Virtual fracture liaison clinics in the COVID era: an initiative to maintain fracture prevention services during the pandemic associated with positive patient experience.

We introduced virtual fracture liaison clinics during the COVID-19 pandemic in order to support clinical care while DXA services were down-turned. We observed that virtual FLS clinics are effective in delivering fracture risk assessment, health promotion, and clinical management and are well received by patients with positive patient experience. INTRODUCTION: We examined the impact of virtual FLS telephone clinics, as an alternative to face-to-face clinics during the COVID-19 lockdown. METHODS: Patients presenting with low trauma fracture were recruited according to standard criteria. A structured telephone clinic appointment was offered, which included fracture risk and health promotion assessment and a treatment plan. Risk factors, demographics, fracture type, FRAX scores, and outcomes were analysed. We assessed patient experience with an anonymised patient survey. RESULTS: Clinical outcomes from virtual clinics were assessed (77F/33M; mean age 65.7 years). The mean 10-year observed fracture risk for major osteoporotic fracture was 18.2% and 7.0% for hip fracture. We observed high 'attendance' rates at 79%; however, a significant number were still not available for telephone review (11%) or cancelled their appointment (10%). A recommendation for bisphosphonate treatment was made in 54% of the cohort based on National Osteoporosis Guidelines Group (NOGG) criteria. Follow-up DXA assessment is planned for 64%, according to fracture risk and NOGG guidance. We received 60 responses from the initial patient survey. Ninety percent rated their overall experience of service at 4 or 5 (very good to excellent). Ninety-eight indicated they would recommend the service to others. CONCLUSIONS: Virtual clinics are effective in delivery of fracture risk assessment and clinical management with positive patient experience. While a significant proportion will require DXA follow-up to complete the clinical assessment, virtual clinics have mitigated delays in fracture prevention interventions during the COVID-19 pandemic.

Use of a functional assay to diagnose protein S deficiency; inappropriate testing yields equivocal results.

Inherited deficiency of protein S (PS) is a rare but accepted risk factor for venous thromboembolism. There is accumulating evidence that inherited PS deficiency may be associated with a variety of adverse obstetric events. Acquired PS deficiency may be caused by a variety of clinical states including normal pregnancy. We conducted a retrospective audit of the results of screening for PS deficiency through our reference laboratory. The majority of patients in this audit with significantly reduced (<50%) free functional PS levels had a major confounding factor likely to cause acquired PS deficiency, most frequently pregnancy. Recommendations for PS testing for the diagnosis of hereditary PS deficiency include deferring testing until at least 40 days post-partum. It appears that these recommendations are not being adhered to leading to difficulty in the interpretation of results.

Molecular detection of minimal residual disease in adult and childhood acute lymphoblastic leukaemia reveals differences in treatment response.

Immunoglobulin heavy chain gene (IgH gene) rearrangements are found in the majority of patients with B lineage acute lymphoblastic leukaemia (ALL). Two hundred and three bone marrow samples from 54 patients (33 adults and 21 children) were analysed by PCR within specific time-points after diagnosis (ie 1, 2-3, 4-6 and 7-12 months) using FR1 and JH primers (fingerprinting with a sensitivity > or =1:5 x 10[3]). CDR3-derived allele specific oligoprimers (ASO to achieve a sensitivity between 1:10[4] and 1:10[5]) were applied to 12 children and 18 adults, while size of CDR3 region, oligoclonality and background problems prevented their application to the remaining patients. All patients were followed clinically for > or =24 months. Thirty adults and 16 children presented as newly diagnosed ALL, while the remaining eight patients were analysed in first or subsequent relapse. Patients destined to relapse showed a higher proportion of positive tests (> or =50%), particularly after 1 month, than in the remission group, irrespective of age. Among patients staying in remission, a decrease in MRD-positive tests occurred during the first 12 months in both age groups. However, the proportion of positive tests dropped below 15% at a later stage in adults (4-6 months) than in children (2-3 months). Among children, only patients destined to relapse were MRD positive beyond 1 month, with the exception of only one patient, still positive at 2-3 months in the remission group. The difference in MRD positivity between relapse and remission patients was statistically significant in children (P < 0.03) at any time of testing, but only at 4-6 months in adults (P < 0.01). These data suggest that resolution of MRD in ALL occurs more rapidly in children compared to adults, particularly within the first 6 months. Children and adults, studied in first or subsequent relapse, showed a higher proportion of positive tests during reinduction compared to newly diagnosed patients.

Antimicrobial efficacy of an innovative emulsion of medium chain triglycerides against canine and feline periodontopathogens.

OBJECTIVES: To test the in vitro antimicrobial efficacy of a non-toxic emulsion of free fatty acids against clinically relevant canine and feline periodontopathogens METHODS: Antimicrobial kill kinetics were established utilising an alamarBlue(®) viability assay against 10 species of canine and feline periodontopathogens in the biofilm mode of growth at a concentration of 0·125% v/v medium chain triglyceride (ML:8) emulsion. The results were compared with 0·12% v/v chlorhexidine digluconate and a xylitol-containing dental formulation. Mammalian cellular cytotoxicity was also investigated for both the ML:8 emulsion and chlorhexidine digluconate (0·25 to 0·0625% v/v) using in vitro tissue culture techniques. RESULTS: No statistically significant difference was observed in the antimicrobial activity of the ML:8 emulsion and chlorhexidine digluconate; a high percentage kill rate (>70%) was achieved within 5 minutes of exposure and was maintained at subsequent time points. A statistically significant improvement in antibiofilm activity was observed with the ML:8 emulsion compared with the xylitol-containing formulation. The ML:8 emulsion possessed a significantly lower (P < 0·001) toxicity profile compared with the chlorhexidine digluconate in mammalian cellular cytotoxicity assays. CLINICAL SIGNIFICANCE: The ML:8 emulsion exhibited significant potential as a putative effective antimicrobial alternative to chlorhexidine- and xylitol- based products for the reduction of canine and feline periodontopathogens.

Evaluation of interphase fluorescence in situ hybridization on direct hematological bone marrow smears.

Traditional cytogenetic analysis from bone marrow aspirates is time consuming and frequently suboptimal due to poor viability of cells in culture. Fluorescence in situ hybridization (FISH) with appropriate DNA probes is a potential alternative to routine cytogenetics. Our study examined the reliability of uptake of specific alpha satellite centromere probes from chromosome 18 (D18Z1) and X (DXZ1) and the Yq heterochromatin (pHY3.4) directly from routine hematological bone marrow smears. Altogether 34 separate hybridizations, performed on slides from 20 patients, were scored for fluorescence signals. Cells in interphase were examined with each probe using unstained slides. In addition Giemsa stained slides were destained and then used for interphase FISH. Between 412 and 631 cells were scored for the expected number of signals; 2 for the 18 centromere, 2 for the X centromere in females, one signal for the Yqh in males. The results showed the expected number of signals in 87-97% of cells with the 18 and X probes and 95-97% of cells with the Y probe. Interphase FISH is a reliable, reproducible technique for use on direct bone marrow smears.

The laboratory diagnosis of lupus anticoagulant in patients on oral anticoagulation.

Laboratory-specific cut-off lupus ratios (LR), above which a plasma is judged positive for lupus anticoagulant (LA), were established for both activated partial thromboplastin time-based and dilute Russell viper venom time-based methods. The validity of using these cut-off values to determine the presence of LA in patients on oral anticoagulation (OAC) was assessed. A cohort of 40 patients (23 male and 17 female), aged 22-84 years (mean 52 years) were tested for LA at the time of a thrombotic event. Repeated testing was performed after the same patients were treated with OAC (international normalized ratio 2.0-3.5). For 36 patients (90%), LA status was unchanged pre- and on-OAC. Thirteen of the 40 patients (32.5%) were positive for LA both pre- and on-OAC. Of the 27 patients negative for LA pre-OAC, 23 remained negative on-OAC. The four discordant results were interesting in that LA positivity was demonstrated only after the patient was stable on-OAC. In our cohort of 40 patients, there was a trend for LRs to decrease on-OAC, but this did not reach statistical significance. The subset (4) went against this trend and became positive after the thrombotic event.

Anomalous left anterior descending coronary artery: malignant hospital course of a not so benign anomaly.

Anomalous origin of the left anterior descending coronary artery from the right sinus of Valsalva has been described as a benign anomaly. Typically it takes one of two courses, intraseptal or prepulmonic (though pre-aortic and retro-aortic courses also have been described). We describe the treatment of a patient with prepulmonic route and a malignant course before revascularization.

Innovation adoption behavior among nurses.

This study examined the extent of adoption by clinical nurses of 14 research-based nursing practices and explored characteristics of the nurses which may have influenced their use of innovations. The relationship between the nurses' adoption of innovative practices and their perception of organizational support in the form of a hospital policy about the practice was also examined. The 14 nursing practices used in the study met the criteria established by the 1982 Conduct and Utilization of Research in Nursing (CURN) Project. The Nursing Practice Questionnaire (NPQ) developed by Brett (1987) to explore nurses' stage of innovation adoption was sent to a random sample of nurses in 10 medium sized hospitals throughout North Carolina; 113 nurses responded. The majority of the sample were aware of 9 of the 14 nursing practices. The percentage who were aware of individual practices ranged from 28% to 93.8%. Eight of the 14 practices were used regularly by more than half of the sample.

Revision of dietary analysis software for the Health Habits and History Questionnaire.

The software for analysis of the Health Habits and History Questionnaire (HHHQ) has been revised and is available to researchers. As in earlier versions of the software, questionnaires other than the standard National Cancer Institute versions can be analyzed. Foods can be added or dropped, nutrients can be added or changed, and many other revisions and options are facilitated. Estimates of 33 nutrients and up to 20 user-defined food groups are produced. The validity is unchanged from the previous software. Other features include a data entry key-and-verify system, standardized editing, a computer-assisted interview, and the calculation of health indices including pack-years of smoking and social network index.

Impact of aorto-coronary graft markers on subsequent graft patency: a retrospective review.

The use of aorto-coronary graft markers has not been standard, presumably due to concern about possible adverse effects on subsequent graft patency. Our goal was to determine if there was any increased risk of graft occlusion in patients who received circumferential graft markers at the time of their coronary artery bypass (CAB) surgery. A retrospective review of angiograms was performed for patients with prior CAB. Cohorts with and without graft markers were compared. A total of 405 "unmarked" and 311 "marked" grafts were identified in 335 patients meeting inclusion criteria. Patency is reported in divisions of elapsed time since CAB. Overall patency in the "marked" group (71.1%) was significantly higher than in the "unmarked" group (58.0%, P < 0.001). In this retrospective population, there was no increased risk of graft occlusion in patients who received circumferential graft markers at the time of CAB surgery as compared to those patients who did not.

A dietary and risk factor questionnaire and analysis system for personal computers.

The authors report the adaptation of a dietary and risk factor questionnaire and analysis system for use with IBM (or compatible) personal computers. This system includes a flexible computer-assisted interview program which may be modified to suit investigator needs while preserving a standard output format. It also includes a nutrient analysis program for calculation of usual dietary intake. Each of these two major components has its own set of utilities and options, so that investigators may tailor the system to particular research areas. The nature and capabilities of the two main programs are described, as well as the development of the underlying system and the general flow of data in the system.

Molecular analysis of the leukaemic B cell in adult and childhood acute lymphoblastic leukaemia.

Immunoglobulin heavy chain gene (IgH gene) rearrangements are found in the majority of cases of B-lineage acute lymphoblastic leukaemia (ALL). We have examined bone marrow samples taken at presentation or relapse from 109 patients (79 adults and 30 children) and have performed sequence analysis of the complementarity determining region 3 (CDR3) on 65 alleles from 54 patients. We aimed to define immunoglobulin heavy chain (IgH) variable segment family use and investigate biological and structural features of the B cell in adult and childhood ALL. Using the FR1 fingerprinting method, a rearranged band was identified in 70 (89%) of 79 adult ALL and in 29 (97%) of 30 childhood ALL. This study found no preferential use or selection of IgH VH genes and no statistically significant structural differences between normal and leukaemic B cells in either adult and childhood ALL. An equal proportion of amplifiable cases of adult and childhood ALL uses more than one VH family gene (24/70, 34%, and 8/29, 27.5%, respectively). There were no significant differences in the structure or size of the CDR3 region and the variable (V) or joining (J) segment use in ALL patients compared to normal B cells. We observed that the N2 region was shorter than N1 in children whereas the opposite was observed in adults (not statistically significant). The J4 segment was a more common rearrangement in children than in adults, and in both groups J4 was more frequently associated with multiple D segment VDJ rearrangements. An increase in VH6 use in leukaemic alleles compared to normal B lymphocytes (2%) was observed but it was not statistically significant in our group of patients. Amongst children and adults, in-frame CDR3 junctions occurred in 78% and 64% of rearranged alleles, respectively, compared to 75% of in-frame sequences reported by others to occur among normal B cells.

Effect of venesection on bone mineral density in an eugonadal woman with haemochromatosis.

BACKGROUND: A 41-year-old premenopausal woman with newly diagnosed haemochromatosis was found to have osteopenia on screening bone mineral densitometry. METHODS AND RESULTS: Liver biopsy showed grade 3 haemochromatosis with an hepatic iron index of 4. Investigation for secondary factors for osteopenia revealed no cause. The patient was clinically and biochemically eugonadal. Following venesection of 8 L blood (4 g iron) over 17 months and calcium supplementation, her bone density rose significantly. Neck of femur bone density increased by 6.0% over 13 months and lumbar vertebral bone density increased by 7.2%. There are no previous reports of response of bone density to venesection in eugonadal patients or in women with haemochromatosis.

The use of IgH fingerprinting and ASO-dependent PCR for the investigation of residual disease (MRD) in ALL.

In acute lymphoblastic leukaemia (ALL), investigation of minimal residual disease by conventional morphology and immunology fails to detect levels of residual disease of < 1 leukaemic in 10-100 normal cells. The use of polymerase chain reaction (PCR) to exploit the diversity of the complementarity determining region (CDR) and immunoglobulin variable heavy chain (VH) family specific usage has greatly improved the sensitivity up to one leukaemic cell in 10(5)-10(6) normal bone marrow cells. Here we report on a prospective study of 14 patients with ALL of B-cell lineage by using a combined PCR approach which estimates levels of disease between 1:10(3) and 1:10(5). The sequential use of allele-specific oligoprimer (ASO) independent tests (using framework 1. FR1 and 3, FR3 primers with a JH consensus primer, sensitivity up to 1:5 x 10(3)) and ASO-dependent PCR (sensitivity up to 1:10(5)) assays were applied to 64 bone marrow (BM) follow-up samples in a sequential array of tests. Results presented in this study indicate high concordance of MRD among different tests for samples with level of residual disease > 1:5 x 10(3). Consequently, samples positive by the FR1 and FR3 fingerprinting tests were confirmed by the more sensitive ASO-dependent tests, as expected. However, the ASO-dependent assays revealed levels of disease undetected by the FR1 and FR3 test. Although a higher level of sensitivity is provided by the ASO-dependent tests, the FR1 and FR3 fingerprinting tests allow MRD investigation in patients with oligoclonal B cell proliferations, CDR3 region of size < 15 bp or with ASO primers unsuitable for PCR investigation on technical grounds (i.e. background signal). If a sequential order of investigation from less (e.g. FR1 and FR3 fingerprinting) to more sensitive tests (ASO-dependent) is applied, an indirect estimate of MRD is obtained for patients with level of disease < 1:10(3).

Design and rationale of the ARBITER trial (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol)--a randomized trial comparing the effects of atorvastatin and pravastatin on carotid artery intima-media thickness.

BACKGROUND: As a class, statins are remarkably effective in reducing low-density lipoprotein (LDL) cholesterol, and several of these drugs have now been shown to reduce coronary heart disease morbidity and mortality. However, several important controversies in the use of statins remain to be answered by clinical trials. For example, it is controversial whether marked cholesterol reduction to levels below 100 mg/dL would further reduce the incidence of coronary heart disease. Furthermore, concerns about differences among statins for nonlipid effects has raised the concern that the assumption of a class effect is premature until head-to-head clinical trials are completed. METHODS: Arterial Biology for the Investigation for the Treatment Effects of Reducing Cholesterol (ARBITER) is a single-center, randomized, active-controlled study comparing the efficacy of high-dose atorvastatin (80 mg/d) and pravastatin (40 mg/d) in patients being treated for either the primary or secondary prevention of coronary heart disease. This trial will enroll up to 200 patients for the primary end point of the mean change in intima-media thickness of the common carotid artery. This effect will be evaluated over a treatment duration of 12 months. Secondary end points include the effects of statin therapy on inflammatory and hemostatic markers (C-reactive protein and fibrinogen). CONCLUSION: ARBITER will provide important data on the role of marked LDL reduction and the "class effect" theory of statin therapy in cardiovascular medicine.

Immunoglobulin heavy-chain gene rearrangement in adult acute lymphoblastic leukemia reveals preferential usage of J(H)-proximal variable gene segments.

The aim of this study was to characterize individual-segment and overall patterns of V(H) gene usage in adult B-lineage acute lymphoblastic leukemia (ALL). Theoretical values of V(H) segment usage were calculated with the assumption that all V(H) segments capable of undergoing rearrangement have an equal probability of selection for recombination. Leukemic clones from 127 patients with adult B-lineage acute leukemias were studied by fingerprinting by means of primers for the framework 1 and joining segments. Clones from early preimmune B cells (245 alleles identified) show a predominance of V(H)6 family rearrangements and, consequently, do not conform to this hypothesis. However, profiles of V(H) gene family usage in mature B cells, as investigated in peripheral blood (6 samples), B-cell lymphomas (36 clones) and chronic lymphocytic leukemia (56 clones), are in agreement with this theoretical profile. Sequence analyses of 64 V(H) clones in adult ALL revealed that the rate of V(H) usage is proportional to the proximity of the V(H) gene to the J(H) locus and that the relationship can be mathematically defined. Except for V(H)6, no other V(H) gene is excessively used in adult ALL. V(H) pseudogenes are rarely used (n = 2), which implies the existence of early mechanisms in the pathway to B-cell maturation to reduce wasteful V(H)-(D(H))-J(H) recombination. Finally, similar to early immunoglobulin-H rearrangement patterns in the mouse, B cells of ALL derive from a pool of cells more immature than the cells in chronic lymphoid B-cell malignancies.