Kopczynska, Maja; Sharif, Ben; Unwin, Harry; Cleaver, Sian; Kulikouskaya, Svetlana; Smith, Jessica; Ganesananthan, Sashiananthan; Penney, Harriet; Inns, Joy; Gilbert, Carys; Doyle, Nicholas; Kurani, Amit; Grother, Thomas; McNulty, Paul; Sharma, Angelica; Szakmany, Tamas Author Information

Recent description of the microbiology of sepsis on the wards or information on the real-life antibiotic choices used in sepsis is lacking. There is growing concern of the indiscriminate use of antibiotics and omission of microbiological investigations in the management of septic patients. We performed a secondary analysis of three annual 24-h point-prevalence studies on the general wards across all Welsh acute hospitals in years 2016-2018. Data were collected on patient demographics, as well as radiological, laboratory and microbiological data within 48-h of the study. We screened 19,453 patients over the three 24 h study periods and recruited 1252 patients who fulfilled the entry criteria. 775 (64.9%) patients were treated with intravenous antibiotics. Only in 33.65% (421/1252) of all recruited patients did healthcare providers obtain blood cultures; in 25.64% (321/1252) urine cultures; in 8.63% (108/1252) sputum cultures; in 6.79% (85/1252) wound cultures; in 15.25% (191/1252) other cultures. Out of the recruited patients, 59.1% (740/1252) fulfilled SEPSIS-3 criteria. Patients with SEPSIS-3 criteria were significantly more likely to receive antibiotics than the non-septic cohort (p < 0.0001). In a multivariable regression analysis increase in SOFA score, increased number of SIRS criteria and the use of the official sepsis screening tool were associated with antibiotic administration, however obtaining microbiology cultures was not. Our study shows that antibiotics prescription practice is not accompanied by microbiological investigations. A significant proportion of sepsis patients are still at risk of not receiving appropriate antibiotics treatment and microbiological investigations; this may be improved by a more thorough implementation of sepsis screening tools.

Sir, Sepsis is frequent, potentially fatal condition characterised by organ dysfunction as a result of a dysregulated host response to infection [1]. We estimated that the combined point-prevalence of sepsis is around 5.5% amongst hospital in-patients in Wales [2, 3]. It has been argued that rapid administration of an appropriately chosen antibiotic is the cornerstone of the effective treatment of sepsis [4]. Recently, a standardised sepsis screening tool and the Sepsis 6 treatment protocol has been rolled out across Wales [5]. However, the antibiotic prescribing element has been traditionally based on local guidance and antimicrobial resistance patterns [6]. Evidence suggests that incorrect antibiotic prescribing may lead to an increased emergence of antibiotic resistant organisms [7]. Therefore, it is crucial that local guidance is followed. Our aim was to explore adherence to local guidelines and establish an understanding as to why, in clinical practice, prescribing patterns may differ. We obtained data based on the antibiotic prescribing patterns across hospitals in Wales from the Defining Sepsis on the Wards Study which has been described previously in detail (ISCRTN: 86502304) [3]. Briefly, it was a point-prevalence study in every Welsh hospital over a 24-hour period on the 19/10/2016. Patients with National Early Warning Score of 3 or above with clinical suspicion of infection were recruited following informed consent. Various demographic, care process and outcome data were collected, including antibiotic prescribing and administration. We contacted the critical care outreach or acute intervention teams in the hospitals where this service is provided, to identify barriers to successfully implement early and appropriate antibiotic therapy as part of the Sepsis 6 initiative. Data were analysed using Microsoft excel. Within the study period there were similar numbers of patients with sepsis in each hospital (Table 1). Antibiotic treatment within one hour was administered at a variable rate, from 27% to 64%. In 35% of all cases of sepsis, the cause was unknown and within this sub-group the percentage of antibiotics prescribed was slightly higher, varying from 20% to 90%. In accordance to local guidelines, antibiotic prescribing for patients with sepsis of unknown origin was correct in 22% of cases (Table 2). Out of the patients who did receive antibiotics, the majority of them received either an incorrect antibiotic regime (59%) or a partially correct antibiotic regime (19%). There was significant inter-hospital variability in the correct prescription of antimicrobials. In many cases, partially correct antibiotic regimes were administered, as only one of the two suggested antibiotics were prescribed (Table 2). Four key barriers to effectively implementing the antibiotic therapy in the Sepsis 6 initiative were identified: 1. Lack of education — understanding when to trigger the pathway. 2. Complexity of guidelines. 3. Lack of a leadership role — giving IV antibiotics requires communication. between different healthcare professionals. 4. Practical issues — sourcing equipment or acute bed shortages.

BACKGROUNDPeople with Huntington's disease (HD) have been observed to have lower rates of cancers.OBJECTIVETo investigate the relationship between age of onset of HD, CAG repeat length, and cancer diagnosis.METHODSData were obtained from the European Huntington's disease network REGISTRY study for 6540 subjects. Population cancer incidence was ascertained from the GLOBOCAN database to obtain standardised incidence ratios of cancers in the REGISTRY subjects.RESULTS173/6528 HD REGISTRY subjects had had a cancer diagnosis. The age-standardised incidence rate of all cancers in the REGISTRY HD population was 0.26 (CI 0.22-0.30). Individual cancers showed a lower age-standardised incidence rate compared with the control population with prostate and colorectal cancers showing the lowest rates. There was no effect of CAG length on the likelihood of cancer, but a cancer diagnosis within the last year was associated with a greatly increased rate of HD onset (Hazard Ratio 18.94, p < 0.001).CONCLUSIONSCancer is less common than expected in the HD population, confirming previous reports. However, this does not appear to be related to CAG length in HTT. A recent diagnosis of cancer increases the risk of HD onset at any age, likely due to increased investigation following a cancer diagnosis.