Predictors and consequences of adherence to the treatment of pediatric patients with attention-deficit/hyperactivity disorder in Central Europe and East Asia.

PURPOSE: To assess baseline predictors and consequences of medication non-adherence in the treatment of pediatric patients with attention-deficit/hyperactivity disorder (ADHD) from Central Europe and East Asia. PATIENTS AND METHODS: Data for this post-hoc analysis were taken from a 1-year prospective, observational study that included a total of 1,068 newly-diagnosed pediatric patients with ADHD symptoms from Central Europe and East Asia. Medication adherence during the week prior to each visit was assessed by treating physicians using a 5-point Likert scale, and then dichotomized into either adherent or non-adherent. Clinical severity was measured by the Clinical Global Impressions-ADHD-Severity (CGI-ADHD) scale and the Child Symptom Inventory-4 (CSI-4) Checklist. Health-Related Quality of Life (HRQoL) was measured using the Child Health and Illness Profile-Child Edition (CHIP-CE). Regression analyses were used to assess baseline predictors of overall adherence during follow-up, and the impact of time-varying adherence on subsequent outcomes: response (defined as a decrease of at least 1 point in CGI), changes in CGI-ADHD, CSI-4, and the five dimensions of CHIP-CE. RESULTS: Of the 860 patients analyzed, 64.5% (71.6% in Central Europe and 55.5% in East Asia) were rated as adherent and 35.5% as non-adherent during follow-up. Being from East Asia was found to be a strong predictor of non-adherence. In East Asia, a family history of ADHD and parental emotional distress were associated with non-adherence, while having no other children living at home was associated with non-adherence in Central Europe as well as in the overall sample. Non-adherence was associated with poorer response and less improvement on CGI-ADHD and CSI-4, but not on CHIP-CE. CONCLUSION: Non-adherence to medication is common in the treatment of ADHD, particularly in East Asia. Non-adherence was associated with poorer response and less improvement in clinical severity. A limitation of this study is that medication adherence was assessed by the treating clinician using a single item question.

Predictors of remission in the treatment of major depressive disorder: real-world evidence from a 6-month prospective observational study

BACKGROUND: This study examined potential predictors of remission among patients treated for major depressive disorder (MDD) in a naturalistic clinical setting, mostly in the Middle East, East Asia, and Mexico. METHODS: Data for this post hoc analysis were taken from a 6-month prospective, noninterventional, observational study that involved 1,549 MDD patients without sexual dysfunction at baseline in 12 countries worldwide. Depression severity was measured using the Clinical Global Impression of Severity and the 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). Depression-related pain was measured using the pain-related items of the Somatic Symptom Inventory. Remission was defined as a QIDS-SR16 score ≤5. Generalized estimating equation regression models were used to examine baseline factors associated with remission during follow-up. RESULTS: Being from East Asia (odds ratio [OR] 0.48 versus Mexico; P<0.001), a higher level of depression severity at baseline (OR 0.77, P=0.003, for Clinical Global Impression of Severity; OR 0.92, P<0.001, for QIDS-SR16), more previous MDD episodes (OR 0.92, P=0.007), previous treatments/therapies for depression (OR 0.78, P=0.030), and having any significant psychiatric and medical comorbidity at baseline (OR 0.60, P<0.001) were negatively associated with remission, whereas being male (OR 1.29, P=0.026) and treatment with duloxetine (OR 2.38 versus selective serotonin reuptake inhibitors, P<0.001) were positively associated with remission. However, the association between Somatic Symptom Inventory pain scores and remission no longer appeared to be significant in this multiple regression (P=0.580), (P=0.008 in descriptive statistics), although it remained significant in a subgroup of patients treated with selective serotonin reuptake inhibitors (OR 0.97, P=0.023), but not in those treated with duloxetine (P=0.182). CONCLUSION: These findings are largely consistent with previous reports from the USA and Europe. They also highlight the potential mediating role of treatment with duloxetine on the negative relationship between depression-related pain and outcomes of depression.

Clinical usefulness of the Screen for Cognitive Impairment in Psychiatry (SCIP-S) scale in patients with type I bipolar disorder

Background: The relevance of persistent cognitive deficits to the pathogenesis and prognosis of bipolar disorders (BD) is understudied, and its translation into clinical practice has been limited by the absence of brief methods assessing cognitive status in Psychiatry. This investigation assessed the psychometric properties of the Spanish version of the Screen for Cognitive Impairment in Psychiatry (SCIP-S) for the detection of cognitive impairment in BD. Methods: After short training, psychiatrists at 40 outpatient clinics administered the SCIP three times over two weeks to a total of 76 consecutive type I BD admissions. Experienced psychologists also administered a comprehensive battery of standard neuropsychological instruments to clinical sample and 45 healthy control subjects. Results: Feasibility was supported by a brief administration time (approximately 15 minutes) and minimal scoring errors. The reliability of the SCIP was confirmed by good equivalence of forms, acceptable stability (ICC range 0.59 to 0.87) and adequate internal consistency (Chronbach's alpha of 0.74). Construct validity was granted by extraction of a single factor (accounting 52% of the variance), acceptable correlations with conventional neuropsychological instruments, and a clear differentiation between bipolar I and normal samples. Efficiency was also provided by the adequate sensitivity and specificity. Limitations: The sample size is not very large. The SCIP and the neurocognitive battery do not cover all potentially relevant cognitive domains. Also, sensitivity to change remains unexplored. Conclusion: With minimal training, physicians obtained a reliable and valid estimate of cognitive impairment in approximately 15 minutes from an application of the SCIP to type I BD patients.

Clinical usefulness of the Screen for Cognitive Impairment in Psychiatry (SCIP-S) scale in patients with type I bipolar disorder

Background: The relevance of persistent cognitive deficits to the pathogenesis and prognosis of bipolar disorders (BD) is understudied, and its translation into clinical practice has been limited by the absence of brief methods assessing cognitive status in Psychiatry. This investigation assessed the psychometric properties of the Spanish version of the Screen for Cognitive Impairment in Psychiatry (SCIP-S) for the detection of cognitive impairment in BD. Methods: After short training, psychiatrists at 40 outpatient clinics administered the SCIP three times over two weeks to a total of 76 consecutive type I BD admissions. Experienced psychologists also administered a comprehensive battery of standard neuropsychological instruments to clinical sample and 45 healthy control subjects. Results: Feasibility was supported by a brief administration time (approximately 15 minutes) and minimal scoring errors. The reliability of the SCIP was confirmed by good equivalence of forms, acceptable stability (ICC range 0.59 to 0.87) and adequate internal consistency (Chronbach's alpha of 0.74). Construct validity was granted by extraction of a single factor (accounting 52% of the variance), acceptable correlations with conventional neuropsychological instruments, and a clear differentiation between bipolar I and normal samples. Efficiency was also provided by the adequate sensitivity and specificity. Limitations: The sample size is not very large. The SCIP and the neurocognitive battery do not cover all potentially relevant cognitive domains. Also, sensitivity to change remains unexplored. Conclusion: With minimal training, physicians obtained a reliable and valid estimate of cognitive impairment in approximately 15 minutes from an application of the SCIP to type I BD patients.

Multisystem Developmental Disorder in Children from 2 to 6 Years Old : A Three Years Follow-Up Study

This research studied children who had been diagnosed with Multisystem Developmental Disorder (MSDD) (NC, 2002) under the Diagnostic Classifications of Mental Health and Developmental Disorders of Infancy and Early Childhood (DC: 0 - 3). They all showed, to a varying degree, difficulties in relating to others, play, affective interaction and severe delay in developing communication skills. Some studies have observed continuity in the diagnosis of autism during the first years of life. The objective of this study is to analyse the development of infants with MSDD whose diagnosis of autism was not confirmed. We also attempted to verify any possible psychomotor developmental differences based on, or related to, the severity and typology (B and C) of the MSDD. To enable us to do this we carried out a 3-year follow-up during which we assessed the infants (n = 15) and their parents. They are 2 - 4 years old. Results showed that type B children did present a greater impairment of psychomotor development in assessment tests. However, we did not observe any correlation between the degree of severity of the initial symptoms and later diagnoses. Conclusion: although our sample is small, we can conclude that there isn’t a clear evolution in the diagnosis, but we have found significant differences in the symptomatology between the type B and C

Prognostic Markers and Prolonged Interferon-alpha Therapy in Renal Cell Carcinoma

Molekyylimarkkerit ja pitkäaikainen alfainterferonihoito munuaissyövässä Munuaissyöpäpotilaiden viiden vuoden elossaololuku on noin 50 %. Aikaisempien tutkimuksien mukaan viiden vuoden elossaololuku metastasoituneessa munuaissyövässä on 3-16 %, kun käytettiin alfainterferonia sisältävää hoitoa. Tyypillisesti alfainterferonia on käytetty vähemmäin kuin 6 kuukautta. Avoimia kysymyksiä ovat alfainterferonin optimaalinen hoitoannos ja hoidon kesto yksin tai yhdessä uusien täsmähoitojen kanssa. Tärkeimmät tavoitteet olivat tutkia 1) jaksotetun pitkäaikaisen alfainterferonihoidon tehoa ja siedettävyyttä metastasoituneessa munuaissyövässä ja 2) p53-, Ki-67- ja COX-2-proteiinituotannon ennusteellista merkitystä munuaissyövässä. Tutkimuksessa 117 metastasoituneelle munuaissyöpää sairastaneelle potilaalle etsittiin yksilöllinen hänen sietämänsä maksimaalinen hoitoannos rekombinanttia alfa2a-interferonia (Roferon-ATM). Hoitoa pyrittiin jatkamaan 24 kuukauden ajan. Kolmen hoitoviikon jälkeen pidettiin yhden viikon tauko. Hoito lopetettiin, jos ilmaantui vakavia haittavaikutuksia tai tauti eteni. Toisessa tutkimuksessa proteiinituotanto analysoitiin immunohistokemiallisesti munuaissyöpäpotilaiden kasvainnäytteistä, joita oli säilytetty parafiinissa. Kasvainnäytteet oli otettu talteen munuaisen poistoleikkauksen yhteydessä. Nämä potilaat jaettiin kolmeen eri ryhmään: metastasointi primaarivaiheessa (n=29), metastasointi myöhemmin (n=37) ja ei metastasointia (n=51). Keskimääräinen alfainterferonihoidon kesto oli 11 kuukautta (kk) [0,5 – 32 kk]. Objektiivinen hoitovaste todettiin 17 %:lla, tautitilanne pysyi ennallaan 42 %:lla ja myöhäinen vaste (yli 12 kk:tta hoidon aloittamisesta) todettiin 3 %:lla. Aika vasteen saavuttamisesta taudin etenemiseen oli keskimäärin 8 kk ja elinaika 19,1 kk. Viiden vuoden elossaololuku oli 16 %. Jos metastasoituneella munuaissyöpäpotilaalla oli keuhkometastasointi, hän selvisi todennäköisemmin viisi vuotta kuin muut potilaat. Henkeä uhkaavia sivuvaikutuksia ei todettu. Yli 12 kk:n ajan kestävä alfainterferonihoito on hyödyllistä niille potilaille, jotka ovat saaneet objektiivisen hoitovasteen tai tautitilanne on pysynyt ennallaan. Positiivinen p53- ja Ki-67-ekspressio yhdessä viittaavat suureen metastasoinnin todennäköisyyteen. Positiivinen COX-2-ekspressio viittaa viivästyneeseen metastaasien ilmaantumiseen. Metastasoituneilla potilailla positiiviset p53- ja Ki-67-ekspressiot viittaavat huonoon ennusteeseen, mutta positiivinen COX-2 ekspressio viittaa suotuisaan ennusteeseen. Positiivinen COX-2- ja negatiivinen Ki-67-ekspressio yhdessä viittaavat parantuneeseen ennusteeseen metastasoituneessa munuaissyövässä.

Design and implementation of a leisure program to improve function and wellbeing in people with depressive disorder

Depression is a major cause of disability and disease with significant costs to the health system and for the whole society. Regarding the treatment, in recent years has questioned the effectiveness of antidepressant drugs, with a recognition that although depressive disorders tend to improve with these treatments, residual symptoms seems to be still the norm, which is associated with the risk of new episodes or relapses, and faster its appearance. Otherwise many of the specialized clinical guidelines, propose a based on stepped-care model intervention, prioritizing less intrusive actions, including low-intensity psychosocial-interventions.

Comparison of full-field electroretinogram in diabetic and non diabetic dogs with cataracts

Being the commonest ocular disorder, dense cataracts disable fundoscopic examination and the diagnosis of retinal disorders, which dogs may be predisposed. The aim of this study was to compare the electroretinographic responses recorded according to the International Society for Clinical Electrophysiology of Vision human protocol to evaluate retinal function of diabetic and non diabetic dogs, both presenting mature or hypermature cataracts. Full-field electroretinogram was recorded from 66 dogs, with ages varying from 6 to 15 years old allocated into two groups: (1) CG, non diabetic cataractous dogs, and (2) DG, diabetic cataractous dogs. Mean peak-to-peak amplitude (microvolts) and b-wave implicit time (milliseconds) were determined for each of the five standard full-field ERG responses (rod response, maximal response, oscillatory potentials, single-flash cone response and 30 Hz flicker). Comparing CG to DG, ERGs recorded from diabetic dogs presented lower amplitude and prolonged b-wave implicit time in all ERG responses. Prolonged b-wave implicit time was statistically significant (p< 0.05) at 30 Hz flicker (24.0 ms versus 22.4 ms). These data suggests full-field ERG is capable to record sensible alterations, such as flicker's implicit time, being useful to investigate retinal dysfunction in diabetic dogs.

The study of genetic polymorphisms related to serotonin in Alzheimer's disease: a new perspective in a heterogenic disorder

Genetic and environmental factors have been implicated in the development of Alzheimer's disease (AD), the most common form of dementia in the elderly. Mutations in 3 genes mapped on chromosomes 21, 14 and 1 are related to the rare early onset forms of AD while the e4 allele of the apolipoprotein E (APOE) gene (on chromosome 19) is the major susceptibility locus for the most common late onset AD (LOAD). Serotonin (5-hydroxytryptamine or 5-HT) is a key neurotransmitter implicated in the control of mood, sleep, appetite and a variety of traits and behaviors. Recently, a polymorphism in the transcriptional control region upstream of the 5-HT transporter (5-HTT) gene has been studied in several psychiatric diseases and personality traits. It has been demonstrated that the short variant(s) of this 5-HTT gene-linked polymorphic region (5-HTTLPR) is associated with a different transcriptional efficiency of the 5-HTT gene promoter resulting in decreased 5-HTT expression and 5-HT uptake in lymphocytes. An increased frequency of this 5-HTTLPR short variant polymorphism in LOAD was recently reported. In addition, another common polymorphic variation in the 5-HT2A and 5-HT2C serotonin receptor genes previously analyzed in schizophrenic patients was associated with auditory and visual hallucinations in AD. These observations suggest that the involvement of the serotonin pathway might provide an explanation for some aspects of the affective symptoms commonly observed in AD patients. In summary, research on genetic polymorphisms related to AD and involved in receptors, transporter proteins and the enzymatic machinery of serotonin might enhance our understanding of this devastating neurodegenerative disorder.

Sexual behavior and fertility of male rats submitted to prolonged immobilization-induced stress

In order to investigate whether prolonged stress interferes with the onset of sexual behavior at puberty and with fertility at adulthood, prepubertal male Wistar rats (40 days of age) were immobilized 6 h a day for 15 days (up to early puberty) or for 60 days (until sexual maturity). Pubertal stressed rats showed a two-fold increase in the latency for the first mount (probably due to repeated aversive experience in which a change of environment was always followed by immobilization) and a 2.5-fold increase in the frequency of thrusting (indicative of enhanced sexual performance). The apparently stimulatory effect of prolonged stress on the onset of sexual behavior is discussed in terms of increased testosterone level and interference with the complex interchanges between the neurotransmitters/neuropeptides involved in the central control of male sexual activity. Adult stressed animals were mated with normal females, which became pregnant but exhibited a more than two-fold increase in both pre-implantation and post-implantation loss, probably due to a smaller rate of fertilization and/or fertilization with damaged spermatozoa.

Hyperventilation in panic disorder patients and healthy first-degree relatives

Our aim was to observe the induction of panic attacks by a hyperventilation challenge test in panic disorder patients (DSM-IV) and their healthy first-degree relatives. We randomly selected 25 panic disorder patients, 31 healthy first-degree relatives of probands with panic disorder and 26 normal volunteers with no family history of panic disorder. All patients had no psychotropic drugs for at least one week. They were induced to hyperventilate (30 breaths/min) for 4 min and anxiety scales were applied before and after the test. A total of 44.0% (N = 11) panic disorder patients, 16.1% (N = 5) of first-degree relatives and 11.5% (N = 3) of control subjects had a panic attack after hyperventilating (chi² = 8.93, d.f. = 2, P = 0.011). In this challenge test the panic disorder patients were more sensitive to hyperventilation than first-degree relatives and normal volunteers. Although the hyperventilation test has a low sensitivity, our data suggest that there is no association between a family history of panic disorder and hyperreactivity to an acute hyperventilation challenge test. Perhaps cognitive variables should be considered to play a specific role in this association since symptoms of a panic attack and acute hyperventilation overlap.

Mirtazapine versus fluoxetine in the treatment of panic disorder

Mirtazapine is an antidepressant whose side effect profile differs from that of first-line agents (selective serotonin reuptake inhibitors) used in the treatment of panic disorder. The present study compared the effect of mirtazapine and fluoxetine in the treatment of panic disorder in a double-blind, randomized, flexible-dose trial conducted with outpatients. After a 1-week single-blind placebo run-in, 27 patients entered an 8-week double-blind phase in which they were randomly assigned to treatment with either mirtazapine or fluoxetine. Both groups improved significantly in all but one efficacy measure (P<=0.01). ANOVA showed no significant differences between the two treatment groups in number of panic attacks, Hamilton Anxiety Scale or Sheehan Phobic Scale, whereas measures of patient global evaluation of phobic anxiety were significantly different between groups (F1,20 = 6.91, P = 0.016) favoring mirtazapine. For the 22 patients who completed the study, the mean daily dose of mirtazapine was 18.3 ± 1.3 vs 14.0 ± 1.0 mg for fluoxetine at the endpoint. Weight gain occurred more frequently in the mirtazapine group (50 vs 7.7%, P = 0.04) and nausea and paresthesia occurred more often in the fluoxetine group (P = 0.01). Results suggest that mirtazapine has properties that make it attractive for the treatment of panic disorder.

Respiratory panic disorder subtype and sensitivity to the carbon dioxide challenge test

The aim of the present study was to verify the sensitivity to the carbon dioxide (CO2) challenge test of panic disorder (PD) patients with respiratory and nonrespiratory subtypes of the disorder. Our hypothesis is that the respiratory subtype is more sensitive to 35% CO2. Twenty-seven PD subjects with or without agoraphobia were classified into respiratory and nonrespiratory subtypes on the basis of the presence of respiratory symptoms during their panic attacks. The tests were carried out in a double-blind manner using two mixtures: 1) 35% CO2 and 65% O2, and 2) 100% atmospheric compressed air, 20 min apart. The tests were repeated after 2 weeks during which the participants in the study did not receive any psychotropic drugs. At least 15 of 16 (93.7%) respiratory PD subtype patients and 5 of 11 (43.4%) nonrespiratory PD patients had a panic attack during one of two CO2 challenges (P = 0.009, Fisher exact test). Respiratory PD subtype patients were more sensitive to the CO2 challenge test. There was agreement between the severity of PD measured by the Clinical Global Impression (CGI) Scale and the subtype of PD. Higher CGI scores in the respiratory PD subtype could reflect a greater sensitivity to the CO2 challenge due to a greater severity of PD. Carbon dioxide challenges in PD may define PD subtypes and their underlying mechanisms.

The size and prevalence of the cavum septum pellucidum are normal in subjects with panic disorder

Panic disorder is thought to involve dysfunction in the septohippocampal system, and the presence of a cavum septum pellucidum might indicate the aberrant development of this system. We compared the prevalence and size of cavum septum pellucidum in 21 patients with panic disorder and in 21 healthy controls by magnetic resonance imaging. The length of the cavum septum pellucidum was measured by counting the number of consecutive 1-mm coronal slices in which it appeared. A cavum septum pellucidum of >6 mm in length was rated as large. There was no significant difference in the proportion of patients (16 of 21 or 76.2%) and controls (18 of 21 or 85.7%) with a cavum septum pellucidum (P = 0.35, Fisher's exact test, one-tailed), and no members of either group had a large cavum septum pellucidum. The mean cavum septum pellucidum rating in the patient and control groups was 1.81 (SD = 1.50) and 2.09 (SD = 1.51), respectively. There were also no significant differences between groups when we analyzed cavum septum pellucidum ratings as a continuous variable (U = 196.5; P = 0.54). Across all subjects there was a trend towards a higher prevalence of cavum septum pellucidum in males (100%, 10 of 10) than females (75%, 24 of 32; P = 0.09, Fisher's exact test, one-tailed). Thus, we conclude that, while panic disorder may involve septo-hippocampal dysfunction, it is not associated with an increased prevalence or size of the cavum septum pellucidum.