestion of a preconception multivitamin and supplementation with folic acid. Termination of pregnancy may be considered if a large exomphalos with associated congenital abnormalities is confirmed during prenatal diagnosis.

Diagnosis
Related conditions
Gastroschisis is a similar birth defect, but in gastroschisis the umbilical cord is not involved and the intestinal protrusion is usually to the right of the midline. Parts of organs may be free in the amniotic fluid and not enclosed in a membranous (peritoneal) sac. Gastroschisis is less frequently associated with other defects than omphalocele.Omphaloceles occurs more frequently with increased maternal age. Other related syndromes are Shprintzen Goldberg, pentalogy of Cantrell, Beckwith–Wiedemann and OEIS complex (omphalocele, exstrophy of the cloaca, imperforate anus, spinal defects).After surgery a child with omphalocele will have some degree of intestinal malrotation. Due to intestinal malrotation 4.4% of children with omphalocele will experience a midgut volvulus in the days, months, or years after surgery. Parents of children with omphalocele should seek immediate medical attention if their child displays signs and symptoms of an intestinal obstruction at any point in their childhood to avoid the possibility of bowel necrosis or death.Some experts differentiate exomphalos and omphalocele as 2 related conditions, one worse than the other; in this sense, exomphalos involves a stronger covering of the hernia (with fascia and skin), whereas omphalocele involves a weaker covering of only a thin membrane. Others consider the terms synonymous names for any degree of herniation and covering.

Screening
An omphalocele is often detected through AFP screening or a detailed fetal ultrasound. Genetic counseling and genetic testing such as amniocentesis are usually offered during the pregnancy.

Management
There is no treatment that is required prenatally unless there is a rupture of the exomphalos within the mother. An intact exomphalos can be delivered safely vaginally and C-sections are also acceptable if obstetrical reasons require it. There appears to be no advantage for delivery by C-section unless it is for a giant exomphalos that contains most of the liver. In this case vaginal delivery may result in dystocia (inability of the baby to exit the pelvis during birth) and liver damage. Immediately after birth a nasogastric tube is required to decompress the intestines and an endotracheal intubation is needed to support respiration. The exomphalos sac is kept warm and covered with a moist saline gauze and plastic transparent bowel bag to prevent fluid loss. The neonate also requires fluid, vitamin K and antibiotic administration intravenously.   After management strategies are applied, a baby with an intact sac is medically stable and does not require urgent surgery. This time is used to assess the newborn to rule out associated anomalies prior to surgical closure of the defect. Studies show there is no significant difference in survival between immediate or delayed closure.Surgery can be performed directly for small omphaloceles, which will require a short stay in the nursery department, or in a staged manner for large omphaloceles, which will require several weeks stay. Staged closure requires a temporary artificial holding sac (a silo) to be placed over the abdominal organs and sutured to the abdominal wall. This can be made of non-adhesive dressing. The silo is gradually reduced in size at least once daily until all of the viscera have been returned to the abdominal cavity. This is repeated for several days to a week until surgical closure of the fascia/skin can be done </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 Spasm of accommodation and explain in detail? [/INST] A spasm of accommodation (also known as a ciliary spasm, an accommodation, or accommodative spasm) is a condition in which the ciliary muscle of the eye remains in a constant state of contraction. Normal accommodation allows the eye to "accommodate" for near-vision. However, in a state of perpetual contraction, the ciliary muscle cannot relax when viewing distant objects. This causes vision to blur when attempting to view objects from a distance. This may cause pseudomyopia or latent hyperopia.
Although antimuscarinic drops (homoatropine 5%) can be applied topically to relax the muscle, this leaves the individual without any accommodation and, depending on refractive error, unable to see well at near distances.  Also, excessive pupil dilation may occur as an unwanted side effect. This dilation may pose a problem since a larger pupil is less efficient at focusing light (see pupil, aperture, and optical aberration for more.)
Patients who have accommodative spasm may benefit from being given glasses or contacts that account for the problem or by using vision therapy techniques to regain control of the accommodative system.
Possible clinical findings include:

Normal Amplitude of accommodation
Normal Near point of convergence
Reduced Negative relative accommodation
Difficulty clearing plus on facility testing

Treatments
Cycloplegic Eye Drops (Dilation)
Spasm of accommodation is frequently resistant to treatment. However, some patients do find relief through the use of daily eye dilation with cycloplegic drops. One side effect of cycloplegic drops is that they often have BAK as a preservative ingredient, which, with daily use, can erode the tear shield:

At each administration of an eye drop containing benzalkonium chloride, its detergent effect disrupts the lipid layer of the tear film. This cannot be regenerated and can no longer protect the aqueous layer of the tear film, which evaporates easily. In these circumstances, the cornea is exposed and eye dryness occurs. In addition, benzalkonium chloride has a cellular toxicity on caliciform cells, entailing a reduction in the amount of mucin, an additional reason for disrupting the tear film.
In fact, none of the cycloplegic drops used to treat Spasm of Accommodation in the United States are available without BAK. This unfortunately makes treatment much more difficult as the side effect of dry eyes and corneal damage can occur. France, Australia, Canada, and the United Kingdom do have limited availability of BAK-free eye drops available in unidose, and they must be imported to the United States with a physicians letter to the FDA enclosed with the imported prescription.
Due to the high potential of tear shield damage with long-term use and the associated dry eye condition caused by cycloplegic eye drops with BAK (preservative), many physicians do not recommend cycloplegic eye drops </s>