Prodromal Pain Research Articles

Spontaneous Rupture of Extensor Pollicis Longus Tendon: Clinical and Occupational Implications, Treatment Approaches and Prognostic Outcome in Non-Rheumatoid Arthritis Patients: A Retrospective Study.

BackgroundSpontaneous rupture of extensor pollicis longus (EPL) tendon is a rare condition often found in patients actively having regular extensive use of hands and fingers especially the thumb. In this article, we report 7 cases of spontaneous rupture of EPL tendon and investigate the associated factors and treatment outcome.MethodsRetrospectively, the databases for the 7 cases were retrieved and studied. These cases represent all cases of spontaneous rupture of EPL in our institution. Demographic data, clinical presentation, any history of trauma or steroid injection, laboratory and clinical findings suggestive for rheumatoid arthritis, co-morbidities and imaging findings were obtained. In addition, the operative technique and findings were retrieved. Moreover, histopathological studies and follow-up assessment were included.ResultsSix males and one female were included. The mean age was 45.2 years. No prior history of trauma, rheumatological disease or steroid use was detected in any patient. All patients experienced prodromal pain in the radial side. Clinical examination was the most effective diagnostic measure. Magnetic resonance imaging (MRI) was used to confirm the diagnosis and to look for other abnormalities that may predispose to rupture. Five patients underwent extensor indicis proprius to EPL tendon transfer employing Pulvertaft weave technique and one patient underwent primary repair as there was a little gap in the tendon ends. In this study, one patient refused any treatment. All patients achieved a favorable outcome at the last follow-up.ConclusionDiagnosis of spontaneous ruptures of EPL tendon can be confirmed through clinical examination and MRI for patients with restricted thumb movement even with the absence of any identifiable predisposing risk factor. During surgery, detailed attention must be drawn towards the tendon ends which can have unusual gaps and bone abnormalities.

Study of cases of herpes zoster in tertiary care hospital

Background: Herpes Zoster (HZ) is a viral disease caused by reactivation of varicella zoster virus (VZV) characterised by distinctive prodromal pain followed by herpetiform vesicular eruptions. Immunocomprised state like elderly age, diabetes, HIV infection, immunosuppressive drugs are known predisposing factors. Objectives: The study was conducted to know the clinicoepidemiological profile of the cases of HZ attending to tertiary care centre. Materials and Methods: Clinical profile of patients with HZ was noted on predesigned proforma. Detailed investigation was performed and data was analysed by tabulation, mean, standard deviation on Statistical Package for the Social Sciences verion 20. Results: Total 190 cases of HZ were enrolled. There were 126 males and 64 females with sex ratio of 2:1. 59% had definite history of chicken pox. Eleven cases were HIV positive, 02 were diagnosed HIV infection while evaluating herpes zoster. 91% cases had prodrome before eruptions. Thoracic dermatome was most commonly involved followed by trigeminal. Post herpetic neuralgia (PHN) was present in 41 (27%) cases. Conclusion: Herpes zoster constituted 0.84% of total dermatology OPD in six months reflects sizable burden of herpes zoster in tertiary care centre. There was higher incidence of PHN (27%) on prolonged follow up, however, involvement of thoracic dermatome and association with diabetes mellitus is consistent with other studies.

Sensory neuropathy and nociception in rodent models of Parkinson's disease

ABSTRACTParkinson's disease (PD) often manifests with prodromal pain and sensory losses whose etiologies are not well understood. Multiple genetic and toxicity-based rodent models of PD partly recapitulate the histopathology and motor function deficits. Although far less studied, there is some evidence that rodents, similar to humans, develop sensory manifestations of the disease, which may precede motor disturbances and help to elucidate the underlying mechanisms of PD-associated pain at the molecular and neuron circuit levels. The present Review summarizes nociception and other sensory functions in frequently used rodent PD models within the context of the complex phenotypes. In terms of mechanisms, it appears that the acute loss of dopaminergic neurons in systemic toxicity models (MPTP, rotenone) primarily causes nociceptive hyperexcitability, presumably owing to a loss of inhibitory control, whereas genetic models primarily result in a progressive loss of heat perception, reflecting sensory fiber neuropathies. At the molecular level, neither α-synuclein deposits alone nor failure of mitophagy alone appear to be strong enough to result in axonal or synaptic pathology of nociceptive neurons that manifest at the behavioral level, and peripheral sensory loss may mask central ‘pain’ in behavioral tests. Hence, allostatic combinations or additional challenges and novel behavioral assessments are needed to better evaluate PD-associated sensory neuropathies and pain in rodents.

Prophylactic Fixation Can Be Cost-effective in Preventing a Contralateral Bisphosphonate-associated Femur Fracture.

Bisphosphonates reduce the risk of fractures associated with osteoporosis but increase the risk of atypical subtrochanteric femur fractures. After unilateral atypical femur fracture, there is risk of contralateral fracture, but the indications for prophylactic fixation are controversial. The purpose of this study is to use Markov modeling to determine whether contralateral prophylactic femur fracture fixation is cost-effective after a bisphosphonate-associated atypical femur fracture and, if so, what patient-related factors may influence that determination. Markov modeling was used to determine the cost-effectiveness of contralateral prophylactic fixation after an initial atypical femur fracture. Simulated patients aged 60 to 90 years were included and separated into standard and high fracture risk cohorts. Patients with standard fracture risk were defined as those presenting with one atypical femur fracture but without symptoms or findings in the contralateral femur, whereas patients with high fracture risk were typified as those with more than one risk factor, including Asian ethnicity, prodromal pain, femoral geometry changes, or radiographic findings in the contralateral femur. Outcome probabilities and utilities were derived from studies matching to patient characteristics, and fragility fracture literature was used when atypical femur fracture data were not available. Associated costs were largely derived from Medicare 2015 reimbursement rates. Sensitivity analysis was performed on all model parameters within defined ranges. Prophylactic fixation for a 70-year-old patient with standard risk for fracture costs USD 131,300/quality-adjusted life-year (QALY) and for high-risk patients costs USD 22,400/QALY. Sensitivity analysis revealed that prophylaxis for high-risk patients is cost-effective at USD 100,000/QALY when the cost of prophylaxis was less than USD 29,400, the probability of prophylaxis complications was less than 21%, or if the patient was younger than 89 years old. The parameters to which the model was most sensitive were the cost of prophylaxis, patient age, and probability of prophylaxis-related complications. Prophylactic fixation of the contralateral side after unilateral atypical femur fracture is not cost-effective for standard-risk patients but is cost-effective among high-risk patients between 60 and 89 years of age with a high risk for an atypical femur fracture defined by patients with more than one risk factor such as Asian ethnicity, prodromal pain, varus proximal femur geometry, femoral bowing, or radiographic changes such as periosteal beaking and a transverse radiolucent line. However, our findings are based on several key assumptions for modeling such as the probability of fractures and complications, the costs associated for each health state, and the risks of surgical treatment. Future research should prospectively evaluate the degree of risk contributed by known radiographic and demographic parameters to guide management of the contralateral femur after a patient presents with an atypical femur fracture. Level III, economic and decision analyses.

A novel nonlive, adjuvanted herpes zoster subunit vaccine: a report on the emerging clinical data and safety profile.

Herpes zoster (HZ) is an acute vesicular dermatitis with a typical dermatomal distribution, caused by the varicella zoster virus (VZV), often preceded and accompanied by prodromal pain or pruritus. HZ may be related to several complications such as postherpetic neuralgia (PHN). The incidence and severity of the disease increase with aging, due to immunosenescence and in particular to the decline of the specific cell-mediated immunity (CMI). The impact of HZ in terms of morbidity and short- and long-term complications, the availability of suboptimal treatment options to date, and the high costs for the diagnostic and clinical-therapeutic management of patients have motivated the search for a new preventive approach through the development of a vaccine. The vaccine currently in use with live-attenuated virus (ZVL) has been shown to be effective in reducing the incidence of HZ, its impact, and the onset of PHN, although the efficacy is lower in older subjects and tends to decrease some years after immunization. A new adjuvanted recombinant subunit vaccine (HZ/su), containing the VZV glycoprotein E (gE) and the AS01B adjuvant system, is now a very promising alternative to ZVL; in several clinical studies, it showed a good safety profile and was able to elicit high immune humoral and cell-mediated responses, both maintained up to 9 years. Furthermore, HZ/su vaccine was effective both in preventing HZ and in reducing the onset of PHN and other complications. HZ/su has been recommended and preferred over ZVL by the Advisory Committee on Immunization Practices (ACIP) for the prevention of HZ and its complications in immunocompetent adults aged ≥50 years, even if already vaccinated with ZVL, through a two-dose schedule. HZ/su has been approved in Canada, USA, Europe, and Japan and is currently being approved in Australia. The aim of this review was to describe the epidemiological data, HZ and PHN risks and their impact on the social life and common life of infected people, and ZVL and HZ/su vaccine development including various clinical trials and efficacy, safety, and tolerability profiles.

Varicella meningitis : An atypical presentation in an immunocompetent individual with seizures managed with acyclovir

Viral meningitis, also known as aseptic meningitis, is the most common cause of meningitis and is responsible for between 26,000 and 42,000 hospitalizations yearly in the United States. Bacterial meningitis affects about 4,000 people each year, while viral meningitis affects about 10 people in every 100,000. The most commonly identified pathogens are enterovirus, herpes simplex virus and human immunodeficiency virus. Varicella, rabies and influenza are other viruses that are rarely responsible for viral meningitis. Varicella Zoster is a relatively common disorder in immunocompromised patients characterized by radicular pain and grouped vesicular eruptions. The typical findings in reported cases of VZV meningitis involve skin manifestations and classical signs of meningitis such as neck stiffness. However, only a few cases of meningitis caused by Varicella Zoster Virus (VZV) have been reported. The incidence of VZV meningitis in immunocompetent patients has been reported to be as low as 0.5%. We report an atypical presentation of VZV meningitis in an immunocompetent patient with headache, dizziness, sequalae of seizures without fever and skin manifestations.Our patient is a 59‐year‐ old African American male who presented with worsening dizziness, confusion, ataxia, lethargy and left‐sided frontal headache. Magnetic resonance imaging revealed mild to moderate burden of white matter abnormality, nonspecific but most likely due to chronic microvascular ischemic disease. No acute stroke. The next day sedation was weaned off and patient remained seizure free on continuous EEG and was extubated 3 days later the CSF came back positive for an elevated Varicella PCR of 42016. Patient was seen by infectious diseases consultant and was advised a course of acyclovir 10mg/kg intravenous every 8 hours for 14 days. All other antibiotics were stopped. Upon discharge, the patient had fully recovered from his symptoms with no neurologic sequalae.This unique case illustrates an atypical presentation of VZV meningoencephalitis in an immunocompetent patient that lacks many of the obvious features that usually distinguish the disease. Our patient lacked the vesicular rash, as well as other typical features of aseptic meningitis including nuchal rigidity, headache, photophobia, etc. Additionally, the patient's course was complicated by seizure, another relatively uncommon feature of VZV meningoencephalitis. VZV infection or reactivation is, rightfully, most commonly associated with the vesicular rash and prodromal pain that usually accompanies it.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Surgical outcome of atypical subtrochanteric and femoral fracture related to bisphosphonates use in osteoporotic patients with or without teriparatide treatment

BackgroundAtypical subtrochanteric fracture and femoral fracture have been considered to be rare complications related to long-term bisphosphonates use. A reduced bone turnover rate may lead to delayed bone healing. Limited data have revealed that teriparatide treatment may reverse the effect of bisphosphonates and be effective in bone healing.MethodsWe reviewed patients with atypical subtrochanteric and femoral fracture related to bisphosphonates use between January 2008 and December 2014. Thirteen female patients were enrolled. Radiographic findings were compatible with the characteristics of atypical fracture. Surgical intervention was performed for all, and teriparatide use was advised postoperatively. Outcome measures included perioperative results, and clinical and radiographic outcome.ResultsOf the 13 female patients enrolled, 10 had subtrochanteric and 6 had proximal femoral fracture; 3 had bilateral fractures. The mean age of the patients at surgery was 70.15±6.36 years. Most fractures (68.8%) presented prodromal thigh pain. All patients were treated with an intramedullary fixation system without severe complications. The patients were divided into 2 groups based on whether they had received treatment with teriparatide or not. The mean time to bone union was 4.4 months in the teriparatide-treated group, and 6.2 months in the non-teriparatide-treated group (p=0.116). Six patients (75%) in the teriparatide-treated group and 4 (50%) in the non-teriparatide-treated group (p= 0.3) achieved bone union within 6 months. The means of the modified Harris Hip Score and Numerical Rating Scale were significantly better in the teriparatide-treated group at postoperative 6 months. Seven patients had the same ability to walk at the 1-year follow-up as they did before the atypical fracture.ConclusionsTeriparatide treatment in patients with atypical fracture may help in fracture healing, hip function recovery, and pain relief in this reduced bone turnover patient group.

Chiropractic care and risk for acute lumbar disc herniation: a population-based self-controlled case series study.

Chiropractic care is popular for low back pain, but may increase the risk for acute lumbar disc herniation (LDH). Low back pain is a common early (prodromal) symptom of LDH and commonly precedes LDH diagnosis. Our objective was to investigate the association between chiropractic care and acute LDH with early surgical intervention, and contrast this with the association between primary care physician (PCP) care and acute LDH with early surgery. Using a self-controlled case series design and population-based healthcare databases in Ontario, Canada, we investigated all adults with acute LDH requiring emergency department (ED) visit and early surgical intervention from April 1994 to December 2004. The relative incidence of acute LDH with early surgery in exposed periods after chiropractic visits relative to unexposed periods was estimated within individuals, and compared with the relative incidence of acute LDH with early surgery following PCP visits. 195 cases of acute LDH with early surgery (within 8weeks) were identified in a population of more than 100 million person-years. Strong positive associations were found between acute LDH and both chiropractic and PCP visits. The risk for acute LDH with early surgery associated with chiropractic visits was no higher than the risk associated with PCP visits. Both chiropractic and primary medical care were associated with an increased risk for acute LDH requiring ED visit and early surgery. Our analysis suggests that patients with prodromal back pain from a developing disc herniation likely seek healthcare from both chiropractors and PCPs before full clinical expression of acute LDH. We found no evidence of excess risk for acute LDH with early surgery associated with chiropractic compared with primary medical care.

High and pointed type of femoral localized reaction frequently extends to complete and incomplete atypical femoral fracture in patients with autoimmune diseases on long-term glucocorticoids and bisphosphonates.

Femoral localized reaction (localized periosteal thickening of the lateral cortex, beaking) is reported to precede atypical femoral fractures (AFFs) and to develop in 8-10% of patients with autoimmune diseases taking BPs and glucocorticoids. The aims of the present study were to retrospectively investigate the shapes of localized reaction to consider how to manage the condition. Twenty femora of 12 patients with autoimmune diseases who were on BPs and glucocorticoids exhibited femoral localized reaction. The heights of localized reaction were measured and the shapes classified as pointed, arched, and other. Localized reaction changes were divided into three categories: deterioration, no change, and improvement. A severe form of localized reaction was defined; this was associated with prodromal pain, de novo complete AFF, or incomplete AFF with a fracture line at the localized reaction. The mean height of localized reaction was 2.3±0.8mm (range, 1.0-3.7mm) and the pointed type was 35%. Localized reaction was significantly higher (3.3±0.8 vs. 2.1±0.7mm; p=0.003) and the pointed type more common (78 vs. 27%; p=0.035) in those with the severe form of localized reaction. Seven patients with localized reactions discontinued BPs just after localized reaction was detected, but five continued on BPs for 2years. Localized reaction deterioration was more common in patients who continued than discontinued BPs (100 vs. 29%; p=0.027). After 2years, all patients had discontinued BPs and localized reaction did not deteriorate further in any patient. Once a localized reaction was detected, discontinuation of BPs and switching to vitamin D supplementation or teriparatide therapy effectively improved it. When the localized reaction was high, of the pointed type, and/or accompanied by prodromal pain, the risks of complete and incomplete AFF increased and consideration of prophylactic fixation for such patients was required.

Atypical Femur Fractures and Cortical Thickening in Osteoporotic Patients Treated with Bisphosphonates

Background: Patients treated with bisphosphonates (BP) may present atypical femoral fractures (AFF) as a complication with an incidence of 3.2-50 cases per 10,000 person-years. The existence of cortical thickening is sometimes related to the appearance of atypical fracture. So, from the clinical point of view, in patients treated with bisphosphonates, the appearance of cortical thickening must suggest the change of treatment in order to avoid fractures. Case report: We present a case of atypical fracture, with bilateral cortical thickening as a predictor of atypical femur fracture, in a patient using BP for years. The main symptom developed by the patient through the years BP were taken was bilateral thigh pain. Conclusion: There is some evidence of a relationship between long-term BP and a specific type of femoral fracture with radiographic features (including cortical thickening) and some clinical features as prodromal pain. However, atypical fractures are uncommon, and with correct indication, the utility of antiresorptives are not discussed. Physicians and patients should know the possibility of AFF and the possible bilateral involvement of this rare complication, in order to assess the risk-benefit of continuing/withdrawing treatment with BPs.

Atypical Femoral Fracture

A 66-year-old woman with a 20 year treatment history of rheumatoid arthritis and systemic lupus erythematodes presented to our hospital because of right hip pain after falling. The plain radiograph showed substantial transverse subtrochanteric fracture with a medial spike (Figures 1A and 1B). She insisted that her right hip pain occurred suddenly during walking because of which she fell. It was not after but before falling that she felt an acute pain in her right hip. She had been receiving prednisolone for more than 20 years and bisphosphonate more than 8 years. Operative fixation of the fracture was performed. Her radiograph performed 5 years ago (Figure 2A) revealed the existence of a fracture line on the lateral cortex and its cortical thickness (Figure 2B). During the long-term treatment of bisphosphonate, prodromal hip pain and radiographic findings of an incomplete fracture line might predict a typical femoral fracture. atypical femoral fracture is a rare type of fracture that occurs in the regions between the subtrochanteric and supracondylar areas and initially involves the lateral femoral cortex. Physicians should perform vigilant monitoring of cortical insufficiency and atypical femur fractures in geriatric patients on long-term bisphosphonate treatment.

Simultaneous, bilateral, complete atypical femoral fractures after long-term alendronate use

Over the past decade there have been increasing reports of atypical femoral fractures (AFFs) associated with bisphosphonate use. Reported cases of bilateral involvement usually refer to sequential injuries, or a complete fracture with an incomplete injury to the contralateral limb. In this case report we describe simultaneous, bilateral, complete atypical femoral fractures following a simple fall. A history of prodromal pain, previous radiological evidence of cortical thickening and long term alendronate therapy for osteoporosis secondary to corticosteroid treatment paint a classical picture of the presentation of an atypical fracture pattern of which orthopaedic surgeons should be aware.

Caveats of bisphosphonate abuse.

Background:Bisphosphonates (BPs) are the common drugs used for the treatment of postmenopausal osteoporosis. Short term benefits of the BPs are well known. However, there are concerns regarding their long term use. The aim of the study was to analyze the association between atypical femoral fractures and BP misuse/abuse as well as study the outcome of management of these fractures.Materials and Methods:A retrospective study of a prospectively studied patients who presented with atypical femoral fractures between January 2010 and August 2012 and were followed up upto June 2014. The cohort consisted of nine female patients (12 fractures) with an average age of 71 years (range 58-85 years). Analysis was done for the indications, duration of BP use, configuration of associated fractures and method of treatment.Results:The mean duration of BP use was 6.6 years (range 4-10 years). BP treatment was initiated without sufficient indication and continued without proper review and followup in most cases. Most patients did not followup and continued to consume BPs without any review by the doctors. All patients had prodromal thigh pain of various duration, which was inadequately investigated and managed before the presentation. Two cases with an incomplete fracture and no thigh pain were managed successfully with conservative treatment. The rest were treated by surgery with intramedullary nailing. The average union time was longer and two fractures went into nonunion which required further surgical intervention.Conclusion:Atypical femoral fractures appear to be strongly related to abuse of BPs. Great care is to be exercised at initiation as well as the continuation of BP therapy, and regular review is required. There is a need for improved awareness among physicians about the possibility of such fractures, and interpretation of thigh pain and radiological findings, especially if the patient has been on BPs therapy. Internal fixation for complete fractures and for incomplete fractures with thigh pain is needed. Delayed union is common.

Atypical femur fracture in an adolescent boy treated with bisphosphonates for X-linked osteoporosis based on PLS3 mutation

Long-term use of bisphosphonates has raised concerns about the association with Atypical Femur Fractures (AFFs) that have been reported mainly in postmenopausal women. We report a case of an 18-year-old patient with juvenile osteoporosis based on X-linked osteoporosis due to a PLS3 mutation who developed a low trauma femoral fracture after seven years of intravenous and two years of oral bisphosphonate use, fulfilling the revised ASBMR diagnostic criteria of an AFF. The occurrence of AFFs has not been described previously in children or adolescents. The underlying monogenetic bone disease in our case strengthens the possibility of a genetic predisposition at least in some cases of AFF. We cannot exclude that a transverse fracture of the tibia that also occurred after a minor trauma at age 16 might be part of the same spectrum of atypical fractures related to the use of bisphosphonates. In retrospect our patient experienced prodromal pain prior to both the tibia and the femur fracture. Case reports of atypical fractures in children with a monogenetic bone disease such as Osteogenesis Imperfecta (OI) or juvenile osteoporosis are important to consider in the discussion about optimal duration of bisphosphonate therapy in growing children.In conclusion, this case report 1) highlights that AFFs also occur in adolescents treated with bisphosphonates during childhood and pain in weight-bearing bones can point towards this diagnosis 2) supports other reports suggesting that low trauma fractures of other long bones besides the femur may be related to long-term use of bisphosphonates 3) strengthens the concept of an underlying genetic predisposition in some cases of AFF, now for the first time reported in X-linked osteoporosis due to a mutation in PLS3 and 4) should be considered in decisions about the duration of bisphosphonate therapy in children with congenital bone disorders.

A Review of Atypical Femoral Fractures From a Tertiary Care Teaching Hospital: An Alarming Trend?

To evaluate the experience of a single tertiary care teaching hospital with the association between use of bisphosphonates and atypical femoral fractures, and to identify potential risk factors and chronologic incidence. Retrospective review. Tertiary-care teaching hospital. Thirty-two patients with a total of 43 fractures met inclusion criteria. Treatment for atypical femur fractures. Radiographic assessments, duration of bisphosphonate therapy, prodromal symptoms, associated medications/comorbidities. Thirty-one female patients and 1 male patient, with a total of 43 fractures, with an average age of 71.0 (47-92 years) ± 11.01 years at time of fracture, had an average duration of bisphosphonate therapy of 7.57 (1-12 years) ± 3.07 years. Prodromal thigh pain was reported in 20 of 43 fractures (46.5%). Eleven of the forty-three (25.5%) fractures occurred between 2001 and 2005. From 2006 to May 2011, however, 32/43 (74.5%) were reported. Beta-blockers, ACE/ARBs, and Statins (43.8%) were the most common concomitant medications, whereas Levothyroxine (21.8%), H-2 blockers (15.6%), and Glucocorticoids (12.5%) were less common. There is an increasing trend of atypical femur fractures in the current adult population. Bisphosphonate therapy beyond 7 years may place patients at increased risk. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Atypical femoral fracture in a 51-year-old woman: Revealing a hypophosphatasia

We report a 51-year old woman who suffered 2 atypical subtrochanteric femoral fractures (AFFs). She had a history of several metatarsal fractures. She had a normal bone densitometry. An adult form of hypophosphatasia (HPP) was diagnosed from low serum alkaline phosphatase (ALP), and tissue nonspecific isoenzyme of ALP (TNSALP) mutation analysis revealing 2 heterozygous mutations: c.299C>T (p. T100M) and c.571G>A (p. E191K). Low ALP is the hallmark of the diagnosis of HPP; which is associated in adults with premature loss of deciduous teeth, recurrent metatarsal stress fractures, and joints and tendons disorders. The incidence of AFFs in the population is 5.9 per 100,000 person-years. Physicians and patients with bone fragility must pay attention to prodromal pain, which require urgent radiographic evaluation of both femurs. Rheumatoid arthritis, use of glucocorticoids, and proton pump inhibitors have been associated with an excess risk of AFFs. Healthy subjects carrying a TNSALP mutation with low ALP value may be exposed to develop AFF spontaneously or while receiving potent anti-resorptive drugs. Low ALP must be checked as a cause of bone fragility.

Healing Time and Complications in Operatively Treated Atypical Femur Fractures Associated With Bisphosphonate Use: A Multicenter Retrospective Cohort.

The purpose of this study was to characterize demographics, healing time, and complications of a large series of operatively treated atypical femur fractures. Retrospective multicenter review. Seventeen academic medical centers. Bisphosphonate-related fractures as defined by American Society of Bone and Mineral Research. Fractures had to be followed for at least 6 months or to union or revision. Operative treatment of bisphosphonate-related fracture. Union time and complications of treatment, as well as information about the contralateral limb. There were 179 patients, average age 72, average body mass index 27.2. Average follow-up was 17 months. Twenty-one percent had a previous history of fragility fracture; 34% had prodromal pain. Most (88%) lived independently before injury. Thirty-one percent had radiographic changes suggesting stress reaction. Surgical fixation was with cephalomedullary nail (51%), IM nail (48%), or plate (1%). Complications included death (4), PE (3), and wound infection (6). Twenty (12%) patients underwent revision at an average of 11 months. Excluding revisions, average union time was 5.2 months. For revisions, union occurred at an average of 10.2 months after intervention. No association was identified between discontinuation of bisphosphonates and union time (P = 0.5) or need for revision (P = 0.7). Twenty-one percent sustained contralateral femur fractures; 32% of these had pain and 59% had stress reaction before contralateral fracture. In this series, surgery had a 12% failure rate and delayed average time to union. Twenty-one percent developed contralateral femur fractures within 2 years, underscoring the need to evaluate the contralateral extremity. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

A systematic review and meta-analysis of risk factors for postherpetic neuralgia.

Patients with herpes zoster can develop persistent pain after rash healing, a complication known as postherpetic neuralgia. By preventing zoster through vaccination, the risk of this common complication is reduced. We searched MEDLINE and Embase for studies assessing risk factors for postherpetic neuralgia, with a view to informing vaccination policy. Nineteen prospective studies were identified. Meta-analysis showed significant increases in the risk of postherpetic neuralgia with clinical features of acute zoster including prodromal pain (summary rate ratio 2.29, 95% confidence interval: 1.42-3.69), severe acute pain (2.23, 1.71-2.92), severe rash (2.63, 1.89-3.66), and ophthalmic involvement (2.51, 1.29-4.86). Older age was significantly associated with postherpetic neuralgia; for individual studies, relative risk estimates per 10-year increase ranged from 1.22 to 3.11. Evidence for differences by gender was conflicting, with considerable between-study heterogeneity. A proportion of studies reported an increased risk of postherpetic neuralgia with severe immunosuppression (studies, n = 3/5) and diabetes mellitus (n = 1/4). Systemic lupus erythematosus, recent trauma, and personality disorder symptoms were associated with postherpetic neuralgia in single studies. No evidence of higher postherpetic neuralgia risk was found with depression (n = 4) or cancer (n = 5). Our review confirms a number of clinical features of acute zoster are risk factors for postherpetic neuralgia. It has also identified a range of possible vaccine-targetable risk factors for postherpetic neuralgia; yet aside from age-associated risks, evidence regarding risk factors to inform zoster vaccination policy is currently limited.

Teriparatide for the rapid resolution of delayed healing of atypical fractures associated with long-term bisphosphonate use.

Bisphosphonates (BPs) are the most widely used drugs to treat osteoporosis. However, recent reports associated to long-term BPs use with atypical low-impact fractures and prodromal pain. It is estimated that 26% of the cases of atypical fractures associated with the long-term use of BPs show delayed healing or nonunion. Teriparatide [PTH1-34] (TPTD) is an anabolic drug shown to be effective in stimulating bone formation. The aim was to describe the course of a right diaphyseal femoral fracture sustained by a patient on long-term BPs treatment. A 57-year-old postmenopausal Caucasian female presented with delayed healing of a right femoral diaphyseal fracture 10 months after the fracture, despite having received orthopedic treatment. The fracture was preceded by progressive, severe, and bilateral thigh pain. Her medical history included osteopenia that was treated with alendronate over 7 years. On presentation at our clinic, the patient ambulated with the aid of a walking cane. The diagnosis was an atypical right femoral fracture associated with long-term alendronate use. The levels of the following parameters were measured: mineral metabolism laboratory: intact parathormone, 40 ng/mL (reference values (rv): 10-65 ng/mL); 25-hydroxyvitamin D, 40 ng/mL (rv: >30 ng/mL); serum Crosslaps, 318 ng/mL (rv: 80-590 ng/mL); and bone-specific alkaline phosphatase, 76UI/L (rv: 31-95UI/L)]. Magnetic resonance imaging of the left femur was performed, which revealed a diaphyseal stress fracture. She was prescribed 20 μg/day of subcutaneous (s.c.) TPTD (PTH1-34, Forteo; Eli Lilly Co., Indianapolis, IN, United States). A computed tomography scan performed 3 months later showed that the fracture had healed; the patient was able to resume her usual activities. Twenty micrograms per day of s.c. TPD accelerated the healing of the atypical fracture associated with long-term alendronate therapy, allowing a fast recovery of ambulation and quality of life.

Sex specific impact of prodromal chest pain on pre-hospital delay time during an acute myocardial infarction: Findings from the multicenter MEDEA Study with 619 STEMI patients

BackgroundScarce evidence yields conflicting results regarding the effect of prodromal chest pain (PCP) on pre-hospital delay during an acute myocardial infarction (AMI). We aimed to assess the impact of PCP on delay. MethodsData was collected on 619 ST-elevated MI patients from the multicenter Munich Examination of Delay in Patients Experiencing Acute Myocardial Infarction (MEDEA) study. Patients with any PCP (which was subdivided into undefined PCP, possible and definite angina) within a year before AMI were identified using the Rose questionnaire, administered in bedside interviews. The influence of PCP and its subdivisions (all compared to no PCP) was assessed using logistic regression (with cut-offs of 2h, 6h, and a 4-category ordinal outcome). ResultsAny type of PCP was reported by men (50.6%) more than women (34.6%) (OR=1.9; 95% CI: 1.3 to 2.8; p=.001). The median delay of patients with PCP was not significantly different to delay in patients with no PCP (p=.327). Prolonged delay times were observed in women with PCPs of lesser degree of cardiac confirmation, while the opposite was observed in men. In women, possible angina was more strongly associated with delay <2h (OR=6.8; 95% CI=2 to 23.8) than any PCP (OR=2.6; 95% CI=1.2 to 5.7). ConclusionsFor men, PCPs of increasing cardiac confirmation are associated with prolonged delay. For women, PCPs of lesser cardiac confirmation are more likely to lead to prolonged delay. Future studies should investigate mediating factors.