The role of depression in the association between mobilisation timing and live discharge after hip fracture surgery: Secondary analysis of the UK National Hip Fracture Database.

PURPOSE: The aim was to compare the probability of discharge after hip fracture surgery conditional on being alive and in hospital between patients mobilised within and beyond 36-hours of surgery across groups defined by depression. METHODS: Data were taken from the National Hip Fracture Database and included patients 60 years of age or older who underwent hip fracture surgery in England and Wales between 2014 and 2016. The conditional probability of postsurgical live discharge was estimated for patients mobilised early and for patients mobilised late across groups with and without depression. The association between mobilisation timing and the conditional probability of live discharge were also estimated separately through adjusted generalized linear models. RESULTS: Data were analysed for 116,274 patients. A diagnosis of depression was present in 8.31% patients. In those with depression, 7,412 (76.7%) patients mobilised early. In those without depression, 84,085 (78.9%) patients mobilised early. By day 30 after surgery, the adjusted odds ratio of discharge among those who mobilised early compared to late was 1.79 (95% CI: 1.56-2.05, p<0.001) and 1.92 (95% CI: 1.84-2.00, p<0.001) for those with and without depression, respectively. CONCLUSION: A similar proportion of patients with depression mobilised early after hip fracture surgery when compared to those without a diagnosis of depression. The association between mobilisation timing and time to live discharge was observed for patients with and without depression.

Homelessness in pregnancy.

OBJECTIVES: To evaluate the association, if any, of homelessness or refuge accommodation on delivery and short term perinatal outcomes in an Irish tertiary maternity hospital. METHODS: A retrospective cohort study of 133 singleton pregnancies in women reporting to be homeless or living in refuge at their booking antenatal appointment between 2013 and 2022. Analysis compared sociodemographic characteristics and perinatal outcomes in this cohort to a reference population of 76,858 women with stable living arrangements. RESULTS: Women in the homeless/refuge population were statistically more likely to be single (75.2 % vs 39.5 %, p < 0.001), have an unplanned pregnancy (73.7 % vs 27.2 %, p < 0.001), report a history of psychiatric illness (42.9 % vs 22.4 %, p < 0.001), domestic violence (18.8 % vs 0.9 %, p < 0.001) alcohol consumption in pregnancy (3.0 % vs 0.8 %, p < 0.001) or smoking in pregnancy (41.3 % vs 9.7 %, p < 0.001). They were significantly more likely to have a preterm birth (adjusted OR 1.71 (1.01-2.87) p = 0.04). They also had a significantly lower median birth weight compared to the reference population (birthweight 3270 g vs 3420 g, p < 0.001). CONCLUSION: Women in the homeless and refuge population are more likely to experience poorer perinatal outcomes compared to women with stable living arrangements.

Barriers and facilitators of weight bearing after hip fracture surgery among older adults. A scoping review.

PURPOSE: This scoping review aimed to synthesise the available evidence on barriers and facilitators of weight bearing after hip fracture surgery in older adults. METHODS: Published (Cochrane Central, MEDLINE, EMBASE, CINAHL, and PEDro) and unpublished (Global Health, EThOS, WorldCat dissertation and thesis, ClinicalTrials.gov , OpenAIRE, DART-Europe) evidence was electronically searched from database inception to 29 March 2022. Barriers and facilitators of weight bearing were extracted and synthesised into patient, process (non-surgical), process (surgical), and structure-related barriers/facilitators using a narrative review approach. RESULTS: In total, 5594 were identified from the primary search strategy, 1314 duplicates were removed, 3769 were excluded on title and abstract screening, and 442 were excluded on full-text screening. In total, 69 studies (all from published literature sources) detailing 47 barriers and/or facilitators of weight bearing were included. Of barriers/facilitators identified, 27 were patient-, 8 non-surgical process-, 8 surgical process-, and 4 structure-related. Patient facilitators included anticoagulant, home discharge, and aid at discharge. Barriers included preoperative dementia and delirium, postoperative delirium, pressure sores, indoor falls, ventilator dependence, haematocrit < 36%, systemic sepsis, and acute renal failure. Non-surgical process facilitators included early surgery, early mobilisation, complete medical co-management, in-hospital rehabilitation, and patient-recorded nurses' notes. Barriers included increased operative time and standardised hip fracture care. Surgical process facilitators favoured intramedullary fixations and arthroplasty over extramedullary fixation. Structure facilitators favoured more recent years and different healthcare systems. Barriers included pre-holiday surgery and admissions in the first quarter of the year. CONCLUSION: Most patient/surgery-related barriers/facilitators may inform future risk stratification. Future research should examine additional process/structure barriers and facilitators amenable to intervention. Furthermore, patient barriers/facilitators need to be investigated by replicating the studies identified and augmenting them with more specific details on weight bearing outcomes.

Demographic changes in primiparae of Irish ethnicity between 2000 and 2020.

BACKGROUND: Trends in maternal demographic changes linked to lifestyle and socio-economic conditions reflect greatly on maternal, perinatal and infant mortality rates. Hospital data reflect a heterogenous population where specific demographic changes may not be obvious. OBJECTIVES: To report yearly demographic changes in Irish primiparae from 2000 to 2020, specifically looking at age, BMI, smoking and marital status of patients attending the Coombe Women and Infant's University Hospital (CWIUH). METHODS: Retrospective report of demographic details contemporaneously documented on the CWIUH data base. FINDINGS: In the years 2000 to 2020 inclusive there were 47,659 primiparous women of Irish ethnicity delivered at the CWIUH (70.2% of the total primiparae), of those 99.3% were Caucasian. There was a significant rise in mean age at first delivery in Irish mothers; 26.0 years old in the 2000 to 30.9 years old in 2020 associated with a rise in mean BMI of 9.1%. Smoking rates (ever smoked) showed a significant reduction from 53.9% in 2000 to 39.3% in 2020. There was a significant decrease in rates of marriage, with 61.9% married in 2000 compared to 46.3% in 2020. Birth weight and prematurity rates remained unchanged, with fall in mean gestational age at first delivery from 279.3 days in 2000 to 275.8 days in 2020. CONCLUSION: This study highlights that Irish primiparae are older, heavier, less likely to smoke and to be married than they were 20 years ago. These trends are an interesting glimpse into changing economic and cultural climate over just the past 2 decades.

Prognostic factors of depression and depressive symptoms after hip fracture surgery: systematic review.

BACKGROUND: Patients with hip fracture and depression are less likely to recover functional ability. This review sought to identify prognostic factors of depression or depressive symptoms up to 1 year after hip fracture surgery in adults. This review also sought to describe proposed underlying mechanisms for their association with depression or depressive symptoms. METHODS: We searched for published (MEDLINE, Embase, PsychInfo, CINAHL and Web of Science Core Collection) and unpublished (OpenGrey, Greynet, BASE, conference proceedings) studies. We did not impose any date, geographical, or language limitations. Screening (Covidence), extraction (Checklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies, adapted for use with prognostic factors studies Checklist), and quality appraisal (Quality in Prognosis Studies tool) were completed in duplicate. Results were summarised narratively. RESULTS: In total, 37 prognostic factors were identified from 12 studies included in this review. The quality of the underlying evidence was poor, with all studies at high risk of bias in at least one domain. Most factors did not have a proposed mechanism for the association. Where factors were investigated by more than one study, the evidence was often conflicting. CONCLUSION: Due to conflicting and low quality of available evidence it is not possible to make clinical recommendations based on factors prognostic of depression or depressive symptoms after hip fracture. Further high-quality research investigating prognostic factors is warranted to inform future intervention and/or stratified approaches to care after hip fracture. TRIAL REGISTRATION: Prospero registration: CRD42019138690 .

Bare necessities? The utility of full skin examination in the COVID-19 era.

Full skin examination (FSE) may improve the detection of malignant melanoma (MM). The objective of this study was to assess the safety of targeted lesion examination (TLE) compared with FSE in our Pigmented Lesion Clinic (PLC). Patients attending the PLC were randomized in a 2 : 1 ratio to FSE (intervention) or TLE (standard care). Demographic details and risk factors were documented, and the time taken to perform FSE and TLE was noted. Of 763 participants, 520 were assigned to FSE and 243 were assigned to TLE. On average, FSE took 4.02 min and TLE took 30 s to perform. Of the 520 participants assigned to FSE, 37 (7.1%) had incidental findings, of whom 12 patients (2.3%) had additional lesions biopsied. No additional melanomas were detected that would have been missed by use of the standard protocol. This study suggests that in low-risk patients referred to a PLC with a lesion of concern, the possibility of missing incidental cutaneous malignancies using lesion-directed examination is low.

Skin Cancer Awareness Amongst Irish Golfers.

Aim The aim of this study was to assess skin cancer awareness and identify the UV protective measures used by golfers within the Munster region of Ireland. Methods Subjects were recruited from throughout the Munster region at a regional competition, and at three other local golf clubs and "pro" shops. Participants filled out a short anonymous validated questionnaire when collecting their score cards7. Results One hundred and sixty-three golfers completed the questionnaire with a mean age of 65.6 years. 137 (84%) were male and 26 (16%) were female. We noted a high incidence of both non-melanoma and melanoma skin cancer in our subjects. Sixteen (9.8%) had a previous history of skin cancer, with 8 melanomas and 8 non-melanoma skin cancers. A high percentage, 85%, of the golfers surveyed were compliant with SPF use. However many were using too low a SPF, 63 (44%) were using a SPF less than 30. Knowledge of risk of skin cancer is better amongst the golfers surveyed when compared to the general population. Most respondents (N = 96 (59%)) were aware that melanoma can lead to death if left untreated and 114 (70%) recognized that melanoma can be cured if treated early. Conclusion Golfers may benefit from targeted education emphasizing the importance of higher SPF use. Other interventions that may benefit this population would include availability of sunscreens and educational literature in 'pro' shops at golf courses.

Dynamic sentinel node biopsy for penile cancer: an initial experience in an Irish Hospital.

BACKGROUND: The presence of nodal metastases is the single most important prognostic factor in penile cancer. However, reliable assessment of nodal status in clinically node-negative (cN0) patients poses a challenge. Approximately 20% of these patients harbour occult nodal metastases. Currently available non-invasive radiological investigations are unreliable in excluding micrometastatic disease. AIM: Dynamic sentinel node biopsy (DSNB) is a minimally invasive procedure for assessing lymph node involvement. We report our initial experience with DSNB in assessing the status of regional lymph nodes in cN0 penile cancer patients. METHODS: DSNB was performed in penile cancer patients with at least one cN0 groin. All patients undergoing DSNB at our institution were included. Lymphoscintigraphic images were obtained from all patients, after intradermal, peritumoral injection of a Technetium-99m nanocolloid. The sentinel nodes were defined as the nodes identified on lymphoscintigraphy, which were also radioactive intraoperatively using a gamma probe. RESULTS: In total, 18 groins from 11 patients underwent DSNB. Of these, 11 patients underwent bilateral DSNB and 4 had unilateral DSNB. The mean (range) age of patients at the time of presentation of their primary tumour was 63 (39-78) years. A mean of 1.2 nodes per groin was retrieved. One lymph node was positive in one patient, who subsequently underwent a bilateral inguinal lymph node dissection. Overall, the median (range) follow-up was 12.8 (2.7-31.3) months with no local or regional recurrences. CONCLUSION: Further cases and longer follow-up will define the accuracy of this technique in the Irish population.

Impact of age and medical comorbidity on adjuvant treatment outcomes for stage III colon cancer: a pooled analysis of individual patient data from four randomized, controlled trials.

BACKGROUND: Adjuvant oxaliplatin plus capecitabine or leucovorin/5-fluorouracil (LV/5-FU) (XELOX/FOLFOX) is the standard of care for stage III colon cancer (CC); however, there is disagreement regarding oxaliplatin benefit in patients aged >70. In most analyses, the impact of medical comorbidity (MC) has not been assessed. Efficacy and safety of adjuvant XELOX/FOLFOX versus LV/5-FU were compared with respect to age and MC using pooled data from four randomized, controlled trials, selected for access to patient-level MC data and including commonly endorsed and utilized regimens. PATIENTS AND METHODS: Individual data from patients with stage III CC in NSABP C-08, XELOXA, X-ACT, and AVANT were pooled, excluding bevacizumab-treated patients. Patients were grouped by treatment, MC (low versus high), or age (<70 versus ≥70), and compared for disease-free survival (DFS), overall survival (OS), and adverse events (AEs). Multivariable Cox proportional hazards regression controlled for gender, T stage, and N stage. RESULTS: DFS benefits were shown for XELOX/FOLFOX versus LV/5-FU regardless of age or MC, although benefits were modestly attenuated for patients aged ≥70. Hazard ratios were 0.68 (P < 0.0001) and 0.77 (P < 0.014) for <70 and ≥70 age groups; 0.69 (P < 0.0001) and 0.59 (P < 0.0001) for Charlson Comorbidity Index ≤1 and >1 groups; and 0.70 (P < 0.0001) and 0.58 (P < 0.0001) for National Cancer Institute Combined Index ≤1 and >1 groups. OS was also significantly improved in all groups. Grade 3/4 serious AE rates were comparable across cohorts and MC scores and higher in patients aged ≥70. Oxaliplatin-relevant grade 3/4 AEs, including neuropathy, were comparable across ages and MC scores. CONCLUSIONS: Results further support consideration of XELOX or FOLFOX as standard treatment options for the adjuvant management of stage III CC in all age groups and in patients with comorbidities, consistent with those who were eligible for these clinical trials.

Innovative estimation of survival using log-normal survival modelling on ACCENT database.

BACKGROUND: The ACCENT database, with individual patient data for 20 898 patients from 18 colon cancer clinical trials, was used to support Food and Drug Administration (FDA) approval of 3-year disease-free survival as a surrogate for 5-year overall survival. We hypothesised substantive differences in survival estimation with log-normal modelling rather than standard Kaplan-Meier or Cox approaches. METHODS: Time to relapse, disease-free survival, and overall survival were estimated using Kaplan-Meier, Cox, and log-normal approaches for male subjects aged 60-65 years, with stage III colon cancer, treated with 5-fluorouracil-based chemotherapy regimens (with 5FU), or with surgery alone (without 5FU). RESULTS: Absolute differences between Cox and log-normal estimates with (without) 5FU varied by end point. The log-normal model had 5.8 (6.3)% higher estimated 3-year time to relapse than the Cox model; 4.8 (5.1)% higher 3-year disease-free survival; and 3.2 (2.2)% higher 5-year overall survival. Model checking indicated greater data support for the log-normal than the Cox model, with Cox and Kaplan-Meier estimates being more similar. All three model types indicate consistent evidence of treatment benefit on both 3-year disease-free survival and 5-year overall survival; patients allocated to 5FU had 5.0-6.7% higher 3-year disease-free survival and 5.3-6.8% higher 5-year overall survival. CONCLUSION: Substantive absolute differences between estimates of 3-year disease-free survival and 5-year overall survival with log-normal and Cox models were large enough to be clinically relevant, and warrant further consideration.

A spoonful of sugar makes the melanoma go: the role of heparan sulfate proteoglycans in melanoma metastasis.

Heparan sulfate proteoglycans (HSPGs) have been shown to regulate signaling in many systems and are of increasing interest in cancer. While these are not the only sugars to drive melanoma metastasis, HSPGs play important roles in driving metastatic signaling cascades in melanoma. The ability of these proteins to modulate ligand-receptor interactions in melanoma has been quite understudied. Recent data from several groups indicate the importance of these ligands in modulating key signaling pathways including Wnt and fibroblast growth factor (FGF) signaling. In this review, we summarize the current knowledge regarding the structure and function of these proteoglycans and their role in melanoma. Understanding how HSPGs modulate signaling in melanoma could lead to new therapeutic approaches via the dampening or heightening of key signaling pathways.

Hepatitis C: is there a case for universal screening in pregnancy?

Hepatitis C (HCV) is not routinely screened for antenatally in all maternity hospitals. Most hospitals adopt a policy of targeted screening. The policy in the Coombe Women and Infants University Hospital in Dublin changed from targeted screening in 2006 to universal screening in 2007. We audited the two consecutive years. The prevalence of HCV in our antenatal population was 1.4% for 2006 (67/4666) when targeted screening applied and in 2007--0.71% (66/9222) when universal screening came into affect. One woman in 2007 would not have been detected by targeted screening--1.49% (1/67). Fifty five percent (37/67) of women were HCV-RNA positive in 2006 and 57.5% (38/66) were positive in 2007. We conclude that there were similar detection rates for HCV in 2006 and 2007 and that universal screening is not required if inclusive criteria for selective screening are employed but is of use in research context.

Spontaneous resolution of a giant keratoacanthoma penetrating through the nose.

Although keratoacanthomas are common and spontaneous resolution well recognized, case reports with photographic documentation of resolution are few. The subtype of giant keratoacanthoma (GKA) can give rise to severe cosmetic destruction because of their size and their predilection for cosmetically sensitive areas (nose and eyelids). Spontaneous resolution of GKAs has not been widely reported. We present an impressive series of clinical photographs documenting the spontaneous resolution of a GKS on the nose of a 56-year-old patient.

The cannabinoid receptor inverse agonist AM251 regulates the expression of the EGF receptor and its ligands via destabilization of oestrogen-related receptor α protein.

BACKGROUND AND PURPOSE: AM251 is an inverse agonist of the cannabinoid 1 receptor (CB(1)R) that can exert 'off-target' effects in vitro and in CB(1)R knock-out mice. AM251 is also potent at modulating tumour cell growth, suggesting that growth factor-mediated oncogenic signalling could be regulated by AM251. Since dysregulation of the EGF receptor has been associated with carcinogenesis, we examined AM251 regulation of EGF receptor (EGFR) expression and function. EXPERIMENTAL APPROACH: The various biological functions of AM251 were measured in CB(1)R-negative human cancer cells. Pharmacological and genetic approaches were used to validate the data. KEY RESULTS: The mRNA levels for EGFR and its associated ligands, including HB-EGF, were induced several fold in PANC-1 and HCT116 cells in response to AM251. This event was associated with enhanced expression of EGFR on the cell surface with concomitant increase in EGF-induced cellular responses in AM251-treated cells. Exposure to XCT790, a synthetic inverse agonist of the orphan nuclear oestrogen-related receptor α (ERRα), also induced EGFR and HB-EGF expression to the same extent as AM251, whereas pretreatment with the ERRα-selective agonist, biochanin A, blunted AM251 actions. AM251 promoted the degradation of ERRα protein without loss of the corresponding mRNA. Knock-down of ERRα by siRNA-based approach led to constitutive induction of EGFR and HB-EGF levels, and eliminated the biological responses of AM251 and XCT790. Finally, AM251 displaced diethylstilbestrol prebound to the ligand-binding domain of ERRα. CONCLUSIONS AND IMPLICATIONS: AM251 up-regulates EGFR expression and signalling via a novel non-CB(1)R-mediated pathway involving destabilization of ERRα protein in selected cancer cell lines.

The KineSpring load absorber implant: rationale, design and biomechanical characterization.

Osteoarthritis (OA) of the knee is the leading cause of disability in the adult population. Although a number of treatments for knee OA are available, none effectively prevent OA progression. Currently, a wide therapeutic gap exists for patients who have unsuccessfully exhausted conservative OA treatments but who are hesitant or ineligible to undergo invasive surgery. The KineSpring device is a novel, joint preserving, minimally invasive implant that reduces medial compartment loading without significantly impacting the loading of the lateral compartment. This article describes the rationale for and the design of the KineSpring device and summarizes results of initial biomechanical testing in an OA cadaver model.

Current trends in the follow-up of head and neck cancer patients in the UK.

AIMS: The follow-up of patients with head and neck cancer is an essential aspect of their management. Follow-up provides support and reassurance for patients and will allow early detection of recurrence and second primary tumours. However, there is little evidence of a survival benefit from follow-up. With prolonged follow-up periods, multidisciplinary teams may be under increasing pressure to see more patients and this could have a negative effect on the time and quality of consultations given to individual patients. The aim of the present study was to analyse the current trends in the follow-up of head and neck cancer patients after treatment with curative intent in the UK. MATERIALS AND METHODS: A postal questionnaire was sent to all members of the British Association of Head and Neck Oncologists. RESULTS: Three hundred and twenty-seven questionnaires were sent and 214 were returned, making a response rate of 65.4%. One hundred and ninety-eight (61%) of these were deemed appropriate for evaluation and of these 111 (56%) clinicians followed up patients for a minimum of 5 years with 25 (13%) following patients for 10 years and 44 (22%) for life. Within the set of clinicians following patients for 5 years, 24 (12%) followed up patients with salivary gland and thyroid malignancies for a longer period of time. All clinicians concurred that the reasons for follow-up are to support patients, to detect local recurrences or metastases, second primary tumours and to monitor and manage the complications of treatment. CONCLUSIONS: Most of the clinicians followed up their patients up to a minimum of 5 years, with a significant minority who followed up the patients treated for cancers of the head and neck for longer periods. More studies are needed to elucidate the rationale and evidence for follow-up and to determine the adequate period of surveillance.

Prognostic effect of activated EGFR expression in human colon carcinomas: comparison with EGFR status.

BACKGROUND: Evidence suggests that epidermal growth factor receptor (EGFR)-activation status may better predict the clinical behaviour of colon cancers than does EGFR expression. However, the prognostic effect of phospho-EGFR in primary colon cancer remains undefined. METHODS: Phospho-EGFR (Tyr-1173) and EGFR expression were analysed by immunohistochemistry (IHC) in tissue microarrays of TNM stage II and III colon cancers from completed adjuvant therapy trials (n=388). Staining intensity was scored and correlated with clinicopathological variables, DNA mismatch repair (MMR) status, rates of cell proliferation (Ki-67), apoptosis (caspase-3), and patient survival. RESULTS: Phospho-EGFR expression was detected in 157 of 388 (40%) tumours, whereas EGFR was found in 214 of 361 (59%). Although phospho-EGFR was unrelated to clinicopathological variables, strong EGFR intensity was associated with higher tumour stage (P=0.03). Tumours overexpressing EGFR (P=0.0002) or phospho-EGFR (P=0.015) showed increased Ki-67, but not caspase-3 expression. Phospho-EGFR was not prognostic. EGFR intensity was associated with worse disease-free survival (DFS) (hazard ratio (HR): 1.21 (1.03, 1.41); P=0.019) and overall survival (OS) (HR: 1.19 (1.02, 1.39); P=0.028). Tumours expressing both EGFR and phospho-EGFR had similar survival as EGFR alone. Stage and lymph node number were prognostic for DFS and OS, and histological grade for OS. EGFR was an independent predictor of DFS (P=0.042) after adjustment for stage, histological grade, age, and MMR status. CONCLUSION: Phospho-EGFR and EGFR expression were associated with tumour cell hyperproliferation. Phospho-EGFR was not prognostic, whereas increased EGFR intensity was independently associated with poor DFS.

The orphan tyrosine kinase receptor, ROR2, mediates Wnt5A signaling in metastatic melanoma.

Tyrosine kinase receptors represent targets of great interest for cancer therapy. Here we show, for the first time, the importance of the orphan tyrosine kinase receptor, ROR2, in melanoma progression. Using melanoma tissue microarrays, we show that ROR2 is expressed predominantly in metastatic melanoma. As ROR2 has been shown to specifically interact with the non-canonical Wnt ligand, Wnt5A, this corroborates our earlier data implicating Wnt5A as a mediator of melanoma metastasis. We show here that increases in Wnt5A cause increases in ROR2 expression, as well as the PKC-dependent, clathrin-mediated internalization of ROR2. WNT5A knockdown by siRNA decreases ROR2 expression, but silencing of ROR2 has no effect on WNT5A levels. ROR2 knockdown does, however, result in a decrease in signaling downstream of Wnt5A. Using in vitro and in vivo metastasis assays, we show that ROR2 is necessary for the Wnt5A-mediated metastasis of melanoma cells. These data imply that ROR2 may represent a novel target for melanoma therapy.