Empowering Tomorrow's Cancer Specialists: Evaluating the Co-creation and Impact of Malawi's First Surgical Oncology Summerschool.

Annually more than 1 million newly diagnosed cancer cases and 500,000 cancer-related deaths occur in Sub Saharan Africa (SSA). By 2030, the cancer burden in Africa is expected to double accompanied by low survival rates. Surgery remains the primary treatment for solid tumours especially where other treatment modalities are lacking. However, in SSA, surgical residents lack sufficient training in cancer treatment. In 2022, Malawian and Dutch specialists co-designed a training course focusing on oncologic diseases and potential treatment options tailored to the Malawian context. The aim of this study was to describe the co-creation process of a surgical oncology education activity in a low resource setting, at the same time attempting to evaluate the effectiveness of this training program. The course design was guided and evaluated conform Kirkpatrick's requirements for an effective training program. Pre-and post-course questionnaires were conducted to evaluate the effectiveness. Thirty-five surgical and gynaecological residents from Malawi participated in the course. Eighty-six percent of respondents (n = 24/28) were highly satisfied at the end of the course. After a 2-month follow-up, 84% (n = 16/19) frequently applied the newly acquired knowledge, and 74% (n = 14/19) reported to have changed their patient care. The course costs were approximately 119 EUR per attendee per day. This course generally received generally positively feedback, had high satisfaction rates, and enhanced knowledge and confidence in the surgical treatment of cancer. Its effectiveness should be further evaluated using the same co-creation model in different settings. Integrating oncology into the regular curriculum of surgical residents is recommended.

Optimizing Thiopurine Therapy in Inflammatory Bowel Disease Among 2 Real-life Intercept Cohorts: Effect of Allopurinol Comedication?

BACKGROUND: Thiopurines (azathioprine and mercaptopurine) are frequently used immunosuppressive drugs to maintain remission in patients with inflammatory bowel disease. Half of the conventional thiopurine-derivative users have to discontinue treatment within 5 years, mainly because of intolerable adverse events. Over recent years, different strategies to optimize thiopurine treatment were suggested, yet, studies describing the clinical effectiveness of these strategies remain scarce. The aims of this study were to compare tolerability and sustained clinical benefit of conventional thiopurine derivatives therapy among two 5-year real-life intercept cohorts and to assess the clinical value of specifically allopurinol cotherapy. METHODS: In this retrospective single-center cohort study, we analyzed data from patients in whom weight-based thiopurine monotherapy was initiated between 2005 and 2009 (cohort 1) or between 2010 and 2014 (cohort 2). The initiation of the second cohort was synchronic to the start of allopurinol-based optimization in our center. Optimization strategies were extracted from patient charts. RESULTS: In total, 105 patients were included (60 in cohort 1, and 45 in cohort 2). Metabolite measurement was performed in 37% versus 84% of the patients (P < 0.001). Subsequent optimization strategies were applied in 33% versus 58% of the patients because of inadequate metabolite concentrations, intolerance, or ineffectiveness (P = 0.01). Allopurinol was coadministered to therapy in 18 patients (40%) in the second cohort. Therapy was switched to thioguanine in 11 versus 6 patients (P > 0.05). Overall, total duration was longer in the second cohort (10.8 versus 34.1 months, P < 0.001). The number of ongoing thiopurine users (20% versus 49%) and sustained clinical benefit (13% versus 38%) were higher in the second cohort (both P < 0.05). This was mainly because of a decrease in hepatotoxicity after optimization (P < 0.01). CONCLUSIONS: Optimization of thiopurine therapy by the use of therapeutic drug monitoring with subsequent administration of allopurinol cotherapy successfully enhanced sustained clinical benefit and tolerability in patients with inflammatory bowel disease.

[Fever after visiting the tropics: always exclude malaria]. / Koorts na tropenbezoek: sluit malaria altijd uit.

Malaria usually begins with nonspecific symptoms which could easily be ascribed to other common febrile illnesses and hence be missed. If left untreated, it can lead to severe complicated malaria and death. We describe a case of a 43-year-old male patient with fever who recently returned from West Africa. Initially he was treated for pneumonia; however, after 4 days his symptoms deteriorated and he was diagnosed with severe complicated falciparum malaria for which he was admitted to the ICU. We advocate prompt exclusion of malaria in every patient presenting with fever in the three months following return from an endemic region, and remaining vigilant for an extended period.

Preanalytical stringency: what factors may confound interpretation of thiopurine S-methyl transferase enzyme activity?

BACKGROUND: Measurement of red blood cell thiopurine S-methyl transferase (TPMT) enzyme activity before commencing thiopurine therapy is recommended to avoid severe bone marrow suppression in TPMT-deficient patients. Patient's samples go through preanalytical transportation and storage steps before measurement. We studied patient's TPMT activity sample data to assess the effect of preanalytical variables including transportation time. METHODS: A total of 8524 TPMT enzyme activity analyses were conducted from 2002 to 2010 in a single laboratory, with samples sent from seven centres throughout New Zealand. TPMT activity was correlated with time of arrival at the reference laboratory, patient gender and age and centre of sample collection. RESULTS: The 6348 (74%) selected TPMT measurements that fulfilled selection criteria ranged from 0 to 25.8 IU/mL. Median delay to sample analysis was 42 h. Median TPMT activity was significantly lower for all centres compared with the reference centre (P < 0.001). Delay in sample arrival was significantly and independently correlated with TPMT enzyme activity (ANCOVA; P < 0.001), which showed a 0.011 (95% CI, 0.008-0.014) IU/mL decrease per extra hour of delay. After correcting for these data, one centre still had a significantly lower TPMT enzyme activity compared with the reference centre. CONCLUSIONS: There was a significant negative correlation between TPMT enzyme activity and delay from sample collection to analysis. Transportation time is therefore an important preanalytical variable influencing TPMT activity. Samples from one centre had a lower TPMT activity after correcting for transportation delay, suggesting that other factors related to sample processing may also be relevant.

Biological variation of thiopurine methyltransferase enzyme activity: when has a significant change taken place?

BACKGROUND: Thiopurine methyltransferase (TPMT) enzyme activity is measured before initiating thiopurine therapy to reduce the risk of severe drug-associated myelotoxicity in patients with low enzyme activity. TPMT activity may vary over time in relation to drug treatment and patient clinical condition. What constitutes a significant change in TPMT activity can be derived from biological variation and analytical imprecision. METHODS: A large national laboratory database was used to identify patients with three or more TPMT activity measurements. Variance of TPMT activity was analysed by determining the total coefficient of variation (CVTOT) of repeated measurements and by correlation with parameters including gender and follow-up time. Between-run analytical imprecision (CVa) was determined by replicate analysis (n = 314). RESULTS: Of 7383 patients with TPMT measurements, 136 were identified as having three or more measurements over time (range 3-14). Median CVTOT for individual patient results was 14.5% (range 2.5-36.7%). Analytical imprecision (CVa) was 10.3%. A reference change value (or critical difference) with 95% probability was calculated as 42%. Therefore, a change in measured TPMT activity above 42% should lead to considering sources of variation other than biological variation and analytical imprecision. CONCLUSIONS: TPMT enzyme activity needs to change by at least 42% to determine that a true change has taken place beyond biological variation and analytical imprecision. A single measurement of TPMT activity is sufficient for most clinical purposes.