Canadian Real-World Outcomes of Omnipod Initiation in People with Type 1 Diabetes (COPPER study): Evidence from the LMC Diabetes Registry.

AIMS: To investigate real-world clinical outcomes in adults with type 1 diabetes who initiated the Omnipod Insulin Management System (Insulet Corp., Acton, MA, USA) compared to a matched cohort who maintained multiple daily injection therapy. METHODS: This retrospective observational study used data from the Canadian LMC Diabetes Registry. Adults with type 1 diabetes who switched from multiple daily injections to the Omnipod system as usual standard of care between January 2011 and April 2019 were matched to a cohort of adults with type 1 diabetes who maintained multiple daily injection therapy, using propensity-score matching. The primary outcome was change in HbA1c at 3- to 6-month follow-up. RESULTS: Propensity-score matching resulted in a final analytical cohort of 286 individuals (143/cohort). HbA1c in the Omnipod cohort was reduced by a mean ± sd of -3 ± 10 mmol/mol (-0.2 ± 1.0%; P = 0.005) with no change in the MDI cohort [0 ± 10 mmol/mol (0.0 ± 1.0%); P = 0.74]. HbA1c change was seen only in persons with baseline HbA1c ≥75 mmol/mol (≥9.0%) [Omnipod cohort: -15 ± 12 mmol/mol (-1.4 ± 1.1%); P < 0.001] with a between-treatment difference [mean (95% CI)] of -12 (-18, -6) mmol/mol [-1.1 (-1.6, -0.5) %, P < 0.001]. The median total daily dose of insulin was lower following Omnipod initiation (baseline 0.63 U/kg vs follow-up 0.53 U/kg; P < 0.001), with no change in the MDI cohort (baseline 0.68 U/kg vs follow-up 0.67 U/kg; P = 0.23). CONCLUSIONS: Adults with type 1 diabetes who initiated use of the Omnipod system in a real-world clinical setting had lower HbA1c and total daily dose of insulin at 3- to 6-month follow-up compared to a matched cohort of adults who maintained multiple daily injection therapy. A treatment difference in HbA1c change was seen only in people with baseline HbA1c ≥ 75 mmol/mol (9.0%). (Clinical trials registration: NCT04226378).

Intact olfactory memory in the 5xFAD mouse model of Alzheimer's disease from 3 to 15 months of age.

Alzheimer's disease (AD) is an age-related neurodegenerative disorder that causes profound cognitive dysfunction. Deficits in olfactory memory occur in early stages of AD and may be useful in AD diagnosis. The 5xFAD mouse is a commonly used model of AD, as it develops neuropathology, cognitive and sensori-motor dysfunctions similar to those seen in AD. However, olfactory memory dysfunction has not been studied adequately or in detail in 5xFAD mice. Furthermore, despite sex differences in AD prevalence and symptom presentation, few studies using 5xFAD mice have examined sex differences in learning and memory. Therefore, we tested olfactory memory in male and female 5xFAD mice from 3 to 15 months of age using a conditioned odour preference task. Olfactory memory was not impaired in male or female 5xFAD mice at any age tested, nor were there any sex differences. Because early-onset impairments in very long-term (remote) memory have been reported in 5xFAD mice, we trained a group of mice at 3 months of age and tested olfactory memory 90 days later. Very long-term olfactory memory in 5xFAD mice was not impaired, nor was their ability to perform the discrimination task with new odourants. Examination of brains from 5xFAD mice confirmed extensive Aß-plaque deposition spanning the olfactory memory system, including the olfactory bulb, hippocampus, amygdala and piriform cortex. Overall this study indicates that male and female 5xFAD mice do not develop olfactory memory deficits, despite extensive Aß deposition within the olfactory-memory regions of the brain.

SGLT2 inhibitors and incretin agents: Associations with alanine aminotransferase activity in type 2 diabetes.

AIM: The impact of new classes of glucose lowering medications on markers of non-alcoholic fatty liver disease (NAFLD) associated with type 2 diabetes (T2D) have been inconsistent in their magnitude and independence. This large retrospective study investigates changes in alanine aminotransferase (ALT) levels among subjects initiated on newer classes of T2D medications in comparison to a reference control group. METHODS: We studied people with T2D from a large Canadian diabetes register, who had canagliflozin, dapagliflozin, liraglutide, sitagliptin or no further treatment added to their diabetes treatments. Stepwise multiple regression was used to determine the association of A1c and weight change on ALT. Propensity score weighting was used to balance baseline characteristics between treatment groups. RESULTS: A total of 3667 subjects met study criteria. ALT levels (mean follow-up 4.8 months) were lower after treatment with sodium glucose co-transporter 2 (SGLT2) inhibitors, canagliflozin (-4.3U/L, P<0.01) and dapagliflozin (-3.5U/L, P<0.01), compared to incretin agents, liraglutide (-2.1U/L, P<0.01) and sitagliptin (-1.8U/L, P<0.01), each greater than the control group. Only the SGLT2 inhibitor treatment groups maintained a significant ALT reduction vs. control following multivariable adjustment and propensity score weighting. Greater ALT reductions were seen with higher baseline ALT for both the SGLT2 inhibitor treatment groups. CONCLUSION: SGLT2 inhibitors canagliflozin and dapagliflozin resulted in a weight and A1c-independent reduction of ALT levels compared to incretin agents, with a dose-response observed at higher baseline ALT levels. Further studies investigating the differential effects of these drug classes on NAFLD, and insulin/glucagon levels as potential mechanism explaining these differences, should be performed.

Head imaging in suspected non accidental injury in the paediatric population. In the advent of volumetric CT imaging, has the skull X-ray become redundant?

AIM: To assess whether the inclusion of skull radiography, as part of the skeletal survey performed in suspected non-accidental injury (NAI), is still justified when volume computed tomography (CT) of the head has also been performed. MATERIALS AND METHODS: This was a retrospective study which included 94 patients aged between 24 days and 23 months who presented to the Emergency Department between August 2014 to July 2016 and had subsequent investigations for suspected NAI. Patients were identified from the local radiology systems (Carestream PACS and CRIS) using strict inclusion and exclusion criteria. Inclusion criteria were any suspected NAI patient who had both unenhanced volume CT head and skull radiography during the same episode of presentation. Any child with suspected NAI who only had one of either CT or radiographs of the skull (and not both) were excluded. RESULTS: None of the cases reviewed demonstrated additional findings on skull X-rays that were not demonstrated on the CT head. Due to the starkness of this result, the confidence interval is 0-3.9%. In two cases, additional bony findings were demonstrated on the CT head which were not evident on the skull X-rays. CONCLUSION: Skull X-rays could be excluded from the NAI skeletal survey without missing intracranial injuries or skull fractures in cases where a contemporaneous volumetric CT head is also performed.

Waist circumference at five common measurement sites in normal weight and overweight adults: which site is most optimal?

The aim of this study was to determine (i) if adults would measure their own waist circumference (WC), (ii) which WC site(s) are the most intuitive and easy to measure and (iii) if measurement accuracy and association between WC and blood pressure differs across five measurement sites. Participants (n = 198) measured their WC first with no instruction and then using visual instructions for the iliac crest, last rib, midpoint, minimal waist and umbilicus. Without instruction, men most commonly measured their WC at the umbilicus and iliac crest, while women measured their WC at the umbilicus and minimal WC. Both men and women reported the minimal waist and umbilicus to be moderately easier to self-measure compared to the other sites (P < 0.05). Prevalence of abdominal obesity varied significantly by gender and measurement site, especially for females (normal weight: 0-18%; overweight: 51-79%). Measurement site did not influence accuracy of WC self-measurement or the association between WC and blood pressure (P > 0.05). A universal WC landmark is needed. From these results, there does not appear to be a clear clinical advantage in terms of blood pressure or practical advantage of measuring one WC site over another. However, the umbilicus may be the most intuitive and easy to measure.

Motor function deficits in the 12 month-old female 5xFAD mouse model of Alzheimer's disease.

Motor problems occur early in some patients with Alzheimer's disease (AD) and as the disease progresses many patients develop motor dysfunction. Motor dysfunction has been reported in some mouse models of AD, including the 5xFAD mouse, thus this model may be particularly useful for studying motor dysfunction in AD. In order to determine the extent of motor dysfunction in these mice, we tested 11-13 month old female 5xFAD and wildtype (WT) control mice in a battery of motor behaviour tasks. The 5xFAD mice showed hind limb clasping, weighed less and had slower righting reflexes than WT mice. In the open field, the 5xFAD mice travelled a shorter distance than the WT mice, spent less time moving and had a slower movement speed. The 5xFAD mice fell faster than the WT mice from the balance beam, wire suspension, grid suspension and rotarod tasks, indicating dysfunctions in balance, grip strength, motor co-ordination and motor learning. The 5xFAD mice had a short, shuffling gait with a shorter stride length than WT mice and had a slower swim speed. The 5xFAD mice also failed to show an acoustic startle response, likely due to motor dysfunction and previously reported hearing impairment. The 5xFAD mice did not show deficits in the ability of peripheral motor nerves to drive muscle output, suggesting that motor impairments are not due to dysfunction in peripheral motor nerves. These results indicate that the aged 5xFAD mice are deficient in numerous motor behaviours, and suggest that these mice may prove to be a good model for studying the mechanisms of motor dysfunction in AD, and motor behaviour might prove useful for assessing the efficacy of AD therapeutics. Motor dysfunction in 5xFAD mice must also be considered in behavioural tests of sensory and cognitive function so that performance is not confounded by impaired locomotor or swimming behaviour.

Reduced acoustic startle response and peripheral hearing loss in the 5xFAD mouse model of Alzheimer's disease.

Hearing dysfunction has been associated with Alzheimer's disease (AD) in humans, but there is little data on the auditory function of mouse models of AD. Furthermore, characterization of hearing ability in mouse models is needed to ensure that tests of cognition that use auditory stimuli are not confounded by hearing dysfunction. Therefore, we assessed acoustic startle response and pre-pulse inhibition in the double transgenic 5xFAD mouse model of AD from 3-4 to 16 months of age. The 5xFAD mice showed an age-related decline in acoustic startle as early as 3-4 months of age. We subsequently tested auditory brainstem response (ABR) thresholds at 4 and 13-14 months of age using tone bursts at frequencies of 2-32 kHz. The 5xFAD mice showed increased ABR thresholds for tone bursts between 8 and 32 kHz at 13-14 months of age. Finally, cochleae were extracted and basilar membranes were dissected to count hair cell loss across the cochlea. The 5xFAD mice showed significantly greater loss of both inner and outer hair cells at the apical and basal ends of the basilar membrane than wild-type mice at 15-16 months of age. These results indicate that the 5xFAD mouse model of AD shows age-related decreases in acoustic startle responses, which are at least partially due to age-related peripheral hearing loss. Therefore, we caution against the use of cognitive tests that rely on audition in 5xFAD mice over 3-4 months of age, without first confirming that performance is not confounded by hearing dysfunction.

Neuromuscular responses of the plantar flexors to whole-body vibration.

Enhanced physical performance following whole-body vibration (WBV) has been attributed to increased muscle activity; however, few studies have measured the mechanisms underlying these changes. The objective of this study was to measure the responsiveness of the Ia pathway as well as contractile properties in 16 young adults (24±2 years, eight men, eight women) following repeated bouts of acute WBV (45 Hz, 2 mm). Hoffman reflexes (H-reflex), compound muscle action potentials (M-wave), and twitch contractile properties were measured prior to and immediately following five 1-minute WBV exposures, and at 3, 5, 10, and 20 minute post-WBV. M-wave and H-reflex amplitudes decreased by 8% (P<.001) and by 46% (P<.05), respectively, whereas peak twitch torque decreased by 9% (P<.01) and rate of twitch torque development slowed 8% (P<.05). Percent voluntary activation and maximal plantar flexor torque were unchanged as a consequence of WBV (P>.05). In response to acute WBV, the root mean square of the soleus electromyography signal (EMGRMS ) increased by 8%, while the EMGRMS of the lateral gastrocnemius increased by 3% (P<.05). These data indicate that the responsiveness of the Ia pathway is diminished and contractile function is impaired immediately following WBV, and that the neural mechanisms underlying improved performance following WBV lie in alternative hypotheses possibly involving spindle disfacilitation or Golgi afferent modulation.

The effect of bicycling on PSA levels: a systematic review and meta-analysis.

BACKGROUND: Recent literature has suggested that bicycling may be associated with increases in serum PSA levels, a diagnostic and prognostic marker for prostate cancer. To further investigate this relationship, we conducted a systematic review and meta-analysis of current literature in this field. METHODS: MEDLINE, CENTRAL, CINAHL and SPORTDiscus were searched using MeSH terms and keywords for English publications related to bicycle riding and PSA. Studies were included if PSA was measured relative to cycling activity in healthy men who were free of any prostatic condition. Case studies were excluded. RESULTS: Eight studies met our inclusion criteria, comprising 912 participants that engaged in, or self-reported, bicycling activity. Six studies investigated the acute pre-post change in PSA following bicycling activity that ranged from a single cycling bout of 15 min to a 4-day cycling event. Following cycling activity, two studies reported total PSA increased from baseline by up to 3.3-fold, free PSA increased in one study by 0.08±0.18 ng ml(-)(1) and did not change in four studies. One study compared PSA in elite/professional cyclists versus non-cyclists and demonstrated no significant difference in PSA measurements between groups. Data from six studies were meta-analyzed and demonstrated no significant increase in PSA associated with cycling from pre to post (mean change +0.027 ng ml(-)(1), s.e.m.=0.08, P=0.74, 95% confidence interval (CI)=-0.17-0.23). CONCLUSIONS: Our findings suggest that there is no effect of cycling on PSA; however, the limited number of trials and the absence of randomized controlled trials limit the interpretation of our results. Additionally, the median sample size only consisted of 42 subjects. Therefore, our study may have low statistical power to detect a difference in PSA. Although, a higher sample size may demonstrate statistical significance, it may not be clinically significant. Studies of higher empirical quality are needed.

Measurement site influences abdominal subcutaneous and visceral adipose tissue in obese adolescents before and after exercise.

BACKGROUND/OBJECTIVES: The objective of this study was to determine if abdominal adipose tissue (AT) measurement site influences the association between baseline and change in abdominal subcutaneous (ASAT) and visceral AT (VAT), and metabolic risk factors in obese adolescents. METHODS: Fifty-five obese adolescents (14.9 ± 1.7 years; 51% male; 42% white) participated in an aerobic or resistance exercise intervention three times/week for 3 months. We compared the association between changes in abdominal AT area (spanning 5 cm below to 15 cm above L4-L5) and volume measured by magnetic resonance imaging with concomitant changes in metabolic risk. RESULTS: All AT areas were significantly (p < 0.05) correlated with the respective volume at baseline and follow-up. Baseline VAT areas at 5 and 10 cm above L4-L5 were more strongly associated with VAT volume than VAT area at L4-L5 (p < 0.05). After the intervention, changes in the area at 5 and 10 cm above L4-L5 were more strongly associated with changes in AT volumes than changes in L4-L5 (p < 0.05). Changes in abdominal AT volumes were more strongly associated with insulin area under the curve than any single-slice abdominal AT area. CONCLUSIONS: The measurement site for abdominal AT has significant influence on the relationships with total VAT or ASAT and metabolic risk factors in obese adolescents before and after an exercise intervention.

Consequences of obesity and weight loss: a devil's advocate position.

Obesity is associated with multiple negative health consequences and current weight management guidelines recommend all obese persons to lose weight. However, recent evidence suggests that not all obese persons are negatively affected by their weight and that weight loss does not necessarily always improve health. The purpose of this review is not to trivialize the significant health risks associated with obesity, but to discuss subpopulations of obese people who are not adversely affected, or may even benefit from higher adiposity, and in who weight loss per se may not always be the most appropriate recommendation. More specifically, this review will take a devil's advocate position when discussing the consequences of obesity and weight loss for adults with established cardiovascular disease and type 2 diabetes, weight cyclers, metabolically healthy obese adults, youth, older adults and obese individuals who are highly fit.

The effect of tendon vibration on motor unit activity, intermuscular coherence and force steadiness in the elbow flexors of males and females.

BACKGROUND: Compartmentalized responses in motor unit (MU) activity of the short head (SH) and long head (LH) of the biceps brachii are observed following forearm position change. Differential muscle spindle afferent distribution has been proposed as a potential mechanism underlying this behaviour. Tendon vibration is an effective, non-invasive method of increasing muscle spindle afferent activity of a target muscle group offering a paradigm in which this hypothesis may be investigated further. AIM: To determine the effect of tendon vibration on MU recruitment and discharge rates of the SH and LH, muscle activity of the elbow flexors and triceps brachii, intermuscular coherence among the SH, LH, brachioradialis and triceps brachii and force steadiness in young males and females during isometric elbow flexion. METHODS: Intramuscular electromyography (EMG) of the SH and LH, and surface EMG of the elbow flexors were recorded pre- and post-vibration during low-force isometric contractions. Motor unit recruitment thresholds, MU discharge rates and MU discharge variability; surface EMG amplitude, intermuscular coherence and force steadiness were determined pre- and post-vibration. RESULTS: Differential changes in all MU properties, EMG amplitude and intermuscular coherence were observed among elbow flexors. Although MU properties exhibited differential changes, they accounted for little variance in isometric force steadiness. However, intermuscular EMG coherence among all muscles investigated was reduced post-vibration. CONCLUSION: Uncoupling of common oscillatory input as a result of differential muscle spindle afferent inputs to elbow flexors may be responsible for the reduction in force steadiness following tendon vibration and a forearm position change.

Early detection of cerebral glucose uptake changes in the 5XFAD mouse.

Brain glucose hypometabolism has been observed in Alzheimer's disease (AD) patients, and is detected with (18)F radiolabelled glucose, using positron emission tomography. A pathological hallmark of AD is deposition of brain ß- amyloid plaques that may influence cerebral glucose metabolism. The five times familial AD (5XFAD) mouse is a model of brain amyloidosis exhibiting AD-like phenotypes. This study examines brain ß-amyloid plaque deposition and (18)FDG uptake, to search for an early biomarker distinguishing 5XFAD from wild-type mice. Thus, brain (18)FDG uptake and plaque deposition was studied in these mice at age 2, 5 and 13 months. The 5XFAD mice demonstrated significantly reduced brain (18)FDG uptake at 13 months relative to wild-type controls but not in younger mice, despite substantial ß- amyloid plaque deposition. However, by comparing the ratio of uptake values for glucose in different regions in the same brain, 5XFAD mice could be distinguished from controls at age 2 months. This method of measuring altered glucose metabolism may represent an early biomarker for the progression of amyloid deposition in the brain. We conclude that brain (18)FDG uptake can be a sensitive biomarker for early detection of abnormal metabolism in the 5XFAD mouse when alternative relative uptake values are utilized.

Combating child obesity: impact of HENRY on parenting and family lifestyle.

BACKGROUND: One-quarter of children in England are overweight/obese at school entry. We investigated the impact of a programme designed to provide parents of infants and preschool children with the skills required for a healthier family lifestyle. METHOD: A cohort of families was followed across the 8-week HENRY (Health Exercise Nutrition for the Really Young) parent course at nine locations in England. Seventy-seven parents enrolled on the course, of which 71 agreed to complete questionnaires addressing eating behaviours, dietary intake and parental self-efficacy. Pre- and post-course data was available from 60 (84.5%) parents (8-week follow-up data from 58 parents) and was analysed using repeated measures analyses. RESULTS: Significant changes were observed, with most sustained at follow-up. Parents reported increased self-efficacy and ability to encourage good behaviour (P < 0.001). Increased consumption of fruits and vegetables was reported in both children and adults, together with reduced consumption of sweets, cakes and fizzy drinks in adults (all P < 0.01). There were also positive changes in eating behaviours (e.g., frequency of family mealtimes and eating while watching television or in response to negative emotion [P < 0.01] ) and reduced screen time in adults (P < 0.001). DISCUSSION: The results build upon earlier evaluation, indicating that the HENRY intervention has a beneficial impact upon the families of infants and preschool children. Furthermore, the findings suggest that positive changes inspired by the programme can be maintained beyond its completion. Such changes may serve to protect against later obesity.

The cholinergic agonist carbachol increases the frequency of spontaneous GABAergic synaptic currents in dorsal raphe serotonergic neurons in the mouse.

Dorsal raphe nucleus (DRN) serotonin (5-HT) neurons play an important role in feeding, mood control and stress responses. One important feature of their activity across the sleep-wake cycle is their reduced firing during rapid-eye-movement (REM) sleep which stands in stark contrast to the wake/REM-on discharge pattern of brainstem cholinergic neurons. A prominent model of REM sleep control posits a reciprocal interaction between these cell groups. 5-HT inhibits cholinergic neurons, and activation of nicotinic receptors can excite DRN 5-HT neurons but the cholinergic effect on inhibitory inputs is incompletely understood. Here, in vitro, in DRN brain slices prepared from GAD67-GFP knock-in mice, a brief (3 min) bath application of carbachol (50 µM) increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in GFP-negative, putative 5-HT neurons but did not affect miniature (tetrodotoxin-insensitive) IPSCs. Carbachol had no direct postsynaptic effect. Thus, carbachol likely increases the activity of local GABAergic neurons which synapse on 5-HT neurons. Removal of dorsal regions of the slice including the ventrolateral periaqueductal gray (vlPAG) region where GABAergic neurons projecting to the DRN have been identified, abolished the effect of carbachol on sIPSCs whereas the removal of ventral regions containing the oral region of the pontine reticular nucleus (PnO) did not. In addition, carbachol directly excited GFP-positive, GABAergic vlPAG neurons. Antagonism of both muscarinic and nicotinic receptors completely abolished the effects of carbachol. We suggest cholinergic neurons inhibit DRN 5-HT neurons when acetylcholine levels are lower i.e. during quiet wakefulness and the beginning of REM sleep periods, in part via excitation of muscarinic and nicotinic receptors located on local vlPAG and DRN GABAergic neurons. Higher firing rates or burst firing of cholinergic neurons associated with attentive wakefulness or phasic REM sleep periods leads to excitation of 5-HT neurons via the activation of nicotinic receptors located postsynaptically and presynaptically on excitatory afferents.

Use of a sestamibi-only approach to routine minimally invasive parathyroidectomy.

We performed this study to compare a sestamibi-only radio-guided approach (MIBI) versus using intraoperative parathyroid hormone monitoring (IOPTH) in the performance of minimally invasive parathyroidectomy (MIP) in patients with a clearly positive preoperative sestamibi scan from January 2000 to June 2010. Five of 81 patients in the MIBI group required additional surgery, three at the time of MIP when the intraoperative findings were in conflict with the preoperative sestamibi scan and two required a second operation as a result of an undiscovered second adenoma. In the IOPTH group, five patients had an unnecessary bilateral neck exploration as a result of an inadequate drop in PTH levels, whereas six had their disease cured because the PTH levels predicted additional pathology. One patient in the IOPTH group remains hypercalcemic and represents the only surgical failure in this study. The MIBI group had a shortened operating room time and less cost (P < 0.001). No deaths or complications, including recurrent laryngeal nerve injuries, occurred in this study. Although both strategies are effective in managing hyperparathyroidism, a MIBI-only approach is less expensive and has shorter operative times with an occasional need for reoperation, whereas the IOPTH group results in more extensive surgery that will occasionally be unnecessary.

An Expedient Synthesis of Fluorescent Labeled Ceramide-1-phosphate Analogues.

A synthesis for fluorescent analogs of ceramide-1-phosphate bearing 9-anthrylvinyl or 4,4-difluoro-3a,4a-diaza-s-indacene-8-yl (Me4-BODIPY) fluorophore at co-position of fatty acid residue was carried out. The key stage of the synthesis is hydrolysis of corresponding sphingomyelins catalyzed by phospholipase D from Streptomyces chromofuscus; the enzymatic yield has been raised to 50-70% by appliance of organic solvent in the incubation medium.

Improving animal models for nervous system disorders.

A workshop on 'Improving translation of animal models for nervous system disorders' held at the National Academy of Sciences, Institute of Medicine, in Washington, DC, 28-29 March 2012, was organized to discuss the issues that contribute to the poor translation of results from animal models to human nervous system disorders, to consider strategies to increase the scientific rigor of preclinical testing, to identify methods to maximize bidirectional translation between basic and clinical research, and to determine the next steps for improvement of the development and testing of animal models of nervous system disorders. The proceedings of this workshop will be of great interest to those doing research in genes, brain and behaviour.

The cost of managing genital warts in the UK.

The national cost of managing genital warts (GWs) in the UK has not been fully estimated, yet is required to inform decisions on vaccination against human papillomavirus. This study estimated the 2010 UK costs based on secondary genitourinary (GU) medicine clinic data from the Health Protection Agency (HPA) and primary care data from the Health Improvement Network database. Extrapolating data to 2010 resulted in 173,077 GU medicine clinic and 16,782 primary care GW episodes. Using treatment patterns obtained from key opinion leaders and tariffs from National Health Service Payment by Results (NHS PbR), the national costs were estimated at £52.4 million: £276 per treated GW episode.