Fluoride varnish applications provided in general dental practice for children of primary school age in three areas of the UK.

Introduction Dental guidelines recommend professional application of fluoride varnish (FV) at least twice a year for children from the age of three.Methods NHS dental claims data were reviewed for children born in 2009 for the five-year period 2015-2019 and who attended the dentist in one of three geographical areas, labelled as Bristol, Birmingham and Cardiff. Data for 14,566 children were included in the study.Results Only 3.5% of children had been provided with ten or more FV applications at the dentist in the five-year period. Children in the Cardiff region fared less well for fluoride applications than their Bristol and Birmingham counterparts, including children that were seemingly at high risk of caries for part of the time period reviewed. For all three regions, the mean number of FV applications increased with an increase in the number of fillings provided.Conclusion Awareness of the apparent lack of FV application in the dental surgery may provide an opportunity to improve child dental health.

Local anaesthetic transperineal (LATP) prostate biopsy using a probe-mounted transperineal access system: a multicentre prospective outcome analysis.

OBJECTIVES: To assess the feasibility of local anaesthetic transperineal (LATP) technique using a single-freehand transperineal (TP) access device, and report initial prostate cancer (PCa) detection, infection rates, and tolerability. PATIENTS AND METHODS: Observational study of a multicentre prospective cohort, including all consecutive cases. LATP was performed in three settings: (i) first biopsy in suspected PCa, (ii) confirmatory biopsies for active surveillance, and (iii) repeat biopsy in suspected PCa. All patients received pre-procedure antibiotics according to local hospital guidelines. Local anaesthesia was achieved by perineal skin infiltration and periprostatic nerve block without sedation. Ginsburg protocol principles were followed for systematic biopsies including cognitive magnetic resonance imaging-targeted biopsies when needed using the PrecisionPoint™ TP access device. Procedure-related complications and oncological outcomes were prospectively and consecutively collected. A validated questionnaire was used in a subset of centres to collect data on patient-reported outcome measures (PROMs). RESULTS: Some 1218 patients underwent LATP biopsies at 10 centres: 55%, 24%, and 21% for each of the three settings, respectively. Any grade PCa was diagnosed in 816 patients (67%), of which 634 (52% of total) had clinically significant disease. Two cases of sepsis were documented (0.16%) and urinary retention was observed in 19 patients (1.6%). PROMs were distributed to 419 patients, with a 56% response rate (n = 234). In these men, pain during the biopsy was described as either 'not at all' or 'a little' painful by 64% of patients. Haematuria was the most common reported symptom (77%). When exploring attitude to re-biopsy, 48% said it would be 'not a problem' and in contrast 8.1% would consider it a 'major problem'. Most of the patients (81%) described the biopsy as a 'minor or moderate procedure tolerable under local anaesthesia', while 5.6% perceived it as a 'major procedure that requires general anaesthesia'. CONCLUSION: Our data suggest that LATP biopsy using a TP access system mounted to the ultrasound probe achieves excellent PCa detection, with a very low sepsis rate, and is safe and well tolerated. We believe a randomised controlled trial comparing LATP with transrectal ultrasound-guided biopsy (TRUS) to investigate the relative trade-offs between each biopsy technique would be helpful.

A Retrospective Study of Immunotherapy Treatment with Uro-Vaxom (OM-89®) for Prophylaxis of Recurrent Urinary Tract Infections.

OBJECTIVES: To present our experience with the long-term preventive effect of immunotherapy with Uro-Vaxom® on recurrent urinary tract infections (UTI) in adult patients. MATERIALS AND METHODS: Retrospective analysis of 79 patients with recurrent UTI treated with Uro-Vaxom. Recurrent UTIs were defined as ≥ 2 infections in 6 months or ≥ 3 in 12 months. Patients received a 6 mg Uro-Vaxom capsule daily for 90 days followed by discontinuation for 3 months and then administration for the first 10 days of subsequent months 7, 8 and 9 as a 'booster' regime. The primary outcome measure was the number of UTIs encountered in the 12 months pre-treatment compared to 12 months post-treatment. RESULTS: There was a significant decrease in the mean number of UTIs in the year following initiation of Uro-Vaxom® compared to the year preceding administration 3.14 versus 1.53 (p < 0.05) respectively. CONCLUSION: Uro-Vaxom represents a safe and effective treatment option for prophylaxis of recurrent UTIs. In the UK, Uro-Vaxom is currently unlicensed. This study adds to a growing body of evidence in favor of non-antibiotic immune-prophylaxis for recurrent UTI.

The clinical and financial implications of a decade of prostate biopsies in the NHS: analysis of Hospital Episode Statistics data 2008-2019.

OBJECTIVE: To evaluate the clinical and financial implications of a decade of prostate biopsies performed in the UK National Health Service (NHS) through the transrectal (TR) vs the transperineal (TP) route. METHODS: We conducted an evaluation of the TR vs the TP biopsy approach in the context of 28 days post-procedure complications and readmissions. A secondary evaluation of burden of expenditure in NHS hospitals over the entire decade (2008-2019) was conducted through examination of national Hospital Episode Statistics (HES) data. RESULTS: In this dataset of 486 467 prostate biopsies (387 879 TR and 98 588 TP biopsies), rates of infection and sepsis were higher for the TR compared to the TP cohort (0.53% vs 0.31%; P < 0.001, confidence interval 99% ). Rates of sepsis have more than doubled for TR biopsies in the last 2 years compared to the previous decade (1.12% vs 0.53%). Infective complications were the main reasons for readmissions in the TR cohort, whereas urinary retention was the predominant reason for readmission in the TP cohort. Over the last decade, non-elective (NEL) readmissions seem higher for the TP group; however, in the last 2 years these have reduced compared to the TR group (3.54% vs 3.74%). The cost estimates for NEL readmissions for the entire decade were £33,589,527.00 and £7,179,926.00 respectively, for TR and TP cohorts (P < 0.001). Estimated costs per patient readmission were £2,225.00 and £1,758.00 in the TR and TP groups (P < 0.001). CONCLUSIONS: Evaluation of nearly half a million prostate biopsies in the NHS over the entire decade gives sufficient evidence for the distinct advantages of the TP route over the TR route in terms of reduced infections and burden of expenditure. In addition, there is a potential for savings both in upstream and downstream costs if biopsy is performed under a local anaesthetic.

Appendix or Ileum-Which is the Best Material for Mitrofanoff Channel Formation in Adults?

PURPOSE: We report long-term data on a large cohort of adults who underwent formation of a continent catheterizable channel for various indications. We examined outcomes according to the tissue used for channel formation. MATERIALS AND METHODS: We retrospectively reviewed the case notes of 176 consecutive adult patients in whom a continent catheterizable channel was created using the Mitrofanoff principle for a broad range of indications a median of 142 months (range 54 to 386) previously. We evaluated outcomes in terms of continued use and continence for each type of material used for channel formation. RESULTS: At the time of this review 165 of the 173 patients (95.4%) included in this study were alive. We included 114 women (65.9%) and 59 men (34.1%) who underwent surgery at a median age of 42 years (range 18 to 73) with a mean followup of 78.6 months (median 60, range 2 to 365). The rate of revision for all causes was higher in the ileal group than in the group with an appendiceal channel (channel stenosis rate 22.7% vs 17.2%, p = 0.39, and channel incontinence rate 36.0% vs 19.5%, p = 0.03). Although 38.7% of patients underwent major surgical revision of the channel at some point, 75.9% of channels continued to be used, of which 90.2% were continent. CONCLUSIONS: This study provides a pragmatic overview of the outcome of these challenging cases. Mitrofanoff channel formation represents a durable technique. Appendix and ileum are each a viable choice for tissue use. Tissue selection depends on availability and individual patient factors.

Clinical and Patient-reported Outcome Measures in Men Referred for Consideration of Surgery to Treat Lower Urinary Tract Symptoms: Baseline Results and Diagnostic Findings of the Urodynamics for Prostate Surgery Trial; Randomised Evaluation of Assessment Methods (UPSTREAM).

BACKGROUND: Clinical evaluation of male lower urinary tract symptoms (MLUTS) in secondary care uses a range of assessments. It is unknown how MLUTS evaluation influences outcome of therapy recommendations and choice, notably urodynamics (UDS; filling cystometry and pressure flow studies). OBJECTIVE: To report participants' sociodemographic and clinical characteristics, and initial diagnostic findings of the Urodynamics for Prostate Surgery Trial; Randomised Evaluation of Assessment Methods (UPSTREAM). UPSTREAM is a randomised controlled trial evaluating whether symptoms are noninferior and surgery rates are lower if UDS is included. DESIGN, SETTING, AND PARTICIPANTS: A total of 820 men (≥18 yr of age) seeking treatment for bothersome LUTS were recruited from 26 National Health Service hospital urology departments. INTERVENTION: Care pathway based on routine, noninvasive tests (control) or routine care plus UDS (intervention arm). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome is International Prostate Symptom Score (IPSS) and the key secondary outcome is surgery rates 18 mo after randomisation. International Consultation on Incontinence Questionnaires were captured for MLUTS, sexual function, and UDS satisfaction. Baseline clinical and patient-reported outcome measures (PROMs), and UDS findings were informally compared between arms. Trends across age groups for urinary and sexual PROMs were evaluated with a Cuzick's test, and questionnaire items were compared using Pearson's correlation coefficient. RESULTS AND LIMITATIONS: Storage LUTS, notably nocturia, and impaired sexual function are prominent in men being assessed for surgery. Sociodemographic and clinical evaluations were similar between arms. Overall mean IPSS and quality of life scores were 18.94 and 4.13, respectively. Trends were found across age groups, with older men suffering from higher rates of incontinence, nocturia, and erectile dysfunction, and younger men suffering from increased daytime frequency and voiding symptoms. Men undergoing UDS testing expressed high satisfaction with the procedure. CONCLUSIONS: Men being considered for surgery have additional clinical features that may affect treatment decision making and outcomes, notably storage LUTS and impaired sexual function. PATIENT SUMMARY: We describe initial assessment findings from a large clinical study of the treatment pathway for men suffering with bothersome urinary symptoms who were referred to hospital for further treatment, potentially including surgery. We report the patient characteristics and diagnostic test results, including symptom questionnaires, bladder diaries, flow rate tests, and urodynamics.

Atypical Small Acinar Proliferation and High Grade Prostatic Intraepithelial Neoplasia: Should We Be Concerned? An Observational Cohort Study with a Minimum Follow-Up of 3 Years.

INTRODUCTION: Atypical small acinar proliferation (ASAP) and high grade prostatic intraepithelial neoplasia (HGPIN) are considered precancerous. We aimed to measure the rate of repeat biopsy and adenocarcinoma in patients with ASAP and HGPIN and identify any clinico-pathologic parameters at diagnosis of ASAP/HGPIN that are predictive of adenocarcinoma. MATERIALS AND METHODS: Patients with a diagnosis of ASAP/HGPIN with no previous or concomitant cancer were identified. Prostate specific antigen (PSA) and magnetic resonance imaging (MRI) changes were monitored. Re-biopsy was at clinician discretion. RESULTS: Nineteen were diagnosed with ASAP and 17 with HGPIN. Seven with ASAP (37%) and 6 with HGPIN (35%) underwent re-biopsy. Three (16%) with ASAP and 5 with HGPIN (29%) were diagnosed with adenocarcinoma. The difference in cancer detection rates between ASAP and HGPIN was not significant (p = 0.35). Five (14%) in total required definitive therapy for adenocarcinoma. Twenty-three (64%) did not undergo repeat biopsy. Parameters at diagnosis of HGPIN and ASAP, including PSA, prostate volume and PSA density, were compared between the cancer and non-cancer cohorts with none found to be predictive of adenocarcinoma. CONCLUSION: By monitoring PSA and MRI changes, we managed to spare re-biopsy in two-thirds of patients. Further evaluation is necessary to characterize a surveillance protocol in these populations.

Long-term efficacy of polydimethylsiloxane (Macroplastique) injection for Mitrofanoff leakage after continent urinary diversion surgery.

OBJECTIVE: To assess the long-term efficacy of polydimethylsiloxane (Macroplastique) injection (MPI) in the treatment of Mitrofanoff leakage secondary to valve incompetence. PATIENTS AND METHODS: Between 1995 and 2012, the records of 24 consecutive patients who underwent MPI for Mitrofanoff urinary leakage after continent cutaneous urinary diversion (CCUD) surgery were examined. All patients had a valve deemed of sufficient length (>2 cm) to attempt Macroplastique coaptation. Treatment outcomes were divided into three categories based on physician assessment: success (dry), partial success (>50% reduction in incontinence pads) and failure. Success rates were assessed according to the type of reservoir and conduit channel. RESULTS: The mean (range) follow-up was 30 (6-96) months. One patient had initial difficulty catheterising, and subsequently required major revision surgery. In all, 12 patients (50%) failed the treatment and subsequently underwent operative revision to the channel. Three patients (12.5%) achieved complete success; one patient had an appendix channel through native bladder and the remaining two had Monti channels through colon. Nine patients (37.5%) had partial success; success rates were higher with appendix channels (four of six) and colonic reservoirs (six of seven) when compared with Monti channels (eight of 18, 44%) and ileal reservoirs (zero of two). Five of the nine patients with partial success eventually required further surgical revision for deteriorating continence at a mean (range) of 41 (14-96) months, whilst the other four have maintained sufficient continence with MPI alone. CONCLUSION: Macroplastique bulking cured only 12.5% patients, but leakage was substantially improved in a further 37.5% allowing major surgery to be avoided or postponed in one half of the cohort. Appendix Mitrofanoffs do better than the Monti Mitrofanoff, with channels through colonic segments generally doing better than those through ileal bladders. MPI should be considered as a less invasive alternative to avoid or delay major reconstructive surgery.

A new phenotype of brain iron accumulation with dystonia, optic atrophy, and peripheral neuropathy.

BACKGROUND: Neurodegeneration with brain iron accumulation is clinically and genetically heterogeneous because of mutations in at least 7 nuclear genes. METHODS: We performed homozygosity mapping and whole-exome sequencing in 2 brothers with brain iron accumulation from a consanguineous family. RESULTS: We identified a homozygous missense mutation in both brothers in the very recently identified chromosome 19 open-reading frame 12 gene. The disease presented before age 10 with slowly progressive tremor, dystonia, and spasticity. Additional features were optic atrophy, peripheral neuropathy, and learning difficulties. A raised serum creatine kinase indicated neuromuscular involvement, and compensatory mitochondrial proliferation implicated mitochondrial dysfunction as a pathological mechanism. CONCLUSIONS: Further studies are needed to explore the function of the chromosome 19 open-reading frame 12 gene, and extended genetic analysis on larger patient cohorts will provide more information about the presentation and frequency of this disease.

Adult-onset cerebellar ataxia due to mutations in CABC1/ADCK3.

OBJECTIVE: Inherited ataxias are heterogeneous disorders affecting both children and adults. The primary cause can be identified in about half of the patients and only very few can receive causative therapy. METHODS: The authors performed sequencing of known Coenzyme Q10 (CoQ10) deficiency genes in 22 patients with unexplained recessive or sporadic ataxia. RESULTS: CABC1/ADCK3 mutations were detected in four patients and two siblings presenting with cerebellar ataxia, epilepsy and muscle symptoms. Spasticity, dystonia, tremor and migraine were variably present; cognitive impairment was severe in early childhood cases, but was absent in adults. In contrast to previous reports, two of the patients had a later-onset, very mild phenotype and remained ambulatory in their late forties. Muscle biopsy revealed lipid accumulation, mitochondrial proliferation and cytochrome c oxidase-deficient fibres, but no typical ragged red fibres. Respiratory-chain enzyme activities and CoQ10 were decreased in severely affected patients but remained normal in a mildly affected patient at 46 years of age. CONCLUSIONS: These observations highlight the importance of screening for a potentially treatable cause, CABC1/ADCK3 mutations, not only in severe childhood-onset ataxia, but also in patients with mild cerebellar ataxia in adult life.

Urethral diverticula in females.

What's known on the subject? and What does the study add? This is a review of urethral diverticula in females. In addition to modes of presentation, differential diagnosis, complications and surgical management, the increasingly recognised value of computerised axial imaging, especially with MRI, is highlighted. Urethral diverticula are rare but under-diagnosed entities that may cause a variety of urinary and pelvic symptoms in women. They are best demonstrated by magnetic resonance imaging and micturating cysto-urethrography prior to transvaginal surgical excision. Although unlikely, the possibility of malignant transformation should not be forgotten.

Unrecognized bladder perforation with mid-urethral slings.

OBJECTIVE: To present a series of women with late presentation of mid-urethral synthetic slings perforating the bladder and their management, this is rare but can lead to significant morbidity with medico-legal consequences. PATIENTS AND METHODS: We retrospectively reviewed the case notes of nine women with urinary symptoms referred to our unit for further investigation after synthetic mid-urethral sling placement. RESULTS: The women presented between 8 weeks and 18 months after initial sling placement. Eight patients underwent a tension-free vaginal tape insertion via the retropubic route and one patient had an 'outside-in' obturator sling with the I-Stop device (CL Medical, Lyon, France). The frequencies of presenting symptoms were: dysuria in six; recurrent urinary tract infection in four; frequency and urgency in four and pelvic pain in two. Seven of the nine women developed bladder calculi on the exposed sling material, all of which were visible on plain X-ray. In six women, perforations were present at more than one site; in three urethral perforation had occurred together with an anterolateral bladder injury and in the remaining three there was bilateral bladder perforation. Initial management included cystoscopy and cystolithopaxy followed by transurethral resection (TUR) of the visible prolene mesh into the detrusor muscle. One woman required two TURs to clear all the mesh. Two women required further open surgery to remove all of the remaining mesh, both for ongoing pelvic pain that resolved after revision surgery. All the women had resolution of symptoms but all had recurrent stress urinary incontinence after tape division/excision. We used a novel technique to remove intraurethral mesh using a nasal speculum urethrally and excising the tape under direct vision, where resection proved impossible due to poor endoscopic views, with significant risk of sphincter injury. CONCLUSIONS: The possibility of unrecognized tape perforation or erosion must be considered in women with persistent urinary symptoms, infection or pain after any form of mid-urethral sling procedure. Bladder stones almost invariably develop if the exposed mesh has been present for >3 months. Most patients can be managed with endoscopic resection to remove all intravesical tape. Cystoscopy should remain a mandatory procedure together with any form of mid-urethral sling placement but does not prevent unrecognized perforations in inexperienced hands.

The clinical significance and therapeutic implications of extraprostatic invasion.

Invasion of the prostatic margin by cancer establishes a higher risk of disease progression and treatment failure depending upon its extent and other clinical factors. Pathological stage is the most important single prognostic indicator, but determined reliably only in patients having radical prostatectomy. Tumour beyond the prostatic margin or its invasion into the seminal vesicle defines the local stage category as T3, and when confirmed by pathological examination the extent of prostatic margin involvement has prognostic significance. Prediction of extraprostatic invasion may influence therapeutic decisions, but can be difficult to determine for the individual patient prior to treatment. In some individuals having radical prostatectomy, the finding of extraprostatic invasion is unsuspected, and fortunately for the majority of these men the treatment remains curative. On the other hand, when extraprostatic invasion is suspected prior to or at surgery, wide excision may be necessary to achieve negative surgical margins, with other factors contributing independently to the likelihood of subsequent progression. Radiotherapy is an effective alternative treatment for clinical stage T3 and high-risk clinically localized cancer. Recent technological advances and use of combination modality treatment with radiation and hormone manipulation have improved survival outcomes and reduced side-effects. Radiation also has its place as adjuvant treatment following radical prostatectomy in high-risk disease, or as salvage following PSA recurrence, with ongoing trials evaluating potential benefit and toxicity. For clinically localised stage T3 prostate cancer, treatment with surgery or radiotherapy may be highly effective, but multimodality interventions are increasingly being used for primary treatment where clinical assessment indicates that there would otherwise be a high risk for disease progression and therapeutic failure.

A tertiary experience of vesico-vaginal and urethro-vaginal fistula repair: factors predicting success.

OBJECTIVE: To review the outcomes of all patients referred with vesico-vaginal (V VF) and urethro-vaginal (UVF) fistulae to a tertiary centre, and to investigate the patient, fistula and surgical factors relevant to success. PATIENTS AND METHODS: We reviewed retrospectively the case-notes of 41 consecutive patients (32 with V VF; nine with UVF) treated between January 2000 and January 2006. RESULTS: All patients were tertiary referrals, eight after failed local repairs. Four patients were unsalvageable and had a supravesical diversion. In all there were 47 repairs (23 transvaginal; 24 transabdominal) on 37 patients by two specialist surgeons. The fistula was closed in 92%; five V VF and one UVF required a second procedure, and one V VF a third procedure. One patient with a V VF awaits a second attempt at repair. In one V VF (one attempt) and one UVF (three attempts) the procedure failed and the patient had a diversion. A transvaginal approach cured all 11 patients with a V VF and eight of nine with a UVF, whilst an abdominal approach used for larger/complex fistulae was successful in 18 of 24 (75%) attempts (P = 0.13). The major determinants of success were fistula size (>3 cm; P = 0.02) and the availability of tissue for interposition. V VF repairs using Martius/omental interposition were mostly successful, whilst abdominal repairs in which omentum was unavailable tended to fail (37.5% cure; P = 0.002). CONCLUSIONS: Despite varied aetiology, V VF/UVF were repaired successfully in 92% of patients. Complex (V VF) fistulae were challenging and a quarter of these required more than one attempt. Failure of repair was more likely in larger fistulae (>3 cm) requiring an abdominal approach, if omental interposition was not possible. Good-quality tissue interposition for complex fistula is essential for a successful outcome.

Are prostatic biopsies necessary in men aged > or =80 years?

OBJECTIVE: To examine whether prostatic biopsies are necessary in all men aged > or =80 years, as men found to have prostate cancer are frequently treated with a 'watch and wait' policy or with hormonal withdrawal alone, and biopsies are associated with a small but significant complication rate. PATIENTS AND METHODS: The findings on a digital rectal examination (DRE), the prostate-specific antigen (PSA) level, the biopsy and staging bone scan results for all men aged > or = 80 years who had prostatic biopsies over a 3-year period were reviewed, together with those in a group of men aged <80 years for comparison. All biopsy samples had been examined in one of three histopathology units, and 33 consultant urological surgeons contributed. RESULTS: In all, 210 biopsies from 205 men aged > or = 80 years were identified, of whom 163 (79%) had biopsy-confirmed prostate cancer. All 29 men with a PSA level of > or = 100 ng/mL, 98% of 47 with > or = 50 ng/mL, 97% of 76 with > or = 30 ng/mL and 92% of 101 with > or = 20 ng/mL had biopsy cores containing cancer; 63% of men with a PSA level of <20 ng/mL had cancer on biopsy. In men with cancer and a PSA level of > or = 30 ng/mL, 92% had Gleason grade > or = 7 and 93% were treated with hormonal withdrawal alone. In all men with cancer the DRE was abnormal in 91%, the mean number of positive cores was 59% and the bone scan was positive in 18%. The DRE was abnormal in 77% of men with benign biopsies. CONCLUSIONS: In men aged > or = 80 years with a PSA level of > or = 30 ng/mL, at least 97% had prostate cancer, >90% of whom had high-grade disease, and nearly all with cancer received active pharmacological treatment. In the vast majority of these men prostate biopsies did not alter their cancer management. The value of prostatic biopsy in this age group, with a PSA level of > or = 30 ng/mL, is questionable.

Failure of conservative management after the passage of a distal colonic "cast": report of a case.

PURPOSE: The spontaneous passage per rectum of a full-thickness colon "cast" is a rare consequence of acute colonic ischemia. Previous cases have undergone surgery soon afterward because of intractable symptoms. We report a patient who was managed conservatively for 11 months but ultimately required definitive surgery. METHODS: The clinical, radiographic, pathologic, and endoscopic findings were obtained from the case notes and compared with previously reported cases. RESULTS: A 67-year-old obese patient underwent a Hartmann's procedure for a perforated diverticular abscess, which was reversed six months later. On the first postoperative night after the reversal, she had a brief hypotensive episode, and three weeks later passed a 21-cm, full-thickness infarcted piece of colon. She did not develop peritonitis and for 11 months experienced only mild symptoms. Under colonoscopic surveillance, the granulation tissue conduit connecting the remaining viable bowel became increasingly stenosed proximally and difficult to dilate. After three rapidly consecutive episodes of large-bowel obstruction, she required a laparotomy to resect the stricture and restore bowel continuity. From a literature review, this is the eighth case of its kind and the first in which such prolonged conservative management has been possible. CONCLUSIONS: When symptoms permit, it is feasible to manage patients conservatively in the short-term after this unusual event to allow recovery from the initial insult and planning of future surgery. However, definitive treatment is surgical and colonoscopic management should not delay this once the patient is fit for surgery.