Cost-effectiveness of community versus hospital eye service follow-up for patients with quiescent treated age-related macular degeneration alongside the ECHoES randomised trial.

OBJECTIVES: To assess the cost-effectiveness of optometrist-led follow-up monitoring reviews for patients with quiescent neovascular age-related macular degeneration (nAMD) in community settings (including high street opticians) compared with ophthalmologist-led reviews in hospitals. DESIGN: A model-based cost-effectiveness analysis with a 4-week time horizon, based on a 'virtual' non-inferiority randomised trial designed to emulate a parallel group design. SETTING: A virtual internet-based clinical assessment, conducted at community optometry practices, and hospital ophthalmology clinics. PARTICIPANTS: Ophthalmologists with experience in the age-related macular degeneration service; fully qualified optometrists not participating in nAMD shared care schemes. INTERVENTIONS: The participating optometrists and ophthalmologists classified lesions from vignettes and were asked to judge whether any retreatment was required. Vignettes comprised clinical information, colour fundus photographs and optical coherence tomography images. Participants' classifications were validated against experts' classifications (reference standard). Resource use and cost information were attributed to these retreatment decisions. MAIN OUTCOME MEASURES: Correct classification of whether further treatment is needed, compared with a reference standard. RESULTS: The mean cost per assessment, including the subsequent care pathway, was £411 for optometrists and £397 for ophthalmologists: a cost difference of £13 (95% CI -£18 to £45). Optometrists were non-inferior to ophthalmologists with respect to the overall percentage of lesions correctly assessed (difference -1.0%; 95% CI -4.5% to 2.5%). CONCLUSIONS: In the base case analysis, the slightly larger number of incorrect retreatment decisions by optometrists led to marginally and non-significantly higher costs. Sensitivity analyses that reflected different practices across eye hospitals indicate that shared care pathways between optometrists and ophthalmologists can be identified which may reduce demands on scant hospital resources, although in light of the uncertainty around differences in outcome and cost it remains unclear whether the differences between the 2 care pathways are significant in economic terms. TRIAL REGISTRATION NUMBER: ISRCTN07479761; Pre-results.

Management of complicated chronic anal fissures with high-dose circumferential chemodenervation (HDCC) of the internal anal sphincter.

BACKGROUND: Botulinum toxin injection into the internal anal sphincter (IAS) is gaining popularity as a second line therapy for chronic anal fissures after patients fail medical therapy. The dosage of Botulinum toxin reported in the literature ranged from 20 to 50 IU. Complicated chronic anal fissure is defined as persistent fissure concurrent with other perianal pathology. We report a new approach involving high-dose circumferential chemodenervation (HDCC) of 100 IU in treating these complicated chronic anal fissures. AIM: The aim of this study was to evaluate the fissure healing, complication, and recurrence rates with HDCC. METHODS: Complicated anal fissure was defined as fissure with other perianal pathologies including skin tag, hypertrophied papilla, fistula, symptomatic hemorrhoids, anal condylomata, and abscess. Between 2008 and 2012, 62 consecutive patients (28 Blacks, 33 Whites, 1 Hispanic) with complete follow-up data were included in this single arm study. These patients underwent HDCC-IAS with addition interventions by a single colorectal surgeon. Follow up data were obtained by chart review and office follow up. RESULTS: Of the 62 patients, the overall success rate was greater than 70% at 3 months follow-up. A few patients developed transient flatus or fecal incontinence, but shortly resolved. There was no major complication following HDCC-IAS. CONCLUSIONS: Combination therapy involving HDCC-IAS and local anorectal surgery for associated condition is both safe and effective for fissure healing.

High-dose circumferential chemodenervation of the internal anal sphincter: A new treatment modality for uncomplicated chronic anal fissure: A retrospective cohort study (with video).

BACKGROUND: Botulinum toxin injection into the internal anal sphincter is gaining popularity as a second line therapy for chronic anal fissures if medical therapy fails. The dosage of botulinum toxin reported ranged from 20 to 50 IU with no more than 3 injection sites and results in a healing rate of 41%-88% at 3 months. We propose a new injection method of high-dose circumferential chemodenervation of 100 IU in treating chronic anal fissure. METHODS: This was a retrospective review at a single academic center. 75 patients (50 women and 25 men) with uncomplicated chronic anal fissures underwent high-dose circumferential chemodenervation-internal anal sphincter (100 IU). We measured fissure healing, complication, and recurrence rates at 3 and 6 months post injection. RESULTS: Of the 75 patients, healing rate was 90.7% at 3 months follow up with the first injection and 81.3% with the second injection. The recurrence rates were 20.6% and 12.5% at 6 months after the 1st and 2nd injections respectively. Excluding 5 patients who lost follow up, the total healing rate of the study cohort was 100%. At 2 weeks and 3 months, there were no major complications including hematoma, infection, flatus, fecal, and urinary incontinence. CONCLUSIONS: High-dose circumferential chemodenervation-internal anal sphincter (100 IU) is a safe and effective method for uncomplicated chronic anal fissure.

Effect of restoration volume on stresses in a mandibular molar: a finite element study.

STATEMENT OF PROBLEM: There can be significant disagreement among dentists when planning treatment for a tooth with a failing medium-to-large--sized restoration. The clinician must determine whether the restoration should be replaced or treated with a crown, which covers and protects the remaining weakened tooth structure during function. PURPOSE: The purpose of this study was to evaluate the stresses generated in different sized amalgam restorations via a computational modeling approach and reveal whether a predictable pattern emerges. MATERIAL AND METHODS: A computer tomography scan was performed of an extracted mandibular first molar, and the resulting images were imported into a medical imaging software package for tissue segmentation. The software was used to separate the enamel, dentin, and pulp cavity through density thresholding and surface rendering. These tissue structures then were imported into 3-dimensional computer-aided design software in which material properties appropriate to the tissues in the model were assigned. A static finite element analysis was conducted to investigate the stresses that result from normal occlusal forces. Five models were analyzed, 1 with no restoration and 4 with increasingly larger restoration volume proportions: a normal-sized tooth, a small-sized restoration, 2 medium-sized restorations, and 1 large restoration as determined from bitewing radiographs and occlusal surface digital photographs. RESULTS: The resulting von Mises stresses for dentin-enamel of the loaded portion of the tooth grew progressively greater as the size of the restoration increased. The average stress in the normal, unrestored tooth was 4.13 MPa, whereas the smallest restoration size increased this stress to 5.52 MPa. The largest restoration had a dentin-enamel stress of 6.47 MPa. A linear correlation existed between restoration size and dentin-enamel stress, with an R(2) of 0.97. CONCLUSIONS: A larger restoration volume proportion resulted in higher dentin-enamel stresses under static loading. A comparison of the von Mises stresses to the yield strengths of the materials revealed a relationship between a tooth's restoration volume proportion and the potential for failure, although factors other than restoration volume proportion may also impact the stresses generated in moderate-sized restorations.

Primary care direct access MRI for the investigation of chronic headache.

AIM: To assess the efficacy of a primary-care imaging pathway for neurology outpatients, from inception to deployment, compared with traditional outpatient referral. MATERIALS AND METHODS: After local agreement, guidelines were generated providing pathways for diagnosis and treatment of common causes of headache, highlighting "red-flag" features requiring urgent neurology referral, and selecting patients for direct magnetic resonance imaging (MRI) referral. In addition, reports were clarified and standardized. To evaluate the efficacy of the access pathway, a retrospective sequential review of 100 MRI investigations was performed comparing general practitioner (GP) referral, with traditional neurology referral plus imaging, acquired before the pathway started. RESULTS: No statistically significant difference in rates of major abnormalities, incidental findings or ischaemic lesions were identified between the two cohorts. Reported patient satisfaction was high, with a cost reduction for groups using the pathway. CONCLUSION: The findings of the present study suggest that a defined access pathway for imaging to investigate chronic headache can be deployed appropriately in a primary-care setting.

Placental ischemia impairs middle cerebral artery myogenic responses in the pregnant rat.

One potential mechanism contributing to the increased risk for encephalopathies in women with preeclampsia is altered cerebral vascular autoregulation resulting from impaired myogenic tone. Whether placental ischemia, a commonly proposed initiator of preeclampsia, alters cerebral vascular function is unknown. This study tested the hypothesis that placental ischemia in pregnant rats (caused by reduced uterine perfusion pressure [RUPP]) leads to impaired myogenic responses in middle cerebral arteries. Mean arterial pressure was increased by RUPP (135±3 mm Hg) compared with normal pregnant rats (103±2 mm Hg) and nonpregnant controls (116±1 mm Hg). Middle cerebral arteries from rats euthanized on gestation day 19 were assessed in a pressure arteriograph under active (+Ca(2+)) and passive (0 Ca(2+)) conditions, whereas luminal pressure was varied between 25 and 150 mm Hg. The slope of the relationship between tone and pressure in the middle cerebral artery was 0.08±0.01 in control rats and was similar in normal pregnant rats (0.05±0.01). In the RUPP model of placental ischemia, this relationship was markedly reduced (slope=0.01±0.00; P<0.05). Endothelial dependent and independent dilation was not different between groups, nor was there evidence of vascular remodeling assessed by the wall:lumen ratio and calculated wall stress. The impaired myogenic response was associated with brain edema measured by percentage of water content (RUPP P<0.05 versus control and normal pregnant rats). This study demonstrates that placental ischemia in pregnant rats leads to impaired myogenic tone in the middle cerebral arteries and that the RUPP model is a potentially important tool to examine mechanisms leading to encephalopathy during preeclamptic pregnancies.

Blood pressure and renal hemodynamic responses to acute angiotensin II infusion are enhanced in a female mouse model of systemic lupus erythematosus.

Inflammation and immune system dysfunction contributes to the development of cardiovascular and renal disease. Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disorder that carries a high risk for both renal and cardiovascular disease. While hemodynamic changes that may contribute to increased cardiovascular risk have been reported in humans and animal models of SLE, renal hemodynamics have not been widely studied. The renin-angiotensin system (RAS) plays a central role in renal hemodynamic control, and although RAS blockade is a common therapeutic strategy, the role of RAS in hemodynamic function during SLE is not clear. This study tested whether mean arterial pressure (MAP) and renal hemodynamic responses to acute infusions of ANG II in anesthetized animals were enhanced in an established female mouse model of SLE (NZBWF1). Baseline MAP was not different between anesthetized SLE and control (NZWLacJ) mice, while renal blood flow (RBF) was significantly lower in mice with SLE. SLE mice exhibited an enhanced pressor response and greater reduction in RBF after ANG II infusion. An acute infusion of the ANG II receptor blocker losartan increased RBF in control mice but not in mice with SLE. Renin and ANG II type 1 receptor expression was significantly lower, and ANG II type 2 receptor expression was increased in the renal cortex from SLE mice compared with controls. These data suggest that there are fewer ANG II receptors in the kidneys from mice with SLE but that the existing receptors exhibit an enhanced sensitivity to ANG II.

Tumor necrosis factor-alpha antagonist etanercept decreases blood pressure and protects the kidney in a mouse model of systemic lupus erythematosus.

Chronic inflammation has been implicated in the pathology of hypertension; however, the role for specific cytokines remains unclear. We tested whether tumor necrosis factor-α blockade with etanercept (Etan) reduces mean arterial pressure in a female mouse model of systemic lupus erythematosus (SLE). SLE is a chronic inflammatory disorder with prevalent hypertension. Thirty-week-old SLE (NZBWF1) and control mice (NZW/LacJ) received Etan (0.8 mg/kg SC weekly) for 4 weeks or vehicle. Mean arterial pressure (in millimeters of mercury) was increased in SLE mice (150±5 versus 113±5 in controls; P<0.05) and was lower in Etan-treated SLE mice (132±3) but not controls (117±5). Albuminuria (in micrograms per milligram of creatinine) was elevated in SLE mice (28 742±9032 versus 1075±883; P<0.05) and was lower in Etan-treated SLE mice (8154±3899) but not control animals (783±226). Glomerulosclerosis (in percentage of glomeruli) was evident in SLE mice (2.5±1.6 versus 0.0±0.0 in controls; P<0.05) and was ameliorated in Etan-treated SLE mice (0.1±0.1). Renal cortex CD68(+) cell staining (in percentage of area) was elevated in SLE mice (4.75±0.80 versus 0.79±0.12 in controls; P<0.05) and was lower in Etan-treated SLE mice (2.28±0.32) but not controls (1.43±0.25). Renal cortex NADPH oxidase activity (relative light units per milligram of protein) was higher in SLE mice compared with controls (10 718±1276 versus 7584±229; P<0.05) and lowered in Etan-treated SLE mice (6645±490). Renal cortex nuclear factor κB (phosphorylated and nonphosphorylated) was increased in SLE mice compared with controls and lower in Etan-treated SLE mice. These data suggest that TNF-α mechanistically contributes to the development of hypertension in a chronic inflammatory disease through increased renal nuclear factor κB, oxidative stress, and inflammation.

Review of perinatal management of arthrogryposis at a large UK teaching hospital serving a multiethnic population.

OBJECTIVE: To review the prevalence and perinatal management of cases of arthrogryposis delivering at our hospital over a 6-year period. METHODS: This was a retrospective review of cases of arthrogryposis managed at a UK teaching hospital. Cases were identified from the regional congenital anomalies register and departmental databases. Case notes were reviewed and analysed. RESULTS: From 2002 to 2007, there were 27 cases of arthrogryposis. Sixteen (59.3%) were Caucasians, 7(25.9%) Asians and 4(14.8%) Afro-Caribbean; 17(63%) were nulliparous. In eight (29.6%) cases, there was a family history of congenital anomalies. Three had previously affected siblings and in three cases the parents were affected with arthrogryposis. Five (18.5%) were from consanguineous families. Eighteen (66.7%) cases were diagnosed prenatally at a mean gestational age of 21 weeks. Twelve (57%) were delivered by caesarean section. There were 18 live births. Sixteen (59%) cases were reviewed by clinical geneticist. Following detailed review and investigation including post-mortems, 20 (74%) of our cases had a formal diagnosis or likely cause identified. CONCLUSIONS: Suspected cases of arthrogryposis require multi-disciplinary management to optimise the possibility of making a diagnosis and providing parents with accurate information to enable them to make informed choices regarding the pregnancy and providing information regarding likelihood of recurrence.

Sexual dimorphism in the blood pressure response to angiotensin II in mice after angiotensin-converting enzyme blockade.

BACKGROUND: The incidence of hypertension and progression of renal disease are greater in men than in women. Data suggest that there is a dimorphic response to angiotensin II (Ang II) in rats, with male rats exhibiting a greater increase in mean arterial pressure (MAP) than females. However, during endogenous renin-angiotensin system (RAS) blockade with angiotensin-converting enzyme (ACE) inhibition, female rats have a greater MAP response to Ang II. We tested whether female mice exhibit a greater MAP response to chronic Ang II during ACE inhibition. METHODS: Twenty-week-old male and female C57BL/6J mice (n > or = 6/group), treated with enalapril (40 mg/kg/day in drinking water), were assigned to groups receiving either Ang II (800 ng/kg/min) or saline for 2 weeks. Enalapril treatment began 4 days before and continued throughout the experiment. RESULTS: MAP was higher in male mice than female mice treated with enalapril and Ang II (male: 144 +/- 3 vs. female: 121 +/- 6 mm Hg, P < 0.05) and was not different between mice treated with enalapril alone (male: 99 +/- 3 vs. female: 100 +/- 3 mm Hg). F2-isoprostanes were not increased by Ang II; however, female mice had significantly higher levels than males. Renal cortical expression of catalase and Cu/Zn-superoxide dismutase (SOD) was not different between experimental groups. Urinary protein was higher in male mice when compared to females, but was not changed after treatment with Ang II in either group. CONCLUSIONS: These data suggest that there are species and sex-specific differences in the mechanism of the blood pressure response to Ang II, even during ACE inhibition.

Rosiglitazone decreases blood pressure and renal injury in a female mouse model of systemic lupus erythematosus.

Women with systemic lupus erythematosus (SLE) exhibit a high prevalence of hypertension and renal injury. Rosiglitazone (Rosi), a peroxisome proliferator activator receptor gamma (PPARgamma) agonist, has renal protective and antihypertensive effects. We tested whether Rosi ameliorates hypertension and renal injury in a female mouse model of SLE (NZBWF1). Thirty-week-old SLE and control (NZW/LacJ) mice (n > or = 6/group) were fed Rosi (5 mg.kg(-1).day(-1) in standard chow) or standard chow for 4 wk. SLE mice had increased blood pressure (BP in mmHg) compared with controls (139 +/- 4 vs. 111 +/- 4, P < 0.05). Rosi treatment lowered BP in SLE mice (127 +/- 4, P < 0.05) but not in controls (111 +/- 4). Urinary albumin (mug/mg creatinine) was increased in SLE mice compared with controls (12,396 +/- 6,525 vs. 50 +/- 6) and reduced with Rosi treatment (148 +/- 117). Glomerulosclerosis (% of glomeruli with sclerosis) was reduced in Rosi-treated SLE mice (4.2 +/- 1.6 vs. 0.4 +/- 0.3, P < 0.05). Renal monocyte/macrophage numbers (cell number/1,320 points counted) were reduced in SLE mice treated with Rosi (32.6 +/- 11.0 vs. 10.6 +/- 3.6, P < 0.05) but unchanged in controls (3.7 +/- 1.6 vs. 3.7 +/- 2.0). Renal osteopontin expression, a cytokine-regulating macrophage recruitment, was reduced in Rosi-treated SLE mice. Urinary endothelin (in pg/mg creatinine) was increased in SLE mice compared with controls (1.9 +/- 0.59 vs. 0.6 +/- 0.04, P < 0.05) and reduced in SLE mice treated with Rosi (0.8 +/- 0.11, P < 0.05). PPARgamma protein expression in the renal cortex was significantly lower in SLE mice compared with controls and was unaffected by Rosi. These data suggest that Rosi may be an important therapeutic option for the treatment of SLE hypertension and renal injury.

Laparoscopic hand-assisted nephrectomy for crossed fused ectopia with polycystic kidney disease.

Polycystic kidney disease occurring in individuals with crossed fused renal ectopia is an extremely rare occurrence. The treatment of individuals with this condition is a unique surgical challenge for the operating physician. Today's advances in laparoscopic techniques provide us with new and innovative ways of performing complex procedures while subjecting patients to relatively minimal surgical trauma. We describe the laparoscopic removal of a severely diseased polycystic crossed fused kidney.

Laryngeal ultrasound to assess vocal fold paralysis in children.

The purpose of this study was to assess the practicality and validity of laryngeal ultrasound to establish vocal fold movement in children with suspected vocal fold palsy. Fifty-five consecutive patients (age range three days to 12 years) with suspected vocal fold palsy underwent both laryngoscopy and laryngeal ultrasound. Ultrasonographic findings correlated with endoscopic findings in 81.2 per cent of cases. This, however, rose to a concordance rate of 89.5 per cent in patients aged over 12 months. Laryngeal ultrasound is well-tolerated, safe and non-invasive and the authors feel that it is a useful adjunct to endoscopy in the diagnosis of vocal fold palsy.

The craft of urologic surgery: modern radical perineal prostatectomy.

Radical perineal prostatectomy (RPP) is the original approach used by urologists for removing the entire prostate for cancer treatment. From its original description approximately 100 years ago, it has gone through periods of increased and decreased popularity. RPP has not been performed as commonly in the United States since the late 1970s, with the introduction of the radical retropubic prostatectomy. With increased emphasis on reducing morbidity associated with radical prostatectomy by less-invasive techniques, however, more surgeons are revisiting RPP. As discussed in this article, RPP offers several advantages over the retropubic or laparoscopic approach for certain patients.

Direct gastrointestinal toxicity of flutamide: comparison of irradiated and nonirradiated cases.

PURPOSE: Gastrointestinal (GI) side effects of flutamide in cases treated for advanced prostate cancer are well documented. Proposed mechanisms for these side effects include increased serum blood levels, direct vehicle effects and/or local toxicity. If local toxicity, the focus of this study, mediates GI side effects of flutamide then cases exposed to external beam radiation (XRT) should have more symptoms. We hypothesize that GI side effects of flutamide are not a direct local toxic effect resulting in a similar side effect profile for irradiated and nonirradiated cases. Thus, the present study compares GI effects of flutamide in irradiated and nonirradiated cases. MATERIALS AND METHODS: We identified 106 of 440 cases from a prior flutamide dose comparison study as having undergone XRT (56 cases) or radical prostatectomy (50 patients). The prevalence of GI side effects (abdominal pain/distention, diarrhea, constipation, nausea/vomiting and anorexia) was tallied for each treatment group and/or dosing regimen, 250 mg every 8 hours or 500 mg daily. Chi-square analysis with Yates' correction was performed for statistical analysis. RESULTS: The overall prevalence in 106 cases of GI side effects with flutamide was 22%. Treatment specific differences revealed no differences between the XRT and radical prostatectomy groups at 21% and 22%, respectively. Furthermore, independent analysis of treatment groups for each distinct side effect and dosing regimen did not identify significant differences. CONCLUSIONS: Irradiated cases are not at greater risk for the development of GI side effects from flutamide, suggesting that drug induced local toxicity does not mediate GI distress.

Effect of global hypoxia-ischaemia followed by 24 h of mild hypothermia on organ pathology and biochemistry in a newborn pig survival model.

BACKGROUND: Perinatal asphyxia may lead to multiorgan damage as well as brain injury. Posthypoxic hypothermia (HT) may protect other organs in addition to the brain. The aim of this study was to assess the systemic effects of our global hypoxic-ischaemic (HI) insult and compare the effect of mild 24-hour HT with normothermia (NT) during unsedated recovery. METHOD: Thirty-eight newborn pigs were subjected to 45 min of global HI by ventilating them with approximately 6% O2. On reoxygenation, pigs were randomised to NT or HT. The 18 NT piglets were maintained at rectal temperature 39.0 degrees C for 72 h. Twenty-three HT pigs (20 experimental HT and 3 sham controls) were cooled to rectal temperature 35 degrees C for 24 h before NT was resumed and the animals then survived a further 48 h. RESULTS: All lesions were small with no apparent clinical effect. The incidence of any damage to the heart (6 HT vs. 9 NT), liver (9 HT vs. 7 NT), kidney (6 HT vs. 9 NT) or intestinal injury (8 HT vs. 2 NT, p = 0.07) was not different in the two groups. More HT piglets developed lung injury, 10 HT and 3 NT. Plasma [Na], [K], [Ca] and [Mg] increased significantly after the HI insult as compared to baseline values. For the 24-hour period plasma [K] and [Ca] were significantly higher in the HT group, the mean area under the curve (AUC) being for [K] AUC(HT) 4.4 mmol/l vs. AUC(NT) 3.9 mmol/l, p = 0.04 and for [Ca] AUC(HT) 2.7 mmol/l vs. AUC(NT) 2.5 mmol/l, p = 0.01, respectively. Aspartate aminotransferase peaked at 48 h in the HT group and at 24 h in the NT group. Creatinine peaked at >72 h in the HT pigs and at 48 h in the NT pigs. White blood cells (WBC) peaked at 12 h for the HT pigs and at 6 h for the NT animals. AUC of the WBC during the cooling was significantly lower in the HT pig (AUC(HT) 11.1 vs. AUC(NT) 15.3 10(3)/mm3, p = 0.04). The HT pigs needed more glucose to maintain normal glucose during the last 12 h of HT. Also HT animals needed more oxygen during cooling to maintain PaO2. CONCLUSION: Twenty-four hours of mild HT did not reduce damage in any organ. There was a slight increase in lung damage in the HT group. None of the biochemical or pathological changes were of clinical significance. We conclude that mild HT for 24 h does not affect the organ systems adversely when compared to NT. Additional glucose and oxygen is needed during cooling to maintain normal values.

Case selection and outcome of radical perineal prostatectomy in localized prostate cancer.

Radical prostatectomy continues to play a central role in the management of localized prostate cancer. The majority of patients diagnosed with prostate cancer will undergo radical prostatectomy. A decrease in the morbidity of this surgical procedure has been accomplished through an improved understanding of pelvic anatomy and a greater understanding of the natural history of prostate cancer. Recently, minimally invasive techniques have been applied to radical prostatectomy (laparoscopic prostatectomy) in order to further decrease the morbidity of this operation. What remains to be determined is whether this approach confers the same long term surgical outcomes as the open approach. One method which offers known long term outcomes coupled with decreased morbidity is the radical perineal prostatectomy. The purpose of this paper is to review the criteria for patient selection as well as outcomes of the radical perineal prostatectomy.