Evaluation of 20?years experience of fibrodysplasia ossificans progressiva in Iran: lessons for early diagnosis and prevention

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic inflammatory disorder characterized by progressive heterotopic ossification presenting as recurrent soft tissue masses and swelling which may cause disabling, restricted joint mobility. Congenital malformations of the hallux are characteristic features of classic FOP, predating the appearance of disabling features. As no definite treatment is available, the early diagnosis and prevention of exacerbating factors may lead to significant benefits in terms of the life quality of patients. A retrospective study of 12 consecutive FOP patients referred to and admitted in the rheumatology unit at an urban tertiary care academic center between 1991 and 2011. Data, such as age, gender, and past medical history, were collected from the medical history, physical examination, and skeletal survey in order to characterize the clinical presentations. All 12 children (six boys and six girls; ages 2.0-13.5 years) had congenital malformations of the great toes (microdactyly and hallux valgus deformity), in addition to heterotopic ossification presenting as multiple soft tissue tumor-like swellings. Spinal involvement, most notably in the cervical region, suggestive of an early FOP, was present in 83.3 %. Eleven patients (91.6 %) had a prior history of direct physical trauma, while 7 of 11 (63.6 %) had undergone invasive diagnostic procedures, both correlating with the exacerbations of their condition. Clinical awareness of fibrodysplasia ossificans progressiva and its early diagnostic features, particularly congenital malformations of the hallux, during a thorough neonatal examination may lead to an early diagnosis preventing the development of disabling, practically irreversible lesions of heterotopic ossification. Genetic and molecular studies can play a considerable role in the diagnosis of FOP in suspected cases. Early institution of prophylactic and precautionary measures, such as categorical avoidance of trauma and invasive procedures, can significantly reduce the debilitating acute exacerbations of the condition.     

Is there life without work?

The present study examined the way retirees perceive retirement and continue to work post-retirement. Using a longitudinal design, qualitative and quantitative analyses were performed to examine the effect of preoccupation with work on adjustment to retirement. The findings indicate a wide range of attitudes toward cessation of the working life on the eve of retirement. In addition, most retirees reported increased well-being and decreased distress one year after retirement. Although for all participants a correlation was found between adjustment and preoccupation with work on the eve of retirement, no difference in the adjustment measures emerged a year later between those who were fully retired and those who continued to work. The implications of the findings for both personal well-being and social policy are discussed.     

Is antibiotic prophylaxis ever necessary before transoesophageal echocardiography?

Evidence strongly suggests that antibiotic prophylaxis should not be used routinely for transoesophageal echocardiography for any indication.     

Is it ever enough to die of old age?

OBJECTIVE: To determine how often 'old age' was given as a cause of death in patients presenting for cremation, with particular reference to their characteristics and the medical conditions known to the certifying doctor at the time of death. DESIGN: Prospective review of all cremation papers presented to one crematorium over a two-year period. SETTING: An English crematorium serving a population of about 250,000. MAIN OUTCOME MEASURES: Deaths certified as being associated with 'old age' and those solely registered as due to this cause. Demographics of the patients and whether further enquiries by the medical referee revealed un-notified co-morbid conditions. RESULTS: Of 4300 cremation papers studied, 300 (7%) deaths were said to be associated with old age, of which 98 were to old age alone. Simple further enquiry discovered between one and six unrecorded co-morbid conditions in at least two-thirds of those certified as dying solely from old age. IMPLICATIONS: If this experience were reflected throughout the country, it would suggest significant underestimation of the incidence of medical conditions, with resultant effects on national and international health policy and investment.     

Crohn's disease and smoking: Is it ever too late to quit?

BackgroundSmoking increases CD risk. The aim was to determine if smoking cessation at, prior to, or following, CD diagnosis affects medication use, disease phenotypic progression and/or surgery.MethodsData on CD patients with disease for ≥ 5 yrs were collected retrospectively including the Montreal classification, smoking history, CD-related abdominal surgeries, family history, medication use and disease behaviour at diagnosis and the time when the disease behaviour changed.Results1115 patients were included across six sites (mean follow-up—16.6 yrs). More non-smokers were male (p = 0.047) with A1 (p < 0.0001), L4 (p = 0.028) and perianal (p = 0.03) disease. Non-smokers more frequently received anti-TNF agents (p = 0.049). (p = 0.017: OR 2.5 95%CI 1.18–5.16) and those who ceased smoking prior to diagnosis (p = 0.045: OR 2.3 95%CI 1.02–5.21) progressed to complicated (B2/B3) disease as compared to those quitting at diagnosis. Patients with uncomplicated terminal ileal disease at diagnosis more frequently developed B2/B3 disease than isolated colonic CD (p < 0.0001). B2/B3 disease was more frequent with perianal disease (p < 0.0001) and if i.v. steroids (p = 0.004) or immunosuppressants (p < 0.0001) were used. 49.3% (558/1115) of patients required at least one intestinal surgery. More smokers had a 2nd surgical resection than patients who quit at, or before, the 1st resection and non-smokers (p = 0.044: HR = 1.39 95%CI 1.01–1.91). Patients smoking > 3 cigarettes/day had an increased risk of developing B2/B3 disease (p = 0.012: OR 3.8 95%CI 1.27–11.17).ConclusionProgression to B2/B3 disease and surgery is reduced by smoking cessation. All CD patients regardless of when they were diagnosed, or how many surgeries, should be strongly encouraged to cease smoking.     

Dobutamine-induced hypoperfusion without transient wall motion abnormalities: Less severe ischemia or less severe stress?

Objectives. This study sought to compare the clinical characteristics, hemodynamic response and severity of ischemia in patients with coronary artery disease and reversible perfusion defects on dobutamine 2-methoxy isobutyl isonitrile (MIBI) single-photon emission computed tomography (SPECT) with or without transient wall motion abnormalities.Background. The occurrence of reversible perfusion defects without concomitant wall motion abnormalities in patients with coronary artery disease was attributed to less severe ischemia. However, little data are available to support this observation.Methods. Fifty-four consecutive patients with significant coronary artery disease and reversible perfusion defects on dobutamine (up to 40 μg/kg body weight per min) MIBI SPECT were studied (mean [±SD] age 59 ± 11 years; 38 men, 16 women). All patients underwent simultaneous echocardiography. The myocardium was divided into six matched segments, and ischemic perfusion score was quantitatively derived in myocardial segments with reversible defects.Results. New or worsening wall motion abnormalities occurred in 40 patients (74%) (group A) and were absent in 14 (26%) (group B). There was no significant difference between the two groups with respect to age, previous myocardial infarction, number of abnormal coronary arteries (1.8 ± 0.8 vs. 1.6 ± 0.9), number of reversible perfusion defects (1.6 ± 0.9 vs. 1.8 ± 0.7) or ischemic perfusion score (412 ± 750 vs. 526 ± 553). Patients in group A had a higher prevalence of male gender (80% vs. 43%, p < 0.01), higher risk systolic blood pressure (147 ± 30 vs. 127 ± 31 mm Hu: < 0.05), higher peak rate-pressure product (19,632 ± 4,081 vs. 16,939 ± 4,344, p < 0.01) and a higher prevalence of angina (53% vs. 14%) and ST segment depression (55% vs. 14%) than group B (p < 0.05 for both).Conclusions. In patients with coronary artery disease and ischemia on dobutamine MIBI SPECT, the absence of transient wall motion abnormalities is associated with a similar extent and severity of reversible perfusion defects, a lower stress rate-pressure product and a higher prevalence of female gender than patients with transient wall motion abnormalities. Mechanically silent with transient wall motion abnormalities. Mechanically silent ischemia should not be regarded as a marker of less severe ischemia on myocardial perfusion scintigraphy.     

Is endoscopic papillary large balloon dilatation without endoscopic sphincterotomy effective?

AIM: To evaluate the safety and efficacy of endoscopic papillary large balloon dilatation(EPLBD) without endoscopic sphincterotomy in a prospective study.METHODS: From July 2011 to August 2013, we performed EPLBD on 41 patients with nae papillae prospectively. For sphincteroplasty of EPLBD,endoscopic sphincterotomy(EST) was not performed,and balloon diameter selection was based on the distal common bile duct diameter. The balloon was inflated to the desired pressure. If the balloon waist did not disappear, and the desired pressure was satisfied, we judged the dilatation as complete. We used a retrieval balloon catheter or mechanical lithotripter(ML) to remove stones and assessed the rates of complete stone removal, number of sessions, use of ML and adverse events. Furthermore, we compared the presence or absence of balloon waist disappearance with clinical characteristics and endoscopic outcome.RESULTS: The mean diameters of the distal and maximum common bile duct were 13.5 ± 2.4 mm and16.4 ± 3.1 mm, respectively. The mean maximum transverse-diameter of the stones was 13.4 ± 3.4mm, and the mean number of stones was 3.0 ± 2.4.Complete stone removal was achieved in 97.5%(40/41)of cases, and ML was used in 12.2%(5/41) of cases.The mean number of sessions required was 1.2 ± 0.62.Pancreatitis developed in two patients and perforation in one. The rate of balloon waist disappearance was73.1%(30/41). No significant differences were noted in procedure time, rate of complete stone removal(100% vs 100%), number of sessions(1.1 vs 1.3, P= 0.22), application of ML(13% vs 9%, P = 0.71),or occurrence of pancreatitis(3.3% vs 9.1%, P =0.45) between cases with and without balloon waist disappearance.CONCLUSION: EST before sphincteroplasty may be unnecessary in EPLBD. Further investigations are needed to verify the relationship between the presence or absence of balloon waist disappearance.     

When to initiate beta-blockers in heart failure: Is it ever too early?

Overwhelming clinical trial evidence confirms the efficacy and safety of β-blockers in patients with heart failure (HF) caused by systolic dysfunction. β-Blockers are recommended in national HF guidelines as standard of care therapy. Yet there is also a large body of evidence demonstrating that the use of β-blockers for HF is seriously inadequate under conventional care. This HF treatment gap is due, in part, to the persistence of perceptions—despite recent evidence to the contrary—that β-blocker therapy should be delayed until HF patients have been titrated to target doses of angiotensin-converting enzyme inhibitors and have been stable for at least 2 to 4 weeks after hospital discharge, and that early β-blocker initiation results in a substantial risk of worsening HF. Conversely, recent clinical trial evidence substantiates that β-blockers significantly reduce the risk of mortality and morbidity, including hospitalization for worsening HF, and have produced early survival benefits in patients with HF. It has also become evident that in-hospital initiation of lifeprolonging cardiovascular therapies, including β-blockers, has a positive impact on clinical outcomes and on longterm patient compliance. Overwhelming clinical evidence suggests that β-blockers should be administered to all stable HF patients without contraindication and that this therapy should be initiated as soon as possible to ensure that patients derive early and long-term improvements in clinical outcomes.     

Comment on: Is it ever appropriate to discharge patients with rheumatoid arthritis?

SIR, the importance of appropriate standards of care for peoplewith RA cannot be overstated. The Arthritis and MusculoskeletalAlliance (ARMA) welcomes the editorial of Drs Bukhari,     

Endoscopic screening for esophageal varices in cirrhosis: Is it ever cost effective?

Current guidelines for the management of patients with compensated cirrhosis recommend universal screening endoscopy followed by prophylactic beta-blocker therapy to prevent initial hemorrhage in those found to have esophageal varices. However, the cost-effectiveness of this recommendation has not been established. Our objective was to determine whether screening endoscopy is cost-effective compared with empiric medical management in patients with compensated cirrhosis. Decision analysis with Markov modeling was used to calculate the cost-effectiveness of 6 competing strategies: (1) universal screening endoscopy (EGD) followed by beta-blocker (BB) therapy (EGD-->BB) if varices are present, (2) EGD followed by endoscopic band ligation (EBL) (EGD-->EBL) if varices are present, (3) selective screening endoscopy (sEGD) in high risk patients followed by BB therapy if varices are present (sEGD-->BB), (4) selective screening endoscopy followed by EBL (sEGD-->EBL) if varices are present, (5) empiric beta-blocker therapy in all patients, and (6) no prophylactic therapy ("Do Nothing"). Cost estimates were from a third-party payer perspective. The main outcome measure was the cost per initial variceal hemorrhage prevented. The "Do Nothing" strategy was the least expensive yet least effective approach. Compared with the "Do Nothing" strategy, the empiric beta-blocker strategy cost an incremental $12,408 per additional variceal bleed prevented. Compared with the empiric beta-blocker strategy, in turn, both the EGD-->BB and the EGD-->EBL strategies cost over $175,000 more per additional bleed prevented. The sEGD-->BB and sEGD-->EBL strategies were more expensive and less effective than the empiric beta-blocker strategy. In conclusion, empiric beta-blocker therapy for the primary prophylaxis of variceal hemorrhage is a cost-effective measure, as the use of screening endoscopy to guide therapy adds significant cost with only marginal increase in effectiveness.