Dropout rate during prolonged physical stress training in the military may be determined by haematological changes

A public health research paper on sustained physical training in the military leading to high drop-out rates amongst new recruits in the Zimbabwe National Army.Sustained physical training has profound effects on haematological adaptive changes and these may influence physical performance, the dropout rates and casualties in a military setting. Prompted by reports of increases in the number of dropouts during military training, the impact of haematological changes on dropout rates and physical performance was studied in 60 male Zimbabwe National Army (ZNA) recruits during 60 days of military training at the Nyanga training camp. The training programme included, among other things, bush exercises in the rugged terrain of the Nyangani range of mountains. Blood for full blood count (FBC) were collected by venepuncture in a forearm vein in a seated position two weeks pre-training (day zero). Subsequent samples were collected at seven, 30 and 60 days. FBC analyses was carried out by Sysmex K800 (Kobe, Japan) and urine samples were analyzed for urobilinogen. The results showed significant decreases in the red blood cells (RBC) and haemoglobin (Hb) (P<0.05) and (P<0.04) on day seven and day 30 respectively when compared to day zero. The persistent increase in haematocrit throughout the 60 days suggested haemoconcentration and a fall in plasma volume (PV). When compared to pre-training, granulocytes were significantly higher on day 60 than on day 30 (P<0.004). Lymphocytes and eosinophils were lower on day seven (P<0.001) when compared to day zero and (P<0.04) and (P<0.013) when compared to day 30 and 60 respectively, suggesting that the subjects had a decreased protection against infection. However, lymphocytes were higher on day 60 than on day seven (P<0.01). This observed recovery in lymphocytes on day 60 when compared to day seven and 30, suggested that acclimatization and adaptation had occurred. Of the 60 subjects, 18 percent were hospitalized [four with pulmonary TB and a hypochromasia blood picture while three had bronchopneumonia and a raised neutrophil count]. The number of dropouts was 16 (27 percent) of the 60 subjects under study. Laboratory observations showed proteinuria, a shift to the left in the myeloid series, nucleated red blood cells, platelet clumps, macrocytosis and red cell fragments. These were associated with casualties, dropouts and poor physical performance. These results suggested that severe haematological changes might be associated with poor performance, high rates of casualties and dropouts. Therefore, monitoring the trends of haematological changes at regular intervals during stress training can minimize casualties and the rates of dropouts

Efficacy and safety of once-weekly and twice-weekly bortezomib in patients with relapsed systemic AL amyloidosis: results of a phase 1/2 study

AbstractThis first prospective phase 2 study of single-agent bortezomib in relapsed primary systemic AL amyloidosis evaluated the recommended (maximum planned) doses identified in phase 1 testing (1.6 mg/m2 once weekly [days 1, 8, 15, and 22; 35-day cycles]; 1.3 mg/m2 twice weekly [days 1, 4, 8, and 11; 21-day cycles]). Among all 70 patients enrolled in the study, 44% had ≥ 3 organs involved, including 73% and 56% with renal and cardiac involvement. In the 1.6 mg/m2 once-weekly and 1.3 mg/m2 twice-weekly groups, the hematologic response rate was 68.8% and 66.7% (37.5% and 24.2% complete responses, respectively); median time to first/best response was 2.1/3.2 and 0.7/1.2 months, and 78.8% and 75.5% had response durations of ≥ 1 year, respectively. One-year hematologic progression-free rates were 72.2% and 74.6%, and 1-year survival rates were 93.8% and 84.0%, respectively. Outcomes appeared similar in patients with cardiac involvement. Among all 70 patients, organ responses included 29% renal and 13% cardiac responses. Rates of grade ≥ 3 toxicities (79% vs 50%) and discontinuations/dose reductions (38%/53% vs 28%/22%) resulting from toxicities appeared higher with 1.3 mg/m2 twice-weekly versus 1.6 mg/m2 once-weekly dosing. Both bortezomib dose schedules represent active, well-tolerated regimens in relapsed AL amyloidosis. This study was registered at www.clinicaltrials.gov as #NCT00298766

Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase III VISTA trial

[EN]The purpose of this study was to confirm overall survival (OS) and other clinical benefits with bortezomib, melphalan, and prednisone (VMP) versus melphalan and prednisone (MP) in the phase III VISTA (Velcade as Initial Standard Therapy in Multiple Myeloma) trial after prolonged follow-up, and evaluate the impact of subsequent therapies. Previously untreated symptomatic patients with myeloma ineligible for high-dose therapy received up to nine 6-week cycles of VMP (n = 344) or MP (n = 338). With a median follow-up of 36.7 months, there was a 35% reduced risk of death with VMP versus MP (hazard ratio, 0.653; P < .001); median OS was not reached with VMP versus 43 months with MP; 3-year OS rates were 68.5% versus 54.0%. Response rates to subsequent thalidomide- (41% v 53%) and lenalidomide-based therapies (59% v 52%) appeared similar after VMP or MP; response rates to subsequent bortezomib-based therapy were 47% versus 59%. Among patients treated with VMP (n = 178) and MP (n = 233), median survival from start of subsequent therapy was 30.2 and 21.9 months, respectively, and there was no difference in survival from salvage among patients who received subsequent bortezomib, thalidomide, or lenalidomide. Rates of adverse events were higher with VMP versus MP during cycles 1 to 4, but similar during cycles 5 to 9. With VMP, 79% of peripheral neuropathy events improved within a median of 1.9 months; 60% completely resolved within a median of 5.7 months. VMP significantly prolongs OS versus MP after lengthy follow-up and extensive subsequent antimyeloma therapy. First-line bortezomib use does not induce more resistant relapse. VMP used upfront appears more beneficial than first treating with conventional agents and saving bortezomib- and other novel agent-based treatment until relapse

Is antenatal antibody screening worthwhile in the Zimbabwean population

No Abstract. Central African Journal of Medicine Vol. 46 (2) 2000: pp. 38-4

Use of packed red cells in a major hospital in Harare, Zimbabwe

No Abstract. Central African Journal of Medicine Vol. 45 (3) 1999: pp. 54-5

DARATUMUMAB Anti-CD38 Monoclonal Antibody, Treatment of Multiple Myeloma

<p>CD38 is a type II transmembrane glycoprotein that is highly expressed in hematological malignancies, including multiple myeloma (MM). Therefore, CD38 is a promising target for antibody immunotherapy. Daratumumab is a human monoclonal antibody with broad-spectrum killing activity. In vitro, daratumumab induces anti-MM effects via complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis. Synergistic activity was demonstrated in vitro in combination with standard MM therapies, including bortezomib and lenalidomide. Protective bone marrow stromal cells did not influence daratumumab-induced CDC and ADCC, suggesting that daratumumab may have activity in the bone marrow microenvironment in vivo. Indeed, significant daratumumab-mediated tumor growth inhibition was shown in MM mouse xenograft models. A phase I/II clinical study is ongoing in patients with relapsed/refractory MM. This review discusses the preclinical pharmacology, pharmacokinetics and preliminary clinical efficacy of daratumumab and its potential in MM therapy.</p>