The ANT Home Care Model in Palliative and End-of-Life Care. An Investigation on Family Caregivers' Satisfaction with the Services Provided.

The World Health Organization plan for a Decade of Healthy Ageing 2020-2030 has established some priorities in the field of palliative and end-of-life care. It states that "people require non-discriminatory access to good-quality palliative and end-of-life care" and recommends the "implementation of strategies for the provision of information, training, respite and support for informal caregivers". The priorities described are in line with the home care services that National Tumor Assistance (ANT) Foundation has been providing in Italy. This 5-years investigation was designed to measure caregivers' satisfaction and determine what types of support services are associated with greater satisfaction. 5.441 family caregivers filled out autonomously a 6-item questionnaire at the end of home care assistance, focusing on the level of satisfaction with the social and health services received. The overall data indicate a high satisfaction rate for the home care assistance received. In particular, participants rate positively the assistance provided by healthcare professionals (physicians, nurses and psychologists). The most appreciated aspects of assistance are those ensuring a global management of patients and their families, whereas an area of deficiency emerged was the continuity of care, suggesting the importance to implement the networks between the health care facilities and home care services. The present investigation constitutes a mean to highlight the aspects associated with greater satisfaction and the ones perceived as less satisfactory by caregivers. Moreover, this research constitutes a crucial instrument to improve home care assistance provided by ANT ensuring the best quality of life for both patients and their families.

Caregivers in home palliative care: gender, psychological aspects, and patient's functional status as main predictors for their quality of life.

PURPOSE: This study aims to investigate the impact of possible predictors of quality of life (QoL) in a group of Italian caregivers assisting a cancer patient in home palliative care. METHODS: Data from 570 adult informal caregivers and their cancer-affected relatives were collected. A multivariate regression analysis was conducted to assess the effect of three groups of variables on Caregivers Quality of Life Index-Cancer (CQOLC) scale: (a) socio-demographic characteristics of caregivers; (b) psychological characteristics of caregivers assessed by Profile Mood of States (POMS), Caregiver Burden Inventory (CBI), and Preparedness for Caregiving Scale (PCS); (c) Socio-demographic characteristics and functional status of the patients assessed by Karnofsky Performance Status (KPS), Activities of Daily Living (ADL), and Instrumental Activities of Daily Living (IADL). RESULTS: Regression analysis shows that some variables from each of these clusters are significantly associated with CQOLC, in particular: (a) the gender of the caregiver (st.ß = .115, t = 2.765, p = .006) and the time spent for caregiving (st.ß = - .165, t = - 3.960, p < .001); (b) the scores obtained by the caregivers in POMS,CBI (st.ß = - .523, t = - 16.984, p < .001 and st.ß = - .373, t = - 12.950, p < .001, respectively) and PCS (st.ß = .092, t = 3.672, p < .001); (c) the gender (st.ß = - .081, t = - 1.933, p = .045) and the IADL score (st.ß = .195, t = 4.643, p < .001) of the patient. CONCLUSIONS: A multidimensional evaluation is a key strategy to identify the most vulnerable caregivers. Apart from the condition of the patient, the gender of the caregivers, the time spent for caregiving and, above all, their psychological condition are strong predictors of caregivers' QoL.

Clinical and personality profile of depressed suicide attempters: A preliminary study at the open-door policy Mood Disorder Unit of San Raffaele Hospital.

Suicidal behavior is a complex phenomenon with high rates among psychiatric inpatients. Mood disorders and personality dysfunctions represent relevant risk factors for suicides attempts and suicidal ideation. Our study aims to investigate the role of the co-occurrence of clinical variables (duration of depressive state, previous suicide attempts), socio-demographic variables (gender, employment and civil status) and narcissistic personality features in the suicide risk of admitted psychiatric patients affected by a mood disorder. The sample was composed of 93 patients consecutively admitted in an open ward psychiatric Unit. Forty-eight participants had a positive history of previous suicide attempts: the suicide attempters (SA) were mostly female, unemployed and married. The SA group were observed to have suffered from a depressive episode with a longer duration; moreover in the SA group, the presence of active suicidal ideation was significantly related to a higher number of previous suicide attempts. In the whole sample, suicidal ideation was significantly related to narcissistic vulnerability personality features. Using a multidimensional approach, the present study allows a preliminary profiling of patients at risk for suicidal behavior during hospitalization.

Care for Carers: an Investigation on Family Caregivers' Needs, Tasks, and Experiences.

Family caregivers have an essential active role in cancer patients assistance at home. They play a key role in the management of patients and provide some caregiving activities once provided only by professional caregivers. Often they are not adequately trained or prepared, however a systematic assessment of their needs is rarely practiced. For these reasons, this preliminary investigation was designed to better identify the needs and changes in the lifestyles of family caregivers of home cancer palliative care. Participants have completed a battery of self-report questionnaires, including the Caregiving Tasks Consequences and Needs Questionnaire (CaTCoN), that measures caregivers' experiences (the extent of cancer caregiving tasks and consequences) and the caregivers' needs, mainly concerning the interaction with the health care professionals. The results confirmed that cancer caregiving is burdensome. Large proportions of caregivers experienced substantial caregiving workload as well as a range of negative consequences, e.g. lack of time for social relations. Furthermore, considerable proportions of caregivers experienced problems or had unmet needs regarding the interaction with health care professionals. Prominent problematic aspects included the provision of enough information to the caregivers and attention to the caregivers' well-being and feelings. The assessment of caregivers' needs is a critical step for determining appropriate support services, providing high-quality care, achieving caregiver satisfaction, and decreasing caregiver burden. Findings of this investigation will certainly contribute to develop and publish Guidelines and to provide programmes and on-going education where caregivers feel supported in their role.

Determination of orphenadrine plasma levels using HPLC with diode array detection and a novel solid-phase extraction procedure in psychiatric patients.

Orphenadrine is an antimuscarinic agent mainly used for the treatment of parkinsonism and to alleviate the neuroleptic syndrome induced by antipsychotic drugs. A new, rapid analytical method, based on liquid chromatography with diode array detection (DAD), has been developed and applied to the determination of orphenadrine in plasma of schizophrenic patients for therapeutic drug monitoring and toxicological purposes. The chromatographic separation was performed on a pentafluorophenyl reversed phase column with a mobile phase composed of acetonitrile-phosphate buffer mixture. DAD detection was carried out at 220 nm. A careful and rapid solid-phase extraction procedure on cyanopropyl cartridges was chosen for plasma sample purification and pre-concentration obtaining good extraction yield values for the analyte (>96.0%). The assays showed a linear response for orphenadrine (30-1000 ng mL(-1)). The method is also precise and selective. Thus, the method developed seems to be suitable for routine analysis of orphenadrine in psychiatric patients. Moreover, it was applied to plasma samples from a psychotic patient who had tried to poison himself with 1000 mg of orphenadrine and was undergoing polypharmacy.

Metabotropic P2 receptor activation regulates oligodendrocyte progenitor migration and development.

To gain insights into the role of purinergic receptors in oligodendrocyte development, we characterized the expression and functional activity of P2 receptors in cultured rat oligodendrocyte progenitors and investigated the effects of ATP and its breakdown products on the migration and proliferation of this immature glial cell population. Using Western blot analysis, we show that oligodendrocyte progenitors express several P2X (P2X(1,2,3,4,7)) and P2Y (P2Y(1,2,4)) receptors. Intracellular Ca(2+) recording by Fura-2 video imaging allowed to determine the rank potency order of the P2 agonists tested: ADPbetaS = ADP = Benzoyl ATP > ATP > ATPgammaS > UTP, alpha,beta-meATP ineffective. Based on the above findings, on pharmacological inhibition by the antagonists oxATP and MRS2179, and on the absence of alpha,betameATP-induced inward current in whole-cell recording, P2X(7) and P2Y(1) were identified as the main ionotropic and metabotropic P2 receptors active in OPs. As a functional correlate of these findings, we show that ATP and, among metabotropic agonists, ADP and the P2Y(1)-specific agonist ADPbetaS, but not UTP, induce oligodendrocyte progenitor migration. Moreover, ATP and ADP inhibited the proliferation of oligodendrocyte progenitors induced by platelet-derived growth factor, both in purified cultures and in cerebellar tissue slices. The effects of ATP and ADP on cell migration and proliferation were prevented by the P2Y(1) antagonist MRS2179. By confocal laser scanning microscopy, P2Y(1) receptors were localized in NG2-labeled oligodendrocyte progenitors in the developing rat brain. These data indicate that ATP and ADP may regulate oligodendrocyte progenitor functions by a mechanism that involves mainly activation of P2Y(1) receptors.

Reduced sodium appetite and increased oxytocin gene expression in mutant mice lacking beta-endorphin.

Central opioid and oxytocinergic systems have been involved in the regulatory control of sodium appetite. In addition, previous studies support the existence of a functional interaction between opioid peptides and oxytocinergic pathways, and suggest that beta-endorphin neurons would modulate the activity of central oxytocinergic pathways, its pituitary secretion and sodium appetite. To investigate the role of this opioid peptide in the control of oxytocin (OT) synthesis and sodium appetite regulation we used mice with gene dosage-dependent variations in brain beta-endorphin content, expressing either 100%, 50%, or 0% of normal beta-endorphin content. Our results show that beta-endorphin knockout (KO) and heterozygous (HT) mutant mice consume approximately a 50% less 2% NaCl solution compared with wild type mice (WT), after furosemide and low sodium diet treatment. These data suggest that beta-endorphin may facilitate induced sodium appetite, giving new evidence about the role of beta-endorphin on sodium appetite behavior. Our data also indicate that OT mRNA levels evaluated by in situ hybridization significantly increased within the hypothalamic paraventricular nucleus of WT animals after induced sodium ingestion, giving support to former evidence indicating an inhibitory role for central OT in the control of sodium appetite. Moreover, beta-endorphin mutated mice have similar higher levels of OT mRNA expression after the different conditions analyzed: basal, control or experimental, compared with WT mice. Both control HT and KO mice showed higher OT mRNA expression levels than control WT group and these levels did not change after induced sodium intake. Taken together, our data suggest that the reduced sodium ingestion observed in beta-endorphin deficient mice could be due to a higher expression of the OT gene. This conclusion would support the hypothesis that OT inhibits sodium intake and provides new evidence about beta-endorphin modulation of OT synthesis and sodium appetite.

N-terminal truncation of the variable subunit stabilizes spinach ferredoxin:thioredoxin reductase.

The variable subunit of spinach ferredoxin:thioredoxin reductase (FTR) has an extended N-terminus compared to FTRs from other sources and this was proposed to contribute to the instability of the protein. We constructed two N-terminal truncation mutants of recombinant FTR by removing 16 or 24 residues from the variable subunit. The mutant proteins are readily expressed and show half-saturation values (S(0.5)) for ferredoxin and thioredoxin f comparable to WT. However, truncation increases significantly their stability. Using the stabilized FTR an exposed Cys on its thioredoxin contact surface could be substituted without altering its properties, whereas the replacement of an active site Cys by Ser completely destabilized the protein.

Long-term treatment with citalopram in patients with highly recurrent forms of unipolar depression.

The authors evaluated the efficacy and safety of citalopram in a 28-month study in 48 inpatients with highly recurrent forms of unipolar depression. The patients, who each had at least one depressive episode during the 18 months preceding the index episode, were openly treated with citalopram, 40 mg/day. Thirty-six of the patients had a stable response to citalopram and continued treatment as outpatients for 4 months. No relapses were observed. At the time of recovery, 32/36 subjects received maintenance treatment with citalopram (40 mg) for an additional 24 months. At the end of the study, 11/32 patients experienced a single new recurrence.

A neural network approach to the outcome definition on first treatment with sertraline in a psychiatric population.

Therapy decision is one of the most important tasks clinicians have to perform in their clinical practice. The decision process requires taking into account many different factors. The Authors have proposed a neural computing approach for supporting clinical decision analysis. The mathematical model of artificial neural network (ANN) has been applied on a pool of clinical information gathered through case description freely filled by senior psychiatrists into 416 clinical charts. Sertraline, as drug for treatment, has been chosen since its clinical uses range from treatment of depression to that of many other psychiatric clinical conditions so that it has been thought to be a good candidate to this type of study. The ANN performance in forecasting successful and unsuccessful treatment cases showed an overall accuracy of classification of 97.35%. This result suggests a possible future application of this method to obtain a reliable prediction of a given psychiatric patient outcome during a specific psychopharmacological therapy, optimising the decisional making process.

Factors affecting fluvoxamine antidepressant activity: influence of pindolol and 5-HTTLPR in delusional and nondelusional depression.

BACKGROUND: It has been recently reported that the short variant of the serotonin transporter (5-HTT) gene-linked functional polymorphic region (5-HTTLPR) influences the antidepressant response to certain selective serotonin reuptake inhibitors. The aim of the present study was to test this finding in a sample of major and bipolar depressives, with or without psychotic features. METHODS: One hundred fifty-five inpatients were treated with fluvoxamine 300 mg and either placebo or pindolol in a double-blind design for 6 weeks. The severity of depressive symptoms was weekly assessed with the Hamilton Rating Scale for Depression. Allelic variation of 5-HTTLPR in each subject was determined using a polymerase chain reaction-based technique. RESULTS: 5-HTTLPR short variant was associated with a poor response to fluvoxamine treatment, independently from the recorded clinical variables. More specifically, the diagnosis, the presence of psychotic features, and the severity of depressive symptomatology did not influence this association. Conversely, pindolol augmentation may ameliorate the rate of response in 5-HTTLPR short variant subjects, thus reducing the difference in the response rate among the genotype variants. CONCLUSIONS: If confirmed, these results may improve patient care by helping the clinician to individualize treatment according to the patient's genetic 5-HTTLPR pattern.

Will a second prophylactic treatment with a higher dosage of the same antidepressant either prevent or delay new depressive episodes?

Fifty-seven highly recurrent unipolar patients, excluded from previous long-term studies with selective serotonin reuptake inhibitors (SSRIs) after they experienced a new recurrence, were acutely treated with the full dosage of the SSRIs they were on. Fifty-one of them (89.5%) had a sustained response and entered into the 4-month continuation therapy. During this phase, no relapse was observed. At the end of it, all patients gave their written informed consent to be enrolled in a 24-month long-term therapy, maintaining the same treatment dosage of fluvoxamine 300 mg/day, sertraline 150 mg/day, or paroxetine 40 mg/day. At the end of the study, 28 out of the 51 outpatients (54.9%) showed a further recurrence. Nevertheless, second recurrences observed during this second maintenance therapy were less severe than first recurrences, decreasing from 25.1+/-3.4 to 21.6+/-3.3 (P<0.0001), respectively. Considering the clinical characteristics of patients, we found that a high number of prior depressive episodes and an early age at onset of illness may predict a bad outcome. Moreover, patients with a longer duration of euthymia during a first maintenance period are less likely to have a new episode of depression.

A dicistronic construct for the expression of functional spinach chloroplast ferredoxin:thioredoxin reductase in Escherichia coli.

Ferredoxin:thioredoxin reductase (FTR) is a heterodimeric Fe&z.sbnd;S containing disulfide reductase involved in the light-dependent activation of photosynthetic enzymes. We have designed a dicistronic construct for the heterologous expression of this nucleus encoded chloroplast protein in Escherichia coli. The coding sequences for the two mature subunits have been inserted in tandem into the expression vector pET-3d. This dicistronic construct is correctly translated yielding soluble, perfectly functional FTR. The recombinant enzyme is composed of both subunits, contains the correctly inserted Fe&z.sbnd;S cluster as evidenced by its spectral properties and is indistinguishable from the enzyme isolated from leaves in its capacity to activate chloroplast fructose-1,6-bisphosphatase, one of the well known light activated enzymes of the Calvin cycle.

Patterns of symptom improvement during antidepressant treatment of delusional depression.

We assessed the pattern of changes in depressive symptoms in delusional depressed inpatients treated openly with 300 mg/day of fluvoxamine for 6 weeks. We studied 59 inpatients affected by bipolar (n=23) and major depressive (n=36) disorders with psychotic features (DSM-IV) who showed complete responses to fluvoxamine treatment. Responses were evaluated using the Hamilton Rating Scale for Depression (HAMD-21, divided into: Core, Activity, Psychic anxiety, Somatic anxiety and Delusion clusters) administered at baseline and weekly until the 6th week. Random Regression Model (RRM) analysis was used to investigate the longitudinal time course of HAMD clusters. HAMD depressive symptom clusters decreased in a parallel manner from baseline to the end of the 6-week trial. The RRM analysis revealed no significant difference between HAMD clusters and the time course of the total HAMD score during treatment. Our data indicate that there is a simultaneous decrease in depressive symptoms during antidepressant treatment of delusional depressives.

Melancholic features and response to lithium prophylaxis in mood disorders.

Clinical predictors of the efficacy of lithium prophylaxis in mood disorders have great potential value. Melancholic features during depressive phases have been both proposed and rejected as valid predictors of favorable outcome. The aim of the present study is to describe the validity of melancholic features during depressive phases as predictors of the prophylactic efficacy of lithium. Sixty-one subjects affected by bipolar (n = 51) and major depressive (n = 10) disorder were followed prospectively for an average of 53 months. All subjects were evaluated as a lifetime perspective at intake, by the Operational Criteria checklist for psychotic illness (OPCRIT). Melancholic features were correlated with outcome only when controlling for time of first lithium administration. These two variables accounted for more than 30% of the total variance in lithium response. Others clinical factors such as polarity, delusions, gender, onset, personality disorders, and family history of mood disorders did not influence the observed association. Our preliminary findings suggest that melancholic features may be associated with favorable lithium prophylactic outcome in mood disorders.

Four-year follow-up study of sertraline and fluvoxamine in long-term treatment of unipolar subjects with high recurrence rate.

We prolonged from 24 to 48 months a follow-up study of unipolar subjects with high recurrence rate treated with fluvoxamine (N=25) and sertraline (N=22). During the two-year additional period a significant risk of recurrences was observed during the third year of follow-up, without differences in the two long-term therapy groups. During the fourth year no patients showed new episodes of illness.

Venlafaxine versus fluvoxamine in the treatment of delusional depression: a pilot double-blind controlled study.

BACKGROUND: Previous studies have reported the efficacy of selective serotonin reuptake inhibitors as monotherapy in the treatment of delusional depression. The clinical efficacy of venlafaxine, a serotonin-norepinephrine reuptake blocker, has been demonstrated in the treatment of patients with moderate-to-severe depression, but, to date, no evidence is available about its use in depressed patients with psychotic features. METHOD: Under double-blind conditions, 28 hospitalized patients who met DSM-IV criteria for major depression, severe with psychotic features, were randomly assigned to receive fluvoxamine or venlafaxine, 300 mg/day, for 6 weeks. Severity was evaluated using the Hamilton Rating Scale for Depression (HAM-D) and the Dimensions of Delusional Experience Rating Scale (DDERS) administered at baseline and every week thereafter. Side effects were also recorded. Clinical response was defined as a reduction of the scores in the 21-item HAM-D to 8 or below and in the DDERS to 0. RESULTS: At study completion, the response rates were 78.6% (N = 11) and 58.3% (N = 7) for fluvoxamine and venlafaxine, respectively. No significant difference was found between drugs (Fisher exact test, p = .40). Analysis of covariance on HAM-D scores did not reveal a significantly different decrease of depressive symptomatology between the 2 treatment groups (p = .14). Treatment response appeared to be unrelated to the demographic and clinical characteristics recorded. The overall safety profile of both fluvoxamine and venlafaxine was favorable. CONCLUSION: The results of this pilot double-blind trial show that fluvoxamine is useful in the treatment of delusional depression and suggest that venlafaxine may also be an effective compound in the treatment of this disorder. The latter finding, although promising, warrants further replication in a larger sample of patients.

Early onset of lithium prophylaxis as a predictor of good long-term outcome.

The recurrence rates during lithium preventive treatment were investigated in a sample of 270 Mood Disorder subjects subdivided according to their onset time for lithium prophylaxis as very early (within 5 years from the onset of illness), early (6-10 years), late (11-20 years) and very late (more than 21 years). 131 subjects of the sample followed for 4 years prolonged the observation for a further period of 8 years. Results indicated that beginning lithium therapy within the first ten years of illness predicts better preventive outcomes than beginning prophylaxis later, both in major depression, recurrent and bipolar patients.

Social adjustment and self-esteem in remitted patients with mood disorders.

Mood disorders are characterized by manic and depressive episodes alternating with normal mood. While social function is heavily impaired during episodes of illness, there are conflicting opinions about inter-episode function. The present paper focuses on self-esteem and social adjustment in remitted mood disorders patients. Patients with mood disorders (99 bipolar and 86 major depressive subjects, in remission) were compared with a group of 100 control subjects. The self-esteem scale (SES) and the social adjustment scale (SAS) were used to measure self-esteem and social adjustment, respectively, in both groups of subjects. Patients with mood disorder exhibited worse social adjustment and lower self-esteem than control subjects. These results strongly confirm previous observations of poor inter-episode function in patients with mooddisorder.

Dopamine receptor D2 and D4 genes, GABA(A) alpha-1 subunit genes and response to lithium prophylaxis in mood disorders.

Lithium is an effective prophylactic agent in mood disorders, and genetic factors are likely to modulate individual susceptibility to lithium treatment. The aim of this study is to investigate the influence of dopamine receptor D2 (DRD2), D4 exon 3 (DRD4), and gamma-aminobutyric acid type A (GABA(A)) receptor alpha-1 subunit (GABRA1) gene variants on the efficacy of lithium prophylaxis in mood disorders. Patients with mood disorders (N = 125: bipolar subtype, n = 100; major depressive disorder subtype, n = 25) were followed prospectively for an average of 53 months and were typed for DRD2 (Ser311/Cys311: n = 121, VNTR: n = 63), DRD4 (n = 125) and GABRA1 (n = 61) variants using polymerase chain reaction (PCR) techniques. DRD2, DRD4 and GABRA1 variants were not associated with response to lithium. A trend was observed toward a better outcome of DRD4* 2/4 subjects, but it was due to only two subjects. Consideration of possible stratification effects like gender, polarity, family history, age at onset and duration of lithium treatment did not reveal any association either. DRD2, DRD4 and GABRA1 variants therefore do not appear to be associated with the outcome of lithium prophylaxis in mood disorders.