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Special Low Protein Foods Prescribed in England for PKU Patients: An Analysis of Prescribing Patterns and Cost.
No full textPatients with phenylketonuria (PKU) are reliant on special low protein foods (SLPFs) as part of their dietary treatment. In England, several issues regarding the accessibility of SLPFs through the national prescribing system have been highlighted. Therefore, prescribing patterns and expenditure on all SLPFs available on prescription in England ( = 142) were examined. Their costs in comparison to regular protein-containing ( = 182) and products ( = 135) were also analysed. Similar foods were grouped into subgroups ( = 40). The number of units and costs of SLPFs prescribed in total and per subgroup from January to December 2020 were calculated using National Health Service (NHS) Business Service Authority (NHSBSA) ePACT2 (electronic Prescribing Analysis and Cost Tool) for England. Monthly patient SLPF units prescribed were calculated using patient numbers with PKU and non-PKU inherited metabolic disorders (IMD) consuming SLPFs. This was compared to the National Society for PKU (NSPKU) prescribing guidance. Ninety-eight percent of SLPF subgroups ( 39/40) were more expensive than regular and food subgroups. However, costs to prescribe SLPFs are significantly less than theoretical calculations. From January to December 2020, 208,932 units of SLPFs were prescribed (excluding milk replacers), costing the NHS £2,151,973 (including milk replacers). This equates to £962 per patient annually, and prescribed amounts are well below the upper limits suggested by the NSPKU, indicating under prescribing of SLPFs. It is recommended that a simpler and improved system should be implemented. Ideally, specialist metabolic dietitians should have responsibility for prescribing SLPFs. This would ensure that patients with PKU have the necessary access to their essential dietary treatment, which, in turn, should help promote dietary adherence and improve metabolic control
A risk-adjusted and anatomically stratified cohort comparison study of open surgery, endovascular techniques and medical management for juxtarenal aortic aneurysms-the UK COMPlex AneurySm Study (UK-COMPASS): a study protocol.
No full textINTRODUCTION
In one-third of all abdominal aortic aneurysms (AAAs), the aneurysm neck is short (juxtarenal) or shows other adverse anatomical features rendering operations more complex, hazardous and expensive. Surgical options include open surgical repair and endovascular aneurysm repair (EVAR) techniques including fenestrated EVAR, EVAR with adjuncts (chimneys/endoanchors) and off-label standard EVAR. The aim of the UK COMPlex AneurySm Study (UK-COMPASS) is to answer the research question identified by the National Institute for Health Research Health Technology Assessment (NIHR HTA) Programme: 'What is the clinical and cost-effectiveness of strategies for the management of juxtarenal AAA, including fenestrated endovascular repair?'
METHODS AND ANALYSIS
UK-COMPASS is a cohort study comparing clinical and cost-effectiveness of different strategies used to manage complex AAAs with stratification of physiological fitness and anatomical complexity, with statistical correction for baseline risk and indication biases. There are two data streams. First, a stream of routinely collected data from Hospital Episode Statistics and National Vascular Registry (NVR). Preoperative CT scans of all patients who underwent elective AAA repair in England between 1 November 2017 and 31 October 2019 are subjected to Corelab analysis to accurately identify and include every complex aneurysm treated. Second, a site-reported data stream regarding quality of life and treatment costs from prospectively recruited patients across England. Site recruitment also includes patients with complex aneurysms larger than 55 mm diameter in whom an operation is deferred (medical management). The primary outcome measure is perioperative all-cause mortality. Follow-up will be to a median of 5 years.
ETHICS AND DISSEMINATION
The study has received full regulatory approvals from a Research Ethics Committee, the Confidentiality Advisory Group and the Health Research Authority. Data sharing agreements are in place with National Health Service Digital and the NVR. Dissemination will be via NIHR HTA reporting, peer-reviewed journals and conferences.
TRIAL REGISTRATION NUMBER
ISRCTN85731188
Salvage of Extensively Scarred Hands: Wide Awake Tenolysis and Interpositional Free Tissue Transfer.
No full textBackground
This study introduced a dedicated technical approach to extensive hand adhesions, combined with failed primary nerve reconstruction. Wide awakelocal anesthesia no tourniquet (WALANT) tenolysis and interpositional free tissue transfer forge the main facets of the proposed reconstructive strategy.
Methods
A prospective study was conducted, including 22 patients diagnosed with extensive tendon adhesions in addition to failed primary nerve repair. After wide awake tenolysis, 20 adipofascial radial forearm flaps and two ALT flaps were used to wrap the tendons, whereas the nerves were grafted after complete separation from the tendons. Nerve recovery; final total range of motion of the fingers; and the disabilities of the arm, shoulder, and hand score were recorded in detail.
Results
All flaps healed uneventfully. Final assessment of the median nerve revealed M3 or more motor power and S3 sensory recovery in all patients except one patient who attained no muscle power at all and S1 as regards the sensory assessment. The ulnar nerve evaluation revealed that two of five patients did not recover motor power at all (M0), and the remaining three patients recovered M3 motor power with variable sensory outcomes. Final assessment of total range of motion of the fingers and the DASH score showed a statistically significant improvement except for one patient.
Conclusion
WALANT tenolysis and interposition of well-vascularized fascial flaps along with simultaneous nerve grafts in extensively scarred hands provided goodfunctional outcomes
Patient's perspective on a novel psychological therapy approach (flash technique) for neurofibromatosis.
No full textRaman spectroscopy: current applications in breast cancer diagnosis, challenges and future prospects.
No full textDespite significant improvements in the way breast cancer is managed and treated, it continues to persist as a leading cause of death worldwide. If detected and diagnosed early, when tumours are small and localised, there is a considerably higher chance of survival. However, current methods for detection and diagnosis lack the required sensitivity and specificity for identifying breast cancer at the asymptomatic or very early stages. Thus, there is a need to develop more rapid and reliable methods, capable of detecting disease earlier, for improved disease management and patient outcome. Raman spectroscopy is a non-destructive analytical technique that can rapidly provide highly specific information on the biochemical composition and molecular structure of samples. In cancer, it has the capacity to probe very early biochemical changes that accompany malignant transformation, even prior to the onset of morphological changes, to produce a fingerprint of disease. This review explores the application of Raman spectroscopy in breast cancer, including discussion on its capabilities in analysing both ex-vivo tissue and liquid biopsy samples, and its potential in vivo applications. The review also addresses current challenges and potential future uses of this technology in cancer research and translational clinical application
Heparin resistance in severe thermal injury: A prospective cohort study.
No full textBackground
Low molecular-weight heparin (LMWH) is routinely administered to burn patients for thromboprophylaxis. Some studies have reported heparin resistance, yet the mechanism(s) and prevalence have not been systematically studied. We hypothesized that nucleosomes, composed of histone structures with associated DNA released from injured tissue and activated immune cells in the form of neutrophil extracellular traps (NETs or NETosis), neutralize LMWH resulting in suboptimal anticoagulation, assessed by reduction in anti-factor Xa activity.
Methods
Blood was sampled from >15% total body surface area (TBSA) burn patients receiving LMWH on days 5, 10 and 14. Peak anti-factor Xa (AFXa) activity, anti-thrombin (ATIII) activity, cell-free DNA (cfDNA) levels and nucleosome levels were measured. Mixed effects regression was adjusted for multiple confounders, including injury severity and ATIII activity, and was used to test the association between nucleosomes and AFXa.
Results
A total of 30 patients with severe burns were included. Mean TBSA 43% (SD 17). Twenty-three (77%) patients were affected by heparin resistance (defined by AFXa activity <0.2 IU/mL). Mean peak AFXa activity across samples was 0.18 IU/mL (SD 0.11). Mean ATIII was 81.9% activity (SD 20.4). Samples taken at higher LWMH doses were found to have significantly increased AFXa activity, though the effect was not observed at all doses, at 8000 IU no samples were heparin resistant. Nucleosome levels were negatively correlated with AFXa ( = -0.29, = 0.050) consistent with the hypothesis. The final model, with peak AFXa as the response variable, was adjusted for nucleosome levels ( = 0.0453), ATIII activity ( = 0.0053), LMWH dose pre-sample ( = 0.0049), drug given (enoxaparin or tinzaparin) ( = 0.03), and other confounders including severity of injury, age, gender, time point of sample.
Conclusions
Heparin resistance is a prevalent issue in severe burns. Nucleosome levels were increased post-burn, and showed an inverse association with AFXa consistent with the hypothesis that they may interfere with the anticoagulant effect of heparin and contribute to heparin resistance. Accurate monitoring of AFXa activity with appropriate therapy escalation plans are recommended with dose adjustment following severe burn injury
Electrical impedance guides electrode array in cochlear implantation using machine learning and robotic feeder.
No full textCochlear Implant provides an electronic substitute for hearing to severely or profoundly deaf patients. However, postoperative hearing outcomes significantly depend on the proper placement of electrode array (EA) into scala tympani (ST) during cochlear implant surgery. Due to limited intra-operative methods to access array placement, the objective of the current study was to evaluate the relationship between EA complex impedance and different insertion trajectories in a plastic ST model. A prototype system was designed to measure bipolar complex impedance (magnitude and phase) and its resistive and reactive components of electrodes. A 3-DoF actuation system was used as an insertion feeder. 137 insertions were performed from 3 different directions at a speed of 0.08 mm/s. Complex impedance data of 8 electrode pairs were sequentially recorded in each experiment. Machine learning algorithms were employed to classify both the full and partial insertion lengths. Support Vector Machine (SVM) gave the highest 97.1% accuracy for full insertion. When a real-time prediction was tested, Shallow Neural Network (SNN) model performed better than other algorithms using partial insertion data. The highest accuracy was found at 86.1% when 4 time samples and 2 apical electrode pairs were used. Direction prediction using partial data has the potential of online control of the insertion feeder for better EA placement. Accessing the position of the electrode array during the insertion has the potential to optimize its intraoperative placement that will result in improved hearing outcomes
Recognition and Management of Button Battery Ingestion Amongst Emergency Practitioners.
No full textIntroduction Button battery ingestion (BBI) carries a significant risk of morbidity and mortality. We conducted a regional analysis following an NHS England national patient safety alert to evaluate the knowledge base in the emergency management of BBI amongst emergency practitioners. Methods A ten-point questionnaire was distributed electronically and in hardcopy formats to emergency departments across 15 hospitals within the West Midlands, United Kingdom. The questionnaire assessed participants' knowledge of emergency management of BBI. The effect of clinician grade and previous otorhinolaryngology experience on knowledge scores was evaluated. Results A total of 176 responses were received from 11 hospitals. A small proportion (18%) were aware of a local department protocol. The majority of participants (70%) routinely screened for a button battery in their history taking. Our findings highlighted a lack of awareness of the timeframe for mucosal injury, potential complications, radiological signs, and the necessity for immediate retrieval. The median knowledge score was 18.8% (IQR=12.5-31.3%). Both registrars and consultants scored the highest (median 25%). Previous otorhinolaryngology experience was associated with a higher median score (P=0.002). Conclusion Our multi-center regional emergency medicine analysis demonstrated knowledge deficiency in the initial assessment and management of BBI. A high index of suspicion for button battery ingestion is needed. In view of the time-critical nature of button battery impaction in the esophagus, a "golden hour" concept should be integrated into acute management pathways with the early involvement of otorhinolaryngologists
The association between overweight/obesity and double diabetes in adults with type 1 diabetes; a cross-sectional study.
No full textBACKGROUND
Double Diabetes (DD), type 1 diabetes (T1DM) + insulin resistance (IR), is associated with increased risk of micro/macro-vascular complications and mortality. Obesity can contribute to the development of DD. This study explored the prevalence of overweight/obesity and their association with DD in adults with T1DM.
METHODS
Cross-sectional study of consecutive adults with T1DM attending diabetes clinics in a secondary care hospital (January-November 2019). Estimated glucose disposal rate (eGDR) was used as a marker of IR, and an eGDR < 8 was used to identify individuals with DD.
RESULTS
One hundred seven adults with T1DM were included; female/male: 51/56; age [median (inter-quartile range): 30.0 (23-51) years]; BMI 25.4 (22.8-30.0) kg/m. Overweight/obesity prevalence was 57/107 (53.3 %) [overweight: 30/107 (28 %); obesity: 27/107 (25.2 %)]. Compared to those with normal BMI, individuals with T1DM and overweight/obesity had longer diabetes duration; higher total daily insulin dose; and higher DD prevalence: 48/57 (84.2 %) vs. 14/50 (28 %) (p < 0.01); with similar HbA1c. BMI correlated with total daily insulin dose (rho = 0.55; p < 0.01). Individuals with DD were older, had longer duration of diabetes, higher HbA1c, and more adverse lipid profile and microalbuminuria compared to those without DD.
CONCLUSIONS
Overweight/obesity is very common in adults with T1DM, and is associated with double diabetes. BMI is positively associated with total insulin dose. Double diabetes is associated with adverse cardiovascular risk profile and is also common in lean individuals with T1DM. Further research is needed to examine the impact of overweight/obesity in people with T1DM and whether weight loss in this population can improve diabetes-related outcomes
Moving forward in the treatment of cholangiocarcinoma.
No full textDespite being the second most frequent primary liver tumor in humans, early diagnosis and treatment of cholangiocarcinoma (CCA) are still unsatisfactory. In fact, survival after 5 years is expected in less than one fourth of patients diagnosed with this disease. Rare incidence, late appearance of symptoms and heterogeneous biology are all factors contributing to our limited knowledge of this cancer and determining its poor prognosis in the clinical setting. Several efforts have been made in the last decades in order to achieve an improved classification/understanding with regard to the diverse CCA forms. Location within the biliary tree has helped to distinguish between intrahepatic, perihilar and distal CCA types. Sequence analysis contributed to identifying several characteristic genetic aberrations in CCA that may also serve as possible targets for therapy. Novel findings are expected to significantly improve the management of this malignancy in the near future. In this changing scenario our review focuses on the current and future strategies for CCA treatment. Both systemic and surgical treatments are discussed in detail. The results of the main studies in this field are reported, together with the ongoing trials. The current findings suggest that an integrated multidisciplinary approach to this malignancy would be helpful to improve its outcome