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.

Open globe injuries in patients seen at Groote Schuur Hospital, Cape Town, South Africa.

BACKGROUND: Ocular trauma accounts for a significant proportion of admissions to the eye ward at Groote Schuur Hospital (GSH), Cape Town, South Africa. There are few published studies on ocular trauma in South Africa. Some studies elsewhere have shown an association between open globe injuries and recent alcohol use, but no such study has been conducted in this country. OBJECTIVES: To identify causes of and outcomes after open globe injuries at GSH, with emphasis on the association between assault and alcohol use as well as the relationship, if any, between victim and assailant. METHODS: This was a prospective case series of all adult patients admitted to GSH with open globe injuries over a 2-year period. Ocular findings were recorded with a minimum 3-month follow-up period. RESULTS: There were 249 open globe injuries. Assault had occurred in 183 (73.5%), and 66 (26.5%) were accidental. In the assault-related cases, 95 (51.9%) of the assailants were reported to have used alcohol and 121 (66.1%) of the victims admitted to alcohol use prior to the assault. There was a statistically significant relationship between ethanol use and type of injury, 71.4% of assault cases overall being associated with ethanol use. In assault-related cases, the assailant was known to the victim in 113 cases (61.7%). Of the patients, 78.7% had a final acuity of <3/60 in the traumatised eye. CONCLUSION: A significant number of open globe injuries due to assault are related to ethanol abuse and occur when the victim and assailant are known to each other. Such injuries are likely to have a poor prognosis.

Efficacy and safety of nilotinib 300 mg twice daily in patients with chronic myeloid leukemia in chronic phase who are intolerant to prior tyrosine kinase inhibitors: Results from the Phase IIIb ENESTswift study.

BACKGROUND: Some patients receiving a tyrosine kinase inhibitor (TKI) for the first-line treatment of chronic phase chronic myeloid leukemia (CML-CP) experience intolerable adverse events. Management strategies include dose adjustments, interrupting or discontinuing therapy, or switching to an alternative TKI. METHODS: This multicenter, single-arm, Phase IIIb study included CML-CP patients intolerant of, but responsive to, first-line treatment with imatinib or dasatinib. All patients were switched to nilotinib 300 mg bid for up to 24 months. The primary endpoint was achievement of MR4.5 (BCR-ABL transcript level of ≤0.0032% on the International Scale) by 24 months. RESULTS: Twenty patients were enrolled in the study (16 imatinib-intolerant, 4 dasatinib-intolerant); which was halted early because of low recruitment. After the switch to nilotinib 300 mg bid, MR4.5 at any time point up to month 24 was achieved in 10 of 20 patients (50%) in the full analysis set. Of the non-hematological adverse events associated with intolerance to prior imatinib or dasatinib, 74% resolved within 12 weeks of switching to nilotinib 300 mg bid. CONCLUSION: Nilotinib 300 mg bid shows minimal cross intolerance in patients with CML-CP who have prior toxicities to other TKIs and can lead to deep molecular responses.