Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia

<p>Abstract</p> <p>Background</p> <p>One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study.</p> <p>Methods/Design</p> <p>The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome.</p> <p>Discussion</p> <p>The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia.</p> <p>Trial Registration</p> <p><b>Clincaltrials.gov Identifier</b>: NCT00395915</p

Treating Depression: What Patients Want; Findings From a Randomized Controlled Trial in Primary Care

To highlight clinical and sociodemographic factors associated with patients' preference in the treatment of depression, we conducted a randomized controlled trial comparing the efficacy of selective serotonin reuptake inhibitors and interpersonal counseling in patients with a major depressive episode

Genetic diversity and antimicrobial resistance profiles of Campylobacter coli and Campylobacter jejuni isolated from broiler chicken in farms and at time of slaughter in central Italy

Aims: Genetic diversity and antimicrobial resistance of Campylobacter coli and Campylobacter jejuni were investigated along the broiler chicken production chain in central Italy. Methods and Results: Campylobacter sp. isolated from cloacal swabs in farms (n&nbsp;=&nbsp;116) and from the neck skin of chilled and eviscerated carcasses at slaughter (n&nbsp;=&nbsp;24) were identified as C. coli (n&nbsp;=&nbsp;99) and C. jejuni (n&nbsp;=&nbsp;41) by multiplex PCR. Characterization by single amplified fragment length polymorphism (s-AFLP) revealed a specific genotype of Campylobacter for each farm. Minimal inhibitory concentration showed high prevalence of fluoroquinolones (70%), tetracycline (70%) and erythromycin (30%) resistance among C. coli isolates. Campylobacter jejuni isolates showed lower prevalence of fluoroquinolone (39%) and tetracycline (10%) resistance, and all isolates were susceptible to erythromycin. The S-AFLP types of the C. coli and C. jejuni isolates were associated with their antimicrobial resistance profiles (P&nbsp;&lt;&nbsp;0\ub7001). Conclusions: The genetic diversity detected in Campylobacter isolates suggested that a specific genotype was harboured in each farm. A considerable number of C. coli isolates were resistant to erythromycin. Significance and Impact of the Study: Campylobacter coli was detected more frequently than C. jejuni in contrast to common findings for poultry. The high prevalence of 30% resistance to erythromycin in C. coli strains isolated from poultry is worrisome, as this is the first antibiotic of choice to treat human campylobacteriosis

Recommended nomenclature of epidote-group minerals

The key cation-sites M3 and A1 (and, in principle, M2) determine the root name. In both clinozoisite and allanite subgroups no prefix is added to the root name if M1 = Al. The prefixes ferri, mangani, chromo, and vanado indicate dominant Fe 3+ , Mn 3+ , Cr 3+ , and V 3+ on M1, respectively. In the dollaseite subgroup no prefix is added to the root name if M1 = Mg. Otherwise a proper prefix must be attached; the prefixes ferro and mangano indicate dominant Fe 2+ and Mn 2+ at M1, respectively. The dominant cation on A2 (other than Ca) is treated according to the Extended Levinson suffix designation. This simple nomenclature requires renaming of the following approved species: Niigataite (old) = clinozoisite-(Sr) (new), hancockite (old) = epidote-(Pb) (new), tweddillite (old) = manganipiemontite-(Sr) (new). Minor modifications are necessary for the following species: Strontiopiemontite (old) = piemontite-(Sr) (new), androsite-(La) (old) = manganiandrosite-(La) (new). Before a mineral name can be assigned, the proper subgroup has to be determined. The determination of a proper subgroup is made by the dominating valence at M3, M1, and A2 expressed as M 2+ and or M 3+ , not by a single, dominant ion (i.e., Fe 2+ , or Mg, or Al). In addition, the dominant valence on O4: X -or X 2-must be ascertained. The dominant trivalent cation on M3 determines the name, whereas the A2 cation appearing in the suffix has to be selected from among the divalent cations. (2) Allanite and dollaseite subgroups: For the sites involved in the charge compensation of a heterovalent substitution in A2 and O4 (i.e. M3 in the allanite subgroup; M3 and M1 in the dollaseite subgroup), identification of the relevant end-member formula must take into account the dominant divalent charge-compensating octahedral cation (M 2+ ) and not the dominant cation in these sites. Formal guidelines and examples are provided in order to determine a mineral &quot;working name&quot; from electron-microprobe analytical data