Diffuse Large B-Cell Lymphoma Treated With R-CHOP in a Resource-Limited Setting in South Africa: A Real-World Study.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin's lymphoma worldwide and particularly in Africa, where the incidence of HIV is the highest in the world. R-CHOP is the standard of care regimen for DLBCL, but access to rituximab is limited in developing countries. METHODS: This is a retrospective cohort study that included all HIV-negative patients with DLBCL who received R-CHOP at a single institution from January 2012 to December 2017. Clinical and demographic data were collected to assess factors that influenced survival. RESULTS: Seventy-three patients were included. Median age was 55 (17-76), 67.1% of patients were younger than 60 years, and 60.3% were female. Most presented with stages III/IV disease (53.5%) but with good performance status (56.% PS 0 and 1). Progression-free survival at 3 and 5 years was 75% and 69%, and overall survival at 3 and 5 years was 77% and 74%, respectively. Median survival had not been reached with a median follow-up of 3.5 years(0.13-7.9). Overall survival was significantly affected by performance status (P = .04), but not by IPI or age. Survival was significantly associated with response to chemotherapy after 4-5 cycles of R-CHOP (P = 0.005). CONCLUSIONS: Treatment of DLBCL with R-CHOP is feasible and can achieve good outcomes in resource-limited settings with rituximab-based chemotherapy. Poor performance status was the most important adverse prognostic factor in this cohort of HIV-negative patients.

Platelets Independently Recruit into Asthmatic Lungs and Models of Allergic Inflammation via CCR3.

Platelet activation and pulmonary recruitment occur in patients with asthma and in animal models of allergic asthma, in which leukocyte infiltration, airway remodeling, and hyperresponsiveness are suppressed by experimental platelet depletion. These observations suggest the importance of platelets to various characteristics of allergic disease, but the mechanisms of platelet migration and location are not understood. The aim of this study was to assess the mechanism of platelet recruitment to extravascular compartments of lungs from patients with asthma and after allergen challenge in mice sensitized to house dust mite (HDM) extract (contains the DerP1 [Dermatophagoides pteronyssinus extract peptidase 1] allergen); in addition, we assessed the role of chemokines in this process. Lung sections were immunohistochemically stained for CD42b+ platelets. Intravital microscopy in allergic mice was used to visualize platelets tagged with an anti-mouse CD49b-PE (phycoerythrin) antibody. Platelet-endothelial interactions were measured in response to HDM (DerP1) exposure in the presence of antagonists to CCR3, CCR4, and CXCR4. Extravascular CD42b+ platelets were detected in the epithelium and submucosa in bronchial biopsy specimens taken from subjects with steroid-naive mild asthma. Platelets were significantly raised in the lung parenchyma from patients with fatal asthma compared with postmortem control-lung tissue. Furthermore, in DerP1-sensitized mice, subsequent HDM exposure induced endothelial rolling, endothelial adhesion, and recruitment of platelets into airway walls, compared with sham-sensitized mice, via a CCR3-dependent mechanism in the absence of aggregation or interactions with leukocytes. Localization of singular, nonaggregated platelets occurs in lungs of patients with asthma. In allergic mice, platelet recruitment occurs via recognized vascular adhesive and migratory events, independently of leukocytes via a CCR3-dependent mechanism.

DYNAMIC: Dynamic glucose management strategies delivered through a structured education program improves time in range in a socioeconomically deprived cohort of children and young people with type 1 diabetes with a history of hypoglycemia.

OBJECTIVES: Create and evaluate the effectiveness of a structured education program in children and young people (CYP) with type 1 diabetes using continuous glucose monitoring (CGM). DESIGN AND METHODS: Step 1: CGM devices were evaluated for predetermined criteria using a composite score. Step 2: The education program was developed following review of international structured education guidance, dynamic glucose management (DynamicGM) literature, award-winning diabetes educators' websites, and CGM user feedback. Step 3: Program effectiveness was assessed at six months by change in time below range (TBR) (<3.9mmol/L), time in range (TIR) (3.9-10.0mmol/L), time above range level 2 (TAR2) (>13.9mmol/L), severe hypoglycemia and HbA1c using a paired T-test. A DynamicGM score was developed to assess proactive glucose management. Factors predicting TBR and TIR were assessed using regression analysis. RESULTS: Dexcom G6 was chosen for integrated CGM (iCGM) status and highest composite score (29/30). Progressive DynamicGM strategies were taught through five sessions delivered over two months. Fifty CYP (23 male) with a mean (±SD) age and diabetes duration of 10.2 (±4.8) and 5.2 (±3.7) years respectively, who completed the education program were prospectively evaluated. Evaluation at six months showed a significant reduction in TBR (10.4% to 2.1%, p<.001), TAR2 (14.1% to 7.3%, p<.001), HbA1c [7.4 to 7.1% (57.7 to 53.8 mmol/mol), p<.001] and severe hypoglycemic episodes (10 to 1, p<.05); TIR increased (47.4% to 57.0%, p<.001). Number of Dexcom followers (p<.05) predicted reduction in TBR and DynamicGM score (p<.001) predicted increased TIR. CONCLUSION: Teaching DynamicGM strategies successfully improves TIR and reduces hypoglycemia.

The determinants and impact of diagnostic delay in lymphoma in a TB and HIV endemic setting.

BACKGROUND: Little is known about the pathway to diagnosis of lymphoma in Sub-Saharan Africa, despite the increased risk of lymphoma in people living with HIV (PLHIV). The challenges of diagnosis in this setting include diagnostic confusion with extrapulmonary tuberculosis (EPTB), which commonly causes lymphadenopathy in PLHIV. METHODS: We analysed the time to diagnosis and treatment in patients using predetermined time intervals. Univariate and multivariable analyses were performed to determine the relationship between patient and disease-specific variables with delays to diagnosis. We were particularly interested in the impact of HIV, empiric tuberculosis therapy and fine-needle aspirate for cytology (FNAC) in contributing to delay. RESULTS: Patients (n = 163), 29% HIV-infected, waited a median of 4 weeks before seeking medical attention. It took a median of 7 weeks for the diagnosis of lymphoma to be made from the time the patient sought medical attention, termed the healthcare practitioner interval. In multivariable logistic regression analysis, diagnostic delay > 6 weeks was associated with late-stage disease (OR 2.3, 95% CI 1.1-5.2) and Hodgkin lymphoma (HL) (OR 3.0, 95% CI 1.1-8.0). HIV status was not associated with diagnostic delay (OR 0.9, 95% CI 0.3-2.2). The median time to diagnosis was a median of 4 weeks longer for patients on tuberculous (TB) therapy (n = 16, p = 0.28) and patients who underwent an FNAC (n = 63, p = 0.04). Where FNAC was performed, it was diagnostic for lymphoma in only 11%. Diagnostic delay was not associated with overall survival. CONCLUSIONS: Time-to-diagnosis of lymphoma in South Africa was similar to that reported from high-income countries and shows significant periods of delay between the onset of symptoms to diagnosis and treatment. The longest period of delay was in the health practitioner interval. Education regarding the significance of lymphadenopathy for both patients and health care practitioners and appropriate investigative steps preferably by best-practice algorithms specific to TB-endemic areas are needed to shorten the time-to-diagnosis of lymphoma.

Hodgkin lymphoma at Groote Schuur Hospital, South Africa: the effect of HIV and bone marrow infiltration.

Human immunodeficiency virus (HIV) is associated with an increased risk of developing Hodgkin lymphoma (HL). South Africa (SA) has the highest HIV prevalence rate in the world. There is currently no outcome-based data for HIV-associated HL from SA. A bone marrow database was compiled of all bone marrow biopsies (BMB) reported at National Health Laboratory Service (NHLS) Groote Schuur Hospital (GSH) between January 2005 and December 2012. Patients who had a BMB performed for staging of HL or where HL was diagnosed on the BMB were included for further analysis. Clinical and laboratory data was extracted from medical and laboratory records. Primary outcome measures included histological subtype, bone marrow infiltration (BMI) by HL, CD4 count, HIV-viral load (HIV-VL), tuberculosis (TB) data, treatment with chemotherapy and 5-year overall survival (OS). The database included 6569 BMB and 219 patients of these had HL and were included for analysis. The median age at presentation (32 years) was similar in the HIV+ and HIV- populations. While males predominated in the HIV- group, females predominated in the HIV+ group (male:female ratio of 1.5:1 vs 0.7:1, respectively). The majority of patients (71%) were HIV negative (HIV-) and 29% were HIV positive (HIV+). The diagnosis of HL was made on BMB in 17% of cases. BMI was seen in 37% (82/219) overall, and was found in more HIV+ patients (61%; 39/64) than HIV- patients (28%; 43/155; p = 0.03). The histological subtype varied according to HIV status with nodular sclerosis classical Hodgkin lymphoma (NSCHL) being most frequent in the HIV- group and classical Hodgkin lymphoma (CHL)-unclassifiable the most frequent in the HIV+ group. HIV+ patients had a median CD4 count of 149 × 106/L and 39% were anti-retroviral therapy (cART) naive at HL diagnosis. HIV+ patients had received anti-TB therapy more frequently than HIV- patients (72% vs 17%; p = 0.007). More HIV+ patients did not receive chemotherapy than HIV- patients (31% vs 3%; p = 0.001). The 5-year OS was 56%. HIV+ patients with BMI had a 5-year OS of 18%. BMI, HIV status, low CD4 count, histological subtype and TB therapy had a statistical significant impact on 5-year OS (p < 0.01). The 5-year OS was 56%, with both BMI and HIV+ status being associated with poor survival. BMB provided the diagnosis of HL in 17% of cases, confirming its diagnostic utility in our setting. Our cohort showed similar survival outcomes to other countries in Africa, Asia and Central America with comparable socio-economic constraints to SA.

Thermodynamics of the S2-to-S3 state transition of the oxygen-evolving complex of photosystem II.

The room temperature pump-probe X-ray free electron laser (XFEL) measurements used for serial femtosecond crystallography provide remarkable information about the structures of the catalytic (S-state) intermediates of the oxygen-evolution reaction of photosystem II. However, mixed populations of these intermediates and moderate resolution limit the interpretation of the data from current experiments. The S3 XFEL structures show extra density near the OEC that may correspond to a water/hydroxide molecule. However, in the latest structure, this additional oxygen is 2.08 Šfrom the Oε2 of D1-E189, which is closer than the sum of the van der Waals radii of the two oxygens. Here, we use Boltzmann statistics and Monte Carlo sampling to provide a model for the S2-to-S3 state transition, allowing structural changes and the insertion of an additional water/hydroxide. Based on our model, water/hydroxide addition to the oxygen-evolving complex (OEC) is not thermodynamically favorable in the S2g = 2 state, but it is in the S2g = 4.1 redox isomer. Thus, formation of the S3 state starts by a transition from the S2g = 2 to the S2g = 4.1 structure. Then, electrostatic interactions support protonation of D1-H190 and deprotonation of the Ca2+-ligated water (W3) with proton loss to the lumen. The W3 hydroxide moves toward Mn4, completing the coordination shell of Mn4 and favoring its oxidation to Mn(iv) in the S3 state. In addition, binding an additional hydroxide to Mn1 leads to a conformational change of D1-E189 in the S2g = 4.1 and S3 structures. In the S3 state a fraction of D1-E189 release from Mn1 and bind a proton.

Focal Congenital Hyperinsulinism as a Cause for Sudden Infant Death.

Congenital hyperinsulinism (CHI) is the commonest cause of persistent and severe hypoglycemia in infancy due to unregulated insulin secretion from pancreatic ß-cells. Prompt early diagnosis is important, as insulin reduces glucose supply to the brain, resulting in significant brain injury and risk of death. Histologically, CHI has focal and diffuse forms; in focal CHI, an inappropriate level of insulin is secreted from localized ß-cell hyperplasia. We report a 4-month-old male infant, who presented with sudden illness and collapse without a recognized cause and died. Postmortem examination revealed pancreatic histopathology compatible with focal CHI. Immunofluoresence staining showed limited expression of p57kip2 ß-cells reinforcing the diagnosis. Mutation testing for genes associated with CHI from DNA from the focal lesion was negative. This case highlights the recognition of focal CHI as a possible cause for sudden infant death. In children dying suddenly and unexpectedly, postmortem pancreatic sections should be carefully examined for focal CHI.

Combined QM/MM and Monte Carlo study for redox leveling in Mn and Fe superoxide dismutase.

Superoxide dismutases (SOD) are vital enzymes for disproportionation of superoxide molecules in mammals. Despite the high similarity between the Mn-SOD and Fe-SOD, they are inactive if the metals in the active sites are exchanged. Here, we use DFT, QM/MM and Monte Carlo sampling to optimize the crystal structure and to calculate the mid-point potential for the native and substituted Mn/Fe-SOD. The optimized DFT and QM/MM structures of the Mn-SOD show a major conformational change for the conserved TYR34 compared to the X-ray structure. These changes reduce the distance between TYR34 and Mn ion to 2.59 Å, which yields a lower reduction potential for the Mn. On contrary, there is no significant difference between optimized and crystal structures in the Fe-SOD. The calculated E m values starting from the DFT structures of the active sites show similar pattern, in good agreement with those observed experimentally. However, the calculated E m values starting with the QM/MM structures that include the whole protein are significantly higher due to the desolvation penalty. In addition, the pK a values for the water ligand in the reduced state Mn(II) and Fe(II) were calculated. The water pK a in Mn-SOD is higher than that in Fe-SOD by 3.5 pH units, which is similar to the shift measured experimentally. Finally, we investigated the role of HIS30 and the effect of its protonation state on the E m values.

Characterizing Focused Attention and Working Memory Using EEG.

Detecting the cognitive profiles of learners is an important step towards personalized and adaptive learning. Electroencephalograms (EEG) have been used to detect the subject's emotional and cognitive states. In this paper, an approach for detecting two cognitive skills, focused attention and working memory, using EEG signals is proposed. The proposed approach consists of the following main steps: first, subjects undergo a scientifically-validated cognitive assessment test that stimulates and measures their full cognitive profile while putting on a 14-channel wearable EEG headset. Second, the scores of focused attention and working memory are extracted and encoded for a classification problem. Third, the collected EEG data are analyzed and a total of 280 time- and frequency-domain features are extracted. Fourth, several classifiers were trained to correctly classify and predict three levels (low, average, and high) of the two cognitive skills. The classification accuracies that were obtained on 86 subjects were 84% and 81% for the focused attention and working memory, respectively. In comparison with similar approaches, the obtained results indicate the generalizability and suitability of the proposed approach for the detection of these two skills. Thus, the presented approach can be used as a step towards adaptive learning where real-time adaptation is to be done according to the predicted levels of the measured cognitive skills.

Clinical Significance of Elevated KSHV Viral Load in HIV-Related Kaposi's Sarcoma Patients in South Africa.

Kaposi's sarcoma (KS) is an AIDS-defining illness caused by Kaposi's sarcoma-associated herpesvirus (KSHV) predominantly in the context of HIV-related immune suppression. We aimed to explore the usefulness of KSHV DNA viral load (VL) measurement in predicting the severity, response to treatment and outcome of KS. We retrospectively assessed a cohort of KS patients (n = 94) receiving treatment at Groote Schuur Hospital, Cape Town, South Africa. Demographic and clinical data, KS staging and response to treatment were extracted from patient files, while long-term survival was ascertained from hospital records. KSHV serology and VL and hIL-6 were determined empirically from patients' blood. All patients were HIV-positive adults, the majority of whom were on HAART at the time of recruitment. KSHV VL was detectable in 65 patients' blood (median: 280.5/106 cells (IQR: 69.7-1727.3)) and was highest in patients with S1 HIV-related systemic disease (median 1066.9/106 cells, IQR: 70.5-11,269.6). KSHV VL was associated with the S1 stage in a binomial regression controlling for confounders (adjusted odds ratio 5.55, 95% CI: 1.28-24.14, p = 0.022). A subset of six patients identified to have extremely high KSHV VLs was predominantly T1 stage with pulmonary KS, and most had died at follow-up. In our cohort, elevated KSHV VL is associated with systemic HIV-related illness in KS disease. Extremely high KSHV VLs warrant further investigation for patients potentially requiring intensive treatment and investigation for progression or diagnosis of concurrent KSHV lytic syndromes.

Pediatric and adult liver transplantation in Bahrain: The experiences in a country with no available liver transplant facilities.

BACKGROUND: Liver transplantation (LT) is a life-saving procedure for patients with end-stage liver disease and has become the standard and most effective treatment method for these patients. There are many indications for LT that vary between countries and settings. The outcome of LT depends on the available facilities and surgical expertise, as well as the types of liver graft donors available. AIM: To assess the clinical characteristics of patients from Bahrain who underwent LT overseas, and analyze factors affecting their survival. METHODS: In this retrospective cohort study, we reviewed the medical records and overseas committee registry information of all pediatric and adult patients who were sent overseas to undergo LT by the Pediatric and Medical Departments of Salmaniya Medical Complex and Bahrain Defence Force Hospital via the Overseas Treatment Office, Ministry of Health, Kingdom of Bahrain, between 1997 and 2023. Demo graphic data, LT indication, donor-recipient relationship, overseas LT center, graft type, post-LT medications, and LT complications, were collected. Outcomes measured included the overall and 5-year LT survival rate. Fisher's exact, Pearson χ2, and Mann-Whitney U tests were used to compare the pediatric and the adults' group in terms of clinical characteristics, donor-recipient relationship, medication, complications, and outcome. Survival analysis was estimated via the Kaplan-Meier's method. Univariate and multivariate analyses were used to detect predictors of survival. RESULTS: Of the 208 eligible patients, 170 (81.7%) were sent overseas to undergo LT while 38 (18.3%) remained on the waiting list. Of the 170 patients, 167 (80.3%) underwent LT and were included in the study. The majority of the patients were Bahraini (91.0%), and most were males (57.5%). One-hundred-and-twenty (71.8%) were adults and 47 (28.3%) were children. The median age at transplant was 50.0 [interquartile range (IQR): 14.9-58.4] years. The main indication for pediatric LT was biliary atresia (31.9%), while that of adult LT was hepatitis C-related cirrhosis (35.0%). Six (3.6%) patients required re-transplantation. Most patients received a living-related liver graft (82%). Pediatric patients received more living and related grafts than adults (P = 0.038 and P = 0.041, respectively), while adult patients received more cadaveric and unrelated grafts. Most patients required long-term immunosuppressive therapy after LT (94.7%), of which tacrolimus was the most prescribed (84.0%), followed by prednisolone (50.7%), which was prescribed more frequently for pediatric patients (P = 0.001). Most patients developed complications (62.4%) with infectious episodes being the most common (38.9%), followed by biliary stricture (19.5%). Tonsilitis and sepsis (n = 12, 8.1% for each) were the most frequent infections. Pediatric patients experienced higher rates of infection, rejection, and early poor graft function than adult patients (P < 0.001, P = 0.003, and P = 0.025, respectively). The median follow-up time was 6.5 (IQR: 2.6-10.6) years. The overall survival rate was 84.4%, the 5-year survival rate, 86.2%, and the mortality rate, 15.6%. Younger patients had significantly better odds of survival (P = 0.019) and patients who survived had significantly longer follow-up periods (P < 0.001). CONCLUSION: Patients with end-stage liver disease in Bahrain shared characteristics with those from other countries. Since LT facilities are not available, an overseas LT has offered them great hope.

Treatment Patterns and Clinical Outcomes in Patients with Hodgkin Lymphoma from Saudi Arabia, Türkiye, and South Africa: Subgroup Analysis from the International, Multi-center, Retrospective BHOLISTIC Study.

Objective: B-HOLISTIC was a real-world, retrospective study of treatment patterns and clinical outcomes in Hodgkin lymphoma (HL) in regions outside Europe and North America. This subgroup analysis reports findings from Saudi Arabia, Türkiye, and South Africa. Materials and methods: Patients aged ≥18 years and diagnosed with stage IIB-IV classical HL receiving frontline chemotherapy (frontline cHL) and/or relapsed/refractory HL (RRHL) from January 2010-December 2013 were assessed. The primary endpoint was progression-free survival (PFS) in patients with RRHL. Results: Overall, 694 patients (RRHL: n=178; frontline cHL: n=653) were enrolled. Among patients with RRHL, >80% received first salvage chemotherapy. The most common first salvage regimens were etoposide, methylprednisolone, cytarabine, cisplatin (ESHAP) in Saudi Arabia (78.3%) and dexamethasone, cytarabine, cisplatin (DHAP) in Türkiye (36.1%) and South Africa (40%). Median PFS (95% confidence interval [CI]) in the RRHL group was 5.1 (3.0-15.9), 19.7 (7.5-not reached), and 5.2 (1.1- 10.1) months in Saudi Arabia, Türkiye, and South Africa, respectively. The 5-year PFS and overall survival (95% CI) rates in patients with RRHL were 33.2% (21.6-45.2) and 78.2% (65.9-86.5) in Saudi Arabia, 42.5% (29.5-54.9) and 79.4% (67.2-87.5) in Türkiye, and 13.1% (4.2-27.0) and 53% (35.5-67.8) in South Africa, respectively. Conclusions: This study showed that the clinical outcomes in Türkiye and Saudi Arabia were generally comparable with Western countries during the study period, although Saudi Arabia had lower PFS rates. Conversely, the clinical outcomes in South Africa were suboptimal, emphasizing the need for novel therapies and improved progression to stem cell transplantation. Additionally, these data may serve as a control group for future studies in these countries and inform clinical decision-making.

The International Prognostic Score and HIV status predict red cell concentrate transfusion needs in Hodgkin lymphoma.

Despite the burden of anemia among Hodgkin lymphoma (HL) patients, data evaluating red cell concentrate transfusion are limited. We retrospectively studied 285 newly diagnosed HL patients who received first-line adriamycin, bleomycin sulfate, vinblastine sulfate, and dacarbazine (ABVD) treatment at Groote Schuur Hospital, Cape Town. HIV prevalence in the cohort was 39.5% and 74.2% of patients had advanced stage HL. Patient prognosis was scored using the HL International Prognostic Score (IPS-7) and HL IPS-3. Seventy (24.6%) patients were transfused with a median of 2 (IQR 1-5) units per patient. Compared to HIV-negative patients, more HIV-positive patients were transfused (14.1% vs. 40.4%, p < .001) and received more units, median 2 (IQR 1-3) vs. 3 (IQR 2-5), p = .035. HL IPS-7 (OR 2.1, p < .001) and HL IPS-3 (OR 2.6, p < .001) were independently associated with transfusion. HL IPS-7, HL IPS-3, and HIV positivity remained associated with transfusion after adjusting for covariates. For patients with newly diagnosed HL, HL IPS-7, HL IPS-3, and HIV status predicted transfusion.

Standardised practices in the networked management of congenital hyperinsulinism: a UK national collaborative consensus.

Congenital hyperinsulinism (CHI) is a condition characterised by severe and recurrent hypoglycaemia in infants and young children caused by inappropriate insulin over-secretion. CHI is of heterogeneous aetiology with a significant genetic component and is often unresponsive to standard medical therapy options. The treatment of CHI can be multifaceted and complex, requiring multidisciplinary input. It is important to manage hypoglycaemia in CHI promptly as the risk of long-term neurodisability arising from neuroglycopaenia is high. The UK CHI consensus on the practice and management of CHI was developed to optimise and harmonise clinical management of patients in centres specialising in CHI as well as in non-specialist centres engaged in collaborative, networked models of care. Using current best practice and a consensus approach, it provides guidance and practical advice in the domains of diagnosis, clinical assessment and treatment to mitigate hypoglycaemia risk and improve long term outcomes for health and well-being.

Plasmablastic lymphoma: An update.

Plasmablastic lymphoma (PBL) is a highly aggressive B cell non-Hodgkin lymphoma frequently associated with immunosuppression, particularly human immunodeficiency virus (HIV) infection. Although PBL is rare globally, South Africa has a high burden of HIV infection leading to a higher incidence of PBL in the region. Laboratory features in PBL may overlap with plasmablastic myeloma and other large B cell lymphomas with plasmablastic or immunoblastic morphology leading to diagnostic dilemmas. There are, however, pertinent distinguishing laboratory features in PBL such as a plasma cell immunophenotype with MYC overexpression, expression of Epstein-Barr virus-encoded small RNAs and lack of anaplastic lymphoma kinase (ALK) expression. This review aims to provide a summary of current knowledge in PBL, focusing on the epidemiology, pathophysiology, laboratory diagnosis and clinical management.

Symptom prevalence and burden, and the risk of depression among patients with advanced cancer attending two South African oncology units.

BACKGROUND: The incidence of cancer is predicted to increase globally by 47% between 2020 and 2040, largely in low and middle-income countries. The World Health Organisation and World Health Assembly recognise palliative care as an essential component of cancer care. The evidence of palliative care needs among South African oncology patients is sparse. This study aimed to describe the prevalence and burden of symptoms and the risk of depression amongst oncology patients with stage 3 or 4 cancer. METHODS: Demographic and clinical data were collected and the Memorial Symptom Assessment Scale Short Form was used to measure the 7-day period prevalence of 28 physical and 4 psychological symptoms of patients receiving oncology care. The Centre for Epidemiological Studies Depression Scale was used to measure the risk of depression. RESULTS: A total of N = 343 patients were recruited, of which n = 229 (66.8%) had stage 4 cancer. The mean number of symptoms was 11.56 (SD = 5.86). Pain and feeling drowsy/tired were the two most prevalent symptoms. N = 66 (19.3%) were at risk of mild depression and n = 27 (7.9%) for major depression. DISCUSSION: Pain and depression persist in advanced cancer care despite the advances in policy and clinical education. Health services research must now focus on how to enact this in routine practice.

A Delphi study to guide the development of a clinical indicator tool for palliative care in South Africa.

BACKGROUND:  The South African National Policy Framework and Strategy on Palliative Care (NPFSPC) recommends that when integrating palliative care (PC) into the health system, a PC indicators tool should be used to guide clinicians to recognise a patient who should receive PC. The policy document recommends 'a simple screening tool developed for use in South Africa that would assist healthcare professionals (HCPs) to recognise patients who may have unmet palliative care needs'. AIM:  This research study sought to develop South African consensus on indicators for PC to assist clinicians to recognise a patient in need of PC. SETTING:  The South African healthcare setting. METHODS:  A Delphi study was considered suitable as a methodology to develop consensus. The methodology was based on the Conducting and REporting of DElphi studies (CREDES) guidance on Delphi studies to ensure rigour and transparency in conducting and reporting. Six different Delphi rounds were used to develop consensus. Each round allowed participants to anonymously rate statements with predefined rating scales. RESULTS:  Cognisant of the disparities in healthcare provision and access to equitable healthcare in South Africa, the expert advisory group recommended, especially for South Africa, that 'this tool is for deteriorating patients with an advanced life-limiting illness where all available and appropriate management for underlying illnesses and reversible complications has been offered'. The expert advisory group felt that disease-specific indicators should be described before the general indicators in the South African indicators tool, so all users of the tool orientate themselves to the disease categories first. This study included three new domains to address the South African context: trauma, infectious diseases and haematological diseases. General indicators for PC aligned with the original Supportive and Palliative Care Indicators Tool (SPICT) tool. CONCLUSION:  The Supportive and Palliative Care Indicators Tool for South Africa (SPICTTM-SA) is a simple screening tool for South Africa that may assist HCPs to recognise patients who may have unmet PC needs.

Combined submyeloablative and myeloablative dose intense melphalan results in satisfactory responses with acceptable toxicity in patients with multiple myeloma.

We studied in patients with multiple myeloma (MM) the efficacy, cost-effectiveness, and toxicity of a strategy of submyeloablative doses of Mel and stem cell support in the ambulatory setting, followed by a standard myeloablative dose transplant. Patients with recently diagnosed symptomatic MM received dexamethazone to induce clinical response. Cytokine mobilized peripheral blood progenitor cells (PBPC) were split into 2 aliquots and cryopreserved. Patients then received Mel 100 mg/m(2) (Mel100) and infusion of the first PBPC aliquot in an ambulatory facility. Individuals received standard neutropenia prophylaxis and no growth factor support, but were seen regularly at the clinic until recovery. The cost of this step was calculated in a cohort of 23 patients where information for the expenditure was available. Six months later patients were conditioned in the hospital with Mel 200 mg/m(2) (Mel 200) followed by nfusion of the second aliquot. This study tested the cost, effectiveness, and the toxicity of out-patient-based transplantation, as well as the rate of response (complete remission [CR], very good partial remission [VGPR], partial remission [PR], and stable disease [SD]) and overall survival (OS) of this strategy. Twenty-six female and 16 male patients, with a median age of 53 years (range: 33-68 years) and median Salmon & Durie clinical disease stage III (range: II-III) were studied. The paraprotein was IgA in 17%, IgG in 52%, and light chains in 26%. The median harvested CD34(+) x 10(6) cells/kg was 12.03 (2.25-55.4). The median interval between the 2 transplant procedures was 239 (105-376) days. The median Karnofsky presentation score was 40%, but improved to 80% after the Mel 100 and was 90% following Mel 200. Subsequent to MEL 100 response was complete (CR) in 7 and it was VGPR in 9. Mel 100 grade 3-4 toxicity was mainly hematologic, but 15 (36%) required hospital admission for a median of 5 days. The median cost of MEL100 and corresponding supportive therapy was U.S. $2,142.35. In addition, the total median cost of those who needed admission to hospital was U.S. $6,042.78. Thus, pooling costs from patients who needed or did not need admissions the average cost of this strategy was U.S. $3,546.50 per patient. Among Mel 200 patients, except for hematologic toxicity, no patient had greater than grade 2 side effects. On completion of the program, 20 (48%) patients achieved CR, a further 14 (33%) had VGPR, whereas 6 had PR. At a median follow-up of 659 days there were 8 deaths, 1 (2%) was related to the treatment procedures and 6 from disease progression; thus, the 1000 days OS was 73%. Significant adverse factors included older age, lower presentation Hb, and lower Karnofsky %. Nonparametric testing confirmed that good performance scores and VGPR or CR were associated with more favorable outcome. Importantly, these satisfactory results were obtained in the absence of the new biologic cell modifiers. Mel 100 was well tolerated in the outpatient setting and the overall strategy seems to be effective in inducing durable responses with acceptable toxicity.

The need for nationally accepted guidelines for undergraduate nuclear medicine teaching in MBChB programmes in South Africa.

According to the South African Health Professions Act No. 56 of 1974, specific skills outcomes of MBChB programmes are that a medical graduate must be able to utilise diagnostic aids, interpret findings and make diagnoses. Imaging techniques are an integral part of the numerous diagnostic and therapeutic aids used in contemporary medical practice; however, in South Africa, no formal directives exist to guide programme directors or nuclear medicine departments regarding an appropriate undergraduate nuclear medicine educational module. As of 2013, six South African schools of medicine are involved in undergraduate nuclear medicine teaching, in which it forms part of clinical modules taught at varying stages in the academic curriculum. Against this backdrop is the inequitable distribution of nuclear medicine resources, training facilities and staffing in the local state health sector. Inadequate undergraduate teaching and provincial differences in nuclear medicine service provision suggest that many clinicians and graduating medical students are unaware of how radionuclide techniques can facilitate patient management. This high level of imaging illiteracy has been associated with lack of patient referral, poor quality and inadequate referral, poor knowledge of radiation doses and poor awareness of radiation risks. Here we highlight the challenges of undergraduate nuclear medicine teaching in South Africa, emphasising the need for the implementation of guidelines for undergraduate nuclear medicine education. Employing nationally accepted guidelines for undergraduate nuclear medicine teaching in South African MBChB programmes will contribute to the effective utilisation of nuclear medicine and molecular imaging as a diagnostic and therapeutic modality by newly qualified medical practitioners.