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ObjectiveAntenatal anaemia is associated with increased peripartum transfusion requirement in South Africa. We studied whether HIV was associated with the response to treatment of iron-deficiency anaemia.DesignProspective cohort study.SettingHospital-based antenatal anaemia clinic in South Africa.SampleEqual-sized cohorts of pregnant women testing positive for HIV (HIV+) and testing negative for HIV (HIV-) with iron-deficiency anaemia.MethodsHaemoglobin trajectories of women with confirmed iron-deficiency anaemia (ferritin < 50 ng/ml) were estimated from the initiation of iron supplementation using mixed-effects modelling, adjusted for baseline HIV status, ferritin level, maternal and gestational ages and time-varying iron supplementation.Main outcome measuresHaemoglobin trajectories.ResultsOf 469 women enrolled, 51% were HIV+, 90% of whom were on antiretroviral therapy (with a mean CD4+ lymphocyte count of 403 cells/mm3 ). Anaemia diagnoses did not differ by HIV status. A total of 400 women with iron-deficiency anaemia were followed during treatment with oral or intravenous (6%) iron therapy. In multivariable analysis, haemoglobin recovery was 0.10 g/dl per week slower on average in women who were HIV+ versus women who were HIV- (P = 0.001), 0.01 g/dl per week slower in women with higher baseline ferritin (P < 0.001) and 0.06 g/dl per week faster in women who were compliant with oral iron therapy (P = 0.002).ConclusionsCompared with women who were HIV-, women who were HIV+ with iron-deficiency anaemia had slower but successful haemoglobin recovery with iron therapy. Earlier effective management of iron deficiency could reduce the incidence of peripartum blood transfusion.Tweetable abstractAmong pregnant women with iron-deficiency anaemia in South Africa, HIV slows haemoglobin recovery in response to oral iron therapy.

Depot-medroxyprogesterone acetate is a commonly used injectable contraceptive that has been associated with an increased risk of HIV acquisition. This study compares effects of depot-medroxyprogesterone acetate on immune parameters from several upper reproductive tract compartments relevant to HIV-1 susceptibility in repetitive samples from 15 depot-medroxyprogesterone acetate users and 27 women not on hormonal contraceptives. Compared with samples from unexposed women in the mid-luteal phase, depot-medroxyprogesterone acetate use was associated with: increased endocervical concentrations of MCP1 and IFNalpha2; decreased endocervical concentrations of IL1beta and IL6; increased proportions of endometrial CD4+ and CD8+ cells expressing the activation marker HLADR; increased density of endometrial macrophages; and decreased density of endometrial regulatory T cells. Unlike previous reports with samples from the vagina, we did not observe increased expression of the HIV co-receptor CCR5 on CD4+ T cells in the endocervix or endometrium. Our results indicate important differences in anatomic compartments regarding mechanisms by which depot-medroxyprogesterone acetate could be associated with increased risk of HIV acquisition, including increased recruitment of macrophages to the endometrium, decreased levels of pro-inflammatory cytokines in the endocervix possibly leading to enhanced susceptibility to viral infection, and activation of endometrial T cells.

Depot-medroxyprogesterone acetate is a commonly used injectable contraceptive that has been associated with an increased risk of HIV acquisition. This study compares effects of depot-medroxyprogesterone acetate on immune parameters from several upper reproductive tract compartments relevant to HIV-1 susceptibility in repetitive samples from 15 depot-medroxyprogesterone acetate users and 27 women not on hormonal contraceptives. Compared with samples from unexposed women in the mid-luteal phase, depot-medroxyprogesterone acetate use was associated with: increased endocervical concentrations of MCP1 and IFNalpha2; decreased endocervical concentrations of IL1beta and IL6; increased proportions of endometrial CD4+ and CD8+ cells expressing the activation marker HLADR; increased density of endometrial macrophages; and decreased density of endometrial regulatory T cells. Unlike previous reports with samples from the vagina, we did not observe increased expression of the HIV co-receptor CCR5 on CD4+ T cells in the endocervix or endometrium. Our results indicate important differences in anatomic compartments regarding mechanisms by which depot-medroxyprogesterone acetate could be associated with increased risk of HIV acquisition, including increased recruitment of macrophages to the endometrium, decreased levels of pro-inflammatory cytokines in the endocervix possibly leading to enhanced susceptibility to viral infection, and activation of endometrial T cells.

PURPOSE:To determine if asymmetry between hips in pain or radiographic osteoarthritis (RHOA) is associated with worse pain and joint space narrowing (JSN) at baseline and longitudinally in knees contralateral to more affected hips. METHODS:We studied 279 participants in the Osteoarthritis Initiative with baseline asymmetry between hips in pain and 483 with asymmetry in RHOA none of whom had a hip replacement for ≥4 years after baseline. RHOA assessed from pelvis radiographs was categorized as none, possible or definite and hip pain on most days of a month in the past year as present/absent. Knee pain (WOMAC scale) and JSN (fixed flexion radiographs) were categorized as none, mild and moderate-severe. We compared knees contralateral and ipsilateral to more affected hips on baseline knee pain and JSN using clustered multinomial regression and on change in knee pain and JSN over 4-5 years using generalized linear and logistic estimating equations. RESULTS:Knees contralateral to painful hips had less baseline pain ("moderate-severe" vs "none", relative risk ratio [RRR]: 0.39, 95% CI = 0.27-0.57), but greater baseline JSN ("moderate-severe" vs "none", RRR: 1.62, 95% CI = 1.09-2.38) and greater worsening of pain during follow-up (P = 0.001). Knees contralateral to hips with worse RHOA had nonsignificant trends for greater baseline JSN (P = 0.10) and JSN progression (P = 0.17). CONCLUSION:These findings provide limited support for the hypothesis that early asymmetry in hip pain and RHOA is associated with worse pain and structural outcomes in knees contralateral to the more affected hip.

PURPOSE:To determine if asymmetry between hips in pain or radiographic osteoarthritis (RHOA) is associated with worse pain and joint space narrowing (JSN) at baseline and longitudinally in knees contralateral to more affected hips. METHODS:We studied 279 participants in the Osteoarthritis Initiative with baseline asymmetry between hips in pain and 483 with asymmetry in RHOA none of whom had a hip replacement for ≥4 years after baseline. RHOA assessed from pelvis radiographs was categorized as none, possible or definite and hip pain on most days of a month in the past year as present/absent. Knee pain (WOMAC scale) and JSN (fixed flexion radiographs) were categorized as none, mild and moderate-severe. We compared knees contralateral and ipsilateral to more affected hips on baseline knee pain and JSN using clustered multinomial regression and on change in knee pain and JSN over 4-5 years using generalized linear and logistic estimating equations. RESULTS:Knees contralateral to painful hips had less baseline pain ("moderate-severe" vs "none", relative risk ratio [RRR]: 0.39, 95% CI = 0.27-0.57), but greater baseline JSN ("moderate-severe" vs "none", RRR: 1.62, 95% CI = 1.09-2.38) and greater worsening of pain during follow-up (P = 0.001). Knees contralateral to hips with worse RHOA had nonsignificant trends for greater baseline JSN (P = 0.10) and JSN progression (P = 0.17). CONCLUSION:These findings provide limited support for the hypothesis that early asymmetry in hip pain and RHOA is associated with worse pain and structural outcomes in knees contralateral to the more affected hip.

Background(131)I-metaiodobenzylguanidine (MIBG) is an active radiopharmaceutical in neuroblastoma. A previous study demonstrated that MIBG could be combined with vincristine and prolonged irinotecan, although 25% of first courses had grade 3 diarrhoea. The current phase I/II study evaluated MIBG with vincristine and 5 days of higher-dose irinotecan.MethodsPatients 1-30 years old with advanced neuroblastoma were eligible. Patients received cefixime on days -1 to +6, irinotecan (50 mg m(-2) per dose IV) on days 0-4, vincristine (2 mg m(-2)) on day 0, MIBG (555 or 666 MBq kg(-1)) on day 1, and peripheral blood stem cells on day 13. UGT1A1 genotyping was performed in consenting patients.ResultsThirty-two patients (12 phase I ; 20 phase II) received 42 courses. No dose-limiting toxicities were seen during dose escalation and the recommended administered activity was 666 MBq kg(-1). Myelosuppression and diarrhoea were the most common toxicities, with grade 3 diarrhoea in 6% of first courses. Patients homozygous for UGT1A1*28 had more grade 4 thrombocytopenia (80% vs 37%; P=0.14). Responses (five complete and four partial) occurred in 9 out of 32 (28%) patients.ConclusionsMIBG (666 MBq kg(-1)) with vincristine and this irinotecan schedule is tolerable and active, with less severe diarrhoea compared with a regimen using more protracted irinotecan.

Background(131)I-metaiodobenzylguanidine (MIBG) is an active radiopharmaceutical in neuroblastoma. A previous study demonstrated that MIBG could be combined with vincristine and prolonged irinotecan, although 25% of first courses had grade 3 diarrhoea. The current phase I/II study evaluated MIBG with vincristine and 5 days of higher-dose irinotecan.MethodsPatients 1-30 years old with advanced neuroblastoma were eligible. Patients received cefixime on days -1 to +6, irinotecan (50 mg m(-2) per dose IV) on days 0-4, vincristine (2 mg m(-2)) on day 0, MIBG (555 or 666 MBq kg(-1)) on day 1, and peripheral blood stem cells on day 13. UGT1A1 genotyping was performed in consenting patients.ResultsThirty-two patients (12 phase I ; 20 phase II) received 42 courses. No dose-limiting toxicities were seen during dose escalation and the recommended administered activity was 666 MBq kg(-1). Myelosuppression and diarrhoea were the most common toxicities, with grade 3 diarrhoea in 6% of first courses. Patients homozygous for UGT1A1*28 had more grade 4 thrombocytopenia (80% vs 37%; P=0.14). Responses (five complete and four partial) occurred in 9 out of 32 (28%) patients.ConclusionsMIBG (666 MBq kg(-1)) with vincristine and this irinotecan schedule is tolerable and active, with less severe diarrhoea compared with a regimen using more protracted irinotecan.