The African Lupus Genetics Network (ALUGEN) registry: standardized, prospective follow-up studies in African patients with systemic lupus erythematosus.

BACKGROUND: The prevalence and severity of systemic lupus erythematosus (SLE) differs between ethnic groups and geographical regions. Although initially reported as rare, there is growing evidence that SLE is prevalent and runs a severe course in Africa. There is a paucity of prospective studies on African SLE patients. OBJECTIVE: The African Lupus Genetics Network (ALUGEN) is a multicentred framework seeking to prospectively assess outcomes in SLE patients in Africa. Outcomes measured will be death, hospital admission, disease activity flares, and SLE-related damage. We will explore predictors for these outcomes including clinical, serological, socio-demographic, therapeutic and genetic factors. Further, we will investigate comorbidities and health-related quality of life amongst these patients. METHODS: Data of patients recently (≤ 5 yrs) diagnosed with SLE will be collected at baseline and annual follow-up visits, and captured electronically. The ALUGEN project will facilitate standardized data capture for SLE cases in Africa, allowing participating centres to develop their own SLE registries, and enabling collaboration to enrich our understanding of inter-ethnic and regional variations in disease expression. CONCLUSION: Comprehensive, high-quality multi-ethnic data on African SLE patients will expand knowledge of the disease and inform clinical practice, in addition to augmenting research capacity and networking links and providing a platform for future biomarker and interventional studies.

Atypical rosacea in a male patient: case study.

Rosacea fulminans is a rare disorder of unknown cause, almost exclusively affecting women. There are only a few reported cases in men. The condition is characterized by the abrupt onset of pustules and nodules predominantly affecting the cheeks or chin without any systemic upset. We report the case of a 37-year-old man who presented with papulopustules, predominantly localized to his nose. Histopathological features were consistent with rosacea fulminans. The patient was managed with treatments including oral prednisolone, isotretinoin, and trimethioprim.

Lupus in Africa: can we dispel the myths and face the challenges?

The epidemiology of systemic lupus erythematosus (SLE) in Africa is largely undetermined, and the perception persists that the incidence of SLE on the continent is very low. Recent studies as well as our own experience, however, suggest that this is not the case. We have conducted a survey amongst medical practitioners in Africa to determine their experiences of diagnosing and treating SLE patients, and the results suggest that significant numbers of African patients are presenting with SLE. The apparent low incidence rate in Africa may be the result of underdiagnosis due to poor access to health care, low disease recognition within primary health care settings, limited access to diagnostic tools and inadequate numbers of specialist physicians. Treatment of SLE in Africa is also restricted by availability and affordability of immunosuppressive drugs. We have established the African Lupus Genetics Network (ALUGEN), an informal network of clinicians and researchers in Africa who have an interest in SLE, in order to facilitate combined clinical and research efforts towards improved outcomes for African SLE patients.

Clinicopathological insights into lupus nephritis in South Africans: a study of 251 patients.

There are few published studies on biopsy proven lupus nephritis (LN) from sub-Sahara Africa, mainly due to lack of expertise and pathology back-up for performing and interpreting renal biopsies in many centres. The purpose of this study was to document factors associated with biopsy proven LN and to determine clinical and laboratory models that best predict proliferative LN in South Africans. Of the 251 patients studied, 84.1% were females and 79.3% were of mixed ancestry. There were more observed cases of proliferative LN (63%) than non-proliferative LN. Factors associated with proliferative LN were male gender (p = 0.049), haematuria on dipstix (p < 0.0001), proteinuria on dipstix (p = 0.042), low serum albumin (p = 0.032), low complement C3 (p < 0.0001), low complement C4 (p = 0.009) and positive double-stranded DNA (p = 0.039). Using four models designed from various combinations of the factors associated with proliferative LN, the specificity and positive predictive values were highest for the model that combined gender (male), presence of dipstix haematuria and proteinuria, hypoalbuminaemia, low C3 and low C4 and positive double-stranded DNA (100% respectively). Further study is recommended to identify the value of using these demographic and laboratory parameters in identifying patients with proliferative LN in resource limited centres where the performance of a biopsy is not possible.

T-cell pseudolymphoma secondary to ixazomib for multiple myeloma.

We present a case of a 54-year-old male with multiple myeloma (MM) who presented with widespread pruritic erythematous lesions following ixazomib treatment. This occurred after his third cycle of treatment with ixazomib, thalidomide and dexamethasone and was controlled by potent steroids and temporary cessation of ixazomib. The strong correlation between the timeline of the rash, ixazomib treatment and subsequent cessation led to a diagnosis of a drug-induced rash. Skin biopsy histology, immunochemistry and the absence of monoclonal T-cell receptor gene rearrangement further confirmed the diagnosis of a T-cell pseudolymphoma secondary to ixazomib. Ixazomib is an oral proteasome inhibitor used in the treatment of MM. Other proteasome inhibitors have been reported to trigger cutaneous adverse effects. However, to our knowledge, this is the first report of pseudolymphoma following proteasome inhibitor use. Dermatologists should be aware of this potential effect and the possible management pathways such as cessation and dose reduction.

One-year mortality after hospital admission as an indicator of palliative care need: A retrospective cohort study.

BACKGROUND: Globally there is increasing awareness of the need for end-of-life care and palliative care in hospitalised patients who are in their final year of life. Limited data are available on palliative care requirements in low- and middle-income countries, hindering the design and implementation of effective policies and health services for these patients. OBJECTIVES: To determine the proportion of patients who die within 1 year of their date of admission to public hospitals in South Africa (SA), as a proxy for palliative care need in SA. METHODS: This was a retrospective cohort study using record linkage of admission and mortality data. The setting was 46 acute-care public hospitals in Western Cape Province, SA. RESULTS: Of 10 761 patients (median (interquartile range (IQR)) age 44 (31 - 60) years) admitted to the 46 hospitals over a 2-week period in March 2012, 1 570 (14.6%) died within 1 year, the majority within the first 3 months. Mortality rose steeply with age. The median (IQR) age of death was 57.5 (45 - 70) years. A greater proportion of patients admitted to medical beds died within 1 year (21.3%) compared with those admitted to surgical beds (7.7%). CONCLUSIONS: Despite a median age <60 years at admission, a substantial percentage of patients admitted to public sector hospitals in SA are in the final year of their lives. This finding should be seen in the context of SA's high communicable and non-communicable disease burden and resource-limited public health system, and highlights the need for policy development, planning and implementation of end-of-life and palliative care strategies for hospitals and patients.

Direct photographic documentation of ileal mucosa in routine colonoscopy is not an independent valid or reliable proof of completion: quality assurance issues for the national colorectal cancer-screening programme.

INTRODUCTION: The implementation of bowel cancer screening in the UK requires the maintenance of high standards in colonoscopy. Part of this quality control requires the reliable documentation of complete colonoscopy that can be externally audited and assessed. It has been suggested that terminal ileal biopsy is the only definitive and reliable method of confirming caecal intubation, but it is not cost-effective and may now be contraindicated because of potential prion infection. OBJECTIVE: To determine how reliable routine terminal ileal images were as an independent predictor of complete colonoscopy and whether their interpretation was aided with water insufflation or indigo-carmine dye-spraying. Method Forty-nine histologically confirmed terminal ileal images were obtained from a single endoscopist's database; 19 were conventional white-light images, 15 were taken with water insufflation and 15 were taken using chromoscopy enhancement. The images were transferred onto CD-ROM and sent as a questionnaire to 42 colonoscopists who were asked to identify the images as terminal ileum or not. RESULTS: Twenty questionnaires were returned resulting in a total of 980 responses. Overall, the accuracy of positive identification was 53.4%. Water insufflation and chromoscopy improved the accuracy to 68.3% and 63% respectively. Experience of (> 1000 colonoscopies) did not increase overall accuracy. Less experienced endoscopists had an increased accuracy rate with dye-spraying (76.7%vs 59.3%, P < 0.05) but experienced endoscopists had an increased accuracy rate with water insufflation (67.4%vs 63.3%, P > .05). CONCLUSION: Currently, terminal ileal imaging is not a reliable mode of documenting complete colonoscopy. Using water insufflation or dye-spraying coupled with modifications in image acquisition technique may improve its reliability but these methods require further investigation before they can replace the use of caecal landmarks as completion parameters.

Data Centre Profile: The Provincial Health Data Centre of the Western Cape Province, South Africa.

INTRODUCTION: The Western Cape Provincial Health Data Centre (PHDC) consolidates person-level clinical data across government services, leveraging sustained investments in patient registration systems, a unique identifier, and maturation of administrative and clinical digital health systems. OBJECTIVES: The PHDC supports clinical care directly through tools for clinicians which integrate patient data or identify patients in need of interventions, and indirectly through supporting operational and epidemiological analyses. METHODS: The PHDC is housed entirely within government. Data are processed from a range of source systems, usually daily, through distinct harmonisation and curation, beneficiation, and reporting processes. Linkage is predominantly through the unique identifier which doubles as a pervasive folder number, augmented by other identifiers. Further data processing includes triangulation of multiple data sources for enumerating health conditions, with assignment of certainty levels for each enumeration. Outputs include patient-specific email alerts, a web-based consolidated patient clinical viewing platform, filterable line-listings of patients with specific conditions and associated characteristics and outcomes, management reports and dashboards, and data releases in response to operational and research data requests. Strict architectural, administrative and governance processes ensure privacy protection. RESULTS: In the past decade 8 million unique people are recorded as having sought healthcare in the provincial public sector health services, with current utilisation at 15 million attendances or admissions a year. Cross-sectional enumeration of health conditions includes over 430 000 people with HIV, 500 000 with hypertension, 235 000 with diabetes. Annually 110 000 pregnancies and 54 000 patients with tuberculosis are enumerated. Over 50 data requests are processed each year for internal and external requesters in accordance with data request and release governance processes. CONCLUSIONS: The single consolidated environment for person-level health data in the Western Cape has created new opportunities for supporting patient care, while improving the governance around access to and release of sensitive patient data.

In vivo real-time confocal laser scanning endomicroscopic colonoscopy for the detection and characterization of colorectal neoplasia.

BACKGROUND: Conventional colonoscopy has a significant false-negative rate for intraepithelial neoplasia. Chromoendoscopy increases sensitivity but lacks specificity. The aim was to assess prospectively the clinical applicability and predictive power of the EC3870CIFK confocal laser endomicroscope (CLE) for the in vivo diagnosis of intraepithelial neoplasia during colonoscopy. METHODS: Lesions were identified using chromoscopy followed by CLE imaging and graded according to vascular and cellular changes. CLE imaging of circumscribed lesions and four segmental 'normal' colorectal quadrants was performed. Targeted biopsy specimens were then compared with histopathological results. RESULTS: Forty patients completed the protocol (22 men and 18 women; median age 62 (range 39-82) years). The median duration of ileal intubation and total procedure time were 12 (range 5-26) and 55 (range 28-92) min respectively. Chromoscopic colonoscopy revealed 162 lesions in 39 patients. CLE imaging was obtained on all 162 lesions. Some 5422 confocal images were compared with 802 targeted biopsy specimens. Intraepithelial neoplasia was predicted with an accuracy of 99.1 per cent (sensitivity 97.4 per cent and specificity 99.3 per cent) (P = 0.711). CONCLUSION: Confocal laser endomicroscopy permits high-quality cellular, subsurface vascular and stromal imaging, enabling prediction of intraepithelial neoplasia with a high level of accuracy.

In vivo confocal laser scanning chromo-endomicroscopy of colorectal neoplasia: changing the technological paradigm.

Recently, miniaturization of a novel confocal laser endomicroscope (Optiscan Pty, Notting Hill, Victoria, Australia) has permitted functional integration into the distal tip of a conventional video colonoscope (Pentax EC3870K; Pentax, Tokyo, Japan) enabling imaging of the surface epithelium and the underlying lamina propria during ongoing video endoscopy. Using endomicroscopy and intravenous sodium fluorescein as a contrast agent, 'virtual histology' can be created, which allows visualization of both the surface epithelium, and some of the lamina propria (down to a quarter of a millimetre), including the microvasculature. Confocal endomicroscopy may have major implications in the future of colonoscopy as uniquely it allows in vivo diagnosis of colonic intraepithelial neoplasia and carcinoma enabling 'smart' biopsy targeting and hence potentially influencing 'on table' management decisions. Initial pilot data have now shown that confocal imaging in vivo using the newly developed EC3870K has high overall accuracy for the immediate diagnosis of intraepithelial neoplasia and carcinoma in sporadic screened cohorts, but also has a role in the detection of intraepithelial neoplasia detection in chronic ulcerative colitis cancer screening when used in conjunction with methylene blue chromoscopy. We discuss the current evidence in support of confocal endomicroscopy in the colorectum and explore the new diagnostic possibilities for this technology.

EMR using dextrose solution versus sodium hyaluronate for colorectal Paris type I and 0-II lesions: a randomized endoscopist-blinded study.

BACKGROUND AND AIMS: Loss of mucosal 'lift' prior to submucosal dissection or endoscopic mucosal resection (EMR) increases the risk of complications. We conducted a randomized controlled trial comparing dextrose solution with sodium hyaluronic acid (SHA) for the EN BLOC resection of Paris type I/0-II and lateral spreading lesions of the colorectum. PATIENTS AND METHODS: Patients with Paris type I/0-II or lateral spreading tumor lesions of < 30 mm were randomized in a 1 : 1 ratio to undergo EMR using either dextrose solution or SHA. The primary study outcome was complete resection. Secondary outcomes were endoscopic complications (i. e. perforation or bleeding) and polyp recurrence rates. RESULTS: A total of 174 patients were randomized. R0 resection was achieved in 59 of the 82 lesions (72 %) in the dextrose group and 56 of the 81 lesions (69 %) in the SHA group ( P > 0.1), with no significant difference in median lesion diameter ( P > 0.1). The median number of post resection surveillance colonoscopies was 3 (range 2 - 7) in the dextrose group and 4 (range 2 - 6) in the SHA group ( P = NS). The median post index EMR resection follow-up period was 20 months (range 4 - 26) in the DS group and 18 months (range 3 - 22) in the SHA group ( P = NS). Recurrence rates were 1/82 (1.21 %) in the dextrose group and 1/81 (1.23 %) in the SHA group ( P = NS). CONCLUSIONS: EMR using dextrose solution is as effective as SHA in terms of resection completion, recurrence rates, and complications.

Salvage endoscopic submucosal dissection for residual or local recurrent intraepithelial neoplasia in the colorectum: a prospective analysis.

OBJECTIVE: A prospective technical feasibility study of cap assisted ESD for 'curative intent' in patients with residual or local neoplastic recurrence following EMR. Primary end points were second stage R0 resection rate, safety and recurrence. METHOD: Salvage ESD was performed using the Olympus GIF-XQ240 gastroscope and KD-630L insulation tipped knife. Thirty-day mortality, re-admission rates, complications and histological resection status were collected prospectively up to 9 months following index resection. RESULTS: Thirty patients met eligibility criteria. Index R0 resection was achieved in 25/30 (83%) lesions. One patient underwent surgical excision with a second receiving a curative second stage dissection. Ninety-six per cent (29/30) patients were discharged within 24 h of the procedure with a 0% 30-day mortality and re-admission rate. Bleeding occurred in 5/30 (16%) treated successfully with endoluminal haemostasis. There were no perforations. Overall 'cure' rates at short-term follow-up [median 6/12 (range; 3-18)] was 96%. CONCLUSION: This novel application of ESD for first line 'salvage' therapy in treating residual or locally recurrent neoplastic disease may be a safe, minimally invasive and cost effective alternative to direct surgical resection in a select patient cohort.

In vitro prevention of the emergence of multidrug resistance in a pediatric rhabdomyosarcoma cell line.

We have established preclinical models for the development of drug resistance to vincristine (a major drug used in the treatment of pediatric rhabdomyosarcoma) using cell lines. The RD cell line has a mutant P53 phenotype and does not have detectable P-glycoprotein (P-gp) or multidrug resistance-related protein (MRP) despite expressing low levels of mdr-1 mRNA, which encodes P-gp and mrp1 mRNA. Resistant variants of RD were derived by exposure to increasing concentrations of vincristine. This was repeated on six occasions, resulting in three cell lines which could tolerate 64 x the IC(50) concentration. Six independent agents were tested for their ability to prevent the development of resistance in this model. Despite at least 10 attempts, resistance did not develop in the presence of the multidrug resistance (MDR) modulators PSC833, VX710, and XR9576. This strongly suggests that these agents may delay or even prevent the development of resistance to vincristine. This was also confirmed in a second rhabdomyosarcoma cell line, Rh30. In contrast, the agents indomethacin (MRP1 modulator), CGP41251 (protein kinase C inhibitor), and dexrazoxane (putative MDR prevention agent) did not affect the development of resistance in the RD model. Characterization of the resistant cell lines indicated the presence of increased mdr-1 and P-gp expression, which resulted in resistance to the agents doxorubicin, etoposide, and vincristine but not cisplatin. The resistance could be modulated using PSC833 or VX710, confirming that functional P-gp is present. No apparent differences were seen between the resistant cell lines derived in the absence and presence of the various agents. These experiments strongly suggest that the development of MDR may be preventable using modulators of MDR and merit clinical studies to test this hypothesis.

Squamous cell carcinoma arising in epidermoid cysts: report of four cases and review of the literature.

Epidermoid cysts are commonly encountered in clinical practice and while the majority are benign, isolated cases of premalignant and malignant conditions have been identified in their walls. We report four cases of squamous cell carcinoma arising in the walls of epidermoid cysts and review the literature.

Prototype volume-controlled resuscitator for neonates and infants.

Twenty-five infants receiving assisted ventilation in an ICU were manually ventilated for 5-min periods using either a new prototype volume-controlled resuscitator (VCR) or a standard self-inflating resuscitator (SIR). Variables monitored during these 5-min periods included heart rate, respiratory rate, mean arterial pressure, mean airway pressure (Paw), end-tidal CO2 (PetCO2), pulse oximetry oxygen saturation, PaO2, and PaCO2. Significant differences in posttrial values for the following variables were: a) PetCO2 (31.2 +/- 9.1 vs. 25.6 +/- 8.2 torr, p less than .001); b) PaCO2 (38.0 +/- 4.9 vs. 33.2 +/- 6.7 torr, p less than .01); and c) pH (7.4 +/- 0.6 vs. 7.5 +/- 0.1, p less than .04) at comparable Paw (9.5 +/- 7.6 vs. 8.0 +/- 6.0, NS). Eighty-four percent (21/25) of infants in the VCR group had normal PaCO2 values (35 to 45 torr) while only 44% (11/25) in the SIR group achieved normocarbia (p less than .001). Measurements of the highest (Pmax) and lowest (Pmin) inspiratory pressure (cm H2O) in 15 patients demonstrated marked variation in Pmax with the SIR. Differences in Pmax (SIR minus VCR) were significant (10.8 +/- 3.7, p less than .02) but not in Pmin (0.5 +/- 3.5, NS). Our study demonstrates that ventilation with the VCR resulted in less hyperventilation with minimal pressure variability as compared with the SIR. Further studies in the neonate are warranted.

Physiological responses to endotracheal and oral suctioning in paediatric patients: the influence of endotracheal tube sizes and suction pressures.

OBJECTIVE: To study the influence of varying outer suction catheter (SC) diameter (OD) to inner endotracheal tube (ETT) diameter (ID) and suction pressures (SP) on heart rate (HR), respiratory rate (RR), mean arterial pressure (MAP), arterial oxygen saturation (SaO 2) and intracranial pressure (ICP) during ETT and oral suctioning. An additional aim was to define an optimal suction catheter size that would prove easy to introduce and be rapidly effective in clearing secretions with the least physiological alteration. DESIGN: Prospective study. SETTING: Paediatric intensive care unit. PATIENTS: Ventilated paediatric patients. INTERVENTION: Patients had ETT suctioning performed in a random fashion using suction catheters with SC outer diameter to inner ETT diameter of approximately 0.4, 0.7 and 0.9 using varying pressures (80, 100, 120 mmHg). Using the medium size suction catheter (OD/ID = 0.7) at 100 mmHg of suction pressure, oral suctioning was compared to ETT suctioning. MEASUREMENTS AND MAIN RESULTS: Seventeen patients were studied (age 6.5 + 5 months). All suction catheters at varying pressures resulted in similar transient alterations in HR, RR, MAP, SaO 2 and ICP following ETT suctioning. Significant changes were seen in SaO 2, HR and ICP, irrespective of the catheter diameter or suction pressure. Oral suctioning resulted in similar trends and magnitude of changes as for ETT suctioning in MAP, RR, HR, and ICP, but less change occurred in the SaO 2 (p less than 0.05). The catheters with OD/ID of 0.7 were easiest to introduce and most effective in clearing secretions. CONCLUSION: Our study suggests that: 1. Tracheal toilet using variations in OD/ID ratios and SP within limits tested resulted in similar significant adverse changes in HR, ICP and SaO 2 and similar trends in RR and MAP. 2. Based on the ease of introduction and the effectiveness of clearing secretions, a medium SC (OD/ID = 0.7) is most appropriate for infants and children. 3. Oral suctioning also results in adverse physiological changes, therefore similar precautions to those taken during tracheal suctioning should be followed for oral suctioning.

An evaluation of the physical and functional characteristics of resuscitators for use in pediatrics.

OBJECTIVE: To evaluate the physical and functional characteristics of pediatric self-inflating resuscitators. DESIGN: Tested under simulated clinical conditions. Results were analyzed by descriptive analysis. SETTING: A pulmonary laboratory in a university hospital. METHODS: Eight new pediatric self-inflating resuscitators were obtained from the manufacturers and evaluated for functional characteristics including: a) fraction of delivered oxygen at 10 L/min and a tidal volume of 300 mL; b) maximum stroke volume against no resistance; and c) maximum cycling frequency at -5 degrees C, 20 degrees C, and 48 degrees C. The resuscitators were also evaluated for physical characteristics, including potential for misassembly, pressure relief valves, expiratory valve leak, and inspiratory resistance. RESULTS: All resuscitators met the minimum standards of the Canadian Standards Association and American Standards for Testing of Materials. However, one bag cycled at only 32 breaths/min at -5 degrees C, marginally within accepted standards. Only five self-inflating resuscitators had pop-off valves. These valves malfunctioned, with valve activation occurring well above the accepted standards. Three of the self-inflating resuscitators could be misassembled for use. Four of the resuscitators were unable to deliver tidal volumes required for preoxygenation in a 20-kg child. CONCLUSIONS: While these self-inflating resuscitators met the minimum standards, they are all unable to deliver 100% oxygen. One unit is probably not appropriate in the out-of-hospital setting when ambient temperatures are less than 0 degrees C. Those resuscitators that can be misassembled are dangerous in unskilled hands. In addition, reliance on pop-off valve activation to limit airway pressure is dangerous.