Impact of the first Covid-19 pandemic wave on first episode psychosis in Milan, italy.

The ongoing Corona Virus Disease 2019 (COVID-19) pandemic appears to increase risk for mental illness, either directly due to inflammation caused by the virus or indirectly due to related psychosocial stress, resulting in the development of both anxious-depressive and psychotic symptoms. The purpose of the present study was to assess the frequency and characteristics of all patients with First Episodes Psychosis (FEP) without COVID-19 infection hospitalized in the first four months since lockdown in Milan. We recruited sixty-two patients hospitalized between March 8 to July 8, 2020 versus those first  hospitalized in the same period in 2019. The two subgroups were compared for sociodemographic variables and clinical characteristics of the episodes. Patients with FEP in 2020 were significantly older than patients with FEP in 2021, and presented with significantly less substances abuse. Interestingly, patients presenting with FEP in 2020 were significantly older than patients with FEP in 2019. These data are compatible with the greater vulnerability to stressful factors during the pandemic, as well as with the greater concern regarding a possible COVID-19 infection producing brain damage causing the FEP.

A study on the bioequivalence of lithium and valproate salivary and blood levels in the treatment of bipolar disorder.

Lithium (Li) and valproate (VPA) are used in the treatment of bipolar disorder (BD), with narrow therapeutic window requiring periodic control of serum levels. This prevents intoxication, lack of efficacy due to low serum concentrations, and allows monitoring adherence. We aimed at evaluating the bioequivalence of salivary and blood levels of LI or VPA in a sample of adult BD patients. Secondarily, lithium bioequivalence was evaluated across different patients' lifespans. BD patients treated with either Li or VPA underwent contemporary standard serum and salivary measurements. Blood levels of both drugs were taken according to standard procedures. Li salivary levels were performed by an adapted potentiometric method on the AVL9180 electrolyte analyzer. VPA salivary levels were taken with an immune-assay method with turbidimetric inhibition. A total of 50 patients (38 on Li, 12 on VPA) were enrolled. Blood-saliva bioequivalence for VPA was not found due to a high variability in salivary measures. Li measures resulted in a high correlation (r=0.767, p<0.001), showing no partial correlation with age (r=0.147, p=0.380). Li salivary test is a reliable method of measuring Li availability and is equivalent to serum levels. Potential advantages of Li salivary testing are its non-invasive nature and the possibility of doing the test during the usual appointment with the psychiatrist.

Raltitrexed plus levofolinic acid and bolus/continuous infusion 5-fluorouracil on a biweekly schedule for elderly patients with advanced colorectal carcinomas.

BACKGROUND: The aim of the study was to evaluate the safety and efficacy of the raltitrexed/5-fluorouracil/levofolinic acid combination regimen as first-line chemotherapy for elderly patients with advanced/metastatic colorectal cancer. PATIENTS AND METHODS: Previously untreated patients with metastatic colorectal cancer received raltitrexed 2 mg/m(2) i.v. plus levofolinic acid and 5-fluorouracil according to the De Gramont' schedule given every 2 weeks as first-line chemotherapy. Patients were re-evaluated after six cycles and chemotherapy was continued up to tolerance or disease progression. RESULTS: Seventy patients aged >/=65 years were accrued from 11 centers between September 2001 and July 2002. According to the intention-to-treat analysis, the overall response rate was 35% (95% CI 29.5% to 40.5%) including one complete response (1%) and 24 partial responses (34%). Twenty patients (31%) showed a stabilization of disease for a tumor growth control rate of 64% (95% CI 57% to 71%). The median overall survival was 12.5 months and the median time to disease progression was 6.5 months. No toxic deaths or allergic reaction were recorded. Grade 4 toxicities were non-existent. The main hematological toxicity was grade 3 neutropenia, which occurred in 9% of patients, and grade 3 anemia in only one case, while no case of graded 3 thrombocytopenia was observed. Grade 3 non-hematological toxicities were asthenia (11%), transient increase of transaminases (10%) and diarrhea (4%). CONCLUSIONS: The results of this study suggest that the raltitrexed/5-fluorouracil/levolofinic acid combination is an effective and well tolerated regimen for the treatment of elderly patients with advanced colorectal cancer. Its ease of administration and patient's tolerance warrant further investigation over 5-fluorouracil/folinic acid regimens.

Propyl gallate increases in vitro antifungal imidazole activity against Candida albicans.

We looked at the in vitro effect of an antioxidant, propyl gallate (PG), on the antifungal activity of miconazole sulphosalicylate, econazole sulphosalicylate and ketoconazole against 40 clinical isolates of Candida albicans. The combination of imidazole and PG gave MIC values 10-150 times lower than those of imidazole alone. The optimal conditions for this enhanced activity were pH 6.2-8.0 and a fungal cell concentration lower than 3 x 10(5) cells/ml. The mechanism of the interaction between imidazole and PG is not known but may be as a result of an effect of PG on the P-450 cytochrome. Theoretically this combination could reduce the side effects of long treatment with imidazoles and lower the risk of resistance to these antifungal drugs.

Mitomycin "C" and vinorelbine as second line chemotherapy for metastatic breast carcinoma.

AIMS AND BACKGROUND: Patients with metastatic breast carcinoma resistant to first line chemotherapy may require further treatment. Results o second line chemotherapy are still largely unsatisfactory. For this reason a phase II study on the combination of mitomycin C and vinorelbine was carried out. METHODS: Forty patients with anthracycline pretreated metastatic breast cancer were treated with a combination of mitomycin C 10 mg/m2 i.v. on day 1, and vinorelbine 25 mg/m2 i.v. on days 1 and 8. This cycle was repeated every 28 days. Responses were evaluated according to the WHO criteria. RESULTS: A major objective response was recorded in 16 cases (40%; 95% confidence limits 32%-48%), with 2 patients (5%) obtaining a complete response with a median duration of 8.0+ months, and 14 (35%) a partial response with a median duration of 7.3+ months. Nine patients (23%) showed no change, and 15 progressed. Patients who did not meet the minimal required criteria to be evaluable were considered as treatment failures. Responses were seen at all sites of disease, but skin, nodal, and soft tissue lesion were more chemosensitive than liver, lung, and bone ones. The mean survival of patients with complete and partial responses was 8.9+ months, whereas that of patients with no change or progressive disease was 7.8 and 6.0 months respectively. Treatment was very well tolerated by most patients. Gastrointestinal toxicity was mild. Grade 2 leukopenia was recorder in 45% of patients, and grade 3 leukopenia in only 10%. Grade 2 thrombocytopenia was seen in 5%. Reversible mild to moderate constipation occurred in 45%, but no case of severe neurotoxicity was observed. CONCLUSIONS: Our data suggest that the combination of mitomycin C and vinorelbine is active in metastatic breast carcinoma refractory to first line chemotherapy containing anthracyclines, and may be safely administered on an outpatient basis.

A phase I-II study of cyclophosphamide, epidoxorubicin, levofolinic acid/5-fluorouracil and recombinant human granulocyte colony stimulating factor in metastatic breast carcinoma.

Thirty patients with measurable metastatic breast carcinoma were treated with a combination of cyclophosphamide 600 mg/m2 on day 1, levofolinic acid 100 mg/m2 plus 5-fluorouracil 375 mg/m2 on days 1-3, and epidoxorubicin (EDXR) in three refracted doses on days 1-3 with G-CSF rescue for 10 days. In the phase I part of the study, groups of 3 patients received EDXR 20, 25, 30, 35, and 40 mg/m2/day until the dose limiting toxicity (DLT) was reached. At the dose of 40 mg/m2/day prolonged grade 4 leukopenia, severe proctitis, and grade 3 diarrhea represented the DLT. All subsequent patients were treated at the maximal tolerated dose of EDXR (35 mg/m2/day). In the group of 18 patients treated at 35 mg/m2/day the overall response rate was 78%, with 22% CR and 56% PR. Four patients did not respond. Objective responses were seen at all tumor sites including bone and viscera, which usually are rather chemotherapy insensitive. Toxicity was generally acceptable. Although the response rate was quite high, the duration of objective tumor regression and patients' survival were not impressive. In conclusion, we do not recommend routine use of such an aggressive regimen for palliation of advanced breast cancer. Results of the present and similar studies may, however, be useful for planning of neoadjuvant or adjuvant trials with curative intent.

Head and neck carcinoma with distant metastases: a retrospective analysis of 44 cases treated with cisplatin-based chemotherapeutic regimens.

The rarity of medical reports on the chemotherapeutic management of head and neck cancer metastatic to distant organs prompted us to review the effect of cisplatin-based regimens in this clinical setting. Out of 44 eligible patients, 10 patients (23%) achieved a CR, 16 patients (36%) has a PR, 7 (16%) no change, and 11 (25%) progressed. Patients with rhinopharyngeal carcinoma showed a 69% overall response rate, while those with other head and neck carcinomas had a 54% overall response rate. No preferential site of response was detected. The difference in mean survival of responding patients between the rhinopharyngeal group and the non-rhinopharyngeal group was statistically significant (P < 0.05). Responding patients survived longer than non responders (P < 0.05 in both groups). Interestingly, 3 patients in the rhinopharyngeal cancer group survived more than 2 years from the start of chemotherapy for metastatic disease. These data strengthen the observation that rhinopharyngeal carcinoma, even with distant metastases, responds to chemotherapy better than other carcinomas arising in the head and neck region. Moreover, although survival is still dismal, cisplatin-based systemic chemotherapy seems an effective palliative treatment for metastatic head and neck cancer.

Subcutaneous recombinant-human-erythropoietin prevents chemotherapy-related anemia in patients with advanced cancer.

Nineteen patients with advanced cancer were randomly allocated to receive: (i) rhEpo 150 UI/kg subcutanously three times/week starting 24 hours after the completion of cisplatin- or carboplatin-based chemotherapy; or (ii) normal saline. There were 17 patients with advanced head and neck carcinoma and 2 patients with small cell lung cancer. Patients were monitored for hemoglobin level, hematocrit, WBC, PLT and reticulocytes. Patients who received rhEpo overall showed a 7.2 +/- 6.3% mean increase in Hb level over their pretreatment values, while control patients had a 26.4 +/- 12% decrease. This difference was statistically significant (p<0.001). No patients in the rhEpo group required transfusion, while 4 patients in the control group received packed red cell transfusion. No significant side-effects attributable to rhEpo were recorded, but 1 patient showed a transitory increase in PLT count. In conclusion, subcutaneous rhEpo may be safely administered to patients with advanced cancer and effectively prevents cisplatin- or carboplatin-related anemia.