BTX-A is now a common treatment for muscles affected by the upper motor neuron syndrome (UMNS), such as cerebral palsy, for muscles with an impaired ability to effectively lengthen. Muscles affected by UMNS frequently are limited by weakness, loss of reciprocal inhibition, decreased movement control and hypertonicity (including spasticity). In January 2014, Botulinum toxin was approved by UK's Medicines and Healthcare Products Regulatory Agency (MHRA) for the treatment of ankle disability due to lower limb spasticity associated with stroke in adults. Joint motion may be restricted by severe muscle imbalance related to the syndrome, when some muscles are markedly hypertonic, and lack effective active lengthening. Injecting an overactive muscle to decrease its level of contraction can allow improved reciprocal motion, so improved ability to move and exercise.
BOTOX® can be used on the forehead lines, frown lines, crow’s feet, bunny lines (lines in the nose), chin (for dimpling), skin bands on the neck, and around the mouth (for smoker’s lines and down-turned corners of the mouth). Wrinkles caused by sun damage and gravity often will not respond to BOTOX®. It is important to re-emphasize that BOTOX® is NOT a facial filler (that is, it does not fill existing wrinkles) – it merely relaxes the muscles that are creating those wrinkles.
Botox stays only where injected, it does not roam through the body. "If I inject it in your face, it's not going to work [or show up in] your toe," says Rowe. "It does not have a systemic effect." However, it may migrate up to 3 cm from where it was injected. But even if some molecules were to go into the bloodstream and travel to distant sites in the body, the cosmetic doses (typically less than 100 units) used are significantly lower than the toxic dose that would be harmful systemically (2,500-3,000 units).
Besides the volume of product used, Baby Botox is about the technique, says Doris Day, a board-certified dermatologist in New York City and author of Beyond Beautiful. "If you're very precise in where you put the product, you can use lower doses," she tells Allure. These super targeted micro injections deliver the more natural, tailored look Baby Botox is so coveted for.
Allergan says Botox is well established as a drug and that the benefits and risks of toxins are well understood. "With more than 25 years of real-world clinical experience ... approximately 3,200 articles in scientific and medical journals, marketing authorizations in more than 90 markets and many different indications, Botox and Botox Cosmetic are [among] the most widely researched medicines in the world," an Allergan rep wrote in an emailed statement.
A placebo-controlled, double-blind post-approval 52 week study with BOTOX 100 Units (Study NDO-3) was conducted in non-catheterizing MS patients with urinary incontinence due to detrusor overactivity associated with a neurologic condition. Catheterization for urinary retention was initiated in 15.2% (10/66) of patients following treatment with BOTOX 100 Units versus 2.6% (2/78) on placebo at any time during the complete treatment cycle. The median duration of post-injection catheterization for those who developed urinary retention was 64 days for BOTOX 100 Units and 2 days for placebo.
Ophthalmologists specializing in eye muscle disorders (strabismus) had developed the method of EMG-guided injection (using the electromyogram, the electrical signal from an activated muscle, to guide injection) of local anesthetics as a diagnostic technique for evaluating an individual muscle’s contribution to an eye movement. Because strabismus surgery frequently needed repeating, a search was undertaken for non-surgical, injection treatments using various anesthetics, alcohols, enzymes, enzyme blockers, and snake neurotoxins. Finally, inspired by Daniel Drachman’s work with chicks at Johns Hopkins, Alan B Scott and colleagues injected botulinum toxin into monkey extraocular muscles. The result was remarkable: a few picograms induced paralysis that was confined to the target muscle, long in duration, and without side-effects.
Baby Botox can be used pretty much anywhere on your face, but it's best to create subtle changes or to erase fine lines. "Something like this is especially nice for an area like the crow's feet, which is a very delicate area where a subtle treatment is more effective," explains Smith. "If someone has very deep folds, micro Botox probably isn't going to cut it. I would offer this to someone with moderate to fine lines."
Each vial of BOTOX contains either 50 Units of Clostridium botulinum type A neurotoxin complex, 0.25 mg of Albumin Human, and 0.45 mg of sodium chloride; 100 Units of Clostridium botulinum type A neurotoxin complex, 0.5 mg of Albumin Human, and 0.9 mg of sodium chloride; or 200 Units of Clostridium botulinum type A neurotoxin complex, 1 mg of Albumin Human, and 1.8 mg of sodium chloride in a sterile, vacuum-dried form without a preservative.
Reduced blinking from BOTOX injection of the orbicularis muscle can lead to corneal exposure, persistent epithelial defect, and corneal ulceration, especially in patients with VII nerve disorders. Vigorous treatment of any epithelial defect should be employed. This may require protective drops, ointment, therapeutic soft contact lenses, or closure of the eye by patching or other me ans.
With abnormal joint movement and inactivity, muscles can shorten and contract. In the case of muscle spasticity, the joint and soft tissue can be normal, but with constant contraction of a muscle because of spasticity the muscle can shorten. When it can no longer stretch to allow full range of motion, a contracture can happen. Agents that lessen the spasticity of the involved muscles best prevent this type of contracture.
As of 2013, botulinum toxin injections are the most common cosmetic operation, with 6.3 million procedures in the United States, according to the American Society of Plastic Surgeons. Qualifications for Botox injectors vary by county, state and country. Botox cosmetic providers include dermatologists, plastic surgeons, aesthetic spa physicians, dentists, nurse practitioners, nurses and physician assistants.
The median duration of response in study NDO-1 and NDO-2, based on patient qualification for re-treatment was 295-337 days (4248 weeks) for the 200 Units dose group compared to 96-127 days (13-18 weeks) for placebo. Re-treatment was based on loss of effect on incontinence episode frequency (50% of effect in Study NDO-1; 70% of effect in Study NDO-2).
Dubbed as the “little neurotoxin that could,” by USA Today, Botox now boasts sales of well over $1 billion for its manufacturer, Allergan. Many of us who start to see our migraine-furrowed forehead lines show up in our 30s think: hey, maybe Botox for migraine could help me too. But before you say “heck yes!” at the next Botox party or med-spa, be sure you know what you’re getting into.
In a study to evaluate inadvertent peribladder administration, bladder stones were observed in 1 of 4 mal e monkeys that were injected with a total of 6.8 Units/kg divided into the prostatic urethra and proximal rectum (single administration). No bladder stones were observed in male or female monkeys following injection of up to 36 Units/kg (~12X the highest human bladder dose) directly to the bladder as either single or 4 repeat dose injections or in female rats for single injections up to 100 Units/kg (~33X the highest human bladder dose).
Facelift: What you need to know A facelift aims to make the face look more youthful. The procedure can remove excess skin from the face and smooth wrinkles. However, it may not be suitable for everyone. Complications can occur, for example, infections, especially in people with existing health conditions. Relapse and scarring are also possible. Read now
After the injection moves from the dermis and into the desired muscle, the nerves there are blocked—rather, their synapses, are blocked—by the Botox. So even though your brain my fire and signal for your body to move a particular muscle, Botox effectively blocks that firing and keeps the muscle from moving. The injected muscle can no longer contract, which causes the wrinkles to relax and soften, and also helps prevent new ones from forming.
The cost for Botox may range from $125 to $400 per treatment area. Multiple areas may be treated at one time, and repeat treatments are needed every three to four months, on average. When it comes to Botox and other injectables, you get what you pay for. Buyer beware: bargain Botox may increase your risk of complications, including poor cosmetic results. If the cost is prohibitive, ask your doctor about payment plans.
Botox is a drug made from a neurotoxin produced by the bacterium Clostridium botulinum called botulinum toxin. "It's a poison secreted by the bacteria," plastic surgeon Norman Rowe, M.D., tells SELF. Botulinum toxin has proven to be a successful and valuable therapeutic protein when dosage, frequency of treatment and variety of treated clinical conditions are considered, according to Howard Sobel, M.D., a dermatologist in New York. Basically: when it's done right. When it's done wrong—like, really, really wrong—it can cause "botulism-like symptoms," according to Mayo Clinic, which may include muscle weakness, trouble breathing, speaking or swallowing, bladder control issues, and vision problems. That is "very unlikely," but a more than convincing enough reason not to go bargain hunting for Botox.
What Other Factors Determine the Cost of Botox? The fixed cost of Botox or Dysport that the doctor pays for the drugs is relatively expensive and therefore that cost is obviously passed along to the patient. The cost of Botox or Dysport injections also depends upon the number of areas that are required to obtain the best results. The more areas that need treatment the greater the amount of injections that will be required to arrive at the most desirable result. Simply put -the more areas that need treatment the higher the cost of treatment.
The idea of a needle going toward your forehead, in between your eyes, or at your eyebrows might be a little daunting, but rest assured, not only is Botox FDA-approved, but it’s a very common (and highly-requested) procedure. It’s commonly used for cosmetic reasons, but it also helps alleviate a slew of other health concerns.”Botox was first approved by the FDA in 1989 to treat blepharospasm of the eyelid, and now can treat hundreds of medical conditions, such as hyperhidrosis (excessive sweating) or chronic migraines,” dermatologist Jill S. Waibel, MD. She also notes that it was only approved for cosmetic purposes in 2002. “Since then, millions of people have had Botox done safely and effectively. It is important to remember that Botox is safest when used by a board certified dermatologist or a plastic surgeon.”
The FDA approval was based on a large study showing that Botox significantly reduced migraine frequency and severity, as well as headache-related disability, compared to placebo. As just one measure of its effectiveness, many of my patients report that they’ve cut their use of rescue medications in half since starting Botox – a significant benefit for people who previously had to resort to rescue medications 15 or more times every month.
Clinical diagnosis of depression or other mental health disorders, including body dysmorphic disorder and eating disorders. Please discuss any history of mental health disorders prior to surgery. Patients with a diagnosis of depression, or other mental health disorders, should wait until resolution or stabilization of these conditions prior to undergoing breast implantation surgery.
How much is Botox is a frequent question we get in our dermatology offices. The cost of Botox runs typically about $400 – $600 per first treatment area, and up to $300 for each additional area. The most popular areas for Botox treatment are the glabella (those lines in between your eyebrows also known as the “11’s”), the crow’s feet are around the eyes and the horizontal lines on the forehead. When injected by a trained professional who has experience with facial aesthetics, Botox can also give the brows and eye area a mini eye lift. When Botox injections are performed by a trained, licensed and experienced medical expert, the results can be amazing. You will not appear frozen or as though you’ve had work done, when injected properly, Botox makes you look more relaxed, more rejuvenated and just better than before. It’s important to seek out a professional who knows about facial anatomy and can inject you in the exact right places.
Most practices have a flat cost for each injection of BOTOX® Cosmetic, though some will break it down by “units” used per treatment. Flat rates are usually somewhere between $300 and $1000, while per-unit rates are usually around $10-15 per unit. Though the BOTOX® Cosmetic price paid by physicians is normally about $400 for each vial (each vial contains 100 units, or enough for about 4 or 5 treatments), the vial must be used within a few hours of opening, so if the entire vial is not used, the physician will often have to throw the rest out.
Don’t be a pill. You're more likely to get a bruise at the site of the needle injection if you're taking aspirin or ibuprofen; these medications thin the blood and increase bleeding which causes the bruise. Skip the pills for two weeks in advance of your treatment. You should also tell your doctor -- before treatment -- about any supplements you're taking, even if they're "natural," because some (such as fish oil pills, gingko, or vitamin E) also thin blood. Your doctor may ask you not to use those supplements for two weeks before your treatment.
Two double-blind, placebo-controlled, randomized, multi-center, 24-week clinical studies were conducted in patients with OAB with symptoms of urge urinary incontinence, urgency, and frequency (Studies OAB -1 and OAB-2). Patients needed to have at least 3 urinary urgency incontinence episodes and at least 24 micturitions in 3 days to enter the studies. A total of 1105 patients, whose symptoms had not been adequately managed with anticholinergic therapy (inadequate response or intolerable side effects), were randomized to receive either 100 Units of BOTOX (n=557), or placebo (n=548). Patients received 20 injections of study drug (5 units of BOTOX or placebo) spaced approximately 1 cm apart into the detrusor muscle.
This medication is given by injection by an experienced health care professional. It is injected into the affected muscles (intramuscularly) when treating eye disorders, muscle stiffness/spasms, and wrinkles. When used to prevent migraines, it is injected into the muscles of the head and neck. It is injected into the skin (intradermally) for the treatment of excessive sweating. For the treatment of drooling/excess saliva, this medication is injected into the salivary glands. When treating overactive bladder, it is injected into the bladder.
Some doctors and dermatologists recommend lying down and resting after a treatment, but Ravitz says she doesn't think there's any need for downtime unless a patient experiences pain. It can take about two weeks to work, though some patients start to feel relief from chronic migraines sooner than that. Ravitz tells me, "If it’s going to work for a patient, one round of the treatment typically lasts for around three months." Though everybody metabolizes it at a different rate, getting it done every three months or so has been found to be effective.
Some critics say Botox makes you lose all the personality from your face, leaving you with a significantly less range of motion when you laugh, or get angry or upset. While it’s true that your movement will be restricted, a moderate amount of Botox will still allow you to react and communicate in a lively way. “Botox relaxes the wrinkle-forming facial muscles at the sight of injection, such as crow’s feet, glabella (the ‘furrows’ in between the brows), and frontalis (forehead lines),” Dr. Waibel says. “Botox does not affect other facial muscles that are used for overall facial expressions.”
Symptoms of overdose are likely not to be present immediately following injection. Should accidental injection or oral ingest ion occur or overdose be suspected, the person should be medically supervised for several weeks for signs and symptoms of systemic muscular weakness which could be local, or distant from the site of injection [see BOX WARNING and WARNINGS AND PRECAUTIONS]. These patients should be considered for further medical evaluation and appropriate medical therapy immediately instituted, which may include hospitalization.
In general, you’ll find that Botox costs about $10-$20 per unit. While some offices and clinics charge a flat rate, depending on the area that they’re working on, you’ll more often find that you are charged based on how many units of Botox are used to achieve the results you’re looking for. You need around 20 units to treat your forehead and 5-6 units to treat crows feet, making Botox an affordable alternative to going under the knife.
“A younger face has a heart shape, and an older face is a little more bottom-heavy and square,” says Dr. Matarasso. “But if you put toxin in both sides, you are not reducing the movement of the muscle, you are thinning the muscle out a bit. You can restore a youthful look. It’s not as dramatic or quick-acting as other areas, but it can be a nice way to improve the contour of the face.”
Botox injections like other goods and services in New York City are typically more expensive then in the suburbs where the rent and salaries are also less expensive. So it is true that in general Botox cost more in NYC. In one vial of Botox there is 100 units of medicine and each unit costs on average $20. Most patients require between 20 to 60 units.That translates into an average between $400 and $1200.
Lastly, a Botox treatment does not offer permanent results. Botox is most effective when treatments are carried out at regular intervals before the results fully wear off. On average, the results last for three to four months, although Botox metabolizes at different rates in different individuals. The first ever Botox treatment you receive may not last as long as subsequent treatments, plus you may require touch-ups two weeks after the procedure as your injector determines the right dosage for you. Over time, however, many patients notice that they can wait longer intervals between treatments as their treated facial muscles weaken.
Three percent of patients experienced eyelid drooping in the frown lines studies, one percent of patients experienced eyelid swelling in the crow's feet studies, and one percent of patients experienced brow drooping in the forehead lines studies. Other possible side effects include: dry mouth; discomfort or pain at the injection site; tiredness; headache; neck pain; eye problems: double vision, blurred vision, decreased eyesight and dry eyes; and allergic reactions. These are not all of the possible serious side effects of BOTOX® Cosmetic. Please see the Important Safety Information including Boxed Warning and Medication Guide and talk to your specialist.
Preventative Botox has been getting lots of buzz. “It can potentially have a preventive effect on dynamic wrinkles, which are caused by underlying muscle movement,” Shah explains. “That being said, muscle movement is only one factor that contributes to the development of wrinkles, so Botox may not be completely preventive.” (Some other wrinkle causes: sun exposure, smoking, and diet.)
In the mid-1990s, people who received BOTOX for other conditions reported improvement in their chronic migraine pain. A two-phase study was conducted, treating patients who averaged 20 headache days a month. They received BOTOX injections every twelve weeks for 56 weeks. At the end of that period, 70% of the patients had fewer than half the number of headaches they had before treatment. The FDA officially approved BOTOX to treat chronic migraine in October of 2010. Since then, more than 100,000 patients have been treated.
The potency Units of BOTOX® are specific to the preparation and assay method utilized. They are not interchangeable with other preparations of botulinum toxin products and, therefore, Units of biological activity of BOTOX® cannot be compared to nor converted into Units of any other botulinum toxin products assessed with any other specific assay method.
If going back for additional treatments three or four times a year sounds like a lot of treatments, the good news is that the more Botox treatments you get, the fewer Botox units you'll need. With each repeat Botox session, the frontalis muscle and other facial muscles surrounding Botox injection sites get a little weaker and become "trained" to not contract.
BOTOX may be an effective treatment for those who suffer from chronic migraines. Many patients have struggled to find a treatment that truly provides relief from this debilitating condition. While there are migraine medications and a host of natural remedies, for many people, none of these methods bring real relief. BOTOX may be the option that brings the relief from pain that patients have been seeking for so long.
"I had 25 units of Botox done by Dr. Goldberg on my forehead and frown lines. Few days later I could see the result with which I was very happy! [...] I have done Botox few times before with other specialists, after which my face would resemble a doll [...] However, after procedure with Dr. Goldberg, I am still able to lift my eyebrows and frown without forming any wrinkles." – from Dinara D.'s review of Alexander Golberg Physician PC in New York.


Puett’s course Classical Chinese Ethical and Political Theory has become the third most popular course at the university. The only classes with higher enrollment are Intro to Economics and Intro to Computer Science. The second time Puett offered it, in 2007, so many students crowded into the assigned room that they were sitting on the stairs and stage and spilling out into the hallway. Harvard moved the class to Sanders Theater, the biggest venue on campus.
As with acupuncture, Chinese herbs are best administered by licensed acupuncturists, L.Ac.’s, who have advanced medical degrees and clinical training in Chinese herbal medicine. Even among L.Ac.’s there are variances in aptitude with herbal medicine, so when searching for a practitioner to work with make sure to ask them about how active they are in working with Chinese herbs in their clinical practice.
Me, myself, us: looking at human beings as ecosystems that contain many collaborating and competing species could change the practice of medicine.
Scientific studies have suggested that a mind that is present and in the moment indicates well-being, whereas shifting our energy to the past or future can lead to unhappiness. Now, a preliminary UCSF study shows a link between mind wandering and aging, by looking at a biological measure of longevity within our DNA.
In the study, telomere length, an emerging biomarker for cellular and general bodily aging, was assessed in association with the tendency to be present in the moment versus the tendency to mind wander, in research on 239 healthy, midlife women ranging in age from 50 to 65 years.
Autoimmune disease affects an estimated 50 million people at an annual cost of more than $100 billion. And the suffering and monetary costs are sure to grow. Maybe it’s time we talk more about human ecology when we speak of the broader environmental and ecological concerns of the day. The destruction of our inner ecosystem surely deserves more attention as global populations run gut-first into the buzz saw of globalization and its microbial scrubbing diet.
They found that experienced meditators had decreased activity in areas of the brain called the default mode network, which has been implicated in lapses of attention and disorders such as anxiety, attention deficit and hyperactivity disorder, and even the buildup of beta amyloid plaques in Alzheimer’s disease. The decrease in activity in this network, consisting of the medial prefrontal and posterior cingulate cortex, was seen in experienced meditators regardless of the type of meditation they were doing.
A new study suggests that people who regularly practice Buddhist meditation make decisions in a more rational way.
“But the meditators’ brains reacted quite differently, activating brain areas associated with interoception — the representation of the body’s internal state. In fact, the researchers found very little overlap in the two groups’ neural responses.”


Epidemiological Study on Tick-Borne (Acari: Argasidae) Relapsing Fever in Kurdistan Province, Iran, 2000–2004
Tick-borne relapsing fever is an acute infectious disease transmitted to humans by Ornithodoros tholozani, and it is a notifiable disease in Kurdistan Province, Iran. This cross-sectional survey was carried out from 2000 to 2004. The main aim of this study was to ascertain the prevalence of tick-borne relapsing fever in Kurdistan Province. The prevalence and incidence of tick-borne relapsing fever was monitored by daily clinical surveillance and by thin and thick blood smears of individuals
... of individuals with a fever. In confirmed cases, there was febrile illness, and spirochetes were identified on smears of peripheral blood. A field survey on presence of Ornithodoros tholozani in Bijar county villages was carried out and investigated for the detection of Borrelia spp. A total number of 97 cases including 88 cases from rural areas and 9 cases from urban areas were recorded over 5 years. Epidemiological studies on O. tholozani ticks collected from the several locations of villages indicated that 2 of the 20 studied villages (10%) were infested by the vector tick, O. tholozani. The presence of O. tholozani in most villages investigated and its infection rate suggest that tick-borne relapsing fever is a common cause of fever in most rural areas of Kurdistan Province. Results of the study demonstrate that tick-borne relapsing fever is under-recognized and under-reported, and the pathogens may be wrongly identified as malaria parasites. The study showed that tick-borne relapsing fever should be considered as an important public health priority in the study area.


Two patients with cancer requiring removal of specific impalpable lymph nodes for full pathological analysis underwent ultrasound-guided lesion localisation and marking with a low-activity I-125 seed. A gamma probe was used in theatre to localise the signal from the seed and guide excision. Successful removal of the lesions was confirmed with the probe and by specimen radiography. Radioguided Occult Lesion Localisation using I-125 Seeds ("ROLLIS") provides a method of precisely marking impalpable lesions for surgical excision. Copyright 2014 BMJ Publishing Group. All rights reserved.


Molecular panel tsts for infectious diseases have changed the landscape of clinical microbiology. They play an important role in diagnostic testing, as they simultaneously detect several different pathogens associated with similar and overlapping clinical symptomatology. For this reason, they are also known as ‘syndromic panel’ tests. These panels belong to a category of testing known as culture-independent diagnostic tests (CIDTs), which are tests that detect pathogens without the need to grow and isolate them in culture. These tests have shorter turnaround times, often have good test performance characteristics, and require limited technical expertise, making them appealing for use by clinicians as well as clinical laboratories.
Historically, physicians were required to select the specific pathogens most likely thought to be associated with a patient’s disease. They often had to rely on empiric therapy until results from the laboratory could be used in identifying definitive or targeted antimicrobial therapy, with results taking days and sometimes weeks. In recent years, molecular panel tests, including multiplex PCR, have become increasingly used for the detection of pathogens, and clinicians are no longer required to name (or separately test for) many of the bacterial, viral, fungal, and parasitic species sought for a given clinical ‘syndrome'. As the use of multiplex molecular tests have decreased the need to perform multiple assays to diagnose a given infection, results are often available to the physician within minutes to hours. Though culture-based methods of diagnosis are still routinely utilized, and definitive antimicrobial therapy may still lag pending full culture and susceptibility information, these tests have revolutionized infectious disease diagnostics and have made the road from diagnosis to treatment very rapid, in some cases occurring at the point-of-care (POC).
For some conditions, such as respiratory tract infections, RP panels have become the SOC. These respiratory panels are exceptionally rapid, providing results in minutes to hours.4,5 They are unlike the older conventional respiratory viral testing methods such as viral culture and immunofluorescence, which could take days to weeks to obtain a result. Moreover, they display test performance characteristics (sensitivity and specificity) which are often superior to other rapid diagnostic tests for respiratory viruses, such as rapid (antigen-based) influenza detection tests (RIDTs).6-8 For these reasons, many laboratories have stopped offering some of the other diagnostic modalities described for respiratory viral pathogens detection. In fact, many of those methods have become obsolete in routine clinical care.
Finally, some of these multiplex panels are smaller, or ‘targeted', detecting just a few pathogens whereas others are very large, detecting approximately 20 targets. The larger panels are sometimes referred to as ‘expanded'. These distinctions most commonly apply to the RP and GI panels, as panels for BSI and ME (and in some circumstances UG/AG) are expected to detect >5 pathogens (though a UG/AG panel is not expected to detect as many as 20 pathogens, due to the epidemiology of disease in that organ system). Many commercial platforms for multiplex panel testing have been developed for a variety of infection types in different organ systems.4,5 Both smaller and larger panels are being used in clinical laboratories, though their optimal use and application in various settings and for various patient populations and indications remains a challenge.
In recent years, molecular syndromic panels have become routinely used for a number of infection types, including respiratory, gastrointestinal, central nervous system, bloodstream, and urogenital/anogenital. These panels provide rapid turnaround times for results and are often more sensitive than traditional testing for the various organisms included.4,5,9 However, test performance characteristics do vary depending on the specific panels and pathogens. For example, though overall sensitivities and specificities have ranged from 84-100% for various RP platforms evaluated, the sensitivities for adenovirus, influenza A H1/2009, and influenza B using the FilmArray® RP have been reported as low as 57%, 73%, and 77%, respectively, while more recent versions of the platform (the FilmArray® RP2) have shown improved detection (94%-100%) of these pathogens.10,11 Additionally, the FilmArray® PNP and RP panels have targets in common, though the PNP also contains numerous bacterial targets as well as antimicrobial resistance determinants; the PNP is also semiquantitative.12,13 The PNP has shown strong agreement with both SOC methods as well as with the RP in identifying pathogens from lower respiratory tract specimens.12,13 Because the PNP performs similarly to the RP for viral pathogens, but can additionally detect bacterial pathogens and antimicrobial resistance determinants, it should be prioritized in the evaluation of pneumonia from lower respiratory tract specimens.14 A study comparing the performance of additional RP assays reported the following sensitivities and specificities: 98.3% and 99.2% for GenMark Dx® eSensor® Respiratory Viral Panel (RVP), 92.7% and 99.8% for Luminex® xTAG® RVPv1, and 84.4% and 99.9% for Luminex® xTAG® RVP Fast.10 In this study, sensitivities also varied by viral target.10 Smaller targeted panels detecting influenza and respiratory syncytial virus (RSV) have also shown overall high sensitivity and specificity in studies evaluating their performance. A prospective and retrospective evaluation of the Xpert® Flu/RSV XC assay reported sensitivity/specificity of 97.8%/100% and 97.9%/100% for influenza and RSV, respectively.15 Another study using prospective patient samples reported 96.6%-100% agreement between the ARIES® Flu A/B & RSV and Cepheid® Xpert® Flu/RSV XC assays.16 This is important, as some of the targeted respiratory panels have been granted Clinical Laboratory Improvement Amendments (CLIA)-waived status and are being used in non-laboratory settings.17,18 In a study evaluating the Roche cobas® Liat® Influenza A/B & RSV assay performed by nonlaboratory staff, reported sensitivities/specificities were 99.6%/97.5%, 99.3%/99.7%, and 96.8%/98.8% for influenza A, B, and RSV, respectively.19 Yet another study comparing rapid POC nucleic acid amplification tests (NAAT) found that the sensitivity of Alere™ i was only 71.3% (compared to 100% for the Liat®).20 The poor sensitivity of the Alere™ i in that study was attributed to the inclusion of many low-positive samples.20
The Biofire® FilmArray® and Luminex® xTAG® GI panels demonstrate overall high sensitivity (>90%) for the majority of their targets.21 However, sensitivities have been very low for certain targets, specifically Aeromonas sp. (23.8%) on the FilmArray® and Yersinia enterocolitica (48.1%) on the xTAG®21; because its low sensitivity, Aeromonas is not included as a reportable analyte on the cleared version of the FilmArray® test.22 A multicenter study evaluating the FilmArray® GI panel found the sensitivity to be 100% for 12 of the 22 targets and >94.5% for an additional 7 targets (performance of the remaining targets was not assessed due to their low prevalence); specificity was >97.1% for all panel targets.22 In a study comparing the Luminex® xTAG® to conventional methods of testing found that the panel had a higher sensitivity than SOC for detecting C. difficile, Campylobacter species, norovirus, and rotavirus.23
The ME panel (the Biofire® FilmArray® ME panel is currently the only commercially available panel) has overall good sensitivity for most targets, but does suffer from a lack of sensitivity for certain targets, such as Cryptococcus species, relative to conventional testing methods for this pathogen.24-26 In 1 prospective multicenter evaluation, the FilmArray® ME panel showed a percent positive agreement (PPA) with SOC methods of 100% for 9 of 14 analytes, with another 2 analytes showing PPA between 85.7-95.7%; the percent negative agreement (NPA) with SOC methods was >99% for all analytes but S. agalactiae.24 Importantly, the ME panel detected 43 pathogens that were not recovered by conventional testing; however, additional testing confirmed the ME panel to be correct in only 43% of these cases.24 In this and other studies, false positive results of the ME panel have been reported, primarily for S. pneumoniae, S. agalactiae, and HSV-1, and false negatives have been reported primarily for HSV-1 and HSV-2, Enterovirus, and Cryptococcus neoformans/gattii.24-26 A systematic review and meta-analysis of 13 studies evaluating the ME panel reported a sensitivity and specificity of 90% and 97%, respectively.26
BSI panel tests also show good overall performance. Studies have found the FilmArray® Blood Culture Identification (BCID) panel and the Verigene® (Gram-positive and Gram-negative blood culture) panels provide correct identification for 87%-99% of monomicrobial samples, compared to conventional methods.27,28 One study comparing the 2 panel tests to SOC found that the FilmArray® and the Verigene® correctly identified 95% and 99% of isolates, respectively, in monomicrobial cultures.27 False positives and false negatives have been reported in these panels, for both organism and resistance gene identification, particularly in polymicrobial samples; however, the failure to detect organisms in polymicrobial samples is often the result of organisms not included on the panels.5,29 Nevertheless, because of limitations inherent in the tests (including the fact that not all organisms are represented on the panels and these are high-stakes infections), both the ME and BSI panel tests must be accompanied by Gram stain and culture.
Molecular panel tests are also increasingly being used for the detection of urogenital and anogenital infections. The BD MAX™ vaginal panel has reported sensitivities and specificities of 89.8%/96.5%, 97.4%/96.8%, and 100%/100% for bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), and trichomoniasis (TV), respectively.30 In another study, the BD Affirm™ VPIII Microbial Identification Test showed a lower specificity of 81.6% for BV and lower sensitivity of 69.4% for VVC, while it performed equally well as the BD MAX™ for TV.31 These panels, however, have been shown to perform better than clinician assessment of vaginitis, for which many diagnoses remain empirical and for which guideline non-adherence is broad.32-34 Further, high rates of coinfection with STIs (24.4%-25.7%) have been observed.35-37 Panels detecting sexually transmitted pathogens have also become routine in clinical laboratories, as they provide a rapid result for organisms like Chlamydia species, that can be difficult to culture. Moreover, it is well-established that N. gonorrhoeae and C. trachomatis not only cause similar clinical syndromes but also coexist in a significant proportion of patients, highlighting the need for panel testing.38
For the evaluation of UTI, multiplex PCR panels have shown agreement of ≥90% with SOC urine cultures for the identification of organisms from urine, though there are currently no United States (U.S.) FDA-approved panels for this indication.39,40 Similarly, there are no currently approved panels for use with sterile body fluids other than blood and CSF, though studies evaluating existing panels (such as the BSI panel) with such fluids have shown pathogen detection in cases where SOC cultures were negative, possibly due to the effect of prior antimicrobial therapy.41,42 Though testing may require assay optimization for use with ‘other’ sterile fluid specimens, 1 study found 100% detection of organisms from sterile fluids inoculated into blood culture bottles when tested using BSI panels.43
There are many commercially available multiplex panels for the diagnosis of infectious diseases, and this review of their performance is not inclusive of all of them. As noted in this review, the performance of these panel tests varies, depending on the platform and specimen types used and the targets included. These panel tests should display performance that is equivalent or superior to SOC or other established tests, with ideal sensitivity and specificity or PPA and NPA of ≥95% for the majority of targets included on their panels. However, it is important to consider the entire picture. For example, as some of these panels are not intended to be used as stand-alone tests, parallel testing by additional methods can be used to support their application in clinical settings, particularly in cases where the assay has not achieved the ideal performance metrics for a given target. Finally, the specific performance limitations of the various panel tests (in some cases due to enhanced sensitivity for targets that may not be pathogenic) must be considered. These issues are further discussed in the Clinical Utility section below.
Clinical Utility - Impact on Patient Management and Interpretation of Results
Rapid diagnostics require rapid intervention to be impactful for patient management. Rapid, user-friendly, multiplexed molecular tests have great potential in this regard, though their impact on patient outcomes is clearer for some types of panels, infections, and patients than for others, as studies are variable in design and quality.4,5,8,44 A systematic review of the impact of rapid point-of-care testing (POCT) (including molecular assays) for influenza found that, in patients with acute respiratory infection, a positive POCT result significantly increased use of antivirals for influenza and decreased unnecessary antibiotic use.45 Another study of adult patients found a decreased time to diagnosis (of influenza and non-influenza viruses) using the FilmArray® RP, compared to conventional methods of testing; moreover, a diagnosis of influenza was associated with lower odds ratio for admission, length of stay (LOS), duration of antimicrobial use, and number of chest x-rays.46 Better influenza detection, a reduced LOS, and improved antiviral use were also found in a study of routine molecular POCT for respiratory viruses (the ResPOC study), for adults presenting to the hospital with acute respiratory illness.47 However, studies have shown that other factors, such as the presence of infiltrates on chest x-ray and uncertainty regarding the possibility of a bacterial infection, also play a significant role in the decision to treat with antibiotics, regardless of the result of the RP test.48 A systematic review of the literature concluded that RPs provide accurate results, and that there is high-quality evidence to support that rapid testing can result in a decreased LOS and can increase appropriate oseltamivir use.8 Notably, the majority of RP studies have focused on the benefits in influenza-positive patients. For example, in a study evaluating antimicrobial prescriptions following RP testing among adult outpatients, antibiotic prescription rates were significantly different between patients who tested positive for influenza virus and those who did not; however, antibiotic prescription rates were not different between the patients who tested positive for viruses other than influenza and those who tested negative.49 Since influenza is 1 of the few respiratory infections that can be treated with antivirals, this suggests that a more targeted testing approach is sufficient for most immune-competent patients with a presumed acute viral respiratory infection. Moreover, guidelines on CAP by the Infectious Disease Society of America (IDSA) recommend NOT obtaining testing (specifically sputum Gram stain and culture) routinely in adults with CAP managed in the outpatient setting; rather, they recommend that empiric antibiotic therapy be initiated in adults with clinically suspected and radiographically confirmed CAP, even if these patients test positive for influenza.1 In other words, RP testing does not impact initial management with antibiotics in such circumstances. However, IDSA guidelines do suggest testing for influenza in adult patients with CAP when influenza is circulating in the community.1 In such cases, a targeted panel for influenza testing can be performed. Finally, specific diagnosis and definitive antimicrobial therapy is needed for pneumonia that is complicated (i.e., by meningitis, endocarditis, or abscess), and testing using expanded panels is warranted in these circumstances; however, these patients are expected to be managed in the inpatient setting.
A more expansive testing approach may be appropriate in patients with underlying pulmonary pathology and in immune-compromised patients, but only in certain circumstances. In a study of adult patients with exacerbation of airway disease, 35% of those testing positive for viruses (using molecular POCT) had early discontinuation of antibiotics compared to 13% of those who tested negative and 6% of controls; moreover, of those positive for viruses, only 20% were positive for influenza and the discontinuation of antibiotics was not different between the various viruses detected.50 The authors of this study stress that many of the patients in this study should not have been treated with antibiotics, on clinical grounds alone, “given that antibiotic use in patients with asthma exacerbation is strongly discouraged by national society guidelines.”2,50 The Global Strategy for Asthma Management and Prevention states “evidence does NOT support the role of antibiotics in asthma exacerbations unless there is strong evidence of lung infection (e.g., fever and purulent sputum or radiographic evidence of pneumonia).”2 Finally, a study evaluating respiratory virus infections prior to hematopoietic cell transplant (HCT) found that patients with viruses detected pre-HCT had fewer days alive and out of the hospital and lower survival at day 100 than patients with negative results (even when the only virus present was rhinovirus); importantly, most patients in this study were asymptomatic when surveillance samples were collected.51 This finding suggests that pre-transplant evaluation is 1 limited circumstance in which expanded RP panel testing may be warranted in asymptomatic patients.
Impact studies of GI panels have been even more mixed, though some have found that implementation of such panels was associated with a decrease in endoscopic procedures, abdominal radiology, and/or antibiotic prescriptions.52,53 A prospective multi-center study evaluating 1887 fecal specimens from patients with acute diarrhea found that use of a GI panel enhanced organism detection and improved clinical sensitivity, and enabled clinicians to provide more timely and targeted antimicrobial therapy; moreover, positive Shiga-like toxin producing E. coli (STEC) results led to the appropriate discontinuation of antimicrobials in the majority of cases when empiric therapy had been initiated.9 However, in outpatients with uncomplicated diarrhea that is likely to be self-limited, testing is often not warranted.5 Guidelines from the American College of Gastroenterology regarding acute diarrheal infections in adults state that diagnostic studies may be used in cases of “dysentery, moderate-to-severe disease, and symptoms lasting >7 days to clarify the etiology of the patient’s illness and enable specific directed therapy.”54 Regarding the use of the GI panel in special populations, an impact study in patients with IBD found that GI panel testing led to lower rate of IBD treatment modification.55 In outpatients with relapse of IBD, testing with a GI panel was associated with significantly lower rates of IBD therapy escalation and endoscopy, compared to patients who underwent conventional testing.56 Finally, in a study evaluating gastrointestinal infections prior to HCT in asymptomatic patients found that 62% of patients colonized with C. difficile pre-transplantation developed a clinical C. difficile infection post-transplantation, and 80% of patients colonized with enteropathogenic Escherichia coli (EPEC) or enteroaggregative E. coli developed clinical infections due to their colonizing pathogen post-transplantation.57 As noted above with respiratory infections, these findings suggest that pre-transplant evaluation is 1 limited circumstance in which expanded GI panel testing may be warranted in asymptomatic patients.
Bloodstream and CNS infections are emergency situations that can progress rapidly, even in previously healthy individuals.58 As such, rapid panel testing can prove invaluable in the prompt management of patients with such infections. The following widely cited statistic is sobering –in sepsis, for each hour of delay in effective (appropriate for a given pathogen) antimicrobial administration, there is an average decrease in patient survival of approximately 8%.59 Because bacterial culture and full antimicrobial susceptibility results traditionally take 2 or more days, rapid BSI panels have emerged to rapidly (within hours) identify a causative pathogen such that the most appropriate and targeted antibiotics can be administered. A prospective randomized controlled trial found that use of a BSI panel resulted in a decrease in time between Gram stain to microorganism identification by approximately 21 hours.60 Moreover, the use of broad-spectrum antibiotics and the treatment of bloodstream contaminants were reduced; further, antimicrobial de-escalation occurred with the additional intervention by the ASP.60 Other studies have similarly shown more rapid organism identification and antimicrobial de-escalation with the use of BSI panel (plus ASP intervention) over conventional culture methods, even if the latter also included ASP. 61 However, the effect of BSI panels on other outcome measures such as mortality, 30-day readmission, and LOS has been more variable between studies.5,61 Pre-post intervention studies62 as well as a meta-analysis63 have shown that rapid molecular diagnostic testing is associated with significant decreases in LOS and mortality risk, particularly when combined with an ASP. For patients with multi-drug resistant bacteria, rapid escalation of antimicrobial therapy is also important. In 1 study, use of a BSI panel decreased the mean time to appropriate antimicrobial therapy by more than 30 hours in a study of patients with vancomycin-resistant enterococci (VRE) bacteremia.64 In another, more rapid implementation of effective therapy was observed in cases of extended-spectrum beta-lactamase-producing organisms, but not overall; this same study reported a significantly decreased length of intensive care unti (ICU) stay, 30-day mortality, and mortality associated with multidrug-resistant organisms after the implementation of a BSI panel.62 There are fewer outcome studies evaluating the clinical utility of ME panels, particularly for patients generalizable to the Medicare population. One study found that use of the FilmArray® ME panel reduced time to diagnosis by approximately 3 days, allowed an earlier discontinuation of empiric therapy in 32% of patients, and led to an earlier hospital discharge in 18%, saving 82 hospital days.65 Another study found that use of the panel significantly reduced the turnaround time for HSV detection, days of therapy for antivirals (acyclovir) and antimicrobials, and hospital LOS, in adults undergoing a lumbar puncture for a suspected community-onset CNS infection.66
Results from molecuar panel tests must be interpreted with caution. First, they detect significantly more pathogens than were detected in the past using conventional methods of testing.5,9 For example, studies evaluating multiplex urine panels (UPs) have detected up to 26% additional organisms that culture methods did not.39 Importantly, multiplex UPs have detected more organisms in polymicrobial infections than urine cultures in symptomatic patients,39,67 and a modeling study has shown bacterial combinations that increase the probability of antibiotic resistance.68 As with all such panel tests, it is important to determine whether these additional organisms detected are pathogens or colonizers that simply could not be detected before, using traditional SOC methods. As these tests detect microbial nucleic acid, they do not require live and actively replicating organisms. Therefore, not all positive results indicate current active infection. However, in 1 study of 150 urogynecology patients, standard urine culture missed 50% of uropathogens in patients with severe urinary symptoms; moreover, approximately 40% percent of patients with missed uropathogens reported no symptom resolution after treatment based on standard urine culture results.69 Importantly, all of the missed uropathogens were detected using the study’s comparator method (an enhanced quantitative culture technique), though additional bacteria of unknown pathogenicity were also detected.69
Asymptomatic carriage and prolonged shedding (days to weeks) of viral nucleic acid are common, particularly for respiratory and GI pathogens. In BIG-LoVE, a study of 108 adults and children who underwent weekly respiratory panel testing for a year, approximately half of all viral detection episodes were asymptomatic.70 Further, PCR detection of viruses at ≥3 weeks was a fairly frequent finding, occurring in 16% of episodes; prolonged viral detection was particularly common in children and in individuals living with children.70 Prolonged shedding is also common in immune-compromised patients.71 On the GI panels, interpretation of a positive C. difficile result in a patient without risk factors for infection with this organism can be difficult, as 4%-15% of healthy adults, and up to 21% of those admitted to a hospital, are asymptomatically colonized; moreover, detection by PCR does not indicate active infection, particularly in patients without classic clinical symptoms.72,73 The high rate of mixed infections observed when using expanded RP (in 30%-40% of positive cases)74,75 and GI panels (up to 27% of positive cases)5,21-23 can be difficult to interpret. The significance of previously unidentified organisms in stool samples (such as Sapovirus and Astrovirus) can also be clinically challenging to interpret, as it is unclear whether detection of these organisms represents colonization or infection. Mixed infections detected by GI panels most commonly occur with enteropathogenic E. coli, Y. enterocolitica, Norovirus, and C. difficile.9,21,53 Moreover, in some studies with very high rates of observed C. difficile there are also high rates of inappropriate GI panel testing. In 1 study evaluating more than 440 GI panels at a community hospital, 61% of the panels ordered were deemed inappropriate, for reasons including lack of documented diarrhea, laxative use, and having a duplicate C. difficile PCR test ordered.53 Notably, in this study, rates of C. difficile were 51%.53
ME and BSI panels also have their own challenges. For example, though co-infections are less commonly observed with multiplex panel testing from sterile body sites (such as from CSF or blood), they do occur and can cause interpretive challenges.24 Additionally, the ME panel cannot differentiate active from latent infection. It detects certain organisms, such as human herpesvirus 6 (HHV-6) and cytomegalovirus (CMV), that may be latent and not the causative agents of disease, particularly if the host is immunocompetent. Moreover, there are a number of organisms that can cause meningitis and encephalitis that are not included on the panel, including bacteria (such as non-K1 E. coli serotypes and non-encapsulated strains of Neisseria meningitidis), viruses (including arboviruses), and Mycobacterium tuberculosis. Therefore, there are significant limitations associated with the use of this panel; however, these are mitigated, in part, by a requirement for additional testing (i.e., bacterial culture, cryptococcal antigen) to occur in parallel, as well as by clinician education and laboratory stewardship. It is important to remember, however, that traditional means of diagnosing CNS infections also come with diagnostic challenges that can delay a diagnosis. Such challenges include the low sensitivity of CSF culture (particularly in patients with antimicrobial exposure prior to lumbar puncture)76 as well as the historically unrecognized etiology in most cases of encephalitis.77 The large nature of the panels may cause an ordering clinician to assume that, because so many organisms are being tested, a negative result makes infection a less likely cause of the patient’s symptoms. It is, therefore, important for clinicians to realize that, even in expanded syndromic panels, not all pathogens will be detected. New strains of viruses may also go undetected, and the panels are limited to only those organisms found on the ‘menu'. Though the ME panel cannot fully replace current assays, it can provide unparalleled rapid results for a syndrome that can be rapidly fatal. Similarly, BSI panels are limited by the targets available on the panels, both for identification of microbes as well as identification of genes responsible for resistance mechanisms. In fact, many Gram-negative organisms harbor resistance mechanisms not encoded by any genes on these BSI panels, adding another diagnostic hurdle to overcome. However, they do tend to detect the most common bloodstream pathogens and can provide rapid results for rapid targeted antimicrobial therapy.4,5,60
Additional Challenges and Appropriate Use of Panel Tests
With few exceptions, the FDA-approved molecular panels for a given platform are ‘fixed’, i.e., they consist of a predetermined test menu of pathogens. The smaller of these tests, sometimes referred to as ‘targeted panels’, typically detect about 3-5 pathogens. The commonly used commercially available larger, or ‘expanded’, panels detect approximately 20 targets or pathogens, and some include pathogens that typically cause different clinical presentations, such that simultaneously testing for these pathogens should not be a common event. In other words, they deviate from being ‘syndromic’ in their approach to diagnosis. For example, the classic infection associated with Bordetella pertussis is whooping cough. The clinical case definition of a probable case of pertussis is a cough illness lasting at least 2 weeks, in the absence of a more likely alternate diagnosis or epidemiologic linkage, and 1 of the following symptoms: paroxysms of coughing, inspiratory whoop, post-tussive emesis, or apnea.78 Though some individuals (such as those with a history of prior infection or vaccine-induced immunity) may not show classic manifestations or may be altogether asymptomatic,79 diagnosis of this organism generally should require a high index of suspicion. Although it is a respiratory infection, in most patients, the clinical presentation of whooping cough is unlike that of most other viral respiratory syndromes. Yet, it is included on many respiratory syndromic panels and a patient who is likely infected with influenza or RSV may still end up being tested for B. pertussis, simply because it is a target on a fixed panel. Finally, the targets and organisms on a panel can vary between manufacturers, with some panels differentiating among numerous subtypes and strains of species, many of which are not clinically meaningful for the majority of patients.5 For example, differentiating among the different types and subtypes of parainfluenza virus may be good for epidemiologic tracking, but is not likely to result in any meaningful impact to patient care.
Further, large (fixed) panels do not appropriately regard patient risk factors, or a pre-test probability of a particular pathogen causing infection. The patient’s medical history and exposures are important to assess prior to testing. For example, infection with Clostridioides difficile (formerly known as Clostridium difficile) is typically associated with specific risk factors including exposure to antimicrobials, healthcare facilities and hospitals, chemotherapy, and GI procedures.80 Conversely, many of the other pathogens on the panels are typically associated with foodborne transmission.81,82 Variables like season and geography are also pertinent to a specific diagnostic case or patient. In the case of respiratory panels, a patient can be tested for more than 20 pathogens, when in fact only a couple of viruses may be the predominant ones circulating in the community during a given season. For example, though influenza can circulate throughout the year, it primarily occurs and peaks during the winter months, whereas certain other viruses are more prevalent during other seasons.83 Fixed panels may also not be applicable across populations, and immune-competent patients who are not severely ill may not require testing at all, or may require limited testing.84 Viral infections in immune-competent patients are often self-limiting and resolve without complication. Further, with few exceptions, there is often no specific treatment for viral infections, other than supportive care, and testing may not change patient management. All of this may result in an excess of unnecessary testing in immune-competent individuals. On the other hand, in immune-compromised patients, common and rare pathogens can cause severe illness, and concurrent infection with multiple respiratory viruses (which occur more commonly than previously thought, thanks to these multi-analyte panels) have been identified as predictors of in-hospital mortality.85 Moreover, immune-compromised patients often do not present with classic symptoms of infection. Therefore, casting a wider diagnostic net for this population may be both reasonable and necessary.
However, even in immune-competent individuals, expanded panels can provide rapid, highly impactful, and epidemiologically important information.86 They can lead to the diagnosis of some infections that, in the past, may have been missed altogether. In 1 study, 75% of Mycoplasma pneumoniae infections were unintentionally detected by multiplex PCR; in this study, clinicians had only specifically requested testing for M. pneumoniae in 2 (10%) of 20 patients positive for this pathogen. Importantly, this was an actionable finding, as infection with M. pneumoniae is treatable with antibiotics.87 Expanded panels can also help rapidly diagnose and, in some cases, avert public health outbreaks. For example, during an outbreak of a ‘mystery’ respiratory illness among children in 2014, hospitals were able to rapidly identify the presumptive cause, which turned out to be enterovirus D68.88 Similarly, use of rapid multiplex GI panels significantly contributed to the recognition of a large Cyclospora outbreak in 2018.89
For all these reasons, instituting the appropriate use of these panels can be challenging. Notably, these tools do not necessarily replace certain conventional methods of microbial detection, such as bacterial and fungal culture, in the diagnosis of infection. These many challenges and opportunities have led to the implementation of measures to promote diagnostic stewardship. Some of these include limiting expanded syndromic panels to certain groups of patients, such as the immune-compromised, hospitalized, critically ill, or patients from specialty clinics (such as pulmonary for respiratory panels). Others include the implementation of test ordering algorithms and ‘controls’, decision support tools, and the prohibition of repeat testing within a specific timeframe.5,53,90,91
Summary of Contractor Advisory Committee (CAC) Meeting
A multi-jurisdictional CAC Meeting to discuss the clinical literature related to Molecular Diagnostic Testing for Pathogens took place on Monday, January 11, 2021. The general consensus from the CAC panel is that there is accuracy and reliability in these pathogen panels and that the results from panel testing may improve patient health outcomes. However, the CAC panel also noted that outcome studies from use of these panels is limited, depending on the specific panel (and use) in question. The panel emphasized the importance of regarding patient population and setting, as indications for testing can vary among beneficiaries with different medical backgrounds and needs, and highlighted differences in testing requirements between immune-compromised and immune-competent patients. Overall, the panel expressed that a key consideration is whether a result is going to positively impact patient care. Finally, there was consensus from the CAC participants that the use of this technology in the diagnosis of onychomycosis (fungal infections) of the nail was unnecessary.


Tell us something about Cleveland Clinic’s “Patients First” philosophy.
At Cleveland Clinic Abu Dhabi, the “Patients First” philosophy guides everything we do. It works to ensure exceptional outcomes and deliver an excellent patient experience. The vision is to provide sustainable patient satisfaction and have highly engaged caregivers serve patients – and fellow caregivers – with high quality, cost-effective, and safe patient care. To achieve this optimal patient experience, Cleveland Clinic Abu Dhabi has developed a patient-centered Institute model, which is built around coordinated, multidisciplinary care. Every step of the patient journey has been designed to provide the best possible experience – from ensuring access to providing a high standard of aftercare. In addition, we work hard on engagement: everybody who works at the hospital is considered a “caregiver,” which has driven employee engagement and helped improved the patient experience.
How has Cleveland Clinic Abu Dhabi revolutionized patient experience in the region?
It starts with focusing on organizational culture and providing the right training and development opportunities for caregivers. We have a number of proprietary programs, including HEART (Hear, Empathize, Apologize, Respond, Thank), which is our standard for teaching staff to communicate with empathy. Developed by healthcare professionals, this program helps employees understand their role in creating positive patient experiences. We have a dedicated Office of Patient Experience, whose role it is to monitor the entire patient journey and share learnings across the organization. We capture and analyze patient feedback in granular detail to ensure we’re making informed, evidence-based decisions.
How has the mindset of patient experience changed in the last few years?
CCAD deploys a “team of team” approach. We incentivize our teams to achieve the best outcome, which is a novel concept because it aligns the organization to the true goal, which is the best outcome for the patient. That’s supported a real shift in mindset: the focus is on the whole experience and starts with the patient’s perspective. There’s a strong emphasis on empathy in all aspects of the patient journey.
One of the results of this has been a move away from the traditional healthcare approach, which is to measure productivity by patient numbers, and more focus on healthcare as a service-oriented profession.
What are the some of the steps taken at Cleveland Clinic Abu Dhabi to measure the patient’s perception of quality of care?
We use the Press Ganey benchmark, which compares patients’ likelihood to recommend against results from more than 100 GCC healthcare facilities. We are currently ranked in the 99th percentile overall. We also have a “Secret Shopper” program, that uses facilities across the hospital and builds these results into our development plan. We are also in the final stages of establishing a patient advisory council, which will be in place by the end of the year and which will make the voice of the patient a permanent part of our leadership culture.


trimethoprim and sulfamethoxazole
Generic Bactrim is used to treat ear infections, urinary tract infections, bronchitis, traveler's diarrhea, and Pneumocystis carinii pneumonia.
Generic Benicar is used to treat high blood pressure (hypertension).
olmesartan - hydrochlorothiazide
Generic Benicar HCT is a diuretic used to treat high blood pressure (hypertension).
Generic Betagan is used for lowering eye pressure and treating glaucoma.
Generic Betapace is used for treating certain types of irregular heartbeat (ventricular arrhythmias).
Generic Biaxin is in a group of drugs called macrolide antibiotics. It is used to treat many different types of bacterial infections affecting the skin and respiratory system. It i
Generic Bimatoprost reduces pressure in the eye by increasing the amount of fluid that drains from the eye. Bimatoprost ophthalmic (for the eyes) is used to treat certain types of
Generic Boniva is used for preventing and treating osteoporosis (weak bones) in women who are past menopause.
BUTYLSCOLOPAMINE(other names of active ingridient - scopolamine butylbromide, butylhyoscine and hyoscine butylbromide) is an anticholinergic medicine. Butylscopolamine has many eff
Generic BuSpar is used for the short-term relief of anxiety symptoms.
Generic Bystolic is used in treatment of hypertension and for left ventricular failure.


How you can enhance the immunity health of body naturally? This can be a common query been told by people. Let us see here ayurvedic natural remedy to improve immunity strength. We’ll begin with Echinacea. Echinacea is among the top selected herbal treatments for enhancing the immunity health of body. It improves producing white-colored bloodstream cells naturally.
Echinacea can be simply acquired by means of capsules, powders and capsules. If you’re looking for a secure cure to deal with low immunity troubles, you can include Echinacea in diet. Cat’s claw is yet another safe remedy for dealing with low immunity health troubles. Today, it is simple to get cat’s claw extract from market. It improves producing white-colored bloodstream cells in body naturally.
Improving the home of anti-inflammatory action is among the primary options that come with cat’s claw. If you’re looking for a secure remedy for dealing with inflammatory illnesses and occasional immunity troubles, you can utilize cat’s claw. According to studies, astragalus is discovered to be like a safe remedy for boosting the immunity health of body. You will get this herbal product from the ayurvedic store. A few of the primary health advantages of including astragalus in diet are enhancing producing WBC, improving the degree of energy of body and enhancing bloodstream circulation in body. For effective result, it’s suggested to intake astragalus with milk.
Ganoderma, overflowing with health advantages is really a safe remedy for dealing with many ill-health problems. Do you know the advantages of including ganoderma in diet? This can be a common query been told by people. Today, there are lots of ayurvedic firms that take ganoderma like a key component within their medicinal items. It is a kind of mushroom creation that works well for boosting the immunity health of body.
Frequent cold, fever and cough are very common among people. If you want to avoid this health trouble naturally, never hesitate to utilize ganoderma. Much like ganoderma, another herbal cure that may enhance the immunity health of is ginger root. It is simple to add ginger root items in diet by means of capsules and extracts. For effective result, use ginger root in conjunction with herbal cures like garlic clove.
It increases the immunity health of body naturally. Today, garlic clove can be simply acquired from market by means of capsules, extracts and powder. Adding two garlic clove cloves in diet can boost the functioning of white-colored bloodstream cells securely not to mention. Today, there are lots of herbal items available on the web to help you in dealing with low immunity health.
Which herbal cure is the greatest to deal with low immunity troubles? This can be a common query been told by people. Imutol capsule is among the best suggested herbal cures to deal with this ailment. You can use Imutol capsule to deal with many health disorders like cold, cough and fever. It assures guaranteed safety for individuals under all age ranges. For effective result, make use of this herbal cure two times or 3 times each day.


Much of this paper is taken up with a consideration of osteopontin in macular degeneration, but the authors also note that ostopontin levels in blood plasma are higher in older individuals. This may be connected to increased production in the vasculature, associated with rising levels of chronic inflammation in later life. Past work has also shown that osteopontin levels decline in bone marrow tissue with age, and that this is connected to the dysfunction of the hematopoietic system responsible for generating immune cells. Nothing is simple in the biochemistry of aging.
A common clinical phenotype of several neurodegenerative and systemic disorders including Alzheimer's disease and atherosclerosis is the abnormal accumulation of extracellular material, which interferes with routine cellular functions. Similarly, patients with age-related macular degeneration (AMD), the leading cause of vision loss among the aged population, present with extracellular lipid- and protein-filled basal deposits in the back of the eye. While the exact mechanism of growth and formation of these deposits is poorly understood, much has been learned from investigating their composition, providing critical insights into AMD pathogenesis, prevention, and therapeutics.
We identified human osteopontin (OPN), a phosphoprotein expressed in a variety of tissues in the body, as a newly discovered component of basal deposits in AMD patients, with a distinctive punctate staining pattern. OPN expression within these lesions, which are associated with AMD disease progression, were found to co-localize with abnormal calcium deposition. Mechanistically, we found that retinal pigment epithelial cells, cells vulnerable in AMD, will secrete OPN into the extracellular space, under oxidative stress conditions, supporting OPN biosynthesis locally within the outer retina.
Finally, we report that OPN levels in plasma of aged (non-AMD) human donors were significantly higher than levels in young (non-AMD) donors, but were not significantly different from donors with the different clinical subtypes of AMD. Collectively, our study defines the expression pattern of OPN as a function of disease, and its local expression as a potential histopathologic biomarker of AMD.


This Commonly Eaten Food Can Fight Mercury Poisoning
Past News ReleasesRSS
Boston, MA (PRWEB) December 06, 2012
Doctors Health Press, a division of Lombardi Publishing Corporation, and publisher of various natural health newsletters, books, and reports, including the popular online Doctors Health Press e-Bulletin, is reporting on a new study out of Canada that has found that eating tomatoes can stave off mercury poisoning.
As Doctors Health Press e-Bulletin (http://www.doctorshealthpress.com/food-and-nutrition-articles/this-commonly-eaten-food-can-fight-mercury-poisoning) notes, mercury is even more toxic than lead. It is immune to the body’s defenses, allowing mercury to travel straight to the brain. There, it lodges itself in the pain center of the brain, and moves out into the nervous system. Mercury then prevents nutrients from entering the cells, and inhibits the removal of wastes.
As the article “This Commonly Eaten Food Can Fight Mercury Poisoning” states, even having a little mercury in the body can make an individual sick. Unfortunately, mercury is in our water and soil, which means it’s also in our food, making it hard for anyone to avoid mercury in their diet. So, though common, mercury ingestion can lead to conditions like arthritis, depression, fatigue, and muscle weakness.
The Doctors Health Press e-Bulletin article reports that researchers at the Universite Laval in Canada examined the effect of the consumption of tomatoes and tomato products on blood mercury levels in Inuit preschool children. A sample of 155 Inuit children was recruited from 2006 to 2008 in Nunavik childcare centers in northern Quebec. Food frequency questionnaires were completed at home and at the childcare center, and total blood mercury concentration was measured by the research team.
As the article outlines, these children regularly eat seal meat, fish, and other foods from lakes and rivers contaminated with mercury, so their exposure levels are quite high. The researchers found that every time one of the children ate something with tomato in it, there was a 4.6% drop in blood mercury levels. This suggests that tomatoes neutralize mercury.
The article concludes that one of the best ways to avoid the build-up of mercury in one’s brain and nervous system is to eat more tomatoes, tomato sauce, salsa, or any other tomato-based product.
(SOURCE: Gagne, D., et al., “Consumption of tomato products is associated with lower blood mercury levels in Inuit preschool children,” Food and Chemical Toxicology, November 2, 2012; pii: S0278-6915(12): 00776–4.)
Doctors Health Press e-Bulletin is a daily e-letter providing natural health news with a focus on natural healing through foods, herbs, and other breakthrough health alternative treatments. For more information on Doctors Health Press, visit http://www.doctorshealthpress.com.
Doctors Health Press believes in the healing properties of various alternative remedies, including Traditional Chinese Medicine. To see a video outlining the Doctors Health Press’ views on Traditional Chinese Medicine, visit http://www.doctorshealthpress.com/chinesemedicine.


“My hormones are off.”
Probably more than 50% of my intake forms for new female patients have this kind of sentence written in the “Reason for Appointment” section. There are a wide variety of hormonal problems that women experience and aside from PMS, Polycystic Ovarian Syndrome (PCOS) is one of the most common.
What is PCOS actually?
Polycystic Ovarian Syndrome (PCOS) is an inadequately named condition that affects much more than just a woman’s ovaries. Women with PCOS can experience a wide variety of symptoms including those of having high testosterone such as hair growth in abnormal places and acne, symptoms of insulin resistance such as weight gain and high blood sugar and, of course, menstrual irregularities. It is very important to understand the whole-body effects of PCOS because, without appropriate treatment, it can put a person at higher risk of developing Type 2 Diabetes, cardiovascular disease and endometrial cancer. While all of these issues can cause distress, menstrual problems leading to difficulties getting pregnant is likely to be the most upsetting for women wanting to start a family. 1
Why is it so hard to get pregnant with PCOS?
Simply put, the reason some women with PCOS can’t get pregnant is because they don’t ovulate. Often we see high levels of luteinizing hormone (LH), which in normal amounts causes the ovary to produce testosterone and releases the mature egg during ovulation. There are also lower levels of follicle stimulating hormone (FSH), which in normal amounts converts testosterone to estrogen and causes eggs in the ovary to mature prior to ovulation. This means that when the time comes for ovulation, there is no mature egg to release. I also mentioned insulin resistance above. Insulin acts in the ovaries to increase the action of LH and having high levels of insulin is probably another main cause of keeping eggs from maturing completely. So, no ovulation, no mature egg for the sperm to fertilize, and no pregnancy. 2
So, is it still possible to get pregnant with PCOS?
YES! Working with a doctor who understands the complex metabolic and hormonal effects of PCOS is important especially because many of the symptoms associated with PCOS can be minimized or even reversed with diet and exercise.
Conventional medicine uses two main medications to help induce ovulation:
- Metformin is used to normalize insulin-resistance and may reduce risk of miscarriage early in pregnancy.
- Clomiphene (clomid) makes the ovary produce more mature eggs. 3
Naturopathic medicine encourages the body to start ovulating on its own by regulating the hormonal imbalances with:
- Blood sugar regulation and insulin sensitization through diet and exercise and natural products
- Encouraging a balanced ratio of testosterone, estrogen and progesterone in order to ovulate
- Improving egg health and quality
- Addressing emotional health and stress 4
Small changes with a big impact.
By using one or a combination of both of the above approaches, studies have shown a significant increase in pregnancy rate for women with PCOS. Diet and exercise are essential to successful treatment for both pregnancy and long-term outcomes as they can decrease, or even reverse, insulin resistance and development of Type 2 Diabetes and cardiovascular disease. Weight loss alone has been shown to be very effective. For example, in one study, a weight loss of 7% of body weight was associated with 63% of participants regaining their menstrual cycle after 3 months. 5
Some natural products that may also be recommended include myoinositol, cinnamon, flaxseed, Gymnema sylvestre, Black Cohosh and n-acetyl cysteine among others. Click on the hyperlinks to read more information about these individual herbs and nutrients. Some of these therapies may take time (several months to a year) for hormones to balance and to improve egg quality (an egg takes 3 months to mature before ovulation), but overall health improvement will likely be experienced very quickly. 6
Emotional stress is also just as important to address as physical health since stress is directly related to ovulation, insulin sensitivity and weight gain.
Lastly, adopting new habits for the purpose of a successful pregnancy will also help you raise healthy kids who start off life with healthy habits and grow up to healthy adults who produce healthy kids. Like the butterfly effect, your healthy habits will ripple through all your generations to come.
For more information on a naturopathic approach to PCOS you may want to check out Dr. Tori Hudson’s Polycystic Ovarian Syndrome overview.
- (J Obstet Gynaecol Can. 2010 May;32(5):423-5, 426-8; Nat Rev Endocrinol. 2011 Apr;7(4):219-31; N Engl J Med. 2005 Mar 24;352(12):1223-36.)
- (Endocrinol Metab Clin North Am. 1999 Jun;28(2):361-78; Am Fam Physician. 2000 Sep 1;62(5):1079-1088)
- (Hum Reprod. 2002 Nov;17(11):2858-64; Diabetes Care June 2013 vol. 36 no. 6 1477-1482; J Hum Reprod Sci. 2009 Jan-Jun; 2(1): 18–22)
- (J Acad Nutr Diet. 2013 Apr;113(4):520-45, Gynecol Endocrinol. 2015 Feb;31(2):131-5, Iran J Reprod Med. 2013 Aug;11(8):611-8, m J Obstet Gynecol. 2011 Apr;204(4):352.e1-6, Gynecol Endocrinol. 2015 Aug 4:1-4, N Am J Med Sci. 2015 Jul;7(7):310-6)
- (N Am J Med Sci. 2015 Jul;7(7):310-6).
- (Eur J Obstet Gynecol Reprod Biol. May 2013;168(1):60-63, Diabetes Care. 2003;26:3215-3218., Gynecological Endrocrinology 2014; 30(3): 205-208, European Journal of Obstetrics and Gynecology and Reproductive Biology. 2011;159:127-131


Medical Work in Hospital among Minority People Groups
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Have you ever thought of spending your medical career in God's work? Medical work is part of our holistic strategy to meet human need along with evangelistic outreach to spiritual need. Adequate medical coverage is vital for both patient care and for the hospital's ongoing development.


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Hi friends! Happy Hump Day! I hope your week has been stress free and wonderful thus far!
You probably read that with a humorous chuckle I would guess. Some of you are even wondering if there is such thing as a stress free day anymore.
During my nutrition undergraduate and dietetic internship, there were many days that I didn’t know if I could survive the stress of one more day. One more test, one more project, one more meeting, one more presentation, one more day of marathon training, one more anything and I would collapse. There were many nights that I remember getting 2-3 hours of sleep and then waking up to do it all over again. And if I haven’t told you before, I need my sleep. We all do. My stress during that time and your stress today might look completely different, but none the less, a large amount of stress effects us in a negative way. While too little stress can be a bad thing too (maybe you are not challenging yourself enough), too much stress can wreck havoc on your immune system and is linked to several different illnesses and diseases such as heart disease, cancer, arthritis, respiratory issues, depression, and on and on.
Thankfully, I am currently at a place in my life where I have learned how to better my manage stress. Just because my schooling and internship are complete doesn’t mean that stress is gone too. Now it’s just a different kind of stress and I have to incorporate stress management tricks to properly manage it.
Checklists, to-do lists, organization folders, envelopes and binders, exercise and a healthy diet are all crucial for me to limit my stress. Today I want to share with you my healthy-eating, stress management principles in hopes that you too can incorporate them into your day and help minimize the stress in your life.
- It is especially important to eat a healthy, balanced diet during times of stress. While it might be be easy, tempting and convenient to reach for candy, crackers or chips. That will only lead to more stress. Choose fresh fruits and vegetables, whole grains, lean proteins and healthy fats.
- Sit down while eating your meals. Avoid eating breakfast in the car, lunch at your desk or dinner standing in the kitchen. Make time for eating, after all it’s pretty important. Time can be an issue for all of us, but make time to enjoy your meals, feeling satisfied at the end of each meal. This will also be a prefect time to calm your mind down, take a deep breath and refocus.
- Avoid skipping meals. This will prevent your body from feeling starving, leading to over-eating when you do eat, as well as help your keep you blood sugar balanced throughout the day too, avoiding the highs and lows. You think more clearly with a balanced blood sugar too!
- Pack healthy snacks to prevent an afternoon crash. Apple slices, carrot sticks, rice crackers, hummus, walnuts, peanut butter, etc. Doing anything while hungry isn’t fun, especially fighting through a stressful afternoon.
- Drink plenty of water throughout the day. This will keep you hydrated, help remove toxins, and aid in digestion, all important factors when dealing with stress.
How do you manage stress? As you can see, I put a lot into managing my own stress and good nutrition is one of my key factors.
Half way through the week! I hope you have a great evening!


(RxWiki News) Before reaching for the medicine cabinet, consider cleaning up your diet — it may save your life.
A new study found that falls in blood pressure and total cholesterol levels dramatically reduced the risk of heart disease in British adults. Dietary and lifestyle changes caused most of the reduction in risk factors, the authors of this study said.
"Our results strengthen the case for greater emphasis on preventive approaches, particularly population-based policies to reduce blood pressure and cholesterol," wrote lead study author Maria Guzman-Castillo, MD, of the University of Liverpool, and colleagues. "Such strategies might be more powerful, rapid, cost-effective and equitable than additional preventive medications."
Sarah Samaan, MD, a cardiologist at the Baylor Heart Hospital in Plano, TX, said lifestyle choices play a major role in warding off heart disease.
"Although medications are a critical aspect of heart disease prevention, it is well established that as much as 75 percent of cardiovascular disease can be directly traced to lifestyle," Dr. Samaan told dailyRx News. "Exercising at least 2.5 hours per week, choosing a [healthy] diet, avoiding tobacco and maintaining a healthy body weight are key."
Dr. Guzman-Castillo and team reviewed data from British surveys to find the number of heart disease-related deaths postponed or prevented nationwide between 2000 and 2007.
The total number of deaths from coronary heart disease fell by 38,000 over that period of time, this research showed. Of those, more than 20,000 lives were saved due to drops in blood pressure and cholesterol, according to this study.
Coronary heart disease is a narrowing of the blood vessels that supply blood and oxygen to the heart. In the US, it is the most common cause of death for both men and women, according to the National Institutes of Health.
The decrease in blood pressure prevented more than half of heart disease-related deaths, Dr. Guzman-Castillo and team found. While blood pressure medication helped, most of the reduction came from lifestyle changes, these researchers said.
Drops in cholesterol also saved more than 7,000 lives, Dr. Guzman-Castillo and team found. These drops were mostly due to medications, however.
Public health initiatives to reduce salt and fat in processed foods may be more effective than prescribing medications, Dr. Guzman-Castillo and team said.
"In the U.S., food manufacturers and restaurant chains have been asked to voluntarily reduce the amount of salt in their products, but most have been slow to do so," Dr. Samaan said. "Training your taste buds to appreciate a lower level of sodium is very doable, but it is much harder when the food you choose is already loaded with salt. Making a commitment to fresher, unprocessed foods is a great way to clean up your diet and improve your health."
This study was published Jan. 22 in the journal BMJ Open.
The NIHR School of Public Health Research and the Liverpool PCT FSF funded this research. The authors disclosed no conflicts of interest.