Adherence to osteoporosis guideline: survey among Czech general practitioners

Rationale and objectives

General practitioners (GPs) play an important role in management of patients at risk of osteoporosis (OP). The objectives were to assess (1) knowledge about OP and use of OP clinical guideline in comparison with other information sources and (2) association between the use of individual information sources and knowledge and self-reported quality of care among GPs.

Methods

Survey among random sample of Czech GPs was performed to find out their attitudes and role in OP management. The return rate of the postal questionnaire was 38% (525 respondents). Quality of care was assessed using three indicators: suspicion on OP, referral to the specialist and initial check-up.

Results

Respondents (median age 52 years, 59% women) had a very good knowledge of several risk factors, while others, namely low body mass index, history of hip fracture in mother and smoking were perceived as risk factors by only 40%, 45% and 55% of respondents, respectively. 10% of GPs stated the correct answer regarding daily calcium intake recommended for postmenopausal women. The OP guideline was considered accessible by 83% of respondents and used repeatedly by 54%. Use of the guideline correlated positively with knowledge score (P < 0.001), while use of each individual other source of information did not. Use of the guideline correlated with all three indicators of quality of care. Use of each other information source correlated only with a maximum of two indicators.

Conclusion

We identified areas of insufficient knowledge that should be targeted in educational activities for GPs. It is recommended to further motivate GPs to use their clinical guidelines regularly.     

Pediatric surgery during the COVID-19 pandemic

The coronavirus disease 2019 (COVID-19) pandemic has had a major impact on pediatric surgery. The infection is often asymptomatic and atypical in children, while overlapping presentations with other infectious diseases generate additional diagnostic challenges. The high probability of missed pediatric cases and the invasive nature of surgery generate great concern for widespread transmission in this setting. Current guidelines suggest that triage of cases should be made on a case-by-case basis by a multidisciplinary team of experts. Decision-making can be assisted by classifying cases as elective, urgent, or an emergency according to the risks of delaying their surgical management. A workflow diagram should ideally guide the management of all cases from admission to discharge. When surgery is necessary, all staff should use appropriate personal protective equipment, and high-risk practices, such as aerosol-generating tools or procedures, should be avoided if possible. Furthermore, carefully designed organizational protocols should be established to minimize transmission while ensuring the uninterrupted operation of pediatric surgery units. For example, surgical teams can be divided into small weekly rotating groups, and healthcare workers should be continuously monitored for COVID-19 symptoms. Additionally, team protocols in the operating room can optimize communication and improve adherence to personal protective equipment use. Isolated operating rooms, pediatric intensive care units, and surgical wards should be specifically designed for suspected or confirmed COVID-19 cases. Finally, transportation of patients should be minimal and follow designated short routes. All these measures can help mitigate the effects of the COVID-19 pandemic on pediatric surgery units.     

Whom to treat? The contribution of vertebral X-rays to risk-based algorithms for fracture prediction. Results from the European Prospective Osteoporosis Study

Introduction Vertebral fracture is a strong risk factor for future spine and hip fractures; yet recent data suggest that only 5–20% of subjects with a spine fracture are identified in primary care. We aimed to develop easily applicable algorithms predicting a high risk of future spine fracture in men and women over 50 years of age.Methods Data was analysed from 5,561 men and women aged 50+ years participating in the European Prospective Osteoporosis Study (EPOS). Lateral thoracic and lumbar spine radiographs were taken at baseline and at an average of 3.8 years later. These were evaluated by an experienced radiologist. The risk of a new (incident) vertebral fracture was modelled as a function of age, number of prevalent vertebral fractures, height loss, sex and other fracture history reported by the subject, including limb fractures occurring between X-rays. Receiver Operating Characteristic (ROC) curves were used to compare the predictive ability of models.Results In a negative binomial regression model without baseline X-ray data, the risk of incident vertebral fracture significantly increased with age [RR 1.74, 95% CI (1.44, 2.10) per decade], height loss [1.08 (1.04, 1.12) per cm decrease], female sex [1.48 (1.05, 2.09)], and recalled fracture history; [1.65 (1.15, 2.38) to 3.03 (1.66, 5.54)] according to fracture site. Baseline radiological assessment of prevalent vertebral fracture significantly improved the areas subtended by ROC curves from 0.71 (0.67, 0.74) to 0.74 (0.70, 0.77) P=0.013 for predicting 1+ incident fracture; and from 0.74 (0.67, 0.81) to 0.83 (0.76, 0.90) P=0.001 for 2+ incident fractures. Age, sex and height loss remained independently predictive. The relative risk of a new vertebral fracture increased with the number of prevalent vertebral fractures present from 3.08 (2.10, 4.52) for 1 fracture to 9.36 (5.72, 15.32) for 3+. At a specificity of 90%, the model including X-ray data improved the sensitivity for predicting 2+ and 1+ incident fractures by 6 and 4 fold respectively compared with random guessing. At 75% specificity the improvements were 3.2 and 2.4 fold respectively. With the modelling restricted to the subjects who had BMD measurements (n=2,409), the AUC for predicting 1+ vs. 0 incident vertebral fractures improved from 0.72 (0.66, 0.79) to 0.76 (0.71, 0.82) upon adding femoral neck BMD (P=0.010).Conclusion We conclude that for those with existing vertebral fractures, an accurately read spine X-ray will form a central component in future algorithms for targeting treatment, especially to the most vulnerable. The sensitivity of this approach to identifying vertebral fracture cases requiring anti-osteoporosis treatment, even when X-rays are ordered highly selectively, exceeds by a large margin the current standard of practice as recorded anywhere in the world.This work was presented in part at the 30th European Symposium on Calcified Tissues, 8–12 May 2003, Rome, Italy.A.J. Silman and J. Reeve are the EU Grant holders and Project Leaders.     

Peripartum cardiomyopathy-the (un)known obstetricalcardiologic emergency situation

Peripartum cardiomyopathy (PPCM) is rare cardiac complication afflicting women during pregnancy or until 5 months post partum with the typical signs of acute cardiac failure. PPCM is similar to dilated cardiomyopathy (DCM) in terms of symptoms, histopathology and treatment but is characterized by a better outcome with a high rate of spontaneous normalization of left-ventricular size and function. The understanding of the etiology is limited. However, viral myocarditis and autoimmune factors might be involved in the development of PPCM. Clinically, PPCM shows pulmonary symptoms such as dyspnea, tachypnea and coughing. The diagnosis is finally established by echocardiography. It has to be assumed that PPCM is often undetected or misdiagnosed because of the low incidence, the unspecific symptoms and the fact that other pregnancy-related factors have similar clinical appearance. The treatment is also unspecific and similar to DCM and acute cardiac failure. The severity of the disease requires an interdisciplinary approach in a perinatal center with consequent follow-up of the patients for risk stratification including echocardiography.     

Modification of pancreatic carcinogenesis in the hamster model. 6. The effect of ductal ligation and excision

The effect of ligation and excision of the pancreatic duct in pancreatic carcinogenesis was examined in the hamster model. Animals were treated with a single dose (20 mg/kg body weight) of N-nitrosobis(2-oxopropyl)amine (BOP) either immediately (Group 1) or on Days 1 (Group 2), 3 (Group 3) or 7 (Group 4) after ligation and excision of the duct of the splenic lobe. Group 5 received BOP shortly after laparoscopy, and Group 6 consisted of BOP-treated controls. All hamsters were killed 46 weeks after BOP treatment. The results showed that despite advanced atrophy of the splenic lobe distal to the excised duct in Groups 1-4, some hamsters in Groups 2, 3, and 4 showed hyperplasia, dysplasia, and increased mitotic activities of ductal and ductular cells. However, carcinomas in the duct-excised atrophic lobe were found only in Groups 1-3. These data indicate that BOP carcinogenesis is mediated through blood circulation, and that cancer development is not inhibited in the duct-excised lobe for up to 3 days after surgery. However, in the entire pancreas, a significant reduction in tumor incidence was seen when the carcinogen was given immediately, or to a lesser extent, 1 day after surgery, regardless of whether or not excision was made. On the contrary, BOP, when given 3 and 7 days after duct excision, enhanced tumor development in the nonexcised (intact) pancreas, compared with other test groups and with BOP controls. Both inhibition and enhancement seemed due to a proportional decrease and increase, respectively, of BOP-responsive cells throughout the intact pancreas.     

S-Adenosylhomocysteine, but not homocysteine, is toxic to yeast lacking cystathionine β-synthase

Elevated plasma homocysteine is associated with a variety of diseases in humans including coronary heart disease, stroke, peripheral vascular disease, and birth defects. However, the mechanism by which plasma homocysteine affects cells is unknown. We have examined the growth of isogenic wild-type and cystathionine beta-synthase (CBS) deficient yeast in response to homocysteine and its immediate metabolic precursor, S-adenosylhomocysteine (SAH). CBS deficient yeast export significantly more homocysteine into the media than wild-type yeast and have elevated internal pools of homocysteine and SAH. We found that 5 mM homocysteine added to the media had very little effect on the growth of wild-type or CBS deficient yeast, although intracellular homocysteine concentrations increased five- to tenfold. In contrast, as little as 25 microM S-adenosylhomocysteine inhibited the growth of CBS deficient yeast, but had no effect on wild-type yeast. Measurements of the intracellular S-adenosylmethionine (SAM) and SAH indicate that CBS deficient yeast contain reduced SAM/SAH ratios relative to wild-type, and this ratio is further reduced by adding SAH to the media. Growth inhibition by SAH in CBS deficient yeast can be totally reversed by addition of SAM to the media, indicating that the ratio and not absolute level is critical for cell growth. These results suggest that CBS plays a key role in the regulation of the SAM/SAH ratio inside cells and that excessive perturbations of this ratio can inhibit growth. We hypothesize that elevated extracellular homocysteine present in humans may reflect an altered intracellular SAM/SAH ratio and that this may be related to disease pathogenesis.     

VEGF expression and angiogenesis in oral squamous cell carcinoma: an immunohistochemical and morphometric study

Angiogenesis is involved in tumor progression of oral squamous cell carcinoma (OSCC). In this study, we have investigated by immunohistochemistry vascular endothelial growth factor (VEGF) expression in tumor cells and we have correlated VEGF expression to microvessel area, evaluated by using CD105 as a marker of endothelial cells, in bioptic specimens of 54 human OSCC. Results demonstrated that VEGF is highly expressed in OSCC tumor specimens when compared to pre-neoplastic and normal tissues, without differences between the edge and inside the tumor. Moreover, VEGF expression is reduced in poor differentiated OSCC tumors when compared to moderate and good differentiated forms, and tumor microvessel area is higher in tumors when compared to pre-neoplastic lesions and normal tissues. Finally, VEGF and CD105 may be considered as reliable markers of tumor angiogenesis and progression in OSCC, even if we did not demonstrate any correlation between VEGF expression, tumor microvascular area, clinical stage, and lymph node status.     

Secondary cataract treatment with laser YAG-ND

The purpose of the study is to present the favorable results of YAG: Nd laser capsulotomy for the treatment of secondary opacification of the posterior capsule, in our department. A 3 years retrospective study was performed. For 1440 cataract operations, most of them extracapsular extractions with PMMA IOL placed in the posterior chamber (ciliary sulcus or capsular bag), 285 laser capsulotomies were done. The results are presented statistically, including sex and age distribution, type of cataract surgery and implant, treatment protocol (number of sessions, number of impulses per session, energy per impulse) and complications. The frequency of secondary capsular opacification in our study is 19.78%. It is most important in the age group 60-70 years, where the surgery for cataract is performed more often. Capsulotomy was done after extracapsular extraction with IOL placed in the posterior chamber, but especially after extracapsular extraction without implant placement or with complications that have permitted only the use of an anterior chamber implant. Capsulotomy is performed in only one session in 88% of the cases. The energy per impulse is usually 3-5 mJ and the mean number of impulses per session is 10-30. There are few complications: transient elevation of intraocular pressure in 14.73%, discrete laser marks on the implant in 8.77% and moderate iritis in 1% of the cases. YAG: Nd laser capsulotomy appears to be a safe and efficient method of treating secondary cataract; it improved visual acuity in all cases, if different ocular pathology had not influenced it.     

Low BMD is less predictive than reported falls for future limb fractures in women across Europe: results from the European Prospective Osteoporosis Study

We have previously shown that center- and sex-specific fall rates explained one-third of between-center variation in upper limb fractures across Europe. In this current analysis, our aim was to determine how much of the between-center variation in fractures could be attributed to repeated falling, bone mineral density (BMD), and other risk factors in individuals, and to compare the relative contributions of center-specific BMD vs. center-specific fall rates. A clinical history of fracture was assessed prospectively in 2451 men and 2919 women aged 50-80 from 20 centers participating in the European Prospective Osteoporosis Study (EPOS) using standardized questionnaires (mean follow-up = 3 years). Bone mineral density (BMD, femoral neck, trochanter, and/or spine) was measured in 2103 men and 2565 women at these centers. Cox regression was used to model the risk of incident fracture as a function of the person-specific covariates: age, BMD, personal fracture history (PFH), family hip fracture history (FAMHIP), time spent walking/cycling, number of 'all falls' and falls not causing fracture ('fracture-free') during follow-up, alcohol consumption, and body mass index. Center effects were modeled by inclusion of multiplicative gamma-distributed random effects, termed center-shared frailty (CSF), with mean 1 and finite variance theta (theta) acting on the hazard rate. The relative contributions of center-specific fall risk and center-specific BMD on the incidence of limb fractures were evaluated as components of CSF. In women, the risk of any incident nonspine fracture (n = 190) increased with age, PFH, FAMHIP, > or =1 h/day walking/cycling, and number of 'all falls' during follow-up (all P < 0.074). 'Fracture-free' falls (P = 0.726) and femoral neck BMD did not have a significant effect at the individual level, but there was a significant center-shared frailty effect (theta = 0.271, P = 0.001) that was reduced by 4% after adjusting for mean center BMD and reduced by 19% when adjusted for mean center fall rate. Femoral trochanter BMD was a significant determinant of lower limb fractures (n = 53, P = 0.014) and the center-shared frailty effect was significant for upper limb fractures (theta = 0.271, P = 0.011). This upper limb fracture center effect was unchanged after adjusting for mean center BMD but was reduced by 36% after adjusting for center mean fall rates. In men, risk of any nonspine fracture (n = 75) increased with PFH, fall during follow-up (P < 0.026), and with a decrease in trochanteric BMD [RR 1.38 (1.08, 1.79) per 1 SD decrease]. There was no center effect evident (theta = 0.081, P = 0.096). We conclude that BMD alone cannot be validly used to discriminate between the risk of upper limb fractures across populations without taking account of population-specific variations in fall risk and other factors. These variations might reflect shared environmental or possibly genetic factors that contribute quite substantially to the risk of upper limb fractures in women.