Clinical phenotypes and therapeutic responses in cutaneous-predominant sarcoidosis: 6-year experience in a tertiary referral service.

BACKGROUND: There is a limited evidence base for the treatment of cutaneous sarcoidosis. OBJECTIVE: To describe treatment modalities and responses in patients with predominantly cutaneous sarcoidosis, in addition to clinical characteristics and prevalence of systemic disease. METHODS: Data were prospectively collected over a 6-year period. The Cutaneous Sarcoidosis Activity and Morphology Index was used to assess treatment effectiveness. RESULTS: In total, 47 patients with biopsy-confirmed cutaneous sarcoidosis were identified. Morphologically, the most common lesions were papules (49%) and plaques (42.6%). The most commonly affected sites were the head and neck (79%); 89.4% had systemic as well as cutaneous disease; 77% received systemic corticosteroid therapy, while 87% required further steroid-sparing treatment; 40% achieved clinical remission with hydroxychloroquine (HCQ) and 88% achieved clinical remission with methotrexate (MTX). OR of achieving remission on MTX compared with HCQ was 9.8 (95% CI 2.4-40.4, P = 0.001). MTX was superior to both azathioprine (AZA) (OR = 22; 95% CI 1.7-285.9; P = 0.02) and mycophenolate mofetil (MMF) (OR = 22; 95% CI 1.7-285.9; P = 0.02) in achieving remission. CONCLUSION: HCQ is effective and well-tolerated. MTX was associated with significantly increased probability of achieving clinical remission compared with AZA and MMF.

Evaluation of a minor eye conditions scheme delivered by community optometrists.

BACKGROUND: The establishment of minor eye conditions schemes (MECS) within community optometric practices provides a mechanism for the timely assessment of patients presenting with a range of acute eye conditions. This has the potential to reduce waiting times and avoid unnecessary referrals to hospital eye services (HES). OBJECTIVE: To evaluate the clinical effectiveness, impact on hospital attendances and patient satisfaction with a minor eye service provided by community optometrists. METHODS: Activity and outcome data were collected for 12 months in the Lambeth and Lewisham MECS. A patient satisfaction questionnaire was given to patients at the end of their MECS appointment. A retrospective difference-in-differences analysis of hospital activity compared changes in the volume of referrals by general practitioners (GPs) from a period before (April 2011-March 2013) to after (April 2013-March 2015) the introduction of the scheme in Lambeth and Lewisham relative to a neighbouring area (Southwark) where the scheme had not been commissioned. Appropriateness of case management was assessed by consensus using clinical members of the research team. RESULTS: A total of 2123 patients accessed the scheme. Approximately two-thirds of patients (67.5%) were referred by their GP. The commonest reasons for patients attending for a MECS assessment were 'red eye' (36.7% of patients), 'painful white eye' (11.1%) and 'flashes and floaters' (10.2%). A total of 64.1% of patients were managed in optometric practice and 18.9% were referred to the HES; of these, 89.2% had been appropriately referred. First attendances to HES referred by GPs reduced by 26.8% (95% CI -40.5% to -13.1%) in Lambeth and Lewisham compared to Southwark. CONCLUSIONS: The Lambeth and Lewisham MECS demonstrates clinical effectiveness, reduction in hospital attendances and high patient satisfaction and represents a successful collaboration between commissioners, local HES units and primary healthcare providers.

Severe Meesmann's epithelial corneal dystrophy phenotype due to a missense mutation in the helix-initiation motif of keratin 12.

PURPOSE: To describe a severe phenotype of Meesmann's epithelial corneal dystrophy (MECD) and to determine the underlying molecular cause. METHODS: We identified a 30-member family affected by MECD and examined 11 of the 14 affected individuals. Excised corneal tissue from one affected individual was examined histologically. We used PCR and direct sequencing to identify mutation of the coding regions of the KRT3 and KRT12 genes. RESULTS: Cases had an unusually severe phenotype with large numbers of intraepithelial cysts present from infancy and they developed subepithelial fibrosis in the second to third decade. In some individuals, the cornea became superficially vascularized, a change accompanied by the loss of clinically obvious epithelial cysts. Visual loss from amblyopia or corneal opacity was common and four individuals were visually impaired (≤6/24 bilaterally) and one was blind (<6/60 bilaterally). In all affected family members, there was a heterozygous missense mutation c. 395T>C (p. L132P) in exon 1 of the KRT12 gene, which codes for the helix-initiation motif of the K12 polypeptide. This sequence change was not found in unaffected family members or in 100 unaffected controls. CONCLUSIONS: The Leu132Pro missense mutation is within the helix-initiation motif of the keratin and is predicted to result in a significant structural change of the K12 protein. The clinical effects are markedly more severe than the phenotype usually associated with the Arg135Thr mutation within this motif, most frequently seen in European patients with MECD.

American College of Rheumatology classification criteria for Sjögren's syndrome: a data-driven, expert consensus approach in the Sjögren's International Collaborative Clinical Alliance cohort.

OBJECTIVE: We propose new classification criteria for Sjögren's syndrome (SS), which are needed considering the emergence of biologic agents as potential treatments and their associated comorbidity. These criteria target individuals with signs/symptoms suggestive of SS. METHODS: Criteria are based on expert opinion elicited using the nominal group technique and analyses of data from the Sjögren's International Collaborative Clinical Alliance. Preliminary criteria validation included comparisons with classifications based on the American­European Consensus Group (AECG) criteria, a model-based "gold standard"obtained from latent class analysis (LCA) of data from a range of diagnostic tests, and a comparison with cases and controls collected from sources external to the population used for criteria development. RESULTS: Validation results indicate high levels of sensitivity and specificity for the criteria. Case definition requires at least 2 of the following 3: 1) positive serum anti-SSA and/or anti-SSB or (positive rheumatoid factor and antinuclear antibody titer >1:320), 2) ocular staining score >3, or 3) presence of focal lymphocytic sialadenitis with a focus score >1 focus/4 mm2 in labial salivary gland biopsy samples. Observed agreement with the AECG criteria is high when these are applied using all objective tests. However, AECG classification based on allowable substitutions of symptoms for objective tests results in poor agreement with the proposed and LCA-derived classifications. CONCLUSION: These classification criteria developed from registry data collected using standardized measures are based on objective tests. Validation indicates improved classification performance relative to existing alternatives, making them more suitable for application in situations where misclassification may present health risks.

Safety and efficacy of intravitreal triamcinolone for cystoid macular oedema in uveitis.

PURPOSE: To report the safety and efficacy of intravitreal triamcinolone in the treatment of inflammatory cystoid macular oedema (CMO) in six patients who were resistant to other forms of therapy. METHODS: An open-label unmasked prospective nonrandomized pilot study of six patients with idiopathic uveitis and visually significant macular oedema, resistant to periocular and/or systemic corticosteroid treatment, was carried out. Baseline examination and investigations were performed, including fundus fluorescein angiography, and the patients were given a single intravitreal injection of triamcinolone (4 mg/0.1 mL). The primary outcome measure was angiographic resolution of CMO. Patients were reviewed at intervals of 2-4 weeks for 12 months. RESULTS: A single intravitreal injection of triamcinolone induced clinical and angiographic resolution of inflammatory macular oedema in all patients for varying periods of time up to 6 months. Five patients experienced increased intraocular pressure to 30 mmHg or greater which required treatment. Two patients developed posterior subcapsular cataract. CONCLUSION: One injection of intravitreal triamcinolone was an effective short-term treatment for resistant CMO in uveitis. As with steroids given by other routes, raised intraocular pressure and cataract may occur. As it was so effective in these eyes with resistant CMO, a larger study is warranted to evaluate this form of therapy.

Effect of an administrative intervention on rates of screening for domestic violence in an urban emergency department.

OBJECTIVES: This study measured the effects of an administrative intervention on health care provider compliance with universal domestic violence screening protocols. METHODS: We used a simple, interrupted-time-series design in a stratified random sample of female emergency department patients 18 years or older (n = 1638 preintervention, n = 1617 postintervention). The intervention was a 4-tiered hospital-approved disciplinary action, and the primary outcome was screening compliance. RESULTS: Preintervention and postintervention screening rates were 29.5% and 72.8%, respectively. Before the intervention, screening was worse on the night shift (odds ratio [OR] = 0.46, 95% confidence interval [CI] = 0.31, 0.68) and with psychiatric patients (OR = 0.34, 95% CI = 0.14, 0.85); after the intervention, no previous screening barriers remained significant. CONCLUSIONS: An administrative intervention significantly enhanced compliance with universal domestic violence screening.

Risk of advanced proximal neoplasms in asymptomatic adults according to the distal colorectal findings.

BACKGROUND AND METHODS: The clinical significance of a distal colorectal polyp is uncertain. We determined the risk of advanced proximal neoplasia, defined as a polyp with villous features, a polyp with high-grade dysplasia, or cancer, among persons with distal hyperplastic or neoplastic polyps as compared with the risk among persons with no distal polyps. We analyzed data from 1994 consecutive asymptomatic adults (age, 50 years or older) who underwent colonoscopic screening for the first time between September 1995 and December 1998 as part of a program sponsored by an employer. The location and histologic features of all polyps were recorded. Colonoscopy to the level of the cecum was completed in 97.0 percent of the patients. RESULTS: Sixty-one patients (3.1 percent) had advanced lesions in the distal colon, including 5 with cancer, and 50 (2.5 percent) had advanced proximal lesions, including 7 with cancer. Twenty-three patients with advanced proximal neoplasms (46 percent) had no distal polyps. The prevalence of advanced proximal neoplasia among patients with no distal polyps was 1.5 percent (23 cases among 1564 persons; 95 percent confidence interval, 0.9 to 2.1 percent). Among patients with distal hyperplastic polyps, those with distal tubular adenomas, and those with advanced distal polyps, the prevalence of advanced proximal neoplasia was 4.0 percent (8 cases among 201 patients), 7.1 percent (12 cases among 168 patients), and 11.5 percent (7 cases among 61 patients), respectively. The relative risk of advanced proximal neoplasia, adjusted for age and sex, was 2.6 for patients with distal hyperplastic polyps, 4.0 for those with distal tubular adenomas, and 6.7 for those with advanced distal polyps, as compared with patients who had no distal polyps. Older age and male sex were associated with an increased risk of advanced proximal neoplasia (relative risk, 1.3 for every five years of age and 3.3 for male sex). CONCLUSIONS: Asymptomatic persons 50 years of age or older who have polyps in the distal colon are more likely to have advanced proximal neoplasia than are persons without distal polyps. However, if colonoscopic screening is performed only in persons with distal polyps, about half the cases of advanced proximal neoplasia will not be detected.

Phase I and pharmacokinetic study of farnesyl protein transferase inhibitor R115777 in advanced cancer.

PURPOSE: To determine the maximum-tolerated dose, toxicities, and pharmacokinetic profile of the farnesyl protein transferase inhibitor R115777 when administered orally bid for 5 days every 2 weeks. PATIENTS AND METHODS: Twenty-seven patients with a median age of 58 years received 85 cycles of R115777 using an intrapatient and interpatient dose escalation schema. Drug was administered orally at escalating doses as a solution (25 to 850 mg bid) or as pellet capsules (500 to 1300 mg bid). Pharmacokinetics were assessed after the first dose and the last dose administered during cycle 1. RESULTS: Dose-limiting toxicity of grade 3 neuropathy was observed in one patient and grade 2 fatigue (decrease in two performance status levels) was seen in four of six patients treated with 1,300 mg bid. The most frequent clinical grade 2 or 3 adverse events in any cycle included nausea, vomiting, headache, fatigue, anemia, and hypotension. Myelosuppression was mild and infrequent. Peak plasma concentrations of R115777 were achieved within 0.5 to 4 hours after oral drug administration. The elimination of R115777 from plasma was biphasic, with sequential half-lives of about 5 hours and 16 hours. There was little drug accumulation after bid dosing, and steady-state concentrations were achieved within 2 to 3 days. The pharmacokinetics were dose proportional in the 25 to 325 mg/dose range for the oral solution. Urinary excretion of unchanged R115777 was less than 0.1% of the oral dose. One patient with metastatic colon cancer treated at the 500-mg bid dose had a 46% decrease in carcinoembryonic antigen levels, improvement in cough, and radiographically stable disease for 5 months. CONCLUSION: R115777 is bioavailable after oral administration and has an acceptable toxicity profile. Based upon pharmacokinetic data, the recommended dose for phase II trials is 500 mg orally bid (total daily dose, 1, 000 mg) for 5 consecutive days followed by 9 days of rest. Studies of continuous dosing and studies of R115777 in combination with chemotherapy are ongoing.

Universal screening for intimate partner violence in the emergency department: importance of patient and provider factors.

STUDY OBJECTIVE: Screening for intimate partner violence has been widely advocated in the health care setting, but efforts to assess effectiveness and ensure adequacy of universal screening are largely untested. We sought to identify barriers to screening of female emergency department patients for intimate partner violence during the first year of implementation of a screening protocol. METHODS: A retrospective, structured medical chart review of 1,638 randomly identified visits included demographic factors of age, race, marital status, employment status, insurance status, arrival mode, mechanism of presenting complaint, severity of condition, presentation time, and nurse gender. The study was conducted an an inner-city Level I trauma center with 43,000 annual ED visits and universal procedures for screening for intimate partner violence in place since February 1994. The participants were a cohort of 1,509 female patients, 18 years of age or older, who were discharged from the ED between July 1994 and June 1995. The main outcome measure was the odds of being screened as a function of patient and provider variables. Statistical analyses involved univariate and multivariate logistic regression on screening rates (Yes/No) as derived from universal screening instrument variables. RESULTS: Of 1,638 records reviewed, 483 patients (29.5%) were screened for intimate partner violence. Univariate analyses revealed that women presenting with nonpsychiatric, less acute complaints and those who presented during daylight hours were more likely to be screened than women who presented with psychiatric or more acute complaints, or during the night shift. Male and female nurse providers were equally likely to screen for intimate partner violence. Step-down multivariate analyses agreed with these findings. CONCLUSION: In this random sample of female patients, screening rates varied by severity of the patient's condition, type of presenting complaint, and presentation time.

Results of proximal interphalangeal joint release for flexion contractures: midlateral versus palmar incision.

Forty-two patients (45 fingers) were retrospectively reviewed after operative release of flexion contractures of the proximal interphalangeal (PIP) joint. The release was accomplished through a palmar incision in 19 fingers, usually followed by skin coverage using a lateral transposition flap. A midlateral incision was used in 26 fingers. The 2 groups were comparably matched with respect to degree of contracture and demographic characteristics. Active range of motion (ROM) was measured before and after surgery. In the palmar incision group, preoperative median PIP joint ROM was 60 degrees to 90 degrees (extension/flexion) and 30 degrees to 90 degrees at the 3-year follow-up examination. In the midlateral incision group, preoperative median PIP joint ROM was 50 degrees to 90 degrees (extension/flexion) and 0 degrees to 90 degrees at the 1.5-year follow-up examination. The improvement in ROM was significantly better in the midlateral incision group than in the palmar incision group.

Fixation of metacarpal fractures using absorbable hemi-cerclage sutures.

We retrospectively reviewed the use of biodegradable hemi-cerclage sutures in the treatment of 79 metacarpal fractures in 66 patients. The polyglycolic acid hemi-cerclages achieved sufficient fracture fixation to permit early motion exercises, but fractures were also immobilized for a mean of 3.7 (range, 1.5-6) weeks postoperatively, during which time physiotherapy was given. Adequate bony stability was achieved after a mean of 4.5 (range, 3.5-7) weeks and fracture redisplacement occurred in only one case.

Phacoemulsification and silicone oil removal through a single corneal incision.

OBJECTIVE: Cataracts are a frequent complication after silicone oil infusion for the repair of complicated retinal detachments, occurring in up to 100% of eyes retaining silicone oil for 6 months or more. The authors devised a combined procedure for cataract and silicone oil removal with intraocular lens (IOL) implantation through a single corneal incision and evaluated their results. DESIGN: A prospective, noncomparative case series. PARTICIPANTS: Thirty-four eyes of 34 consecutive patients with a history of retinal detachment repair requiring silicone oil placement in whom a clinically significant cataract subsequently developed were identified when removal of silicone oil was scheduled. INTERVENTION: All 34 eyes were prospectively entered into a study to evaluate the efficacy and potential complications of a combined procedure for cataract and silicone oil removal with posterior chamber lens implantation. All patients underwent uncomplicated phacoemulsification removal of cataract followed by removal of silicone oil and placement of an IOL through a single corneal incision. MAIN OUTCOME MEASURE: Recurrent retinal detachment and IOL-related complications were measured. RESULTS: Ten eyes had recurrent retinal detachments develop. Final visual acuity ranged from 6/12 to hand movements with 25 eyes (74%) showing stabilized or improved vision. Pre-existing macular pathology and recurrent retinal detachment generally were responsible for poor visual outcome. CONCLUSIONS: Combined phacoemulsification, IOL implant with silicone oil removal is a useful procedure in these complicated eyes. Visual outcome generally is good with improvement in visual acuity, even with recurrent retinal detachment or pre-existing macular pathology or both.

Contralateral transplantation of a finger for restoration of thumb function.

Transplantation of a finger from the contralateral hand for thumb reconstruction is seldom done because of possible psychological problems for the patient. We present two cases in which a previously damaged index finger of the contralateral hand was transplanted. In both patients the metacarpophalangeal joint of the index finger replaced that of the thumb. A powerful pinch to the fingers was achieved and the appearance of both the donor and the recipient hands was considerably improved.

Fixed-facility workplace screening mammography.

OBJECTIVE: Potential barriers to compliance with screening mammography guidelines include the cost and inconvenience involved with undergoing the procedure. Workplace screening with mobile mammography is one possible approach to the convenience barrier. However, fixed-facility workplace screening is a viable alternative for any company with a large workforce in one location. This paper describes our initial experience with one such fixed facility. MATERIALS AND METHODS: The facility was a cooperative venture by a large pharmaceutical company and an academic radiology department to provide convenient, no-cost (to the patient) screening mammography to employees, dependents, and retirees more than 40 years old. The pharmaceutical company built the facility within its corporate headquarters and the academic radiology department provided the equipment and personnel. The company was billed a fixed cost per examination. RESULTS: In the first 22 months of operation, 4210 (of 4559 scheduled) screening mammograms were obtained. The mean age of the population was 53 years old. Ninety percent of the screening mammograms were interpreted as negative or benign; 10% required additional workup. Of the screened population, 62 biopsies were recommended and 60 were performed. Of these, 42 were benign and 18 malignant. The cancer detection rate was 4.3 per 1000 (0.43%). At the time of diagnosis, six patients were stage 0, 10 patients were stage I, one patient was stage II, and one patient was stage III. Eleven of the 18 patients had minimal cancers. Of the patients who completed a satisfaction survey, 97% percent expressed a high degree of satisfaction with the screening process and stated they would use the facility in the future. CONCLUSION: A fixed facility for workplace screening mammography is a viable way to provide nearly barrier-free access to high-quality mammography. Patient acceptance is high.

Peripheral transscleral retinal diode laser for rubeosis iridis.

PURPOSE: To evaluate the results of peripheral transscleral retinal diode photocoagulation with or without transscleral cyclodiode therapy in patients with rubeosis iridis with or without elevated intraocular pressure and no fundal view. METHODS: Peripheral transscleral retinal diode photocoagulation was performed in 15 eyes of 13 patients in an attempt to promote regression of rubeosis. The fundus could not be seen in any of the 15 eyes, so conventional panretinal photocoagulation was not possible. Nine eyes had associated elevated intraocular pressure and were treated with concurrent transscleral diode cyclophotocoagulation. RESULTS: All eyes showed regression of rubeosis. Of the nine eyes treated with combination therapy, six had stabilized intraocular pressure, and three developed hypotony. None of the eyes developed a peripheral retinal detachment, and one eye lost the ability to perceive light. CONCLUSIONS: This method is effective in treating patients with rubeosis iridis when the view of the fundus is inadequate for conventional panretinal photocoagulation and more extensive intraocular surgery is precluded. It may be combined with transscleral cyclophotocoagulation therapy to manage concurrent high intraocular pressure in rubeotic glaucoma, but this involves a risk of postoperative hypotony.

Assessment of microcirculation of an axial skin flap using indocyanine green fluorescence angiography.

In many cases the complexities of skin-flap microcirculation are difficult to assess despite all the subjective and objective examination techniques available today. Adequate microcirculation is essential for tissue viability, so any method employed for studying microcirculation should provide as accurate an assessment of the prevailing conditions as possible. Of all the clinical methods, the fluorescence technique using the dye sodium fluorescein has so far provided the most reliable results. However, the pharmacokinetic properties of this tracer have prevented the technique from becoming established in clinical practice. The fluorescent dye indocyanine green (Cardio Green), on the other hand, has far more favorable pharmacokinetics. In an experimental animal model, the fluorescence technique using indocyanine green (indocyanine green angiography, ICGA) was used to study postoperative changes in the microcirculation of a skin flap. On the day of operation, indocyanine green angiography revealed a state of hemodynamic imbalance for which the organism was able to compensate in the postoperative phase with the aid of humoral, physical, and metabolic factors. With indocyanine green angiography it was possible to quantify objectively the new hemodynamic equilibrium. Basically, microcirculation may be quantified in temporal and spatial terms. The significant objectivity of indocyanine green angiography and short intervals between each examination favor its possible and meaningful use in clinical practice and give cause for continuing studies.

Development, repair and regeneration of the retinal pigment epithelium.

An overview is presented of the retinal pigment epithelium (RPE) cell in repair and regeneration. Changes in the RPE associated with repair activities have been described as metaplasia. However, evidence is presented to show that RPE cells do not become either fibroblasts or macrophages but merely adopt the appearance of these cell types in pathological conditions. The phenotypic alterations seem to be substrate-related. The fibroblast form predominates on two-dimensional substrates rich in fibronectin and in three-dimensional collagen matrices. The macrophage form seems to be associated with insubstantial or inadequate substrates such as the vitreous, photoreceptor debris and some cell surfaces. In altered circumstances the dedifferentiated RPE can rapidly revert to an epithelioid form. However, the regeneration of an effective RPE mosaic is more difficult and dependent on many factors including the size of the initial lesion, the condition of the basement area, the status of the neuroretina and the existing pathology in the eye. The importance for the regeneration of a normal functioning RPE of the cells being out of the cell cycle, establishing effective junctioning, reorganising their cytoskeleton and having the required adhesive balance with the basement membrane is emphasised.