Treatment rates and healthcare costs of patients with fragility fracture by site of care: a real-world data analysis.

In a characterization of treatment rates and healthcare costs among patients with an osteoporotic-related fragility fracture overall and by site of care, costs were high and treatment rates were low. PURPOSE: Osteoporotic fractures can be debilitating, even fatal, among older adults. The cost of osteoporosis and related fractures is projected to increase to more than $25 billion by 2025. The objective of this analysis is to characterize disease-related treatment rates and healthcare costs of patients with an osteoporotic fragility fracture overall and by site of fracture diagnosis. METHODS: In this retrospective analysis, individuals with fragility fractures were identified in the Merative MarketScan® Commercial and Medicare Databases among women 50 years of age or older and diagnosed with fragility fracture between 1/1/2013 and 6/30/2018 (earliest fracture diagnosis = index). Cohorts were categorized by clinical site of care where the diagnosis of fragility fracture was made and were continuously followed for 12 months prior to and following index. Sites of care were inpatient admission, outpatient office, outpatient hospital, emergency room hospital, and urgent care. RESULTS: Of the 108,965 eligible patients with fragility fracture (mean age 68.8), most were diagnosed during an inpatient admission or outpatient office visit (42.7%, 31.9%). The mean annual healthcare costs among patients with fragility fracture were $44,311 (± $67,427) and were highest for those diagnosed in an inpatient setting ($71,561 ± $84,072). Compared with other sites of care at fracture diagnosis, patients diagnosed during an inpatient admission also had highest proportion of subsequent fractures (33.2%), osteoporosis diagnosis (27.7%), and osteoporosis therapy (17.2%) during follow-up. CONCLUSION: The site of care for diagnosis of fragility fracture affects treatment rates and healthcare costs. Further studies are needed to determine how attitude or knowledge about osteoporosis treatment or healthcare experiences differ at various clinical sites of care in the medical management of osteoporosis.

Hormone therapy for postmenopausal osteoporosis management.

Menopausal hormone therapy (MHT) has been used for prevention and treatment of postmenopausal osteoporosis for several decades. However, public concerns were raised over the safety of MHT after the initial report was published in 2002 by the Women's Health Initiative. We conducted a historical review on this subject, primarily focusing on level I evidence from randomized controlled trials, systematic reviews and meta-analyses, and summarized high-quality evidence on the efficacy and safety of MHT in management of postmenopausal osteoporosis. Clinical issues were also discussed on MHT initiation, identification of treatment candidates and treatment duration, as well as discontinuation of MHT.

Uterine bleeding with hormone therapies in menopausal women: a systematic review.

Uterine bleeding is a common reason why women discontinue menopausal hormone therapy (HT). This systematic review compared bleeding profiles reported in studies for continuous-combined HT approved in North America and Europe for moderate to severe vasomotor symptoms in postmenopausal women with a uterus. Non-head-to-head studies showed that uterine bleeding varies by formulation and administration route, with oral having a better bleeding profile than transdermal formulations. Cumulative amenorrhea over a year ranged from 18 to 61% with oral HT and from 9 to 27% with transdermal HT, as reported for continuous-combined HT containing 17ß-estradiol (E2)/progesterone (P4) (56%), E2/norethisterone acetate (NETA) (49%), E2/drospirenone (45%), conjugated equine estrogens/medroxyprogesterone acetate (18-54%), ethinyl estradiol/NETA (31-61%), E2/levonorgestrel patch (16%), and E2/NETA patch (9-27%). Amenorrhea rates and the mean number of bleeding/spotting days improved over time. The oral E2/P4 combination was amongst those with lower bleeding rates and may be an appropriate alternative for millions of women seeking bioidentical HT and/or those who have bleeding concerns with other HT.

TX-004HR clinically improves symptoms of vulvar and vaginal atrophy in postmenopausal women.

Objective: This study aimed to evaluate improvement of dyspareunia and associated vaginal dryness with a 17ß-estradiol softgel vaginal insert (TX-004HR; TherapeuticsMD, Boca Raton, FL, USA) in women with postmenopausal vulvar and vaginal atrophy (VVA). Methods: Postmenopausal women with VVA and moderate to severe dyspareunia received TX-004HR (4, 10, or 25 µg) or placebo in the 12-week, randomized, double-blind, placebo-controlled, phase 3 REJOICE trial. Post hoc analyses examined improvement levels in dyspareunia and concurrent vaginal dryness with TX-004HR and assessed the effects of patient characteristics on vaginal dryness treatment. Results: Significantly more women treated with TX-004HR (all doses) than placebo had complete resolution or substantial improvement in dyspareunia or vaginal dryness (concurrent with dyspareunia) by 12 weeks, observed as early as week 2 with most doses. TX-004HR significantly improved both dyspareunia and vaginal dryness at least one level versus placebo by week 12 in women with both symptoms. Subgroup analyses showed TX-004HR improved vaginal dryness associated with dyspareunia regardless of age, body mass index, uterine status, prior pregnancy, and vaginal birth number. Conclusion: TX-004HR provided clinically meaningful improvements in dyspareunia and vaginal dryness associated with dyspareunia in postmenopausal women with VVA. Clinicians may be able to use this information when discussing patients' expectations regarding symptom improvement with the estradiol vaginal insert.

Treatment of moderate to severe dyspareunia with intravaginal prasterone therapy: a review.

The loss of sex steroids (e.g. estradiol, dehydroepiandrosterone [DHEA], progesterone) that causes menopause commonly affects a woman's general health and produces bothersome physical changes that may interfere with normal sexual and genitourinary functioning. Although both over-the-counter and prescription treatments are available, there remains a large unmet need, as less than 10% of women are treated. Adrenal DHEA and its sulfate are the most abundant steroids in humans. Here we review the development of intravaginal prasterone, the synthetic equivalent to endogenous DHEA. Prasterone is approved by the US Food and Drug Administration for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause. Prasterone has been shown to decrease the pain associated with dyspareunia, and to improve vaginal pH, as well as superficial and parabasal cell counts, while maintaining serum hormone levels within the range of those seen in normal postmenopausal women. Unlike other menopausal prescription therapies, intravaginal prasterone does not carry a boxed warning, thus allowing the clinician and patient to engage in meaningful and reassuring discussion around a new approach that treats this common, debilitating condition.

Estrogen therapy for osteoporosis in the modern era.

Menopause predisposes women to osteoporosis due to declining estrogen levels. This results in a decrease in bone mineral density (BMD) and an increase in fractures. Osteoporotic fractures lead to substantial morbidity and mortality, and are considered one of the largest public health priorities by the World Health Organization (WHO). It is therefore essential for menopausal women to receive appropriate guidance for the prevention and management of osteoporosis. The Women's Health Initiative (WHI) randomized controlled trial first proved hormonal therapy (HT) reduces the incidence of all osteoporosis-related fractures in postmenopausal women. However, the study concluded that the adverse effects outweighed the potential benefits on bone, leading to a significant decrease in HT use for menopausal symptoms. Additionally, HT was not used as first-line therapy for osteoporosis and fractures. Subsequent studies have challenged these initial conclusions and have shown significant efficacy of HT in various doses, durations, regimens, and routes of administration. These studies support that HT improves BMD and reduces fracture risk in women with and without osteoporosis. Furthermore, the studies suggest that low-dose and transdermal HT are less likely associated with the adverse effects of breast cancer, endometrial hyperplasia, coronary artery disease (CAD), and venous thromboembolism (VTE) previously observed in standard-dose oral HT regimens. Given the need for estrogen in menopausal women and evidence supporting the cost effectiveness, safety, and efficacy of HT, we propose that HT should be considered for the primary prevention and treatment of osteoporosis in appropriate candidates. HT should be individualized and the once "lowest dose for shortest period of time" concept should no longer be used. This review will focus on the prior and current studies for various HT formulations used for the prevention and treatment of osteoporosis, exploring the safety profile of low-dose and transdermal HT that have been shown to be safer than oral standard-dose HT.

Electrocution of Raptors on Power Lines: A Review of Necropsy Methods and Findings.

Decades after the problem was first identified, power line electrocution continues to be a cause of avian mortality. Currently, several federal laws protect eagles and other migratory birds, meaning that utility companies may be liable for electrocution-related deaths. Veterinarians and veterinary pathologists called upon to diagnose and treat electrocuted birds should keep this in mind when conducting clinical and postmortem examinations. This review details necropsy findings and methods used to diagnose electrocution. A combination of gross, subgross, and radiographic examinations can aid in identification of subtle injury. Diagnosis is made based on the presence of skin and/or feather burns. Other necropsy findings may include skin lacerations, subcutaneous burns, bruising, limb avulsion, hemopericardium, and vascular rupture. At the US Fish and Wildlife Service's National Forensics Laboratory, from 2000 to 2015, 417 raptor deaths were determined to have been caused by electrocution. Bald eagles and golden eagles were the most commonly submitted species. In a retrospective review of 377 cases, for which whole bodies were submitted, 18% of the electrocuted birds had only a single, small (less than 3 cm in diameter) external burn. Small, isolated burns tended to occur on the undersides of the wings at and distal to the elbow and on the lower legs and feet. These areas should be most carefully examined in cases where electrocution injury is not immediately apparent.

Hypothalamic and basal ganglia projections to the posterior thalamus: possible role in modulation of migraine headache and photophobia.

Migraine attacks are typically described as unilateral, throbbing pain that is usually accompanied by nausea, vomiting, and exaggerated sensitivities to light, noise and smell. The headache phase of a migraine attack is mediated by activation of the trigeminovascular pathway; a nociceptive pathway that originates in the meninges and carries pain signals through meningeal nociceptors to the spinal trigeminal nucleus and from there to the cortex through relay neurons in the thalamus. Recent studies in our lab have identified a population of trigeminovascular neurons in the posterior (Po) and lateral posterior (LP) thalamic nuclei that may be involved in the perception of whole-body allodynia (abnormal skin sensitivity) and photophobia (abnormal sensitivity to light) during migraine. The purpose of the current study was to identify sub-cortical areas that are in position to directly regulate the activity of these thalamic trigeminovascular neurons. Such process begins with anatomical mapping of neuronal projections to the posterior thalamus of the rat by performing discrete injections of the retrograde tracer Fluorogold into the Po/LP region. Such injections yielded retrogradely labeled neurons in the nucleus of the diagonal band of Broca, the dopaminergic cells group A11/A13, the ventromedial and ventral tuberomammillary nuclei of the hypothalamus. We also found that some of these neurons contain acetylcholine, dopamine, cholecystokinin and histamine, respectively. Accordingly, we speculate that these forebrain/hypothalamic projections to Po and LP may play a role in those migraine attacks triggered by disrupted sleep, skipping meals and emotional reactions.

Osteoporosis management in post-menopausal women.

Osteoporosis is most prevalent in women over the age of 50 as the hormonal influence of estrogen on bone health dissipates with the onset of menopause. The progressive changes in bone structure, quality and density lead to pathological fractures and an increase in morbidity and mortality among menopausal women. This review will examine the 2010 North American Menopause Society (NAMS) position statement and other recent publications to summarize the data and combinations of therapies used to treat women 50 years or older with osteoporosis. To review the latest research and guidelines for osteoporosis management we performed a PubMed search using the parameters Linked to free full text, Humans, Female, Review, English, Middle Age (45-64 years and 45+ years), Age 65+ years, and published in the last five years. Articles were sorted by relevance and hand searching of these articles was done to further increase the yield. While a perfect treatment has yet to be discovered to completely cure this progressive disease, many breakthroughs have been made in order to prevent fractures and improve quality of life. Calcium and vitamin D supplementation are recommended for patients undergoing pharmacological treatment, however, trials looking at their effectiveness have mixed findings. Bisphosphonates are considered the first line therapy in the treatment of osteoporosis and reduce vertebral fractures by 40% to 70% and non-vertebral fractures by 20% to 35%. Calcitonin showed promise during early trials in 2000 with a 33% reduction in fractures but these results have not been replicated and this therapy is now relegated to a second line treatment. Teriparatide is recommended for patients with severe osteoporosis and has been shown to reduce vertebral fractures 65% and non-vertebral fractures 53%. Selective estrogen receptor modulators (SERMs) are another useful therapy resulting in a 55% reduction in vertebral fractures without any documented advantage when looking at non-vertebral fractures. The currently available SERMs for this indication include raloxifene, available in the USA, and bazedoxifene, in Europe. Estrogen is effective, with a 27% reduction in fractures, but often is reserved for concomitant use for other menopausal symptoms or in patients intolerant of other available osteoporosis therapies. The newly approved monoclonal antibody for osteoporosis treatment in postmenopausal women, denosumab, leads to a 68% and 19% reduction of vertebral and non-vertebral fractures, respectively. In conclusion, the 2010 NAMS position statement provides an excellent framework to discuss treatment options with patients. Lifestyle optimization should be the bedrock of any good treatment approach. When pharmacological intervention is warranted, many good therapies are available which have been shown to reduce the risk of fractures in osteoporotic patients. Any treatment plan, however, will be ineffective if the patient is not compliant. Therefore, a detailed discussion regarding each therapeutic intervention should ensue, including its usefulness and side effects.

Neuronal embryonal tumors in fish.

This article describes 11 cases of neuronal embryonal neoplasia in captive adult teleost fish. Neoplasms were located within 1 or both eyes of 8 fish and the skin of 3 other fish. Ocular neoplasms most often presented as unilateral or bilateral exophthalmia. Seven ocular and 1 cutaneous mass were composed of small triangular (carrot-shaped) neoplastic cells with Flexner-Wintersteiner-type rosette formation. Mass location and histologic and ultrastructural features were suggestive of retinoblastomas. One ocular mass was composed of ribbons and rosettes of neoplastic cells with multiple areas of neuronal differentiation and was diagnosed as a teratoid medulloepithelioma. A cutaneous mass from an electric eel (Electrophorus electricus) consisted of rosettes and streams of elongate neoplastic cells. The epidermal electroreceptor (ampullary) organ was considered as an origin. Although distant metastases were not observed, neoplasms were generally locally aggressive with postexcision recurrence. There was occasional spread to or de novo occurrence within the contralateral eye.

Morphologic evidence suggestive of hypertension in western gray kangaroos (Macropus fuliginosus).

Marked renal vascular changes, suggestive of hypertension, were present in adult western gray kangaroos (Macropus fuliginosus) from a single facility over a 14-year period. A subset of these kangaroos also had vague clinical nervous system deficits, including blindness. To characterize the vascular lesions, determine prevalence, and document other changes, case histories and archival tissue sections from 21 adult kangaroos (8 male, 13 female) that died or were euthanatized between 1994 and 2008 were reviewed. Relevant lesions included increased thickness of the renal arteriolar tunica media with smooth muscle hypertrophy and/or hyperplasia, accumulation of extracellular matrix within arterioles, increased vascular tortuosity, and varying degrees of juxtaglomerular hyperplasia. Renal tissue from two more severely affected animals was further examined by transmission electron microscopy, highlighting arteriolar endothelial cell hypertrophy and disruption of the medial architecture. Hypertrophy of arteries and arterioles in other organ systems was also present (3/21), including vessels in the brain and spinal cord of one animal with clinical neurologic signs. Four kangaroos had antemortem retinal detachment, a potential sequel of hypertension in humans and domestic mammals. The cause of these vascular lesions in this mob is uncertain. Lesions were not associated with an infectious disease process, age, underlying renal disease, or thyroid abnormalities. In the absence of other causes, hypertension was a differential. Further investigation into clinical significance and predisposing factors, such as genetics and diet, is warranted.

Molecular basis of antagonism between K70E and K65R tenofovir-associated mutations in HIV-1 reverse transcriptase.

The K70E mutation in HIV-1 reverse transcriptase was observed in 10% of virologic non-responders of the abacavir/lamivudine/tenofovir arm of ESS30009, alone, or in mixtures with K65R by population sequencing. Clonal analysis of six ESS30009 K70E isolates failed to identify double mutants carrying K65R+K70E. Site-directed K70E mutants had a replication capacity of 97+/-29%, but only 2.4+/-0.9% for K65R+K70E and 0.01% for K65R+K70E+M184V mutants. K65R+K70E phenotypic fold changes for abacavir, lamivudine and tenofovir were comparable to reported values for K65R alone. In molecular dynamic simulations, the epsilon-amino group of K65 was positioned 2.7+/-0.1A from the gamma-phosphate of the dTTP ligand and stabilized the triphosphate. In the R65 mutant, this distance increased to 4.2+/-0.4A and the interaction energy with the ligand was less favorable, but the K70 epsilon-amino group was repositioned closer to the gamma-phosphate and had a more favorable interaction energy. In the double mutant, E70 could not stabilize the gamma-phosphate, resulting in a more severe defect. The net effect of the atomic-level changes in the double mutant may be to destabilize the pyrophosphate leaving group of the ligand, more severely affecting the catalytic rate of the polymerization reaction than the R65 single mutation.

Increasing prevalence of HIV-1 protease inhibitor-associated mutations correlates with long-term non-suppressive protease inhibitor treatment.

Treatment of human immunodeficiency virus type 1 with protease inhibitors (PIs) is associated with the emergence of resistance-associated mutations. Treatment-characterized datasets have been used to identify novel treatment-associated protease mutations. In this study, we utilized two large reference laboratory databases (>115,000 viral sequences) to identify non-established resistance-associated protease mutations. We found 20 non-established protease mutations occurring in 82% of viruses with a PI resistance score of 4-7, 62% of viruses with a resistance score of 1-3, and 35% of viruses with no predicted PI resistance. We correlated mutational prevalence to treatment duration in a treatment-characterized dataset of 2161 patients undergoing non-suppressive PI therapy. In the non-suppressed dataset, 24 mutations became more prevalent and three mutations became less prevalent after more than 48 months of non-suppressive PI-therapy. Longer durations of non-suppressive treatment correlated with higher PI resistance scores. Mutations at eight non-established positions that were more common in viruses with the longest duration of non-suppressive therapy were also more common in viruses with the highest PI resistance score. Covariation analysis of 3036 protease amino acid substitutions identified 75 positive and nine negative correlations between resistance associated positions. Our findings support the utility of reference laboratory datasets for surveillance of mutation prevalence and covariation.

Opsonization effects on Mycobacterium avium subsp. paratuberculosis--macrophage interactions.

High antibody titers in ruminants infected with Mycobacterium avium subsp. paratuberculosis correlates with disease progression. Effects of humoral responses during mycobacterial infection are not completely understood. This study suggests that activation status may be an important factor in determining macrophage ability to limit proliferation of opsonized M. avium subsp. paratuberculosis.

Serial measurements increase the accuracy of laser Doppler assessment of burn wounds.

Traditional methods of judging burn depth by clinical evaluation of the wound based on appearance and sensation remain in wide use but are subject to individual variation by examiner. In addition to the clinical difficulties with burn wound management, observer dependency of wound assessment complicates clinical trials of burn wound therapy. A laser Doppler flowmeter with a multichannel probe was used to measure burn wound perfusion as a tool to predict wound outcome. Serial measurement with laser Doppler flowmetry had an 88% specificity and a positive predictive value of 81% for identifying nonhealing wounds. These results suggest that laser Doppler flowmetry is a potentially useful tool for burn wound assessment.

Current management of purpura fulminans: a multicenter study.

Seven burn centers performed a 10-yr retrospective chart review of patients diagnosed with purpura fulminans. Patient demographics, etiology, presentation, medical and surgical treatment, and outcome were reviewed. A total of 70 patients were identified. Mean patient age was 13 yr. Neisseria meningitidis was the most common etiologic agent in infants and adolescents whereas Streptococcus commonly afflicted the adult population. Acute management consisted of antibiotic administration, volume resuscitation, ventilatory and inotropic support, with occasional use of corticosteroids (38%) and protein C replacement (9%). Full-thickness skin and soft-tissue necrosis was extensive, requiring skin grafting and amputations in 90% of the patients. One fourth of the patients required amputations of all extremities. Fasciotomies when performed early appeared to limit the level of amputation in 6 of 14 patients. Therefore, fasciotomies during the initial management of these patients may reduce the depth of soft-tissue involvement and the extent of amputations.

A multicenter review of toxic epidermal necrolysis treated in U.S. burn centers at the end of the twentieth century.

Toxic epidermal necrolysis (TEN) is a potentially fatal disorder that involves large areas of skin desquamation. Patients with TEN are often referred to burn centers for expert wound management and comprehensive care. The purpose of this study was to define the presenting characteristics and treatment of TEN before and after admission to regional burn centers and to evaluate the efficacy of burn center treatment for this disorder. A retrospective multicenter chart review was completed for patients admitted with TEN to 15 burn centers from 1995 to 2000. Charts were reviewed for patient characteristics, non-burn hospital and burn center treatment, and outcome. A total of 199 patients were admitted. Patients had a mean age of 47 years, mean 67.7% total body surface area skin slough, and mean Acute Physiology and Chronic Health Evaluation (APACHE II) score of 10. Sixty-four patients died, for a mortality rate of 32%. Mortality increased to 51% for patients transferred to a burn center more than one week after onset of disease. Burn centers and non-burn hospitals differed in their use of enteral nutrition (70 vs 12%, respectively, P < 0.05), prophylactic antibiotics (22 vs 37.9%, P < 0.05), corticosteroid use (22 vs 51%, P < 0.05), and wound management. Age, body surface area involvement, APACHE II score, complications, and parenteral nutrition before transfer correlated with increased mortality. The treatment of TEN differs markedly between burn centers and non-burn centers. Early transport to a burn unit is warranted to improve patient outcome.

Functional correlates of insertion mutations in the protease gene of human immunodeficiency virus type 1 isolates from patients.

Twenty-four of over 24,000 patients genotyped over the past 3 years were found to have human immunodeficiency virus (HIV) isolates that possess an insert in the protease gene. In this report, we evaluated the spectrum of protease gene insertion mutations in patient isolates and analyzed the effect of these various insertion mutations on viral phenotypes. The inserts were composed of 1, 2, 5, or 6 amino acids that mapped at or between codons 35 and 38, 17 and 18, 21 and 25, or 95 and 96. Reduced susceptibility to protease inhibitors was found in isolates which possess previously reported drug resistance mutations. Fitness assays, including replication and competition experiments, showed that most of the isolates with inserts grew somewhat better than their counterparts with a deletion of the insert. These experiments demonstrate that, rarely, insertion mutations can develop in the HIV type 1 protease gene, are no more resistant than any other sequences which have similar associated resistance mutations, and can provide a borderline advantage in replication.

Care of minor burn injuries: an analysis of burn clinic and emergency room charges.

Most burn injuries are minor in nature and can be managed on an outpatient basis. Such patients are usually evaluated and treated in emergency departments (ED) rather than in specialized outpatient burn care facilities. Although many burn centers maintain such facilities for the initial care of these patients, this practice is not commonplace because of conflicting interests of the ED and burn team. We first analyzed the hospital charges for all thermally injured patients admitted for a period of < or = 24 hours between April 1996 and August 1998. This was followed by an independent analysis of the hospital charges for all outpatient visits to the burn clinic and ED during calendar year 1998. Physician charges were not included in the second study. Patients admitted for < or = 24 hours had mean hospital charges of $1185 when initially evaluated in the ED compared with $691 if they were directly admitted to the burn unit (P < 0.001). This difference was largely because of higher charges for medication, laboratory, radiologic studies, and the ED visit charges. In the second study the mean charge for care administered in the ED was $192 compared with $139 for treatment in the outpatient burn clinic (P < 0.0001). Patients treated in the burn clinic had significantly lower radiology and treatment charges but significantly higher pharmacy charges than patients treated in the ED. These data have supported our efforts to develop a walk-in burn treatment center. Such a program should not only result in reduced charges for care, but also enhance patient access to the expertise of the multidisciplinary burn team and help ensure optimal outcomes.

Peanut challenge: a retrospective study of 140 patients.

BACKGROUND: Accurate diagnosis of peanut allergy is essential given that it is a lifelong and potentially fatal food allergy. Diagnosis relies on patient history, prick skin test (PST), and in many situations, food challenge. More information is required on the safety of food challenge and the informational value of a PST. OBJECTIVES: Primary: to assess the safety of peanut challenges. Secondary: to estimate the sensitivity, specificity, and the positive and negative predictive values of PST to peanut performed in those who underwent a peanut challenge. METHODS: A retrospective study of peanut challenges performed at a tertiary care paediatric hospital allergy clinic between January 1994 and November 1998. RESULTS: Of the 140 peanut challenges performed on 140 patients, 18 were positive. The most frequent adverse clinical effects of positive peanut challenges were: urticaria, oropharyngeal irritation, rhinitis, vomiting and abdominal pain. Among the 18 patients who had a positive result, 10 required medical treatment (antihistamines, +/- epinephrine, +/- salbutamol) to control the allergic reaction. The sensitivity, specificity, and the positive and negative predictive values of PST to peanut in this group of children undergoing a peanut challenge were 100%, 62.3%, 28.1% and 100%, respectively. CONCLUSIONS: Given the poor positive predictive value and specificity of PST, a peanut challenge is usually required to diagnose peanut allergy with certainty when the PST is positive. In cases of a clear history of anaphylaxis to peanut and a positive PST, challenges are unwarranted. When the history is strongly suggestive and the PST is borderline positive, i.e. 3 or 4 mm, peanut challenge is generally necessary to confirm the diagnosis. Given the excellent negative predictive value and sensitivity of PST, a blinded peanut challenge is usually unnecessary in the context of a negative PST except for patients with a history strongly suggestive of immediate hypersensitivity. These patients should be individually assessed for the need to undergo a blinded challenge. The peanut challenge is a useful and safe diagnostic tool when performed by qualified personnel under appropriate conditions.