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Background No published studies have evaluated in pregnant women with HIV weight gain with different antiretroviral drug classes.Methods Data from a national cohort study were used. We compared absolute weight gain and occurrence of excessive weight gain in women with HIV who received during pregnancy integrase inhibitors (INSTI), protease inhibitors (PI), or non-nucleoside reverse transcriptase inhibitors (NNRTI). Excessive weight gain was defined according to the Institute of Medicine recommendations. Possible predictors of weight gain were assessed using univariate and multivariate analyses.Results Among 273 cases (PI: 191, NNRTI: 43, INSTI: 39), the mean weight increase was 11.3 kg, and 25.4% of the mothers had an excessive weight increase. No significant differences were found among the three treatment groups for absolute weight increase, occurrence of excessive weight gain, infant birthweight, and other pregnancy and laboratory outcomes. The comparisons of individual drugs, although based on a limited number of cases, suggested no major differences. A significant positive correlation was found between weight gain and CD4+T-cell increase during pregnancy. In multivariate analyses, drug class and nucleoside backbone were not associated with absolute or excessive weight increase. Excessive weight increase was significantly associated with week of delivery (adjusted odds ratio: 1.74, 95% CI 1.15, 2.63), obesity (5.21, 95% CI 1.85, 14.64), overweight (7.95, 95% CI 3.26, 19.39), recent substance use (5.96, 95% CI 1.13, 31.40) and fasting 2nd trimester hyperglycaemia (3.94, 95% CI 1.14, 13.65).Conclusions No significant differences in absolute weight change or occurrence of excessive weight gain were found among women with HIV who received during pregnancy different classes of antiretroviral drugs.

We analysed the characteristics of the pregnancies with a previously undetected HIV infection in a national observational study of pregnant women with HIV in Italy. In a total of 443 pregnancies with available date of HIV diagnosis, 118 were characterized by a previously undetected HIV infection (26·6%, 95% CI 22·5–30·8). The following factors were independently associated with this occurrence in a multivariate analysis (adjusted odds ratios; 95% CIs): foreign nationality (5·1, 2·8–9·3); no pre-conception counselling (35·9, 4·8–266·1); first pregnancy (2·1, 1·2–4·0); asymptomatic status (6·8, 1·5–30·6). Women with previously undetected infection started antiretroviral treatment significantly later during pregnancy (P<0·001). Missed diagnosis was responsible for one case of transmission. A high rate of previously undetected HIV infection was observed. This suggests a good HIV detection during pregnancy, but also the need to reinforce HIV testing strategies among women of childbearing age. We identified some determinants which may be considered for intervention measures.

In the present multicentre randomized phase II trial, the activity and toxicity of three platinum-based combination regimens for the treatment of advanced non-small-cell lung cancer (NSCLC) were evaluated. The three regimens were: MVP (mitomycin-C 6 mg m(-2) on day 1, vindesine 3 mg m(-2) on days 1 and 15, and cisplatin 80 mg m(-2) on day 1 every 28 days), PIN (cisplatin 80 mg m(-2) day 1, ifosfamide 3 g m(-2) day 1 and vinorelbine 25 mg m(-2) day 1 and 8 every 21 days) and CaN (carboplatin 350 mg m(-2) day 1 and vinorelbine 25 mg m(-2) days 1 and 8 every 28 days). A total of 140 chemotherapy-naive patients entered the study; 49 patients were treated with MVP, 48 with PIN and 43 with CaN. Sixty-seven per cent of the patients had stage IV disease. Response rates, calculated on an 'intention to treat' basis, were as follows: MVP, 14.3% (95% CI 5.94-27.2%); PIN, 16.7% (95% CI 7.4-30.2%); and CaN, 14% (95% CI 5.3-27.9%). The overall median survivals were 256, 269 and 243 days for patients treated with MVP, PIN and CaN respectively. Myelosuppression was the most frequent toxicity: grade 3-4 leucopenia was observed in 14.3%, 25% and 18.6% of patients treated with MVP, PIN and CaN respectively. This multicentre phase II randomized trial shows that MVP, PIN and CaN can be administered on an outpatient basis with acceptable toxicities. Unfortunately, the three regimens showed an activity significantly lower than that reported in previous single-institution phase II trials.

We present optical measurements (Shadow and Schlieren pictures) of a 12.5 Joule exploding wire experiment. After performing a large number of shots some sort of time evolution can be reconstructed from the pictures. The pictures were taken during the dark phase (zero current) and the plasma phase. Although the electrical signals are quite reproducible from shot to shot (allowing a good time correlation and indicating that the global dynamics is reproducible) we observed that the individual details are quite different, probably due to the non-uniformity of the wire. We observed a uniform expansion (the volume increases almost linearly with time) with the presence of surface instabilities and there is no evident difference in the density distribution between the dark and the plasma phases. Finally, we derive a mean radius and velocity evolution with time and an approximate energy balance.

We have performed a phase I study In MBC patients (pts) to determine the maximum tolerated dose (MTD) of P to be administered in association with E at a fixed dose of 90mg/sqm. P was given i.v. by a 3hrs infusion, immediately after E, starting from a dose of 135mg/smq and escalating by 20mg/sqm for each dose level until DLT. DLT was defined as follows: absolute neutrophil count (ANC) <500μL for 7 days or <100μL for 3 days, febrile neutropenia or any G3 non hemalologic toxicity. G-CSF was allowcd to accelerate recovery of G4 neutropenia lasting more than 3 days. An Holter EKG was performed at each course and the left ventricular ejection fraction (EF) was evaluated every 2 courses by echo-doppler. 32 patiens with the following characteristics have been treated: median age 54 (34–66) yrs; median (ECOG) PS 0 (0-1); 84% of the patients had failed adjuvant chemotherapy (including anthracycline in 14 cases), The dominant metastatic sites were: viscera 20 pts (62%). sort lissue 11 pts (34%), and bone 1 pts (3%). The DLT is febrile neutropenia which occurred at the first course in 2 8 pts patients treated with P 225mg sqm. A total of 176 courses have been administered; a G4 neutropenia occurred in 66% of the courses, lasting a median of 4 days (range 1–8). G-CSI (300μg die) was given in 34% of the courses for a median of 5 days range (2-12). Most significant non hematologic toxicities were: a G 1-2 mucositis in 29% of the courses and a G 1-2 peripheral neuropathy in 56% of the pts. The cardiac toxicity was low: only 2 pts showed a drop of the EF below 50% after 6 courses; no sign of congestive heart failure was observed. The overall response rate is: 76% with 14% of complete responses (95% C.I. 56-90%). In conclusion we have demonstrated that the combination of E and P is feasible. devoid of cardiac toxicity and active in a population of pts who failed adjuvant chemotherapy. Our recommended phase II dose of P is 200mg/sqm.

We have started a phase I study in ABC and AOC pts to determine the maximum tolerated dose (MTD) of P to be given with E. Up to now, 21 pts (10 MBC and II AOC) have been accrued. Patient characteristics: median age 59 y (36–71); median PS (ECOG) 0 (0–1); all MBC pts had received adjuvant chemotherapy and all AOC pts were pretreated with cisplatin regimens; 18 pts were pretreated with a cumulative E dose of 360mg/sqm. P was given i.v. by a 3 hrs c.i. at 135mg/sqm (9 pts); 155mg/sqm (6 pts); 175mg/sqm (5 pts) and 200mg/sqm (1 pt). E was given at a fixed dose of 90mg/sqm i.v. bolus. Courses were repeated every 21 days. All the pts have been submitted to a clinical and instrumental cardiological monitoring including: physical examination, EKG, EKG Holter, late potentials, transoesofageal electrophysiologic study, cardiac echo-doppler. 81 courses have been administered: 46 at level 1, 26 at level 2, 12 at level 3 and 1 at level 4. The main side effects was: G4 neutropenia in 57% of the courses lasting a median of 4 days (1–6). No cardiac toxicity has been observed; the median left ejection fraction was 59% at study entry and 54% after 7 courses (total cumulative dose of E=990mg/mq). Response rate was 62.5% in ABC and 44.4% in AOC. PE is an active regimen; the main toxicity is short-lasting neutropenia and the MTD has not yet been reached. The study is ongoing.

We are performing a multicentric phase II study to evaluate the activity and the toxicity of the combination regimen EPl + NVB as first line chemotherapy in ABC patients.Treatments: EPI 90mg/sqm i.v. bolus day 1, NVB 25mg/sqm i.v. day 1 and 8: the courses are repeated every 21 days. The treatment is administered on day 1 if WBC ≥ 3,500u/L and/or ANC ≥ 1,500u/L and PLT ≥ 100,000u/L. The dose of NVB on day 8 is modified as follows: G 2 neutropenia: 25% dose reduction, G 3 netropenia: 50% dose reduction, G 4 neutropenia: NVB omitted. In case of G 4 neutropenia lasting more than 72 hours or febrile neutropenia, G-CSF (300ug/die subcutaneously) is administered until recovery and a 25% dose reduction is applied in the subsequent courses.Patient characteristics: so far 30 pts have been enrolled and 63% of the pts had visceral metastases: median age 64 years (range 39–72), PS 0=15, PS 1=6, PS 2=9. A total of 121 courses have been administered, with a median of 5 courses (range 1–7) for each patient. The worst toxicities (WHO grade) observed al nadir are:TableG3(%)G–4(%)Neutropenia21.170.4Thrombocytopenia1.6Anemia/0.8Emesis2.4Mucositis4.9Diarrhoca1.6The median duration of G 4 neutropenia is 5 days (range 2–7). The doses on day 1 were reduced at 75% in 30.5% of the courses while the treatment was delayed in 14.8% of the courses. On day 8 NVB was omitted in 14.8% of the courses and reduced as 75% or 50% in 23.1% and 8% of the courses respectively. G-CSF was administered in 15.7% of the courses. Seven episodes of febrile neutropenia not requiring hospitalization have been reported.Results: 25 pts are evaluable for response: the overall response rate is 68% (95% C.I. 46.5%–85%) with 3 CR, 14 PR, 6 SD. and 2 PD. Five pts are not evaluable: 4 pts too early, 1pt worsening PS.Conclusions: EPI + VNR is a very active combination regimen in ABC: however, considering the high pecentage of neutropenia on day 8 requiring NVB dose reduction, we have modified the original schedule and NVB is now administered on day 1 and 5. The study is ongoing.