Patient engagement in clinical guidelines development: input from > 1000 members of the Canadian Osteoporosis Patient Network.

Patient engagement in clinical guidelines development is essential. The results of a self-administered online survey identified themes important to people living with osteoporosis and will inform the development of Osteoporosis Canada clinical guidelines recommendations. INTRODUCTION: Patient engagement is essential in the development of high-quality and relevant guidelines for osteoporosis management. Osteoporosis Canada (OC) is updating its national clinical practice guidelines in collaboration with people living with osteoporosis in the process. METHODS: Using electronic mail, we contacted 6937 members of the Canadian Osteoporosis Patient Network (COPN) to provide input on the selection of relevant content, outcomes, and research questions via a self-administered online survey. Close-ended questions were analyzed using descriptive statistics, and conventional content analysis was conducted for open-ended questions. RESULTS: A total of 1108 individuals completed the survey (97% women, 86% stated they lived with osteoporosis). Most participants considered it critical to have recommendations on physical activity and exercise (74%), fall prevention (69%), nutrition (68%), and initial bone mineral density testing (67%). In addition to preventing fractures, over 75% of respondents stated that consideration of preserving quality of life and ability to perform daily activities, preventing admission to long-term care and fracture-related death, and avoiding serious harms from medications were essential outcomes to consider in evaluating the evidence. In terms of selection of research questions, seven themes emerged from the content analysis including pharmacotherapy, screening and monitoring, diet and supplements, education, exercise, alternative therapies, and pain management. CONCLUSIONS: Patients emphasized that autonomy, mobility, and quality of life are highly valued outcomes and must be integral to practice guideline development. As expected, guidance on pharmacotherapy, screening and monitoring, and fracture prevention were priorities identified to be included in osteoporosis management guidelines.

Preparation and characterization of nano-hydroxyapatite within chitosan matrix.

Nano-composites that show some features of natural bone both in composition and in microstructure have been prepared by in situ precipitation method. Apatite phase has been prepared from cost-effective precursors (calcite and urea phosphate) within chitosan (CS) matrix dissolved in aqueous acetic acid solution. The compositional and morphological properties of composites were studied by means of Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) thermogravimetric analysis (TGA) and transmission electron microscopy (TEM). Depending on the reaction conditions (temperature, reaction time, glucose addition and pH control) in addition to hydroxyapatite (HA) as a major phase, octacalcium hydrogen phosphate pentahydrate (OCP) and dicalcium phosphate anhydrate (DCPD) were formed as shown by XRD and FTIR. Crystallite lengths of precipitated HA estimated by Scherrer's equation were between 20 and 30 nm. A fibrous morphology (~400 nm) of HA observed by TEM indicates that HA nucleates on chitosan chains.

Preparation of highly porous hydroxyapatite from cuttlefish bone.

Hydroxyapatite structures for tissue engineering applications have been produced by hydrothermal (HT) treatment of aragonite in the form of cuttlefish bone at 200 degrees C. Aragonite (CaCO(3)) monoliths were completely transformed into hydroxyapatite after 48 h of HT treatment. The substitution of CO(3) (2-) groups predominantly into the PO(4) (3-) sites of the Ca(10)(PO(4))(6)(OH)(2) structure was suggested by FT-IR spectroscopy and Rietveld structure refinement. The intensity of the nu(3)PO(4) (3-) bands increase, while the intensity of the nu(2)CO(3) (2-) bands decrease with the duration of HT treatment resulting in the formation of carbonate incorporating hydroxyapatite. The SEM micrographs have shown that the interconnected hollow structure with pillars connecting parallel lamellae in cuttlefish bone is maintained after conversion. Specific surface area (S (BET)) and total pore volume increased and mean pore size decreased by HT treatment.

Telomere dynamics and genome stability in the human pancreatic tumor cell line MIAPaCa-2.

Telomeres are specialized structures found at the ends of eukaryotic chromosomes serving as guardians of genome stability. In normal cells telomeres shorten with each cell division, but immortal cells undergoing multiple divisions constantly have to maintain telomere lengths above a critical level. This is accomplished either through expression of telomerase or the alternative recombination pathway (ALT). In the present study, we analyzed telomere dynamics of the telomerase positive human pancreatic tumor cell line MIAPaCa-2. The cells demonstrated genomic instability with a high frequency of chromosomal aberrations resulting in differences between individual karyotypes within the same cell population. The telomeres were short when compared with normal human fibroblasts, and about 39% of the chromosome ends did not have detectable telomere repeats as demonstrated by PNA-FISH. In many cases telomere signals were missing even when sister chromatids were strongly labeled. In addition, we used an internal PNA probe specific for the X chromosome, present in a single copy in these cells, in order to follow telomere dynamics on individual chromatids. High heterogeneity in telomere signals among individual X chromosomes as well as between their sister chromatids suggested sudden and stochastic loss or gain of telomere repeats. Such constant genomic instability often results in apoptosis and death of a fraction of cells present in the culture at all times. We discuss possible molecular mechanisms that may explain this observed telomere heterogeneity and possible adaptive repair mechanisms by which these cells maintain their chromosomes in order to survive such extreme and permanent genomic instability.

Spontaneous senescence in the MDA-MB-231 cell line.

Normal human somatic cells have a limited division potential when they grow in vitro. It is believed that shortening of telomeres, specialized structures at the ends of chromosomes, controls cell growth. When one telomere achieves a critical minimal length, the cell cycle control mechanism recognizes it as DNA damage and causes the cell's exit from the cycle in G1-phase. Because it is not possible to extend telomeres in normal cells, this non-dividing state is prolonged indefinitely, and is known as cellular senescence. The immortal cell line MDA-MB-231 has active telomerase, which prevents telomere shortening and allows cells' permanent divisions. However, there is a fraction of cells that do not divide over several days in culture as documented for some other tumour cell lines. Combination of methods has made it possible to isolate these non-growing cells and compare them with the fraction of fast-growing cells from the same culture. Although the non-growing fraction contains a significant percentage of typical senescent cells, both fractions have equal telomerase activity and telomere length. In this paper we discuss possible mechanisms that cause the appearance of this non-growing fraction of cells in cultures of MDA-MB-231, which indicate stress and genome instability rather than variation in telomerase activity or telomere shortening to affect individual cells.

Sex chromosome pentasomy (49,XXXXY) presenting as cystic hygroma at 16 weeks' gestation.

The pentasomy 49,XXXXY is one of the rarest sex chromosome defects, occurring with an estimated incidence of 1 in 85 000 male births. This condition is associated with pre- and postnatal growth deficiency, severe mental retardation, hypogenitalism, and other skeletal, facial and cardio-vascular anomalies. In this report we present such a case diagnosed prenatally by chorionic villus sampling after the ultrasound detection of cystic hygroma at 16 weeks' gestation. Although the prenatal diagnosis of cystic hygroma and its association with aneuploidy has been documented in numerous reports, sex chromosome aneuploidy, other than the 45,X karyotype, accounts for only 0.3 per cent of cases.

Clinical significance of first trimester umbilical cord cysts.

A cystic mass of the umbilical cord was identified by transvaginal sonography in 10 first trimester pregnancies at a mean gestational age of 8 weeks 4 days (range, 8 weeks 1 day to 9 weeks 3 days) and at a mean crown-rump length of 20.5 mm (range, 15 to 25 mm). The cyst was solitary in all cases, the mean diameter was 4.6 mm (range, 3 to 6 mm), and the location was closer to the fetal insertion in two cases, in the middle of the cord in seven cases, and closer to the placental insertion in one case. Gestational sac and yolk sac diameters as well as the fetal heart rate were within normal ranges for gestational age in all cases. Information on detailed second trimester scans was available in nine cases, demonstrating complete resolution of the cyst and normal fetal anatomic survey in each case. These nine pregnancies were followed to delivery, and normal healthy infants were delivered at term in all cases. This series suggests that the incidental detection of umbilical cord cysts in early pregnancy is not associated with an adverse pregnancy outcome.

Bleeding time in preeclampsia.

The association of preeclampsia with thrombocytopenia and prolonged bleeding time is reported. The analysis of bleeding time (Simplate II) and the platelet count (Automatic Coulter Counter) in 41 patients with different grades of preeclampsia is presented. Our results suggest that the decrease in the bleeding time observed in moderate preeclampsia and the increase observed in severe preeclampsia are not mainly dependent on the platelet count.

Intrahepatic cholestasis of pregnancy: a retrospective case-control study of perinatal outcome.

OBJECTIVES: Intrahepatic cholestasis of pregnancy has been related to a high frequency of abnormal intrapartum fetal heart rate, amniotic fluid meconium, prematurity, and perinatal mortality. To determine whether these adverse perinatal outcomes could be improved with active intervention, we evaluated our results. STUDY DESIGN: We report a retrospective case-control study of 320 consecutive patients with intrahepatic cholestasis of pregnancy management with antepartum testing and active intervention over a 2-year period. RESULTS: Our results indicate a higher incidence of meconium staining in amniotic fluid at delivery (25% vs 16%, p < 0.05) and spontaneous preterm delivery (12.1% vs 3.9%, p < 0.05), without an increase in the frequency of abnormal intrapartum fetal heart rate (12% vs 11%, not significant), 5-minute Apgar score < 7 (2.0% vs 1.0%, not significant), or perinatal mortality (18/1000 vs 13/1000, not significant). CONCLUSION: Antenatal testing and timed intervention of patients with intrahepatic cholestasis of pregnancy is associated with a reduction of the previously reported adverse perinatal outcomes.

Relationship of circadian rhythms of uterine activity with term and preterm delivery.

OBJECTIVE: Our aim was to document the presence or significance of circadian uterine activity rhythms in pregnant women who delivered at term and preterm. STUDY DESIGN: We measured uterine activity in 19 women divided into a control group (low risk for preterm labor, term delivery, n = 7), a group at high risk for preterm labor, term delivery (n = 6), and a group at high risk for preterm labor, preterm delivery (n = 6). Patients were hospitalized for 24 hours every 2 weeks from 26 weeks' gestation until delivery. Uterine activity was measured continuously by external tocodynamometer. RESULTS: Patients delivering at term demonstrated a nocturnal surge (4 to 7 AM) in uterine activity the last 80 days before delivery (p < 0.05, analysis of variance). Patients delivered preterm showed an initial nocturnal surge of uterine activity similar to those delivered at term, but this disappeared 24 days before delivery (p > 0.05, analysis of variance). CONCLUSION: Uterine activity nocturnal surges normally precede term delivery. These surges are lost in women who deliver prematurely.

[Etiopathogenesis of varicosities of the lower extremities]. / Prilog etiopatogenezi varikoziteta na donjim ekstremitetima.

This study was performed to validate the importance of heredity in the development of varicosities of lower extremities and to establish the correlation between the sclerotherapy and the pathological changes on the perforating and deep veins. The aim was also to determine the share of trauma in the development of insufficiency of the perforating veins of the lower leg. The author studied 484 hospitalized patients. By application of modern diagnostic procedures, pathological changes in the system of veins were discovered and located and varicose veins were classified into five groups. A positive family history was found in 64.5% of the treated patients. The relationship between the heredity and the pathological changes in the venous system has been given in tables. Of all the treated patients, 12.2% underwent sclerotherapy earlier. Among these patients, 50.8% showed pathological changes on the perforating veins; in 22% pathological changes, however, were found on the deep veins as well. One hundred and thirty-five patients were operated on due to insufficiency of the communicating veins. Of those patients, 21.4% stated a positive trauma in their past history, while 14.1% showed some degenerative changes in the fatty-connective tissue of the deep fascia of leg. In conclusion these results tissue of the deep fascia of leg. In conclusion these results confirm the hypothesis that trauma of lower extremities may lead to insufficiency of the communicating veins.

[The Edward method of subfascial resection in communicating vein insufficiency in the calf]. / Vrednosti Edwardsove methode subfascijalne sekcije kod insuficijentinih komunikatnih vena potkolenice.

The purpose of this study was to identify the operative method that gives the best immediate and remote results. The study includes: a retrospective study, a prospective study and remote results. In the retrospective and prospective studies the immediate complication and the results of surgical treatment were evaluated. The total number of immediate complications amounts to 30% and the least of them has Edwards section (3.8%). The best immediate results have been achieved by Edwards method, too (the curing rate of insufficient perforating veins and varix is 93.3%, and of insufficient perforating veins and ulcer is 90.9%). The best remote results have been established at the subfascial section, combined with stripping of insufficient superficial veins and extirpation of varix (the curing rate at 71.4%). This operative procedure can be considered as a selective method in surgical treatment of blood reflux through insufficient perforating veins, and particularly in those regions of the calf characterised by strong indurative and sclerotic changes, as well as by cured and fresh ulcers.

[The value of the Nankovic internal fixator in surgical treatment and rehabilitation of spinal fractures]. / Vrijednost internog fiksatora po Nankovicu kod operativnog lijecenja i rehabilitacije prijeloma kraljesnice.

By fixateur interna light for spine fractures introduced and used by Magerl and Dick, we wanted to estimate fixateur interna validity by Nankovic. We considered 37 patients with spine fracture, operated by method previously mentioned. With no patient there was no deformation or fixateur fracture during the rehabilitation. With 3 patients (8%) fixateur was removed according to documentation because of infection. Because of all the things mentioned we consider the fixateur to be good and applied in the case of any indication for it.

[Etiopathogenesis of varicosities of the lower extremities]. / Prilog etiopatogenezi varikoziteta na donjim ekstremitetima.

To investigate the significance of heredity in the development of varicosities of the lower extremities, and to establish the association between the sclerotherapy and the pathologic changes of the perforating and deep veins as well as the share of trauma in the development of perforating venous insufficiency of the lower part of the leg, the author studied 484 hospitalized patients. By using modern diagnostic procedures, the pathologic changes of the venous system were identified and located and varicosities were classified into five groups. A positive family anamnesis was found in 64.5% of the treated patients. The relationship between the heredity and the pathologic changes of the venous system is shown in tables. Of all the treated patients, 12.2% underwent sclerotization before the admission to the hospital. In 50.8% of these patients, the author found pathologic changes of the perforating veins and in 22% pathologic changes of the deep veins, as well. Due to perforating venous insufficiency 135 patients were operated. Among these patients, 21.4% reported positive history of trauma, while in 14.1% of surgically treated patients some degenerative changes of the fatty-connective tissue of the crural fascia were found. This speaks in favour of the assumption that trauma of the lower extremities may lead to perforating venous insufficiency.

[Retroperitoneal tumors]. / Retroperitonealni tumori.

The authors have referred their fifteen-year-old experiences in the treatment of the pathologically proved retroperitoneum tumours, classified according to Patel. The number of the affected persons is a very small one-only seven patients out of 100,000 inhabitants during the fifteen years' period. At the very beginning, the clinical symptomatology in a very poor one, so that it is not easy to diagnose a tumour. An early diagnosis as well as a timely surgical treatment are very important in the illness prognosis. As to our practice, malignancies prevail (57%). All patients, by whom a tumour has been diagnosed, have undergone surgery, its span of time depending on the local analysis, tumour restricted area, infiltration into the neighbouring tissues and its adherentness to the neighbouring organs. The post-surgical mortality amounts to 28%. The surgical results among benignancies are satisfactory. The results among malignancies depend on the pathohistological structure and their prevalence. We can partially improve the prognosis, if, besides a partial resection of these malignancies, we can add a cytostatic resection and a radio-therapy.