Using an innovative mixed method methodology to investigate the appropriateness of a quantitative instrument in an African context: Antiretroviral treatment and quality of life.

The relationship between quality of life (QoL) and antiretroviral treatment (ART) has mainly been studied using quantitative scales often not appropriate for use in other contexts and without taking peoples' lived experiences into consideration. Sub-Saharan Africa has the highest incidence of HIV and AIDS yet there is paucity in research done on QoL. This research report is intended to give an account of the use of a mixed method convergent parallel design as a novice approach to evaluate an instrument's context specificity, appropriateness and usefulness in another context for which it was designed. Data were collected through a qualitative exploration of the experiences of QoL of people living with HIV or AIDS (PLHA) in Africa since being on ART, as well as the quantitative measurements obtained from the HIV/AIDS-targeted quality of life (HAT-QoL) instrument. This study was conducted in three African countries. Permission and ethical approval to conduct the study were obtained. Purposive voluntary sampling was used to recruit PLHA through mediators working in community-based HIV/AIDS organisations and health clinics. Interviews were analysed through open coding and the quantitative data through descriptive statistics and the Cronbach's alpha coefficient. A much wider range and richness of experiences were expressed than measured by the HAT-QoL instrument. Although an effective instrument for use in the USA, it was found not to be sensitive, appropriate and useful in an African context in its present form. The recommendations focus on adapting the instrument using the data from the in-depth interviews or to develop a context-sensitive instrument that could measure QoL of PLHA in Africa.

Synthesis and antitumor activity evaluations of albumin-binding prodrugs of CC-1065 analog.

An albumin-binding prodrug of the extremely potent CC-1065 analog, (+)-FDI-CBI, has been synthesized. This analog, (+)-FDI-CBIM, formed an albumin conjugate when added to human albumin in vitro. A greater amount (>3-fold) of the prodrug can be administered to animals compared to the free drug. The prodrug had significantly improved antitumor efficacy compared to the free drug in animal models using syngeneic animal tumors and human ovarian xenografted tumor cells. Antitumor drug delivery by in situ formation of drug-albumin conjugate is a promising strategy to improve antitumor efficacy.

CC-1065 analogues bearing different DNA-binding subunits: synthesis, antitumor activity, and preliminary toxicity study.

CC-1065 analogues bearing different DNA-binding subunits were synthesized. A terminal C5-NO2 and -F moiety at the DNA-binding subunit increased the drug's potency and antitumor efficacy. A C5-OCH3 reduced the potency and antitumor efficacy. Compound (+/-)-7, bearing a trans double bond, had increased antitumor efficacy. A preliminary toxicity study indicated that terminal C5-OCH3 and -acetamido moieties at the DNA-binding subunit caused delayed death in mice.

Health maintenance and low socio-economic status: A family perspective.

The socio-economic status of people has a profound influence on health, as higher rates of morbidity and mortality are reported for individuals with lower socio-economic status. Due to the increased burden of disease, research exploring how families maintain their health in a low socio-economic situation is an urgent priority. The objective of the study was to gain an understanding of the reality families are confronted with in terms of their health due to their socio-economic status. The study was contextual, qualitative and exploratory using purposive sampling methods. The sample size was governed by data saturation and realised as 17 families (n=17). The participants for the study were families residing in Soshanguve Extension 12 and 13, South Africa. The data collection method was self-report using a semi-structured interview. Content analysis was done according to Tesch's approach using open coding. Five themes based on the theoretical basis of the study, including age, sex and genetic constitution, individual lifestyle factors, social and community networks, living and working conditions and general socio-economic status were used. Maintaining the health of people living in a physically and psychosocially disadvantaged position requires a different approach from registered professional nurses. No community-specific intervention can be planned and implemented to reduce the burden of communicable and non-communicable disease in the community without evidence based on a family perspective.

Caring during clinical practice: Midwives' perspective.

BACKGROUND: Caring forms the core of nursing and midwifery. Despite caring being an important emotional aspect of midwifery and nursing, there are general public complaints about uncaring behaviour in midwifery. Therefore, there is a need to explore caring from midwives' point of view with the hope of identifying solutions and recommendations for midwifery practice. Furthermore, the study aimed to stimulate debate and discussion about the caring behaviour of midwives. OBJECTIVE: To explore caring during clinical practice as perceived and experienced by midwives. METHOD: The study was contextual, exploratory and qualitative. The participants were midwives working in state and private hospitals in Tshwane, South Africa where BTech II and III midwifery learners were allocated for work integrated learning (WIL). Data collection was carried out through self-report using a questionnaire and focus group. Questionnaires were distributed to 40 midwives at private and state hospitals in Tshwane. This was followed by two focus group sessions to ensure that data is enriched. The hermeneutic interpretive approach was used to analyse data, and analysis continued until saturation. RESULTS: Themes of caring and uncaring related to patient care and midwives emerged. The findings illustrated that the midwives had excellent theoretical knowledge of caring, but some of them did not display caring behaviour during clinical practice. CONCLUSION: Some of the midwives did not display caring behaviour. Implication for practice was provided based on the research findings. Recommendations included measures of improving caring behaviours during midwifery practice.

Synthesis and evaluation of antibacterial activities of andrographolide analogues.

Andrographolide (Andro), the main active component of the herb Andrographis paniculata, has been used for many years to treat a variety of diseases including bacterial and viral infections. Andro was recently reported to act by inhibiting the bacterial quorum sensing system. We have synthesized several Andro analogues and investigated their antibacterial activity and mechanism of action. The new compounds were found to be much more potent than the parent Andro in inhibiting bacterial growth and quorum sensing system. Compounds 5 and 7 significantly reduced virulence factor production. Compound 7 completely inhibited Pseudomonas aeruginosa (P. aeruginosa) biofilm formation, and exhibited synergistic activity with conventional antibiotics. These findings suggest that compound 7 may be the basis for future drug development to combat the unmet needs of virulence factor production, biofilm formation and antibiotic resistance.

Caring as a Core Concept in Educating Midwifery Learners: A qualitative Study

Caring is the core business of nursing and midwifery; involving a relationship in which the carer is committed to the needs of the one being cared for (Mason-Whitehead; Mcintosh; Bryan et Mason). Caring is the emotion which drives a midwife to care; the motive aimed at assisting someone to grow and self-actualise (Watson). The concern in midwifery is that irrespective of caring being central to the midwifery profession; caring taught in theoretical learning does not always translate into caring behaviour in practice. A qualitative exploratory study examined how midwifery educators impart the skill of caring during theoretical learning and clinical accompaniment; in order to respond to the general complaint made both locally and internationally that midwives are uncaring. The aim was to explore caring during theoretical learning and clinical accompaniment from the perspective of midwifery educators. Participants in the study were midwifery educators teaching midwifery in institutions of learning in Tshwane; South Africa. The naive sketch was used to gather data; wherein one central question was asked and the educators were invited to narrate and respond. Three themes emerged: the meaning of caring; how caring was conveyed during theoretical learning; and how it was conveyed during clinical accompaniment. Although the midwifery educators expressed how they conveyed caring to the learner midwives; it was not evident how caring competencies were assessed in order to ensure caring midwives at the end of training

Simple educational intervention to improve the recovery from acute whiplash: results of a randomized, controlled trial.

OBJECTIVES: To determine if an educational intervention in the acute stage of whiplash injury may improve the recovery rate. METHODS: Consecutive subjects were randomized to one of two treatment groups: educational intervention or usual care. The intervention group received an educational pamphlet based on the current evidence. The control group did not receive these materials but received usual emergency department care and a standard nondirected discharge information sheet. Both groups underwent follow-up by telephone interview at two weeks and three months. The primary outcome measure of recovery was the patient's response to the question, "How well do you feel you are recovering from your injuries?" RESULTS: A total of 112 subjects agreed to participate. Age, gender, precollision employment level and health, initial symptoms, collision parameters, and emergency treatments were similar between the groups. At two weeks postcollision, 7.3% in the treatment group reported recovery compared with 8.8% in the control group (absolute risk difference, -1.5%; 95% confidence interval = -12.6% to 9.7%). At three months postcollision, 21.8% in the treatment group reported complete recovery compared with 21.0% in the control group (absolute risk difference, 0.8%; 95% confidence interval = -14.4% to 16.0%). At three months, there were no clinically or statistically significant differences between groups in severity of remaining symptoms, limitations in daily activities, therapy use, medications used, lost time from work, or litigation. CONCLUSIONS: An evidence-based educational pamphlet provided to patients at discharge from the emergency department is no more effective than usual care for patients with grade 1 or 2 whiplash-associated disorder.

Synthesis and preliminary cytotoxicity of nitrogen mustard derivatives of distamycin A.

Distamycin and nitrogen mustard conjugates, in which the nitrogen mustard unit was coupled to the C-terminus of the pyrrole, were synthesized. The switching of the nitrogen mustard unit from the N-terminus to the C-terminus did not compromise the compound's cytotoxicity. Compound 3, bearing three pyrrole units, was highly toxic to human K562 leukemia cells in vitro with an IC(50) value of 0.03 microM. Addition of a trans double bond to the molecule had little effects on cytotoxicity.

Synthesis and preliminary cytotoxicity study of glucuronide derivatives of CC-1065 analogues.

Glucuronide derivatives of CBI-bearing CC-1065 analogues have been synthesized, and their cytotoxicities tested against U937 leukemia cells. The new compounds show potent antitumor activity in vitro. Compounds 1 and 2, and their corresponding glucuronides 3 and 4 have IC(50) values of 0.6, 0.1, 1.4 and 0.6 nM, respectively. Glucuronide 3 is approximately 2-fold less toxic than its hydroxyl counterpart 1, and glucuronide 4 is approximately 6-fold less toxic than its hydroxyl counterpart 2. Glucuronides 3 and 4 may have limited use in the ADEPT approach. However, they may be used as antitumor agents in a conventional way.

Synthesis and preliminary cytotoxicity study of a cephalosporin-CC-1065 analogue prodrug.

BACKGROUND: Antibody-directed enzyme prodrug therapy (ADEPT) is a promising new approach to deliver anticancer drugs selectively to tumor cells. In this approach, an enzyme is conjugated to a tumor-specific antibody. The antibody selectively localizes the enzyme to the tumor cell surface. Subsequent administration of a prodrug substrate of the enzyme leads to the enzyme-catalyzed release of the free drug at the tumor site. The free drug will destroy the tumor cells selectively, thus, reducing side effects. RESULTS: A CC-1065 analogue was conjugated to a cephalosporin affording prodrug 2. The prodrug and its corresponding free drug, 1, have IC50 values of 0.9 and 0.09 nM, respectively, against U937 leukemia cells in vitro. CONCLUSIONS: For the first time, a prodrug comprised of a cephalosporin and a CC-1065 analogue has been synthesized. The preliminary in vitro studies show that the prodrug was 10-fold less toxic than the free drug. Prodrug 2 has the potential to be useful in cancer treatment using the ADEPT approach.

Synthesis and cytotoxicity of a biotinylated CC-1065 analogue.

BACKGROUND: The use of pretargeting technology for cancer imaging and treatment has made significant progress in the last few years. This approach takes advantage of the fact that biotin binds strongly to proteins avidin and streptavidin. Thus, a non-toxic tumor cell specific antibody is conjugated with avidin/streptavidin, and is administered to patients. After the antibody binds to tumor cells (usually 24--48 h); a clearing agent is given to remove the residual circulating antibodies in blood. Lastly, a toxic biotin-radioisotope conjugate is administered. Due to the small size of the biotin-radioisotope molecule and tight binding between biotin and avidin/streptavidin, the biotin-radioisotope rapidly binds to tumor cells with high specificity. CC-1065 (1) is one of a few classes of extremely potent antitumor agents, and a biotinalyted CBI-bearing CC-1065 analogue is a promising candidate to be used in the pretargeting technology to treat cancer. RESULTS: A biotinalyted CBI-bearing CC-1065 analogue, 6, was synthesized. The IC50 of 6 was 0.7 nM against U937 cells. Compound 6 caused apototsis of U937 cells. CONCLUSIONS: For the first time, a biotinalyted CBI-bearing CC-1065 analogue, 6, was synthesized. The biotinylated 6 can serve as a model compound to explore the usefulness of non-radioactive small molecule anticancer drugs in the pretargeting strategy for cancer imaging and therapy.