A Randomised Phase II Trial of Hippocampal Sparing Versus Conventional Whole Brain Radiotherapy After Surgical Resection or Radiosurgery in Favourable Prognosis Patients With 1-10 Brain Metastases.

AIMS: To assess in patients with 1-10 brain metastases, each of which has been treated by neurosurgery or stereotactic radiosurgery, whether hippocampal sparing whole brain radiotherapy (HS-WBRT) better spares neurocognitive function (NCF) than standard WBRT. Further, to assess whether a phase III randomised trial of HS-WBRT would be feasible in the UK. MATERIALS AND METHODS: A multicentre, randomised, open label phase II trial was undertaken, randomising patients to 30Gy in 10 fractions of WBRT or HS-WBRT. The primary endpoint was decline in Total recall using Hopkins Verbal Learning Test Revised (HVLT-R) at 4 months post treatment. To assess this, we aimed to recruit 84 patients over 3 years. Secondary endpoints included further measures of NCF, quality of life, duration of functional independence, local control of treated metastases, development of new metastases, disease control within the hippocampal regions, overall survival, steroid and antiepileptic medication requirements, and toxicity. RESULTS: The trial closed prematurely due to slower than anticipated recruitment. From April 2016 to January 2018, 23 patients were randomised. Follow up was a median of 25 months. Fifteen patients (6 WBRT, 9 HS-WBRT) were assessed for the primary endpoint; of these, 1 in each arm experienced significant decline in the 4-month HVLT-R Total recall score (p = 0.8). Patients in the HS-WBRT arm experienced less insomnia (p < 0.01) and drowsiness (p < 0.01). There were no differences in other secondary endpoints. CONCLUSION: A phase III randomised trial of HS-WBRT was shown not to be feasible at this time in the UK. As most randomised trials of HS-WBRT reported to date share common endpoints, including NCF, an individual patient data meta-analysis should be undertaken.

Systematic review: dorsal bridge plating in distal radius fractures.

PURPOSE: Distal radius fractures are the most common upper limb fractures in adults (up to 18% of all fractures in the Emergency Department). Conservative management is possible for the majority, the preferred surgical technique being volar plate fixation. Dorsal bridge plating (DBP) is an alternative method of treatment for complex fractures. DBP acts as an internal fixator and can be used in patients needing early rehabilitation. This systematic review assesses the demographics, functional and radiological outcomes and complications of using DBP in patients with distal radius fractures compared to volar plate fixation. METHODS: A literature search of PubMed, Cochrane, EMBASE and Google Scholar was performed according to PRISMA guidelines. Seven hundred and sixty-one articles were found; 11 articles met the inclusion criteria. Cadaveric studies and case studies of less than five patients were excluded. Primary outcome measures were functional and radiological outcomes. Complications were recorded as secondary outcomes. RESULTS: Three hundred and ninety-four patients were included in the study with an average age of 54.8 years (53.9% male and 46.1% female). Weighted mean follow-up was 55.2 weeks; the mean time to plate removal was 17.3 weeks with a mean DASH score of 25.7. The weighted range of movement was 46.9° flexion, 48.8° extension, 68.4° pronation and 67.5° supination. The radiological parameters show satisfactory outcomes with a mean radial height of 10mm, volar tilt of 3.1°, ulnar variance of 0.5mm and radial inclination of 18.8°. The complication rate was 11.4%. Digital stiffness was the most common complication but improved if tenolysis was performed at plate removal. CONCLUSIONS: DBP is a good alternative to volar plating for complex distal radius fractures. The functional outcomes showed a slight loss of range of movement, whereas the radiological outcomes were within recommended limits. A significant disadvantage of the plate is the need for further surgical removal.

Endoscopic stapler versus laser diverticulotomy for Zenker's diverticulum: a systematic review and meta-analysis.

OBJECTIVE: A literature review and meta-analysis was performed to assess for difference in rate of complications and need for revision surgery between endoscopic stapler-assisted diverticulotomy and endoscopic carbon dioxide laser diverticulotomy. The hypothesis was that endoscopic stapler-assisted diverticulotomy has a lower complication rate but endoscopic carbon dioxide laser diverticulotomy has a lower need for revision surgery. METHOD: This was a systematic review of English-language studies comparing endoscopic stapler-assisted diverticulotomy and endoscopic carbon dioxide laser diverticulotomy for the treatment of Zenker's diverticulum. Meta-analysis of results with regard to rate of pharyngeal perforation, major post-operative complication and need for re-operation was performed. RESULTS: Nine retrospective studies were included with pooled analysis of 417 endoscopic stapler-assisted diverticulotomy and 413 endoscopic carbon dioxide laser diverticulotomy cases. Meta-analysis found no significant difference in rate of pharyngeal perforation, major complication or need for re-operation between the two groups. CONCLUSION: This study demonstrated both endoscopic stapler-assisted diverticulotomy and endoscopic carbon dioxide laser diverticulotomy to be a safe alternative to open surgery for Zenker's diverticulum. Both appear to be similar in terms of adverse events and efficacy. The authors recommend either approach, guided by surgeon's preference and experience, where patients are unsuitable for an open surgery approach.

Unilateral tonsil enlargement in children and adults: is routine histology tonsillectomy warranted? A multi-centre series of 323 patients.

BACKGROUND: This study aimed to establish whether histology tonsillectomy is justified for unilateral tonsil enlargement. METHODS: A retrospective review was conducted of histology tonsillectomies in three health organisations over five years, with strict exclusion criteria, focusing on benign-appearing unilateral tonsil enlargement. RESULTS: Ninety paediatric and 233 adult cases were included. No paediatric cases and five adult cases of malignancy were detected. All malignant cases presented with other symptoms. Using binary logistic regression, a history of rapid unilateral tonsil enlargement was the only factor found to be significantly associated with malignant outcome. Thirty-three per cent of subjectively larger tonsils were smaller on post-operative histological measurement. Of the cases, 12.1 per cent re-presented with post-tonsillectomy bleeding. CONCLUSION: The authors recommend avoiding histology tonsillectomy for unilateral tonsil enlargement unless 'red flag' signs of malignancy are present, with particular attention to rapid unilateral tonsil enlargement. This study demonstrated discrepancy between clinical examination findings and true tonsil asymmetry; there may be a role for cross-sectional imaging prior to histology tonsillectomy in high-risk patients.

Comparison of baseline lymphoma and HIV characteristics in Malawi before and after implementation of universal antiretroviral therapy.

Access to antiretroviral therapy (ART) led to epidemiological changes in human immunodeficiency virus (HIV) associated lymphoma in high-income countries such as reductions in diffuse large B-cell lymphoma (DLBCL) and stable or increased Hodgkin lymphoma (HL) and Burkitt lymphoma (BL). In 2016, Malawi implemented a universal ART (UART) policy, expanding ART eligibility to all persons living with HIV (PLWH). We compare the distribution of lymphoma subtypes and baseline HIV and prognostic characteristics for lymphoma patients in Malawi before and after implementation of UART. We enrolled patients with pathologically confirmed incident lymphoproliferative disorders into a observational clinical cohort. At diagnosis, a comprehensive clinicopathological evaluation was performed. Of 412 participants, 156 (38%) were pre-UART (2013-June 2016) and 256 (62%) post-UART (July 2016-2020). HIV prevalence was 50% in both groups. The most common pre-UART diagnoses were DLBCL [75 (48%)], low-grade non-Hodgkin lymphoma (NHL) [19 (12%)], HL [17 (11%)] and, BL [13 (8%)]. For post-UART they were DLBCL [111 (43%)], NHL [28 (11%)], BL [27 11%)] and, HL [20 (8%)]. Among PLWH, 44 (57%) pre-UART initiated ART prior to lymphoma diagnosis compared to 99 (78%) post-UART (p = 0.02). HIV-ribonucleic acid was suppressed <1000 copies/mL in 56% (33/59) pre-UART and 71% (73/103) post-UART (p = 0.05). CD4 T-cell counts were similar for both groups. We observed similar findings in the subset of participants with DLBCL. Overall, there were no significant changes in incident lymphoma subtypes (p = 0.61) after implementation of UART, but HIV was better controlled. Emerging trends bear monitoring and may have implications for prognosis and health system priority setting. Trial registration: ClinicalTrials.gov identifier: NCT02835911.

Association between occupational exposures and sarcoma incidence and mortality: systematic review and meta-analysis.

BACKGROUND: Sarcomas are a rare and heterogeneous group of tumors originating from mesenchymal or connective tissue. They represent less than 1% of all adult cancers. The etiology and epidemiology of sarcomas remain understudied and poorly understood. The main objective of our study was to systematically assess the association between various occupational exposures and risk of sarcomas. METHODS: We performed a systematic literature search using the PubMed, Scopus, EMBASE and Cochrane databases to identify relevant cohort and case-control studies. A meta-analysis method was applied on the incidence and mortality outcomes where the estimate with 95% confidence interval (CI) was obtained. RESULTS: We included a total of 50 publications in our systematic review and 35 in meta-analysis. For exposures to phenoxy herbicides and chlorophenols, the pooled odds ratio (OR) for sarcoma was 1.85 (95% CI: 1.22, 2.82), based on 16 studies with 2254 participants, while the pooled standardized mortality ratio was 40.93 (95% CI 2.19, 765.90), based on 4 cohort studies with 59,289 participants. For exposure to vinyl chloride monomers the pooled risk ratios for angiosarcoma of the liver and other STS were 19.23 (95% CI 2.03, 182.46) and 2.23 (95 CI 1.55, 3.22) respectively based on 3 cohort studies with 12,816 participants. Exposure to dioxins was associated with an increased STS mortality; the pooled standardized mortality ratio was 2.56 (95% CI 1.60, 4.10) based on 4 cohort studies with 30,797 participants. Finally, woodworking occupation was associated with an increased risk of STS with the pooled OR of 2.16 (95% CI 1.39, 3.36). CONCLUSIONS: Our findings suggest a positive association between higher exposure to dioxins and increased mortality from STS, between cumulative exposure to vinyl chloride monomers and increased mortality from angiosarcoma of the liver and STS, and between woodworking occupation and STS incidence. These findings were all statistically significant.

Survival and function following pharyngo-laryngo-oesophagectomy in Wales: a twelve-year case series.

OBJECTIVE: Treatment of locally advanced hypopharyngeal cancer can cause significant morbidity and late toxicity. Pharyngo-laryngo-oesophagectomy can achieve adequate surgical margins, but data on survival and functional outcome are limited, especially in Wales. This study aimed to describe mortality, morbidity and functional outcome following pharyngo-laryngo-oesophagectomy in a Welsh population. METHOD: This study was a retrospective case note review of pharyngo-laryngo-oesophagectomy cases in Wales over 12 years. RESULTS: Fifteen patients underwent pharyngo-laryngo-oesophagectomy; all but one underwent gastric pull-up. Median survival and disease-free survival were 17 months (range, 2-53 months) and 14 months. Censored 3-month, 1-year and 3-year survival was 93, 71 and 50 per cent, respectively. Common Terminology Criteria for Adverse Events grading of long-term dysphagia was 1 in 58 per cent, 2 in 33 per cent and 3 in 8 per cent, and 87.5 per cent achieved a 'moderate' or 'good' voice rehabilitation. CONCLUSION: These results demonstrate favourable survival and reasonable functional outcome following pharyngo-laryngo-oesophagectomy, suggesting pharyngo-laryngo-oesophagectomy should be considered in all appropriate surgical candidates.

Norwich COVID-19 testing initiative pilot: evaluating the feasibility of asymptomatic testing on a university campus.

BACKGROUND: There is a high prevalence of COVID-19 in university-age students, who are returning to campuses. There is little evidence regarding the feasibility of universal, asymptomatic testing to help control outbreaks in this population. This study aimed to pilot mass COVID-19 testing on a university research park, to assess the feasibility and acceptability of scaling up testing to all staff and students. METHODS: This was a cross-sectional feasibility study on a university research park in the East of England. All staff and students (5625) were eligible to participate. All participants were offered four PCR swabs, which they self-administered over two weeks. Outcome measures included uptake, drop-out rate, positivity rates, participant acceptability measures, laboratory processing measures, data collection and management measures. RESULTS: 798 (76%) of 1053 who registered provided at least one swab; 687 (86%) provided all four; 792 (99%) of 798 who submitted at least one swab had all negative results and 6 participants had one inconclusive result. There were no positive results. 458 (57%) of 798 participants responded to a post-testing survey, demonstrating a mean acceptability score of 4.51/5, with five being the most positive. CONCLUSIONS: Repeated self-testing for COVID-19 using PCR is feasible and acceptable to a university population.

Calcium phosphate injection of symptomatic bone marrow lesions of the knee: what is the current clinical evidence?

BACKGROUND: Chronic bone marrow lesions (BML) in the weight-bearing portions of the knee are often associated with symptomatic degenerative arthritis resulting in pain and dysfunction. Injection of bone substitute material like calcium phosphate has been described. Whilst some studies have reported encouraging results others have shown limited benefit of this technique. AIM: The aim was to collate the available evidence on the injection of calcium phosphate and systematically evaluate the results to answer the questions encountered in clinical decision making: (1) does it provide effective long-lasting pain relief to avoid further surgical intervention? (2) which factors (patient/surgical) significantly influence the outcome? and (3) does it adversely affect the outcomes of subsequent arthroplasty? METHODS: A literature search was performed to identify the studies describing the clinical outcomes of calcium phosphate injection for treatment of BML. We evaluated the reported clinical outcomes with respect to pain, function and complications. Isolated case reports and studies with no objective assessment of clinical outcomes were excluded. RESULTS: We noted 46 articles in the current literature of which 8 described clinical outcomes of calcium phosphate injection. Mean (plus/minus SD) score on the visual analog scale (VAS) has been reported to improve from 7.90 (± 0.38) to 2.76 (± 0.90), whereas the International Knee Documentation Committee (IKDC) score improved from 30.5 (SD not reported (NR)) to 53.0 (SD NR). Pre and post procedure Short form survey (SF-12) scores were 29.8 (SD NR) and 36.7 (SD NR), respectively. In one study, scores on the Tegner Lysholm knee scoring scale improved in 12 out of 22 patients, whereas the remainder had no change in symptoms. Extravasation of calcium phosphate into the joint was the most common complication, whereas no adverse effect has been reported on subsequent arthroplasty. CONCLUSION: Limited data from the published studies would suggest that calcium phosphate injection of BML may potentially improve pain and function. However, no evidence is currently available to clearly identify patient/surgical factors that may influence the long-term outcomes of this procedure. Hence pragmatic, prospective studies with stratified patient cohorts and robust reporting of outcome measures are essential to improve the understanding of the indications and clinical effectiveness of this novel procedure.

Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis.

Uterine leiomyomata (UL) are the most common neoplasms of the female reproductive tract and primary cause for hysterectomy, leading to considerable morbidity and high economic burden. Here we conduct a GWAS meta-analysis in 35,474 cases and 267,505 female controls of European ancestry, identifying eight novel genome-wide significant (P < 5 × 10-8) loci, in addition to confirming 21 previously reported loci, including multiple independent signals at 10 loci. Phenotypic stratification of UL by heavy menstrual bleeding in 3409 cases and 199,171 female controls reveals genome-wide significant associations at three of the 29 UL loci: 5p15.33 (TERT), 5q35.2 (FGFR4) and 11q22.3 (ATM). Four loci identified in the meta-analysis are also associated with endometriosis risk; an epidemiological meta-analysis across 402,868 women suggests at least a doubling of risk for UL diagnosis among those with a history of endometriosis. These findings increase our understanding of genetic contribution and biology underlying UL development, and suggest overlapping genetic origins with endometriosis.

Targeting acute myeloid leukemia by drug-induced c-MYB degradation.

Despite advances in our understanding of the molecular basis for particular subtypes of acute myeloid leukemia (AML), effective therapy remains a challenge for many individuals suffering from this disease. A significant proportion of both pediatric and adult AML patients cannot be cured and since the upper limits of chemotherapy intensification have been reached, there is an urgent need for novel therapeutic approaches. The transcription factor c-MYB has been shown to play a central role in the development and progression of AML driven by several different oncogenes, including mixed lineage leukemia (MLL)-fusion genes. Here, we have used a c-MYB gene expression signature from MLL-rearranged AML to probe the Connectivity Map database and identified mebendazole as a c-MYB targeting drug. Mebendazole induces c-MYB degradation via the proteasome by interfering with the heat shock protein 70 (HSP70) chaperone system. Transient exposure to mebendazole is sufficient to inhibit colony formation by AML cells, but not normal cord blood-derived cells. Furthermore, mebendazole is effective at impairing AML progression in vivo in mouse xenotransplantation experiments. In the context of widespread human use of mebendazole, our data indicate that mebendazole-induced c-MYB degradation represents a safe and novel therapeutic approach for AML.

PI3Kδ and PI3Kγ isoforms have distinct functions in regulating pro-tumoural signalling in the multiple myeloma microenvironment.

Phosphoinositide-3-kinase and protein kinase B (PI3K-AKT) is upregulated in multiple myeloma (MM). Using a combination of short hairpin RNA (shRNA) lentivirus-mediated knockdown and pharmacologic isoform-specific inhibition we investigated the role of the PI3K p110γ (PI3Kγ) subunit in regulating MM proliferation and bone marrow microenvironment-induced MM interactions. We compared this with inhibition of the PI3K p110δ (PI3kδ) subunit and with combined PI3kδ/γ dual inhibition. We found that MM cell adhesion and migration were PI3Kγ-specific functions, with PI3kδ inhibition having no effect in MM adhesion or migration assays. At concentration of the dual PI3Kδ/γ inhibitor duvelisib, which can be achieved in vivo we saw a decrease in AKT phosphorylation at s473 after tumour activation by bone marrow stromal cells (BMSC) and interleukin-6. Moreover, after drug treatment of BMSC/tumour co-culture activation assays only dual PI3kδ/γ inhibition was able to induce MM apoptosis. shRNA lentiviral-mediated targeting of either PI3Kδ or PI3Kγ alone, or both in combination, increased survival of NSG mice xeno-transplanted with MM cells. Moreover, treatment with duvelisib reduced MM tumour burden in vivo. We report that PI3Kδ and PI3Kγ isoforms have distinct functions in MM and that combined PI3kδ/γ isoform inhibition has anti-MM activity. Here we provide a scientific rationale for trials of dual PI3kδ/γ inhibition in patients with MM.

People with dementia: what is known about their experience of cancer treatment and cancer treatment outcomes? A systematic review.

OBJECTIVE: The objective of the study is to report a systematic review of what is currently known about the experience of cancer treatment and cancer treatment in adults with dementia. METHODS: The analytic plan and inclusion/exclusion criteria were specified in advance of the search process in a protocol. Searches were conducted in MEDLINE, CINAHL, PsycINFO and the Cochrane Library for publications about people with cancer and a pre-existing dementia. Limits were English language; 2000 to 12/2015; adults; >18 years old. The search identified 5214 titles and abstracts that were assessed against eligibility criteria and 101 were selected for full-text examination by two researchers who agreed inclusion of nine papers, extracted data independently then conducted a content analysis and narrative synthesis. RESULTS: Nine studies conducted in four resource rich countries were included in the review. These studies evidence that when compared with other cancer patients, those with dementia are diagnosed at a later stage, receive less treatment, are more likely to experience complications from treatment and have poorer survival. The experience of supportive care and preferences of people with dementia receiving cancer services and cancer treatment have not been investigated. Research into how the cancer team manage the particular needs of people with dementia and their family members has been limited to one study that reported how a cancer team managed the particular needs of seven people with dementia. CONCLUSION: Further work is needed to establish practice guidelines for the management of cancer in people with dementia. Copyright © 2016 John Wiley & Sons, Ltd.

Trauma-related amputations in war and at a civilian major trauma centre-comparison of care, outcome and the challenges ahead.

The Afghanistan conflict has resulted in a large number of service personnel sustaining amputations. Whilst obvious differences exist between military and civilian trauma-related amputations both settings result in life changing injuries. Comparisons offer the potential of advancement and protection of the knowledge gained during the last 12 years. This paper compares the military and civilian trauma-related amputee cohorts' demographics, management and rehabilitation outcomes measures. The UK military Joint Theatre Trauma Registry and a civilian major trauma centre database of trauma-related amputees were analysed. 255 military and 24 civilian amputees were identified. A significant difference (p>0.05) was seen in median age (24, range 18-43, vs. 48, range 24-87 years), mean number of amputations per casualty (1.6±SD 0.678 vs. 1±SD 0.0), mean ISS (22±SD 12.8 vs. 14.7±SD 15.7) and gender (99% males vs. 78%). Rehabilitation outcome measures recorded included the Special Interest Group in Amputee Medicine score where the military group demonstrated significantly better scores (91% Grade E+ compared to 19%). Differences in patients underlying physiology and psychology, the military trauma system and a huge sustained investment in rehabilitation are all contributing factors for these differing outcomes. However the authors also believe that the use of a consultant-led MDT and central rehabilitation have benefited the military cohort in the acute rehabilitation stage and is reflected in the good short-term outcomes.

Risk stratification for the recurrence of trigger thumb after surgical release in the paediatric patient.

Trigger thumb, or stenosing tenovaginitis, is a relatively uncommon condition affecting the flexor pollicis longus tendon of children. The condition is characterized by the formation of a nodule within the tendon and thickening of the tendon sheath as it passes through the flexor pulley of the thumb at the level of the metacarpo-phalangeal joint. The optimum age for surgical intervention continues to be discussed. The aim of this study is to establish the temporal relationship and surgical variables to determine factors that may contribute to recurrence of the condition. A retrospective analysis of the entire surgical logbook and patient notes of a stand-alone consultant paediatric orthopaedic practice was scrutinized. 94 patients, 107 thumbs, over a 13-year period were operated on for trigger thumb. The recurrence rate was found to be 5.61 %. The average age of patients at primary release who went on to recurrence was 2.8 years, which is significantly younger than those that did not recur (p = 0.044). Sensitivity analysis revealed that the primary procedure at an age of less than 2.5 years confers a higher risk of recurrence. The data presented here advocate surgical release of trigger thumb after 2½ years of age, a senior surgeon as lead operator and a transverse skin incision at the level of the nodule or a more extensive "zig-zag" one to clearly see the structures to be released. We recommend that the surgeon ensures the stenosing pulley and sheath are released in their entirety.

Surgical advances during the First World War: the birth of modern orthopaedics.

The First World War (1914-1918) was the first truly industrial conflict in human history. Never before had rifle fire and artillery barrage been employed on a global scale. It was a conflict that over 4 years would leave over 750,000 British troops dead with a further 1.6 million injured, the majority with orthopaedic injuries. Against this backdrop, the skills of the orthopaedic surgeon were brought to the fore. Many of those techniques and systems form the foundation of modern orthopaedic trauma management. On the centenary of 'the War to end all Wars', we review the significant advances in wound management, fracture treatment, nerve injury and rehabilitation that were developed during that conflict.

Posterior mini-incision total hip arthroplasty controls the extent of post-operative formation of heterotopic ossification.

Heterotopic ossification (HO) is the formation of bone at extra-skeletal sites. Reported rates of HO after hip arthroplasty range from 8 to 90 %; however, it is only severe cases that cause problems clinically, such as joint stiffness. The effects of surgical-related controllable intra-operative risk factors for the formation of HO were investigated. Data examined included gender, age of patient, fat depth, length of operation, incision length, prosthetic fixation method, the use of pulsed lavage and canal brush, and component size and material. All cases were performed by the same surgeon using the posterior approach. A total of 510 cases of hip arthroplasty were included, with an overall rate of HO of 10.2 %. Longer-lasting operations resulted in higher grades of HO (p = 0.047). Incisions >10 cm resulted in more widespread HO formation (p = 0.021). No further correlations were seen between HO formation and fat depth, blood loss, instrumentation, fixation methods or prosthesis material. The mini-incision approach is comparable to the standard approach in the aetiology of HO formation, and whilst the rate of HO may not be controllable, a posterior mini-incision approach can limit its extent.

Oral disease profiles in chronic graft versus host disease.

At least half of patients with chronic graft-versus-host-disease (cGVHD), the leading cause of morbidity and non-relapse mortality after allogeneic stem cell transplantation, have oral manifestations: mucosal lesions, salivary dysfunction, and limited mouth-opening. cGVHD may manifest in a single organ or affect multiple organ systems, including the mouth, eyes, and the skin. The interrelationship of the 3 oral manifestations of cGVHD with each other and with the specific manifestations of extraoral cGVHD has not been studied. In this analysis, we explored, in a large group of patients with cGVHD, the potential associations between: (1) oral mucosal disease and erythematous skin disease, (2) salivary gland dysfunction and lacrimal gland dysfunction, and (3) limited mouth-opening and sclerotic skin cGVHD. Study participants, enrolled in a cGVHD Natural History Protocol (NCT00331968, n = 212), underwent an oral examination evaluating: (1) mucosal cGVHD [NIH Oral Mucosal Score (OMS)], (2) salivary dysfunction (saliva flow and xerostomia), and (3) maximum mouth-opening measurement. Parameters for dysfunction (OMS > 2, saliva flow ≤ 1 mL/5 min, mouth-opening ≤ 35 mm) were analyzed for association with skin cGVHD involvement (erythema and sclerosis, skin symptoms), lacrimal dysfunction (Schirmer's tear test, xerophthalmia), Lee cGVHD Symptom Scores, and NIH organ scores. Oral mucosal disease (31% prevalence) was associated with skin erythema (P < 0.001); salivary dysfunction (11% prevalence) was associated with lacrimal dysfunction (P = 0.010) and xerostomia with xerophthalmia (r = 0.32, P = 0.001); and limited mouth-opening (17% prevalence) was associated with skin sclerosis (P = 0.008) and skin symptoms (P = 0.001). There was no association found among these 3 oral cGVHD manifestations. This analysis supports the understanding of oral cGVHD as 3 distinct diseases: mucosal lesions, salivary gland dysfunction, and mouth sclerosis. Clear classification of oral cGVHD as 3 separate manifestations will improve clinical diagnosis, observational research data collection, and the definitions of outcome measures in clinical trials.

Systematic review and meta-analysis of the performance of clinical risk assessment instruments for screening for osteoporosis or low bone density.

UNLABELLED: We performed a systematic review and meta-analysis of the performance of clinical risk assessment instruments for screening for DXA-determined osteoporosis or low bone density. Commonly evaluated risk instruments showed high sensitivity approaching or exceeding 90% at particular thresholds within various populations but low specificity at thresholds required for high sensitivity. Simpler instruments, such as OST, generally performed as well as or better than more complex instruments. INTRODUCTION: The purpose of the study is to systematically review the performance of clinical risk assessment instruments for screening for dual-energy X-ray absorptiometry (DXA)-determined osteoporosis or low bone density. METHODS: Systematic review and meta-analysis were performed. Multiple literature sources were searched, and data extracted and analyzed from included references. RESULTS: One hundred eight references met inclusion criteria. Studies assessed many instruments in 34 countries, most commonly the Osteoporosis Self-Assessment Tool (OST), the Simple Calculated Osteoporosis Risk Estimation (SCORE) instrument, the Osteoporosis Self-Assessment Tool for Asians (OSTA), the Osteoporosis Risk Assessment Instrument (ORAI), and body weight criteria. Meta-analyses of studies evaluating OST using a cutoff threshold of <1 to identify US postmenopausal women with osteoporosis at the femoral neck provided summary sensitivity and specificity estimates of 89% (95%CI 82-96%) and 41% (95%CI 23-59%), respectively. Meta-analyses of studies evaluating OST using a cutoff threshold of 3 to identify US men with osteoporosis at the femoral neck, total hip, or lumbar spine provided summary sensitivity and specificity estimates of 88% (95%CI 79-97%) and 55% (95%CI 42-68%), respectively. Frequently evaluated instruments each had thresholds and populations for which sensitivity for osteoporosis or low bone mass detection approached or exceeded 90% but always with a trade-off of relatively low specificity. CONCLUSIONS: Commonly evaluated clinical risk assessment instruments each showed high sensitivity approaching or exceeding 90% for identifying individuals with DXA-determined osteoporosis or low BMD at certain thresholds in different populations but low specificity at thresholds required for high sensitivity. Simpler instruments, such as OST, generally performed as well as or better than more complex instruments.