The Effect of COVID-19 on 30-Day Mortality Rates Amongst Fragility Hip Fracture Patients.

Aim Fragility hip fracture patients have always been vulnerable to high rates of short term mortality, an issue that may have been exacerbated by the ongoing COVID-19 pandemic. To date, published data regarding Irish hip fracture patients in the era of COVID-19 is limited. This study aims to assess the effect of COVID-19 on 30-day mortality rates amongst a group of Irish hip fracture patients. Additionally, patient demographics, length of stay, admission haematological parameters, fracture type and surgical procedure will be assessed. Methods A multicentre, observational, retrospective study of hip fracture patients (n = 1,017) admitted to six Dublin teaching hospitals during the COVID-19 pandemic (4th February to 9th July 2020) was performed. For comparative purposes, equivalent data was retrospectively collected relating to hip fracture patients admitted to the same six teaching hospitals during the same time period in 2019. Results 481 patients were admitted during the specified timeframe in 2020, compared with 536 in 2019. The mean patient age was 77.6 years and 65.9% of patients were female. There was no statistically significant overall difference in 30-day mortality rates between the study and control groups, at 5.4% in 2020 and 4.3% in 2019 (p=0.338). There was an insignificant decrease in mean length of stay (17.85 days in 2020 vs. 18.82 days in 2019; p=0.106). Advancing age (p=0.021), male gender (p=0.019), low admission haemoglobin (p=0.024) and high admission white cell count (p=0.019) were all associated with increased 30-day mortality. Conclusion We found no significant difference in 30-day mortality rates amongst our cohort of hip fracture patients at the height of the COVID-19 pandemic in Ireland. Advancing age, male gender, anaemia at admission and leucocytosis at admission were associated with increased 30-day mortality. The continuation of COVID-19 related safety protocols in the treatment of hip fracture patients is essential in maintaining a safe hip fracture service.

The Patient's Second Hip Fracture - One in Ten.

Introduction The number of fragility hip fractures (>60 years) are estimated to triple/quadruple by 2050. It is estimated that the prevalence of patient's contralateral hip fractures (HF2s) will increase also. Methods Single hospital, Retrospective review, 2013-2017, Radiograph review, n = 822. Results Management of patient's 2nd hip fractures accounted for 10.5% of all hip fracture surgeries. ~50% occurred within 3 years of the 1st hip fracture. There was no statistically significant difference in discharge destination, length-of-stay or mortality between the HF1 and HF2 cohorts. Discussion Patients with HF2s comprised a significant and stable proportion of all hip fractures treated. We advocate for the provision of a Fracture Liaison Service in each of the 16 hip fracture operating hospitals in Ireland to optimise the secondary prevention of hip fractures.

Autosomal dominant tubulointerstitial kidney disease (ADTKD) in Ireland.

Introduction: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare genetic cause of renal impairment resulting from mutations in the MUC1, UMOD, HNF1B, REN, and SEC61A1 genes. Neither the national or global prevalence of these diseases has been determined. We aimed to establish a database of patients with ADTKD in Ireland and report the clinical and genetic characteristics of these families. Methods: We identified patients via the Irish Kidney Gene Project and referral to the national renal genetics clinic in Beaumont Hospital who met the clinical criteria for ADTKD (chronic kidney disease, bland urinary sediment, and autosomal dominant inheritance). Eligible patients were then invited to undergo genetic testing by a variety of methods including panel-based testing, whole exome sequencing and, in five families who met the criteria for diagnosis of ADTKD but were negative for causal genetic mutations, we analyzed urinary cell smears for the presence of MUC1fs protein. Results: We studied 54 individuals from 16 families. We identified mutations in the MUC1 gene in three families, UMOD in five families, HNF1beta in two families, and the presence of abnormal MUC1 protein in urine smears in three families (one of which was previously known to carry the genetic mutation). We were unable to identify a mutation in 4 families (3 of whom also tested negative for urinary MUC1fs). Conclusions: There are 4443 people with ESRD in Ireland, 24 of whom are members of the cohort described herein. We observe that ADTKD represents at least 0.54% of Irish ESRD patients.

Emergency Department Overcrowding And The Full Capacity Protocol Cross Over Study: What Patients Who Have Experienced Both Think About Being An Extra Patient In The Emergency Department Or On A Ward.

Hospital overcrowding is evidenced by Emergency Department (ED) overcrowding. The Full Capacity Protocol (FCP) is activated to move patients to temporary extra beds placed in the inpatient wards. This research aims to establish patient preferences when waiting for a ward bed in an Irish Hospital. The FCP in Beaumont Hospital was updated in the context of national guidelines. Patients' attitudes towards boarding in the ED as opposed to being in extra beds on the wards were assessed using a questionnaire based structured interview. Ninety nine patients took part in the study. Eighty three patients (83.83%) preferred being an additional patient on the ward, 12 (12.12%) had no preference and four (4.04%) preferred being boarded in the ED. Moving patients from the ED into extra beds on the wards creates space, facilitating safer care delivery. The vast majority of patients who have experienced both, prefer being boarded in the ward rather than in the ED.

Pre-transplant histology does not improve prediction of 5-year kidney allograft outcomes above and beyond clinical parameters.

Pre-implant kidney biopsy is used to determine suitability of marginal donor kidneys for transplantation. However, there is limited data examining the utility of pre-implant histology in predicting medium term graft outcome. This retrospective study examined kidney transplants over a 10-year period at a single center to determine if pre-implant histology can identify cases of eGFR ≤35 ml/min/1.73m2 at 5 year follow up beyond a clinical predictive logistic regression model. We also compared outcomes of dual kidney transplants with standard single kidney transplants. Of 1195 transplants, 171 received a pre-implant kidney biopsy and 15 were dual transplants. There was no significant difference in graft and patient survival rates. Median eGFR was lower in recipients of biopsied kidneys compared with standard kidney transplants (44 vs. 54 ml/min/1.73m2, p < .001). Median eGFR of dual transplant and standard kidney transplants were similar (58 vs. 54 ml/min/1.73m2, p = .64). Glomerular sclerosis (p = .05) and Karpinski Score (p = .03) were significant predictors of eGFR at 5-years in multivariate analysis but did not improve discrimination of eGFR ≤35 ml/min/1.73m2 at 5-years beyond a clinical prediction model comprising donor age, donor hypertension and terminal donor creatinine (C-statistic 0.67 vs. 0.66; p = .647). Pre-implant histology did not improve prediction of medium-term graft outcomes beyond clinical predictors alone. Allograft function of dual transplant kidneys was similar to standard transplants, suggesting that there is scope to increase utilization of kidneys considered marginal based on histology.

DVT presentations to an Emergency Department: A study of guideline based care and decision making.

Pre-test probability scoring and blood tests for deep venous thrombosis (DVT) assessment are sensitive but not specific leading to increased demands on radiology services. 385 patients presenting to an Emergency Department with suspected DVT were studied to explore our actual work up of patients with possible DVT relating to risk stratification, further investigation and follow up. Of the 205 patients with an initially negative scan, 36 (17.6%) were brought for review to the Emergency Department Consultant clinic. 34 (16.6%) patients underwent repeat compression ultrasound with 5 (2.4%) demonstrating a DVT on the second scan. Repeat compression ultrasound scans were performed on 34 (16.6%) of patients with an initially negative scan with essentially the same diagnostic yield as other larger studies where 100% of such patients had repeat scanning. Where there is ongoing concern, repeat above knee compression ultrasound within one week will pick up a small number of deep venous thromboses.

Endovascular treatment for acute ischaemic stroke with large vessel occlusion: the experience of a regional stroke service.

AIM: To report the experience of a regional stroke referral service with endovascular treatment for patients with acute ischaemic stroke (AIS) and large vessel occlusion. MATERIALS AND METHODS: A prospective review was undertaken of 93 consecutive cases receiving endovascular treatment for AIS over a 42-month period (January 2010 to June 2013). The National Institutes of Health Stroke Scale (NIHSS), location of large vessel occlusion, details of endovascular procedure, and degree of reperfusion achieved (Thrombolysis In Cerebral Infarction [TICI] score) were recorded. Mortality and functional outcome (modified Rankin Scale [mRS]) were measured at 90 days. RESULTS: The mean patient age was 62 years (range 26-87 years). The mean NIHSS at presentation was 16 (range 6-29). All patients had confirmed proximal large-artery occlusion on computed tomography (CT) angiography: 87 in the anterior circulation, six in the posterior circulation. Of the 93 patients treated, 64 (69%) received intravenous thrombolysis. Successful reperfusion (TICI grade 2a to 3) was achieved in 80 (86%) cases. There were 13 (14%) cases of failed vessel recanalisation (TICI grade 0). Good functional outcome (mRS ≤2) was achieved in 51 (55%) cases. The 90-day mortality was 20 (22%) cases. Fifty-seven (61%) cases were transferred from outside centres. There was no significant increase in morbidity or mortality for transferred patients. CONCLUSION: Successful endovascular recanalisation can result in good functional outcomes for patients with AIS and large vessel occlusion. Our interventional neuroradiology service provides endovascular treatment as part of a regional stroke service without increase in morbidity or mortality for patients transferred from outside institutions.

Referral letters to the emergency department: is the medication list accurate?

Medication errors are common when patients transfer across healthcare boundaries. This study was designed to investigate the quality of information on medicines provided by general practitioners (GPs) on emergency department (ED) referral letters. A convenience sample of referral letters to the ED of a teaching hospital was reviewed. The medication list and/or patient's drug allergy status were noted. Medicines reconciliation including patient (or carer) interview was conducted to determine the patient's actual home medication list. This was compared with the GP list and any discrepancies were identified and addressed. A total of 92 referral letters were included in the analysis of which 60 were computer-generated and 32 were hand-written. GPs provided dose and frequency of administration information in 47 (51%) of the letters sampled i.e. 44 (71%) computer-generated versus 3 (10%) hand-written; p < 0.001. In addition, the patient was taking their medicines exactly as per the GP list in 20 (22%) of cases. The patient's drug allergy status was documented in 13 (14%) of the letters.

Twenty-year survivors of kidney transplantation.

There have been few studies of patients with renal allografts functioning for more than 20 years. We sought to identify clinical factors associated with ultra long-term (>20 year) renal allograft survival and to describe the clinical features of these patients. We performed a retrospective analysis of the Irish Renal Transplant Database and included 1174 transplants in 1002 patients. There were 255 (21.74%) patients with graft function for 20 years or more. Multivariate analysis identified recipient age (HR 1.01, CI 1.01-1.02), gender (male HR 1.25, CI 1.08-1.45), acute rejection (HR 1.26, CI 1.09-1.45) and transplant type (living related donor vs. deceased donor) (HR 0.52, CI 0.40-0.66) as significantly associated with long-term graft loss. Median serum creatinine was 115 µmol/L. The 5-year graft survival in 20-year survivors was 74.7%. The mean age at death was 62.7 years (±10.6). The most common causes of death were cardiovascular disease and malignancy. The two major causes of graft loss were death (with function) and interstitial fibrosis/tubular atrophy. Comorbidities included skin cancer (36.1%), coronary heart disease (17.3%) and other malignancies (14.5%). This study identifies factors associated with long-term allograft survival and a high rate of morbidity and early mortality in long-term transplant recipients.

Genetic polymorphism in Methylenetetrahydrofolate Reductase chloride transport protein 6 (MTHFR CLCN6) gene is associated with keratinocyte skin cancer in a cohort of renal transplant recipients.

Background: Renal transplant recipients (RTRs) are at increased risk of keratinocyte cancer (KC), especially cutaneous squamous cell carcinoma (cSCC). Previous studies identified a genetic variant of the Methylenetetrahydrofolate Reductase (MTHFR) gene, C677T, which conferred a risk for diagnosis of cSCC in Irish RTRs. Objective: We sought to find further genetic variation in MTHFR and overlap genes that may be associated with a diagnosis of KC in RTRs. Methods: Genotyping of a combined RTR population (n = 821) from two centres, Ireland (n = 546) and the USA (n = 275), was performed. This included 290 RTRs with KC and 444 without. Eleven single nucleotide polymorphisms (SNPs) in the MTHFR gene and seven in the overlap gene MTHFR Chloride transport protein 6 (CLCN6) were evaluated and association explored by time to event analysis (from transplant to first KC) using Cox proportional hazards model. Results: Polymorphism at MTHFR CLCN6 (rs9651118) was significantly associated with KC in RTRs (HR 1.50, 95% CI 1.17-1.91, p < 0.00061) and cSCC (HR 1.63, 95% CI 1.14-2.34, p = 0.007). A separate SNP, MTHFR C677T, was also significantly associated with KC in the Irish population (HR 1.31, 95% CI 1.05-1.63, p = 0.016), but not American RTRs. Conclusions: We report the association of a SNP in the MTHFR overlap gene, CLCN6 and KC in a combined RTR population. While the exact function of CLCN6 is not known, it is proposed to be involved in folate availability. Future applications could include incorporation in a polygenic risk score for KC in RTRs to help identify those at increased risk beyond traditional risk factor assessment.

Warfarin use in hemodialysis patients: what is the risk?

BACKGROUND: There is a paucity of data concerning the risks associated with warfarin in hemodialysis (HD) patients. We compared major bleeding episodes in this group with HD patients not receiving warfarin and with a cohort of non-HD patients receiving warfarin. METHODS: A retrospective review of 141 HD patients on warfarin (HDW), 704 HD patients not on warfarin (HDNW) and 3,266 non-dialysis warfarin patients (NDW) was performed. Hospital admissions for hemorrhagic events and ischemic strokes were examined as was hospital length of stay and blood product use. INR variability was also assessed. RESULTS: The incidence rates for major hemorrhage per 100 patient years was 10.8 in the HDW group as compared to 8.0 in the HDNW (p = 0.593) and 2.1 in the NDW (p < 0.001) groups. Mean units of red blood cell transfusions required was higher in patients on dialysis with no significant difference between HDW and HDNW groups. The risk of ischemic stroke per 100 patient years was 1.7 in the HDW group as compared to 0.7 in the HDNW groups (p = 0.636) and 0.4 in the NDW (p = 0.003). The HDW group had higher inter-measurement INR variability compared to the NDW group (p = 0.034). In patients with atrial fibrillation, HDW group had a higher incidence of ischemic stroke than the NDW group (2.2 versus 0.4 events per 100 patient years; p = 0.024). CONCLUSIONS: This study confirms the higher bleeding risk associated with HD/ESRD but suggests that warfarin use in these patients may not add significantly to this risk. We also demonstrated high rates of ischemic stroke in HD patients despite warfarin use. SUMMARY: Our study compares the frequency of major hemorrhage and secondarily, ischemic stroke in HD patients receiving or not receiving warfarin, with non-HD patients receiving warfarin. The major finding was that frequency of hemorrhage was higher in HD patients receiving warfarin than in non-HD patients receiving warfarin, but not different in HD patients with or without warfarin. A secondary finding was that INR variability was significantly higher in HD patients than non-HD patients on warfarin.

Imaging patients with renal colic: a comparative analysis of the impact of non-contrast helical computed tomography versus intravenous pyelography on the speed of patient processing in the Emergency Department.

INTRODUCTION: Non-contrast helical CT (NHCT) became the procedure of choice for investigating Emergency Department (ED) patients presenting with suspected renal colic at Beaumont Hospital, Dublin, in 2008. The impact of NHCT on waiting times and patient management was compared with intravenous pyelography (IVP). METHODS: A retrospective, comparative cohort analysis of 95 patients who had IVP and 109 patients who had NHCT was performed. Length of ED stay from time of scan ordering to referral or discharge was analysed relative to time of day and scan result. RESULTS: Patients having NHCT who attended between 00:00-08:00 h, had a twofold longer length of stay than those who had IVP between the same hours (median 7.07 h vs 3.03 h, p=0.0294). The length of ED stay for patients attending between 08:00 and 24:00 h was similar in both groups. The presence of urolithiasis did not impact on length of stay. A significant alternate/incidental diagnosis was reported in 28 patients having NHCT, of which 12 were cancerous growths. CONCLUSION: NHCT allows for the detection of incidental/alternate diagnoses that may not be otherwise detected in patients with renal colic. Compared to IVP, NHCT has not impacted positively on the speed of patient processing in the ED under study. For patients presenting after midnight, it is associated with over a twofold longer length of stay from the time of scan ordering to referral or discharge. This leads to prolonged patient stays in the ED, and as such contributes to overcrowding.

Aberrant DNA methylation associated with MTHFR C677T genetic polymorphism in cutaneous squamous cell carcinoma in renal transplant patients.

BACKGROUND: Changes in genomic DNA methylation associated with cancer include global DNA hypomethylation and gene-specific hyper- or hypomethylation. We have previously identified a genetic variant in the MTHFR gene involved in the methylation pathway which confers risk for the development of squamous cell carcinoma (SCC) in renal transplant patients. This genetic variant has also been discovered to confer SCC risk in nontransplant patients with low folate status. OBJECTIVES: To explore the methylation profile of SCC compared with adjacent non-neoplastic skin using pyrosequencing, and to elucidate whether the MTHFR polymorphism impacts upon the methylation patterns in SCC. METHODS: We used pyrosequencing to evaluate global (using long interspersed nuclear element 1) and gene-specific (p16 and MGMT) methylation status in 47 SCCs and 40 adjacent autologous non-neoplastic skin samples in those with (n = 16) and without (n = 17) the MTHFR polymorphism. RESULTS: Pyrosequencing methylation analysis revealed that SCC was hypomethylated compared with adjacent non-neoplastic skin (P < 0.04). Patients with the MTHFR polymorphism had higher levels of global methylation in tumours and non-neoplastic skin compared with those without the MTHFR polymorphism (P < 0.002). There was no association between levels of methylation in tumour and non-neoplastic skin for the genes MGMT and p16. CONCLUSIONS: Global hypomethylation appears to be a feature of SCC. Aberrant methylation of DNA appears related to polymorphisms of MTHFR. Such findings suggest that intervention in the form of demethylating agents or folate supplementation might be beneficial in the treatment or prevention of SCC.

Analysis of waiting times on Irish renal transplant list.

INTRODUCTION: A number of recipient variables have been identified which influence waiting list times for a renal allograft. The aim of this study was to evaluate these factors in the Irish population. METHODS: We examined patients accepted onto the transplant list from January 1, 2000 until December 31, 2005. Inclusion criteria were adults listed for kidney only, deceased donor transplants. We included patients previously transplanted. Patients were censored, but still included in the analysis, if they died while on the list, permanently withdrew from the list or if they were not transplanted at the time of the study. RESULTS: There were a total of 984 patients accepted onto the waiting list during the study period, of which 745 of these were transplanted. Factors significantly associated with longer waiting times included age above 50 yr, blood group O and high peak panel reactive antibodies level. Gender and patient body mass index were not associated with longer waiting times. CONCLUSION: We have identified factors associated with a longer waiting time on the Irish cadaveric renal transplant list. This information can help our patients make informed decisions regarding likely waiting times and the merits of living related transplantation.

Encapsulating peritoneal sclerosis: experience of a tertiary referral center.

AIM: Encapsulating peritoneal sclerosis (EPS) is arguably the most serious complication of chronic peritoneal dialysis (PD) therapy with extremely high mortality rates. We aimed to establish the rates of EPS and factors associated with its development in a single center. METHODS: We retrospectively reviewed the records of all our PD patients from 1 January 1989 until 31 December 2008. All suspected cases were confirmed at laparotomy. Multifactorial models adjusted for potentially confounding variables such as age and sex. RESULTS: Eleven cases of EPS were identified giving a prevalence rate of 1.98%. Median duration on PD was substantially longer in affected versus unaffected patients (42.5 months versus 13.8 months; p = 0.0002). EPS patients had experienced a mean of 3.54 previous cases of peritonitis (1 infection per year versus 0.71 per year in unaffected patients; p = 0.075). Six patients died (54.5%) due to intra-abdominal sepsis including all five who presented with small bowel obstruction. Three patients had an omentectomy and adhesiolysis performed with a successful outcome. CONCLUSION: Our study reinforces the link between duration on PD and EPS. While mortality was high in our cohort, emerging surgical techniques demonstrate a favorable outcome that can be achieved even in severely affected cases.

Higher tacrolimus trough levels on days 2-5 post-renal transplant are associated with reduced rates of acute rejection.

We analyzed the association between whole-blood trough tacrolimus (TAC) levels in the first days post-kidney transplant and acute cellular rejection (ACR) rates. Four hundred and sixty-four consecutive, deceased-donor kidney transplant recipients were included. All were treated with a combination of TAC, mycophenolate mofetil and prednisolone. Patients were analyzed in four groups based on quartiles of the mean TAC on days 2 and 5 post-transplant: Group 1: median TAC 11 ng/mL (n = 122, range 2-13.5 ng/mL), Group 2: median 17 ng/mL (n = 123, range 14-20 ng/mL), Group 3: median 24 ng/mL (n = 108, range 20.5-27 ng/mL) and Group 4: median 33.5 ng/mL (n = 116, range 27.5-77.5 ng/mL). A graded reduction in the rates of ACR was observed for each incremental days 2-5 TAC. The one-yr ACR rate was 24.03% (95% CI 17.26-32.88), 22.20% (95% CI 15.78-30.70), 13.41% (95% CI 8.15-21.63) and 8.69% (95% CI 4.77-15.55) for Groups 1-4, respectively (p = 0.003). This study suggests that higher early TACs are associated with reduced rates of ACR at one yr.

DNW--"did not wait" or "demographic needing work": a study of the profile of patients who did not wait to be seen in an Irish emergency department.

BACKGROUND: Patients who fail to wait for medical assessment in the emergency department (ED) have been referred to in the international literature as "did not wait" (DNW) or "left without being seen" (LWBS) patients or, indeed, simply as "walkouts". This is taken as a performance indicator internationally. In common with many countries, Ireland has very considerable problems in the delivery of ED care due largely to inadequate resources and the inappropriate use of EDs as holding bays for admitted patients. This is the first study of this size to profile the DNW phenomenon in Ireland. METHODS: The charts of DNW patients were identified and the DNW status was entered into the ED computer record. Data concerning age, sex, time of arrival, date of arrival, triage category and presenting complaint were recorded. RESULTS: In the study period there were 11 662 patient attendances, of whom 871 patients (7.47%) did not wait for assessment. Triage category was highly statistically significant, with those in the lowest triage category having the highest numbers not waiting to be seen (p<0.001). Those attending at night (p<0.001) and at the weekend (p = 0.03) were most likely to leave without being assessed. CONCLUSION: Failure to provide the service in a timely manner gives rise to patients leaving without receiving the medical assessment they came to obtain. This is a serious clinical problem and puts both those requiring care and those providing it at risk of adverse outcomes.

The Transit/Admission Lounge study.

In response to persistent overcrowding of Emergency Departments in Ireland, the Department of Health and Health Service Executive provided funding for "Transit Lounge" areas to be built. These lounges were to provide a location for patients to wait in beds pending the availability of a ward bed. This research was performed to assess the impact of such a lounge on the overcrowding of the Emergency Department and on patient outcomes. The time period from the opening of the Transit Lounge was compared with the same period a year earlier. The Transit Lounge delivers a comfortable place for patients to wait. It does not reduce Emergency Department overcrowding and has been associated with an increased time waiting for a ward bed. The solution to overcrowding is the creation of real capacity in the system so that ward beds are available in acute hospitals for the "unscheduled unwell".

Polymorphic light eruption and skin cancer prevalence: is one protective against the other?

BACKGROUND: Ultraviolet (UV) radiation (UVR) interacts with chromophores in cutaneous cells with consequent antigenicity. The normal response to this is a downregulation of immune responsiveness. Failure of the immune system to downregulate and to ignore transient photoantigens in human skin results in polymorphic light eruption (PLE), the commonest of the photodermatoses. UVR initiates and promotes skin cancer (SC): UV-induced immunosuppression permits the expansion of UV-mutated clones of cells which ultimately lead to SC. OBJECTIVES: Because there is increased immune surveillance and resistance to immune suppression following UVR exposure in PLE one might expect a protective effect of PLE against SC and, conversely, a reduced risk of PLE among patients with SC. METHODS: We therefore constructed a prospective case-control study to see if this were the case. Two groups were studied: a group comprising 214 patients with SC and 210 gender- and aged-matched controls, and a group comprising 100 patients with PLE and 155 gender- and aged-matched controls. Each participant answered a questionnaire aimed at establishing personal and family history of SC and photodermatoses. Skin type and exposure to UVR were also documented. RESULTS: The prevalence of PLE in people with SC was 7.5%, compared with 21.4% for controls (P<0.001). The prevalence of SC in patients with PLE was 4% compared with 7.1% for controls. CONCLUSIONS: Our results show (i) strong evidence of reduced PLE in patients with SC, and (ii) a trend for reduced SC in patients with PLE. The immunological basis of PLE may therefore confer protection against SC.