Multifocality and multicentricity are not contraindications for sentinel lymph node biopsy in breast cancer surgery

BACKGROUND: After the availability of the results of validation studies, the sentinel lymph node biopsy (SLNB) has replaced routine axillary dissection (AD) as the new standard of care in early unifocal breast cancers. Multifocal (MF) and multicentric (MC) tumors have been considered a contraindication for this technique due to the possible incidence of a higher false-negative rate. This prospective study evaluates the lymphatic drainage from different tumoral foci of the breast and assesses the accuracy of SLNB in MF-MC breast cancer. PATIENTS AND METHODS: Patients with preoperative diagnosis of MF or MC infiltrating and clinically node-negative (cN0) breast carcinoma were enrolled in this study. Two consecutive groups of patients underwent SLN mapping using a different site of injection of the radioisotope tracer: a) "2ID" Group received two intradermal (ID) injections over the site of the two dominant neoplastic nodules. A lymphoscintigraphic study was performed after each injection to evaluate the route of lymphatic spreading from different sites of the breast. b) "A" Group had periareolar (A) injection followed by a conventional lymphoscintigraphy. At surgery, both radioguided SLNB (with frozen section exam) and subsequent AD were planned, regardless the SLN status. RESULTS: A total 31 patients with MF (n = 12) or MC (n = 19) invasive, cN0 cancer of the breast fulfil the selection criteria. In 2 ID Group (n = 15) the lymphoscintigraphic study showed the lymphatic pathways from two different sites of the breast which converged into one major lymphatic trunk affering to the same SLN(s) in 14 (93.3%) cases. In one (6.7%) MC cancer two different pathways were found, each of them affering to a different SLN. In A Group (n = 16) lymphoscintigraphy showed one (93.7%) or two (6.3%) lymphatic channels, each connecting areola with one or more SLN(s). Identification rate of SLN was 100% in both Groups. Accuracy of frozen section exam on SLN was 96.8% (1 case of micrometastasis was missed). SLN was positive in 13 (41.9%) of 31 patients, including 4 cases (30.7%) of micrometastasis. In 7 of 13 (53.8%) patients the SLN was the only site of axillary metastasis. SLNB accuracy was 96.8% (30 of 31), sensitivity 92.8 (13 of 14), and false-negative rate 7.1% (1 of 14). Since the case of skip metastasis was identified by the surgeon intraoperatively, it would have been no impact in the clinical practice. CONCLUSION: Our lymphoscintigraphic study shows that axillary SLN represents the whole breast regardless of tumor location within the parenchyma. The high accuracy of SLNB in MF and MC breast cancer demonstrates, according with the results of other series published in the literature, that both MF and MC tumors do not represent a contraindication for SLNB anymore

Off–label long acting injectable antipsychotics in real–world clinical practice: a cross-sectional analysis of prescriptive patterns from the STAR Network DEPOT study

Introduction: Information on the off–label use of Long–Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on– vs off–label LAIs and predictors of off–label First– or Second–Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice. Method: In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off– or on–label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off–label group. Results: SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on– and off–label use. Approximately 1 in 4 patients received an off–label prescription. In the off–label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p = 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p = 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale. Conclusion: Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off–label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co–morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns

Comparing Long-Acting Antipsychotic Discontinuation Rates Under Ordinary Clinical Circumstances: A Survival Analysis from an Observational, Pragmatic Study

Background: Recent guidelines suggested a wider use of long-acting injectable antipsychotics (LAI) than previously, but naturalistic data on the consequences of LAI use in terms of discontinuation rates and associated factors are still sparse, making it hard for clinicians to be informed on plausible treatment courses. Objective: Our objective was to assess, under real-world clinical circumstances, LAI discontinuation rates over a period of 12 months after a first prescription, reasons for discontinuation, and associated factors. Methods: The STAR Network ‘Depot Study’ was a naturalistic, multicentre, observational prospective study that enrolled subjects initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centres were assessed at baseline and at 6 and 12 months of follow-up. Psychopathology, drug attitude and treatment adherence were measured using the Brief Psychiatric Rating Scale, the Drug Attitude Inventory and the Kemp scale, respectively. Results: The study followed 394 participants for 12 months. The overall discontinuation rate at 12 months was 39.3% (95% confidence interval [CI] 34.4–44.3), with paliperidone LAI being the least discontinued LAI (33.9%; 95% CI 25.3–43.5) and olanzapine LAI the most discontinued (62.5%; 95% CI 35.4–84.8). The most frequent reason for discontinuation was onset of adverse events (32.9%; 95% CI 25.6–40.9) followed by participant refusal of the medication (20.6%; 95% CI 14.6–27.9). Medication adherence at baseline was negatively associated with discontinuation risk (hazard ratio [HR] 0.853; 95% CI 0.742–0.981; p = 0.026), whereas being prescribed olanzapine LAI was associated with increased discontinuation risk compared with being prescribed paliperidone LAI (HR 2.156; 95% CI 1.003–4.634; p = 0.049). Conclusions: Clinicians should be aware that LAI discontinuation is a frequent occurrence. LAI choice should be carefully discussed with the patient, taking into account individual characteristics and possible obstacles related to the practicalities of each formulation

Epidemiology and evolution of the diagnostic classification of factitious disorders in DSM-5

Ivano Caselli, Nicola Poloni, Marta Ielmini, Marcello Diurni, Camilla Callegari Department of Medicine and Surgery, Section of Psychiatry, University of Insubria, Varese, Italy Abstract: A systematic search for all case reports and case series of adult patients with factitious disorders (FD) in the databases MEDLINE, Scopus, and PsycINFO was conducted. FD is a psychiatric disorder in which sufferers intentionally fabricate physical or psychological symptoms in order to assume the role of a patient, without any obvious gain. The clinical and demographic profile of patients with FD has not been sufficiently clear. Thus, the aims of this study were to outline a demographic and clinical profile of a large sample of patients with FD and to study the evolution of the position of FD in the Diagnostic and Statistical Manual of Mental Disorders. One thousand six hundred thirty-six records were obtained based on key search terms, after exclusion of duplicate records. Five hundred seventy-seven articles were identified as potentially eligible for the study, of which 314 studies were retrieved for full-text review. These studies included 514 cases. Variables extracted included age, gender, reported occupation, comorbid psychopathology, clinical presentation, and factors leading to the diagnosis of FD. In the sample, 65.4% of patients were females. Mean age at presentation was 33.5 years. A health care profession was reported most frequently (n=113). Patients were most likely to present in psychiatry, neurology, emergency, and internal medicine departments. The broad survey of sociodemographic profile of the sample has highlighted some important points for early diagnosis and early psychiatric treatment. The study showed that the patients did not meet Diagnostic and Statistical Manual of Mental Disorders-5 diagnostic criteria in 11.3% of cases. Keywords: fabricated illness, factitious disorder, medically unexplained symptoms, Munchausen syndrom

The role of pharmacogenetic testing in the treatment of bipolar disorder: preliminary results

BACKGROUND: Bipolar disorder is a frequent cause of disability and healthcare costs. Variability in outcome leads to a large number of treatment failures, typically followed by a \u201ctrial-and-error\u201d process of medication switches. Pharma-cogenetic tests (PGT) could help clinicians identify the best treatment. The primary aim of this preliminary study was to evaluate if PGT could help clinicians to individuate a better therapy in terms of clinical improvement. Secondary, safety and tolerability improvement, due to possible therapy\u2019s change consistent to PGT, have been evaluated monitoring any treatment-emergent adverse event. METHODS: These study reports the preliminary results of an observational study, dealing with 2 patients affected by Bipolar Disorder I-II, not stabilized by the therapy, recruited from the University Psychiatric Unit of ASST Sette Laghi in Varese and from the ASST Santi Paolo e Carlo Borromeo in Milan, undergoing the Neurofarmagen test (AB Biotics). Patients were assessed using the following scales: the Clinical Global Impression (CGI) scale, the Young Mania Rat- ing Scale (YMRS), the Hamilton Depression Rating Scale (HDRS), and the Dosage Record and Treatment Emergent Symptom Scale (DOTES). Both patients were receiving a suboptimal treatment. In both cases treatment was modified following the Neurofarmagen Test\u2019s results. RESULTS: At one and three months follow-up an improvement in both patients\u2019 psychopathology and tolerability emerged (Case 1: at T0 CGI=5, YMRS=20, HDRS=11; at T1 CGI=3; YMRS=13, HDRS=8; at 3 months the scales\u2019 scores decreased: CGI=2, YMRS=4, HDRS=7; Case 2: at T0 CGI=5, YMRS=14, HDRS=15; at T1 CGI=3, YMRS=10, HDRS=7; at T2 CGI=2, YMRS=6, HDRS=4). CONCLUSIONS: This paper describes only two cases undergone to PGT, and this small sample it is a clear limit, but it suggests an interesting point of view about the important role of pharmacogenomics to help clinicians towards precision and personalized medicineBACKGROUND: Bipolar disorder is a frequent cause of disability and healthcare costs. Variability in outcome leads to a large number of treatment failures, typically followed by a "trial-and-error process of medication switches. Pharmacogenetic tests (PGT) could help clinicians identify the best treatment. The primary aim of this preliminary study was to evaluate if PGT could help clinicians to individuate a better therapy in terms of clinical improvement. Secondary, safety and tolerability improvement, due to possible therapy's change consistent to PGT, have been evaluated monitoring any treatment-emergent adverse event.METIIODS: These study reports the preliminary results of an observational study, dealing with 2 patients affected by Bipolar Disorder I-II, not stabilized by the therapy, recruited from the University Psychiatric Unit of ASST Sette Laghi in Varese and from the ASST Santi Paolo e Carlo Borromeo in Milan, undergoing the Neurofarmagen test (AB Biotics). Patients were assessed using the following scales: the Clinical Global Impression (CGI) scale. the Young Mania Rating Scale (YMRS), the Hamilton Depression Rating Scale (HDRS), and the Dosage Record and Treatment Emergent Symptom Scale (DOTES). Both patients were receiving a suboptimal treatment. In both cases treatment was modified following the Neurofarmagen Test's results.RESULTS: At one and three months follow-up an improvement in both patients' psychopathology and tolerability emerged (Case 1: at TO CG1-5. YMRS=20, HDRS=11; at T1 CGI-3; YMRS-13, HDRS-11; at 3 months the scales' scores decreased: CGI-2. YMRS 4, HDRS=7; Case 2: at TO CGI=5, YMRS-14, HDRS=I5: at T1 CGI=3, YMRS=10, HDRS=7; at T2 CG1=2, YMRS-6, HDRS=4).CONCLUSIONS: This paper describes only two cases undergone to PGT, and this small sample it is a clear limit, but it suggests an interesting point of view about the important role of phannacogenomics to help clinicians towards precision and personalized medicine