Prophylaxis is the new standard of care in patients with haemophilia.

Randomised controlled clinical trial evidence on prophylaxis as optimal care for patients with haemophilia was generated more than a decade ago. However, this knowledge has not translated into clinical practice in South Africa (SA) owing to many barriers to prophylaxis. These include the high treatment burden imposed by prophylaxis (frequent injections two to four times a week), the need for intravenous access to administer replacement clotting factor therapies, and the higher volume of clotting factor required compared with episodic treatment. The recently introduced non-factor therapies in haemophilia care have addressed many of these barriers. For example, emicizumab, which is currently the only globally approved non-factor therapy, can be administered subcutaneously less frequently (weekly, fortnightly or every 4 weeks) and has led to global adoption of prophylaxis as the standard of care in haemophilia by the bleeding disorders community. Haemophilia A is the most prevalent clotting factor deficiency in SA, with >2 000 people diagnosed to date. However, only a few of these patients are currently on prophylaxis. In this 'In Practice' article, we review the rationale for prophylaxis, outline its goals and benefits, and provide evidence-based guidance on which haemophilia patients should be prioritised for emicizumab prophylaxis. This consensus guidance facilitates the adoption of prophylaxis as a national policy and the new standard of care in haemophilia in SA.

A kinetic and thermodynamic investigation into the removal of methyl orange from wastewater utilizing fly ash in different process configurations.

The removal of methyl orange using coal fly ash, which is a widely available low-cost adsorbent, has been investigated. Adsorption studies for dye removal were conducted using various configurations such as batch, column and heap adsorption at various temperatures and adsorbent dosages at neutral pH. The Langmuir, Freundlich and Tempkin isotherm models were used to describe the process. The Freundlich model best represented the adsorption. Kinetic studies show the adsorption followed pseudo-second-order kinetics. Thermodynamic studies show that the process is spontaneous, endothermic and random. Column configuration was found to be the most efficient with a dye removal percentage of 99.95%, followed by heap adsorption at 99.25% removal and lastly batch configuration with 96.68% removal. Economic analysis shows that column operation would be the most effective for practical implementation.

Home therapy for inherited bleeding disorders in South Africa: Results of a modified Delphi consensus process.

BACKGROUND: Optimal care of patients with inherited bleeding disorders requires that bleeding episodes are treated early, or still better prevented, through extension of patient care beyond hospital-based treatment to home-based therapy. In South Africa (SA), adoption of home therapy is variable, in part owing to lack of consensus among healthcare providers on what constitutes home therapy, which patients should be candidates for it, how it should be monitored, and what the barriers to home therapy are. OBJECTIVES: To conduct a modified Delphi process in order to establish consensus on home therapy among haemophilia healthcare providers in SA. METHODS: Treaters experienced in haemophilia care were invited to participate in a consensus-seeking process conducted in three rounds. In round 1, provisional statements around home therapy were formulated as questions and collated in a structured list. In rounds 2 and 3, evolving versions of the questionnaire were administered to participants. Consensus was defined as ≥70% agreement among the participants. RESULTS: The panel composition included an equal number of physicians and non-physicians. The participation rate was 100% through all three consensus rounds. The group reached consensus for 92% of the statements. Consensus of 100% was reached on starting home therapy in paediatric patients, requiring all patients on home therapy to sign informed consent and indemnity, and providing round-the-clock support for patients on home therapy. CONCLUSIONS: The home therapy consensus statements in this report have the potential to translate to policy on home therapy and to guide the initiation, practice and evaluation of home therapy programmes in SA.

HIV and haematopoiesis.

Human immunodeficiency virus (HIV) infection not only leads to a compromised immune system, but also disrupts normal haematopoiesis, resulting in the frequent manifestation of cytopenias (anaemia, thrombocytopenia and neutropenia). Although there is a definite association between the severity of cytopenia and HIV disease stage, this relationship is not always linear. For example, cytopenias such as thrombocytopenia may occur during early stages of infection. The aetiology of these haematological abnormalities is complex and multifactorial, including drug-induced impaired haematopoiesis, bone marrow suppression due to infiltration of infectious agents or malignant cells, HIV-induced impaired haematopoiesis, and several other factors. In this review, we describe the frequencies of anaemia, thrombocytopenia and neutropenia reported for HIV-infected, treatment-naïve cohorts studied in eastern and southern sub-Saharan African countries. We present a rational approach for the use of diagnostic tests during the workup of HIV-infected patients presenting with cytopenia, and discuss how HIV impacts on haematopoietic stem/progenitor cells (HSPCs) resulting in impaired haematopoiesis. Finally, we describe the direct and indirect effects of HIV on HSPCs which result in defective haematopoiesis leading to cytopenias.

HIV and haematopoiesis

Human immunodeficiency virus (HIV) infection not only leads to a compromised immune system, but also disrupts normal haematopoiesis, resulting in the frequent manifestation of cytopenias (anaemia, thrombocytopenia and neutropenia). Although there is a definite association between the severity of cytopenia and HIV disease stage, this relationship is not always linear. For example, cytopenias such as thrombocytopenia may occur during early stages of infection. The aetiology of these haematological abnormalities is complex and multifactorial, including drug-induced impaired haematopoiesis, bone marrow suppression due to infiltration of infectious agents or malignant cells, HIV-induced impaired haematopoiesis, and several other factors. In this review, we describe the frequencies of anaemia, thrombocytopenia and neutropenia reported for HIV-infected, treatment-naïve cohorts studied in eastern and southern sub-Saharan African countries. We present a rational approach for the use of diagnostic tests during the workup of HIV-infected patients presenting with cytopenia, and discuss how HIV impacts on haematopoietic stem/progenitor cells (HSPCs) resulting in impaired haematopoiesis. Finally, we describe the direct and indirect effects of HIV on HSPCs which result in defective haematopoiesis leading to cytopenias

Home therapy for inherited bleeding disorders in south Africa: results of a modified delphi consensus process

Background. Optimal care of patients with inherited bleeding disorders requires that bleeding episodes are treated early, or still better prevented, through extension of patient care beyond hospital-based treatment to home-based therapy. In South Africa (SA), adoption of home therapy is variable, in part owing to lack of consensus among healthcare providers on what constitutes home therapy, which patients should be candidates for it, how it should be monitored, and what the barriers to home therapy are.Objectives. To conduct a modified Delphi process in order to establish consensus on home therapy among haemophilia healthcare providers in SA.Methods. Treaters experienced in haemophilia care were invited to participate in a consensus-seeking process conducted in three rounds. In round 1, provisional statements around home therapy were formulated as questions and collated in a structured list. In rounds 2 and 3, evolving versions of the questionnaire were administered to participants. Consensus was defined as ≥70% agreement among the participants.Results. The panel composition included an equal number of physicians and non-physicians. The participation rate was 100% through all three consensus rounds. The group reached consensus for 92% of the statements. Consensus of 100% was reached on starting home therapy in paediatric patients, requiring all patients on home therapy to sign informed consent and indemnity, and providing round-the-clock support for patients on home therapy.Conclusions. The home therapy consensus statements in this report have the potential to translate to policy on home therapy and to guide the initiation, practice and evaluation of home therapy programmes in SA

DFT and CV data of 4-phenyl-substituted dichloro(bis{2-[1-(phenyl)-1H-1,2,3-triazol-4-yl-κN3]pyridine-κN})iron(II) coordination compounds.

The data presented in this paper are related to the research article entitled "Synthesis, characterisation and electrochemistry of eight Fe coordination compounds containing substituted 2-(1-(4-R-phenyl-1H-1,2,3-triazol-4-yl)pyridine ligands, R=CH3, OCH3, COOH, F, Cl, CN, H and CF3." (Conradie et al., 2019) [1]. This paper presents electrochemical and density functional theory data of 4-phenyl-substituted dichloro(bis{2-[1-(4-R-phenyl)-1H-1,2,3-triazol-4-yl-κN3]pyridine-κN})iron(II) compounds, containing differently substituted 2-(1-(4-R-phenyl)-1H-1,2,3-triazol-1-yl)pyridine ligands (L2 - L9) (Tawfiq et al., 2014) [2]. Density functional theory calculated data of five different structural isomers for each compound, consistently show that the title compounds are octahedral and that the isomer with the chloride atoms, the pyridine nitrogens and the triazol nitrogens trans to each other, has the lowest energy. Natural bonding orbital (NBO) data and quantum theory of atoms in molecules (QTAIM) data of dichloro(bis{2-[1-(phenyl)-1H-1,2,3-triazol-4-yl-κN3]pyridine-κN})iron(II) show origin for the preference of the trans isomer.

Chemical and structural data of (1,2,3-triazol-4-yl)pyridine-containing coordination compounds.

The data presented in this paper are related to the research article entitled "Novel dichloro(bis{2-[1-(4-methylphenyl)-1H-1,2,3-triazol-4-yl-κN3]pyridine-κN})metal(II) coordination compounds of seven transition metals (Mn, Fe, Co, Ni, Cu, Zn and Cd)" (Conradie et al., 2018) [1]. This paper presents characterization and structural data of the 2-(1-(4-methyl-phenyl)-1H-1,2,3-triazol-1-yl)pyridine ligand (L2) (Tawfiq et al., 2014) [2] as well as seven dichloro(bis{2-[1-(4-methylphenyl)-1H-1,2,3-triazol-4-yl-κN3]pyridine-κN})metal(II) coordination compounds, [M(L2)2Cl2], all containing the same ligand but coordinated to different metal ions. The data illustrate the shift in IR, UV/VIS, and NMR (for diamagnetic complexes) peaks when L is coordinated to the metals, as well as the influence of the different metals on the peak positions. Solid state structural data is presented for M = Ni and Zn, while density functional theory calculated energies, structures and optimized coordinates are provided for the lowest energy cis and trans conformations for L2 as well as [M(L2)2Cl2] with M = Mn, Fe, Co, Ni, Cu, Zn and Cd.

Dual-Energy X-Ray Absorptiometry for Measurement of Phalangeal Bone Mineral Density on a Slot-Scanning Digital Radiography System.

OBJECTIVE: In this paper, we assess the feasibility of using two detectors in a slot-scanning digital radiography system to acquire images for measuring bone mineral density (BMD) of the middle phalanx of the middle finger using dual-energy X-ray absorptiometry (DXA). METHODS: Simulations were used to evaluate the spectral separation of the low- and high-energy spectra and detective quantum efficiency was used for assessing image quality. Scan parameters were chosen to optimize spectral separation, image quality, and radiation dose. We introduce the measurement of volumetric BMD (vBMD) using basis material decomposition. We assess the accuracy of our methods by comparing measurements taken using bone images against reference data derived from subsequent incineration of the bones. In vivo scans were conducted to evaluate the system precision (repeatability) and agreement with a clinical densitometer. RESULTS: Average errors for bone mineral content (BMC), areal BMD (aBMD), and vBMD were 4.85%, 5.49%, and 12.77%, respectively. Our system had good agreement with a clinical densitometer based on concordance correlation coefficient values of 0.92 and 0.98 for aBMD and BMC, respectively. Precision studies yielded coefficient of variation (CV) values of 1.35% for aBMD, 1.48% for BMC, and 1.80% for vBMD. The CV values of all measurements were within 2%, indicating that the methods have clinically acceptable precision. CONCLUSION: We conclude that our techniques yield bone measurements with high accuracy, clinically acceptable precision, and good agreement with a clinical densitometer. SIGNIFICANCE: We have shown the clinical potential of phalangeal DXA measurements of aBMD and vBMD on a slot-scanning digital radiography system.

An auditory profile of sclerosteosis.

Objective: To characterise auditory involvement secondary to excessive craniotubular bone growth in individuals with sclerosteosis in South Africa. Methods: This cross-sectional study assessed the auditory profile of 10 participants with sclerosteosis. An auditory test battery was used and results for each ear were recorded using descriptive and comparative analyses. Results: All participants presented with bilateral, mixed hearing losses. Of the 20 ears, hearing loss was moderate in 5 per cent (n = 1), severe in 55 per cent (n = 11) and profound in 40 per cent (n = 8). Air-bone gaps were smaller in older participants, although the difference was not statistically significant (p > 0.05). Computed tomography scans indicated pervasive abnormalities of the external auditory canal, tympanic membrane, middle-ear space, ossicles, oval window, round window and internal auditory canal. Narrowed internal auditory canals corresponded to poor speech discrimination, indicative of retrocochlear pathology and absent auditory brainstem response waves. Conclusion: Progressive abnormal bone formation in sclerosteosis involves the middle ear, the round and oval windows of the cochlea, and the internal auditory canal. The condition compromises conductive, sensory and neural auditory pathways, which results in moderate to profound, mixed hearing loss.

Combined ultrasonic and bioleaching treatment of hospital waste incinerator bottom ash with simultaneous extraction of selected metals.

The mineralogy, as well as elemental composition, of the incinerated hospital waste (HW) ashes are not well known and need to be investigated for the safe handling and disposal of such ash. A study was conducted to investigate the chemical composition, mineralogy and bioleaching of selected metals from incinerated HW bottom ash using Aspergillus niger under the combined effect ofultrasonic radiation. Different techniques were utilized to determine the elemental composition (Electron Dispersive X-ray Spectroscopy [EDX], atomic absorption spectrophotometry, inductively coupled plasma-optical emission spectroscopy, ultraviolet-visible light spectrophotometer) and mineralogy (X-ray Diffraction) of the raw sample, as well as the bioleached samples. Chemical leaching tests were performed to determine the effect of different organic acids on metals dissolution. Microbes were tested for acid production and leaching capabilities of selected metals from medical waste (MW) bottom ash. Wet chemical and EDX analyses showed that the ash was enriched with metallic elements like Na, K, Ca, Fe and Al with a concentration range of 22-115 (g/kg). Furthermore, the ash contained heavy metals such as Cu, Cr, Ni, Sn and Ti in the range of 0.51-21.74 (mg/kg). Citric and oxalic acids generated by fungi could be important leaching agents acting to dissolve these metals. Under ultrasonic treatment, metals dissolution by the acidic metabolites was at its maximum after just 9 d of leaching. The results showed that the dissolution of metals was much higher in citric and oxalic acid than with other acids. Extraction of metals from incinerated MW ash indicated that this ash may be a potential source of metals in the future.

Structural vascular disease in Africans: Performance of ethnic-specific waist circumference cut points using logistic regression and neural network analyses: The SABPA study.

A recently proposed model for waist circumference cut points (RPWC), driven by increased blood pressure, was demonstrated in an African population. We therefore aimed to validate the RPWC by comparing the RPWC and the Joint Statement Consensus (JSC) models via Logistic Regression (LR) and Neural Networks (NN) analyses. Urban African gender groups (N=171) were stratified according to the JSC and RPWC cut point models. Ultrasound carotid intima media thickness (CIMT), blood pressure (BP) and fasting bloods (glucose, high density lipoprotein (HDL) and triglycerides) were obtained in a well-controlled setting. The RPWC male model (LR ROC AUC: 0.71, NN ROC AUC: 0.71) was practically equal to the JSC model (LR ROC AUC: 0.71, NN ROC AUC: 0.69) to predict structural vascular -disease. Similarly, the female RPWC model (LR ROC AUC: 0.84, NN ROC AUC: 0.82) and JSC model (LR ROC AUC: 0.82, NN ROC AUC: 0.81) equally predicted CIMT as surrogate marker for structural vascular disease. Odds ratios supported validity where prediction of CIMT revealed -clinical -significance, well over 1, for both the JSC and RPWC models in African males and females (OR 3.75-13.98). In conclusion, the proposed RPWC model was substantially validated utilizing linear and non-linear analyses. We therefore propose ethnic-specific WC cut points (African males, ≥90 cm; -females, ≥98 cm) to predict a surrogate marker for structural vascular disease.

Establishing a harmonized haemophilia registry for countries with developing health care systems.

Over recent decades tremendous progress has been made in diagnosing and treating haemophilia and, in resource-rich countries, life expectancy of people with haemophilia (PWH) is now close to that of a healthy person. However, an estimated 70% of PWH are not diagnosed or are undertreated; the majority of whom live in countries with developing health care systems. In these countries, designated registries for people with haemophilia are often limited and comprehensive information on the natural history of the disease and treatment outcomes is lacking. Taken together, this means that planning efforts for future treatment and care of affected individuals is constrained in countries where it is most needed. Establishment of standardized national registries in these countries would be a step towards obtaining reliable sociodemographic and clinical data for an entire country. A series of consensus meetings with experts from widely differing countries with different health care systems took place to discuss concerns specific to countries with developing health care systems. As a result of these discussions, recommendations are made on parameters to include when establishing and harmonizing national registries. Such recommendations should enable countries with developing health care systems to establish standardized national haemophilia registries. Although not a primary objective, the recommendations should also help standardized data collation on an international level, enabling treatment and health care trends to be monitored across groups of countries and providing data for advocacy purposes. Greater standardization of data collation should have implications for optimizing resources for haemophilia care both nationally and internationally.

The benefits of Fischer-Tropsch waxes in synthetic petroleum jelly.

This article is an introduction and general discussion regarding the use of Fisher-Tropsch wax in petroleum jelly applications. Traditionally, petroleum jelly is prepared from a blend of microwax, paraffin wax and mineral oil that are all derived from crude oil. Sasol Wax has successfully prepared a petroleum jelly based on predominantly to fully synthetic Fisher-Tropsch wax. Sasol Wax was awarded a patent P53898ZP00-29 November 11 for a predominantly to fully synthetic petroleum jelly based on Fisher-Tropsch wax blends. The benefits of Fisher-Tropsch wax discussed in this article include the absence of aromatic compounds and polycyclic aromatic compounds in Fisher-Tropsch wax as well as the sustainable production that is possible with Fisher-Tropsch wax, as opposed to paraffin wax that may be affected by the closure of group I Base Oil plants. This article will be the first in a series of articles from the same authors, and follow-up articles will include solid-state nuclear magnetic resonance and crystallization studies to determine the influence of predominantly synthetic waxes on petroleum jelly network structures compared with more traditional mineral oil-derived petroleum jellies, final product performance and stability of synthetic petroleum jelly used in, for example, personal care lotions or creams. The influence of oxygenated compounds and product safety and rheological properties (including primary skin feel upon application and secondary skin feel after application) of synthetic petroleum jellies compared with traditional mineral oil-derived petroleum jellies are discussed.

Dissolution kinetics of quicklime in various organic solvents and solutions.

The rate of the dissolution of quicklime was measured in different organic solvents and solutions of methanol, ethylene glycol, glycerol and sucrose. It was found that the rate of dissolution in methanol, glycerol and sucrose was dramatically reduced compared with that in deionized water. However, little difference was measured in a solution of ethylene glycol compared with aqueous solutions. The presence of chloride ions increases the rate of dissolution in all solvents and solutions, except for ethylene glycol, where a decrease was actually observed. It was also found that the presence of sulphate ions decreases the rate in all organic solvents and solutions tested.

Cardiovascular, cortisol and coping responses in urban Africans: the SAPBA study.

OBJECTIVES: To assess the relationships between progression of target-organ damage and cardiovascular, cortisol and coping responses in black urban Africans. METHODS: Urban black African gender groups (n = 200) aged 21-62 years from the Sympathetic Activity and Ambulatory Blood Pressure in Africans study were stratified into normotensive and hypertensive groups. Resting and reactivity Finometer blood pressure, fasting sodium fluoride glucose and salivary cortisol values were obtained before and after applying the Stroop and cold pressor tests. Coping strategies were determined and high-resolution ultrasound carotid intima-media scans were done to determine progression of target-organ damage. RESULTS: A trend of high-normal resting cortisol values during sampling time 1 was demonstrated in all hypertensive men. Both hypertensive gender groups showed increased vascular responses during both mental stressors. During the cold pressor test, vascular responses predicted sub-clinical atherosclerosis in all hypertensive men, independent of sampling time. CONCLUSION: Early morning vascular responses in all the hypertensive men could have occurred secondarily to the permissive effect of cortisol on norepinephrine secretion, with subsequent α-adrenergic vasoconstriction. Their α-adrenergic vascular responses during the cold pressor test, however, predicted sub-clinical atherosclerosis, independent of sampling time and cortisol level.

Metabolic syndrome indicators and target organ damage in urban active coping African and Caucasian men: the SABPA study.

Psychosocial stress relating to an urban environment or acculturation increases the prevalence of metabolic syndrome (MetS). The objectives of this study were firstly to indicate and compare differences regarding appraisal of stress or active coping responses in urban African (n=88) and Caucasian (n=101) male teachers of South Africa, in accord with the prevalence of MetS indicators. And secondly to investigate the extent to which utilisation of active coping responses, together with MetS indicators, predict target organ damage, in these men. The Coping Strategy Indicator determined high and low active coping responses in male teachers from the Sympathetic Activity and Ambulatory Blood Pressure in Africans (SABPA) study. SABPA inclusion and exclusion criteria were used. Additionally, diabetic medication users (n=8), and participants with renal impairment (n=2) or HIV positive (n=13), were excluded. MetS indicators included glucose, triglyceride, high-density lipoprotein cholesterol, blood pressure, and waist circumference, independent of confounders (age, physical activity, gamma glutamyl transferase). Microalbuminuria and carotid intima-media thickness indicated target organ damage. More MetS indicators exceeded the IDF cut-off points in high active coping African men (14.71%) than in their Caucasian counterparts (3.33%), as determined from χ² analyses. Furthermore, stepwise regressions indicated that more MetS indicators predicted endothelial dysfunction, especially in the high active coping African men. High active coping African men showed more manifestation of MetS, compared to their Caucasian counterparts, and revealed progress towards endothelial dysfunction.

Determining the waist circumference cut off which best predicts the metabolic syndrome components in urban Africans: the SABPA study.

Various studies have shown that the relationship between waist circumference (WC) and abdominal obesity is age, gender as well as ethnicity-dependent. WC criteria for Sub Saharan Africans have not been defined by the International Diabetes Federation (IDF). The aim was to determine which WC cut off best predicted Metabolic Syndrome (MetS) in a group of urban African teachers (80 males and 93 females). We determined sphygmomanometer blood pressure, WC, glucose, high density lipoprotein cholesterol (HdL) and triglyceride (TRIG) values. The males' MetS profile was less favourable as their glucose, TRIG and blood pressure levels were higher than the proposed cut off for MetS. The females could be classified as obese, based on their mean BMI (32.78±6.36) and WC (93.48±15.68). Receiver operating characteristic (ROC) WC cut offs of 90, 91, 94 and 96 cm for the respective MetS components in males (blood pressure, HdL, glucose and TRIG) were suggested. In the females, cut offs of 92, 98, 94 and 94 cm for TRIG, blood pressure, HdL and glucose respectively, were put forward. Odds ratios revealed that increased blood pressure best predicted ROC WC in both males (OR 9.59; 95% CI 3.14-29.32) and females (OR 3.11; 95% CI 1.30-7.42) irrespective of age. We suggest that the optimal cut off point for the males be set at 90 cm, as opposed to the current 94 cm; whilst the female cut off be set at 98 cm as opposed to the existing cut off of 80 cm. Larger sample groups are recommended to justify our data.

Cardiovascular function and psychological distress in urbanised black South Africans: the SABPA study.

OBJECTIVE: The increased prevalence of cardiovascular disease risk factors in sub-Saharan Africa has increased the incidence of cardiovascular disease in this region but whether psychological distress contributes to this observed increased risk remains largely unclear. The aim of this study was to investigate the association between cardiovascular function and psychological distress in urbanised black South African men (n = 101) and women (n = 99). METHODS: Resting cardiovascular variables were obtained by making use of the Finometer device and 24-hour ambulatory blood pressure (BP) measurements with the Cardiotens apparatus. Psychological questionnaires assessed the perception of health (General Health questionnaire) and depression status (DSM-IV criteria). The resting ECG (NORAV PC-1200) was used to determine left ventricular hypertrophy (LVH) by making use of the Cornell product. Confounders included age, obesity, alcohol intake, smoking and physical activity. RESULTS: The hypertensive groups were overweight, with lower vascular compliance and higher LVH (only men) compared to the normotensive groups. In hypertensive men, perception of health (somatic symptoms) was positively associated with blood pressure, while in hypertensive women it was associated with heart rate. Major depression was associated with LVH in hypertensive men and mean arterial pressure in hypertensive women. LVH and depression showed odds ratios of 1.02 (95% CI: 0.997-1.05) and 1.15 (95% CI: 1.01-1.32), respectively, in predicting hypertension in women. CONCLUSIONS: Psychological distress was associated with higher blood pressure in hypertensive African men but also with the development of left ventricular hypertrophy in hypertensive African men and women.