Poor Remission Rate Research Articles

Care pathways, prescribing practices and treatment outcomes in major depressive disorder and treatment-resistant depression: retrospective, population-based cohort study.

Despite the availability of effective therapies, many patients with major depressive disorder (MDD) develop treatment-resistant depression (TRD). To evaluate and compare prescribing patterns, contact with specialist services and treatment outcomes in patients with MDD and TRD. This was a retrospective analysis of linked primary and secondary care National Health Service data in the north-west London Discover-NOW data-set. Eligible patients were adults who had diagnostic codes for depression and had been prescribed at least one antidepressant between 2015 and 2020. A total of 110 406 patients were included, comprising 101 333 (92%) with MDD and 9073 (8%) with TRD. Patients with TRD had significantly higher risks of suicidal behaviour and comorbidities such as anxiety, asthma, and alcohol or substance misuse (all P < 0.0001). Citalopram, sertraline, fluoxetine and mirtazapine accounted for 83% of MDD and 71% of TRD prescriptions. Use of antidepressant switching (1% MDD, 7% TRD) and combination therapy (1%, 5%) was rare, whereas augmentation occurred more frequently in the TRD group (4%, 35%). Remission was recorded in 42 348 (42%) patients with MDD and 1188 (13%) with TRD (P < 0.0001), whereas relapse was seen in 20 970 (21%) and 4923 (54%), respectively (P < 0.0001). Mean times from diagnosis to first contact with mental health services were 38.9 (s.d. 33.6) months for MDD and 41.5 (s.d. 32.0) months for TRD (P < 0.0001). There appears to be a considerable difference between treatment guidelines for depression and TRD and the reality of clinical practice. Long-term treatment with single antidepressants, poor remission, and high relapse rates among patients in primary care highlight the need to optimise treatment pathways and access to newer therapies.

Improved efficacy of quizartinib in combination therapy with PI3K inhibition in primary FLT3-ITD AML cells.

Acute myeloid leukemia is a heterogeneous hematopoietic malignancy, characterized by uncontrolled clonal proliferation of abnormal myeloid progenitor cells, with poor outcomes. The internal tandem duplication (ITD) mutation of the Fms-like receptor tyrosine kinase 3 (FLT3) (FLT3-ITD) represents the most common genetic alteration in AML, detected in approximately 30% of AML patients, and is associated with high leukemic burden and poor prognosis. Therefore, this kinase has been regarded as an attractive druggable target for the treatment of FLT3-ITD AML, and selective small molecule inhibitors, such as quizartinib, have been identified and trialled. However, clinical outcomes have been disappointing so far due to poor remission rates, also because of acquired resistance. A strategy to overcome resistance is to combine FLT3 inhibitors with other targeted therapies. In this study, we investigated the preclinical efficacy of the combination of quizartinib with the pan PI3K inhibitor BAY-806946 in FLT3-ITD cell lines and primary cells from AML patients. We show here that BAY-806946 enhanced quizartinib cytotoxicity and, most importantly, that this combination increases the ability of quizartinib to kill CD34+ CD38-leukemia stem cells, whilst sparing normal hematopoietic stem cells. Because constitutively active FLT3 receptor tyrosine kinase is known to boost aberrant PI3K signaling, the increased sensitivity of primary cells to the above combination can be the mechanistic results of the disruption of signaling by vertical inhibition.

SAFETY AND EFFICACY OF MYCOPHENOLATE MOFETIL TREATMENT FOR REFRACTORY CROHN’S DISEASE

Medically refractory Crohn’s disease is a significant challenge with poor remission rates and limited medication options. Mycophenolate mofetil (MMF), a small molecule immune suppressant, has mixed data to support its use in Crohn’s disease and has not been studied in refractory disease or biologic experienced patients.

SAFETY AND EFFICACY OF MYCOPHENOLATE MOFETIL TREATMENT FOR REFRACTORY CROHN'S DISEASE

Abstract BACKGROUND Medically refractory Crohn’s disease is a significant challenge with poor remission rates and limited medication options. Mycophenolate mofetil (MMF), a small molecule immune suppressant, has mixed data to support its use in Crohn’s disease and has not been studied in refractory disease or biologic experienced patients. AIMS We aimed to evaluate the safety and efficacy of off-label clinical MMF treatment for refractory Crohn’s disease as monotherapy or in combination with a biologic. METHODS We retrospectively assessed adverse events (AEs), clinical response (Harvey-Bradshaw Index, HBI), endoscopic response (Simple Endoscopic Score in Crohn’s Disease, SES-CD), and physician’s subjective assessment (scale of 0-3) over 52 weeks at a single medical system including an academic medical center and county hospital. RESULTS 61 patients received MMF as monotherapy (n=41) or in combination with a biologic (n=20) between 2008 and 2021 at a dose ranging from 500 – 2000 mg BID. Median age was 39 years (range 19-69) and median disease duration was 11 years (range 2-54). All patients had failed one or more TNF-alpha antagonist; the median number of failed biologics was 4. Median duration of therapy was 27 weeks. Of patients with requisite data, 14/27 (52%) achieved clinical response (HBI decreased by ≥3) after mean 24.2 weeks (SD 20.4). 6/27 (22%) achieved clinical remission (HBI ≤4). Endoscopic response (SES-CD reduction ≥50%) occurred in 7/26 patients (27%) after mean 43.5 weeks (SD 29.5). Endoscopic remission (SES-CD ≤3) occurred in 4/26 patients (15%) and endoscopic healing (SES-CD =0) in 2/26 patients (8%). Per physician’s subjective assessment, 17/51 patients (33%) achieved clinical response (score improved by ≥1), 16/51 (31%) achieved clinical remission (score of 0 or 1), 10/34 patients (29%) achieved endoscopic response and 9/34 patients (26%) achieved endoscopic remission. Table 1 shows clinical and endoscopic response separated by monotherapy or in combination with a biologic. AEs were reported in 27/61 patients (44%); 16 on monotherapy and 11 on combination. Most common AEs were mild infection, nausea/vomiting, abdominal pain, and diarrhea. Nausea/vomiting and diarrhea led to early discontinuation for several patients. Serious adverse events occurred in 2/61 patients (pneumonia requiring hospitalization and SVT) both on monotherapy. CONCLUSIONS MMF appears well-tolerated and results in clinical and endoscopic benefit for some patients with refractory Crohn’s disease. This study is limited by uncontrolled, retrospective design and small numbers that were eligible for analysis. The results support additional prospective testing of MMF either as monotherapy or in combination with a biologic for patients with refractory Crohn’s disease.

The incidence of eosinophilic oesophagitis in 2007\u20132017 among children in North Denmark Region is lower than expected

BackgroundIn North Denmark Region (NDR), the incidence of Eosinophilic Oesophagitis (EoE) among adults has increased following a new biopsy protocol in 2011, whereas data on the incidence of EoE among children is lacking.AimsTo describe the incidence of EoE in children aged 0–17 in NDR as well as diagnostic delay, clinical manifestations, treatment and complications.MethodsThis retrospective, register-based DanEoE cohort study included 18 children diagnosed with EoE between 2007–2017 in NDR. Medical files were reviewed with attention to symptoms, reason for referral, disease progress, treatment, symptomatic and histological remission as well as diagnostic delay.ResultsThe median incidence per year (2007–2017) was 0.86/100,000 children in NDR aged 0–17 years. The median diagnostic delay among children was four years and six months. Sixty percent presented with food impaction at first hospital visit. After initial treatment, only one of 18 children achieved symptomatic and histologic remission and had a long-term treatment plan.ConclusionsThe calculated incidence among children was lower compared to similar studies. Combined with poor remission rates and lack of follow-up, it is likely that EoE is an underdiagnosed and insufficiently treated disease among children in NDR. Our findings suggest that more knowledge concerning EoE in children could lead to a higher incidence, shorter diagnostic delay and more effective treatment.

Emerging Role of Flavonoids as the Treatment of Depression.

Depression is one of the most frequently observed psychological disorders, affecting thoughts, feelings, behavior and a sense of well-being in person. As per the WHO, it is projected to be the primitive cause of various other diseases by 2030. Clinically, depression is treated by various types of synthetic medicines that have several limitations such as side-effects, slow-onset action, poor remission and response rates due to complicated pathophysiology involved with depression. Further, clinically, patients cannot be given the treatment unless it affects adversely the job or family. In addition, synthetic drugs are usually single targeted drugs. Unlike synthetic medicaments, there are many plants that have flavonoids and producing action on multiple molecular targets and exhibit anti-depressant action by affecting multiple neuronal transmissions or pathways such as noradrenergic, serotonergic, GABAnergic and dopaminergic; inhibition of monoamine oxidase and tropomyosin receptor kinase B; simultaneous increase in nerve growth and brain-derived neurotrophic factors. Such herbal drugs with flavonoids are likely to be useful in patients with sub-clinical depression. This review is an attempt to analyze pre-clinical studies, structural activity relationship and characteristics of reported isolated flavonoids, which may be considered for clinical trials for the development of therapeutically useful antidepressant.

Poor Outcomes With the Use of Checkpoint Inhibitors in Kidney Transplant Recipients.

Checkpoint inhibitors are now frequently used for oncologic conditions. The impact of these therapies in solid organ transplant recipients was not assessed in clinical trials. Subsequent case reports highlight the major detrimental interactions of checkpoint inhibitors and the high risk of allograft rejection with their use. Patient outcomes have not been assessed in long-term follow-up. We conducted a retrospective review of kidney transplant recipients with metastatic cancer who received checkpoint inhibitors at a single center between April 2015 and May 2018. Six kidney transplant recipients with metastatic cancers that were not responding to first-line treatments met study criteria. These include 2 with squamous cell cancers, 2 with melanoma, 1 with renal cell cancer, and 1 with adenocarcinoma of the lung. Four patients received anti-programmed cell death protein-1 (PD-1) antibody and 2 received a combination of anticytotoxic T-lymphocyte-associated protein 4 and anti-PD-1 antibodies. Three out of 6 patients developed acute kidney injury. Two were biopsy-proven acute rejections with subsequent graft failures. The third was attributed to rejection, but improved after discontinuing the checkpoint inhibitor. Five out of 6 patients had cancer progression and only 1 patient had remission. Providers and patients need to be aware of the high risk of rejection and the poor remission rate with the use of checkpoint inhibitors in kidney transplant patients. More research is warranted to assess the optimal maintenance immunosuppression during the use of checkpoint inhibitor therapy that would not diminish the chances of remission.

Inequity of care provision and outcome disparity in autoimmune hepatitis in the United Kingdom.

SummaryBackgroundTreatment paradigms in autoimmune hepatitis (AIH) have remained largely unchanged for decades. Studies report ≤20% of patients have sub‐optimal treatment response with most requiring long‐term therapy.AimThe United Kingdom Autoimmune Hepatitis (UK‐AIH) study was established to evaluate current treatment practice and outcomes, determine the unmet needs of patients, and develop and implement improved treatment approaches.MethodsThe United Kingdom Autoimmune Hepatitis study is a cross‐sectional cohort study examining secondary care management of prevalent adult patients with a clinical diagnosis of autoimmune hepatitis. Enrolment began in March 2014. Prevalent cases were defined as having been diagnosed and treated for >1 year. Demographic data, biochemistry, treatment history and response, and care location were collected.ResultsIn total, 1249 patients were recruited; 635 were cared for in transplant units and 614 in non‐transplant centres (81% female with median age at diagnosis 50 years). Overall, 29 treatment regimens were reported and biochemical remission rate was 59%. Remission rates were significantly higher in transplant compared to non‐transplant centres (62 vs 55%, P = 0.028). 55% have ongoing corticosteroid exposure; 9% are receiving prednisolone monotherapy. Those aged ≤20 years at diagnosis were more likely to develop cirrhosis and place of care was associated with an aggressive disease phenotype.ConclusionsThere are significant discrepancies in the care received by patients with autoimmune hepatitis in the UK. A high proportion remains on corticosteroids and there is significant treatment variability. Patients receiving care in transplant centres were more likely to achieve and maintain remission. Overall poor remission rates suggest that there are significant unmet therapeutic needs for patients with autoimmune hepatitis.

Duration of post-operative hypocortisolism predicts sustained remission after pituitary surgery for Cushing's disease.

PurposeTranssphenoidal surgery (TSS) is the primary treatment modality for Cushing’s disease (CD). However, the predictors of post-operative remission and recurrence remain debatable. Thus, we studied the post-operative remission and long-term recurrence rates, as well as their respective predictive factors.MethodsA retrospective analysis of case records of 230 CD patients who underwent primary microscopic TSS at our tertiary care referral centre between 1987 and 2015 was undertaken. Demographic features, pre- and post-operative hormonal values, MRI findings, histopathological features and follow-up data were recorded. Remission and recurrence rates as well as their respective predictive factors were studied.ResultsOverall, the post-operative remission rate was 65.6% (early remission 46%; delayed remission 19.6%), while the recurrence rate was 41% at mean follow-up of 74 ± 61.1 months (12–270 months). Significantly higher early remission rates were observed in patients with microadenoma vs macroadenoma (51.7% vs 30.6%, P = 0.005) and those with unequivocal vs equivocal MRI for microadenoma (55.8% vs 38.5%, P = 0.007). Patients with invasive macroadenoma had poorer (4.5% vs 45%, P = 0.001) remission rates. Recurrence rates were higher in patients with delayed remission than those with early remission (61.5% vs 30.8%, P = 0.001). Duration of post-operative hypocortisolemia ≥13 months predicted sustained remission with 100% specificity and 46.4% sensitivity. Recurrence could be detected significantly earlier (27.7 vs 69.2 months, P < 0.001) in patients with available serial follow-up biochemistry as compared to those with infrequent follow-up after remission.ConclusionIn our study, remission and recurrence rates were similar to that of reported literature, but proportion of delayed remission was relatively higher. Negative/equivocal MRI findings and presence of macroadenoma, especially those with cavernous sinus invasion were predictors of poor remission rates. In addition to early remission, longer duration of post-operative hypocortisolism is an important predictor of sustained remission. Regular biochemical surveillance may help in identifying recurrence early.

喉頭肉芽腫64例の臨床的検討

Vocal process granulomas are mainly associated with vocal abuse, gastroesophageal reflux disease (GERD), or endotracheal intubation. In the present study, we evaluate the prognostic factors and the usefulness of a grading system in 64 patients with vocal process granulomas. We classified the granuloma which limited the vocal process of the arytenoid cartilage as grade I, and which originated from the vocal process but extended beyond the vocal process of the arytenoid cartilage as grade II, according to the grading system proposed by Wang CP, et al. First, we treated this disease with conservative treatments including a proton pump inhibitor, steroid inhalation, or voice therapy. Surgical treatment was reserved for failures of conservative treatments or when the diagnosis was in doubt. The overall post-surgical recurrence rate was 65.7%, and it was significantly higher in male than female patients, and in younger than older patients. The overall remission rate was 79.7%. A multivariate analysis revealed that Grade II was a significantly poor prognostic factor and the patients with BMI ≥23 or Age <60 had a tendency to have a poor remission rate. The grading system is useful for anticipating the prognosis in cases of vocal process granuloma.

Neuromyelitis optica: Evaluation of 871 attacks and 1,153 treatment courses.

Neuromyelitis optica (NMO) attacks often are severe, are difficult to treat, and leave residual deficits. Here, we analyzed the frequency, sequence, and efficacy of therapies used for NMO attacks. A retrospective review was made of patient records to assess demographic/diagnostic data, attack characteristics, therapies, and the short-term remission status (complete remission [CR], partial remission [PR], no remission [NR]). Inclusion criteria were NMO according to Wingerchuk's 2006 criteria or aquaporin-4 antibody-positive NMO spectrum disorder (NMOSD). Remission status was analyzed with generalized estimating equations (GEEs), a patient-based statistical approach. A total of 871 attacks in 185 patients (142 NMO/43 NMOSD, 82% female) were analyzed. The 1,153 treatment courses comprised high-dose intravenous steroids (HD-S; n = 810), plasma exchange (PE; n = 192), immunoadsorption (IA; n = 38), other (n = 80), and unknown (n = 33) therapies. The first treatment course led to CR in 19.1%, PR in 64.5%, and NR in 16.4% of attacks. Second, third, fourth, and fifth treatment courses were given in 28.2%, 7.1%, 1.4%, and 0.5% of attacks, respectively. This escalation of attack therapy significantly improved outcome (p < 0.001, Bowker test). Remission rates were higher for isolated optic neuritis versus isolated myelitis (p < 0.001), and for unilateral versus bilateral optic neuritis (p = 0.020). Isolated myelitis responded better to PE/IA than to HD-S as first treatment course (p = 0.037). Predictors of CR in multivariate GEE analysis were age (odds ratio [OR] = 0.97, p = 0.011), presence of myelitis (OR = 0.38, p = 0.002), CR from previous attack (OR = 6.85, p < 0.001), and first-line PE/IA versus HD-S (OR = 4.38, p = 0.006). Particularly myelitis and bilateral optic neuritis have poor remission rates. Escalation of attack therapy improves outcome. PE/IA may increase recovery in isolated myelitis.

Prognostic impact of KMT2E transcript levels on outcome of patients with acute promyelocytic leukaemia treated with all-trans retinoic acid and anthracycline-based chemotherapy: an International Consortium on Acute Promyelocytic Leukaemia study.

The KMT2E (MLL5) gene encodes a histone methyltransferase implicated in the positive control of genes related to haematopoiesis. Its close relationship with retinoic acid-induced granulopoiesis suggests that the deregulated expression of KMT2E might lead acute promyelocytic leukaemia (APL) blasts to become less susceptible to the conventional treatment protocols. Here, we assessed the impact of KMT2E expression on the prognosis of 121 APL patients treated with ATRA and anthracycline-based chemotherapy. Univariate analysis showed that complete remission (P=0·006), 2-year overall survival (OS) (P=0·005) and 2-year disease-free survival (DFS) rates (P=0·037) were significantly lower in patients with low KMT2E expression; additionally, the 2-year cumulative incidence of relapse was higher in patients with low KMT2E expression (P=0·04). Multivariate analysis revealed that low KMT2E expression was independently associated with lower remission rate (odds ratio [OR]: 7·18, 95% confidence interval [CI]: 1·71-30·1; P=0·007) and shorter OS (hazard ratio [HR]: 0·27, 95% CI: 0·08-0·87; P=0·029). Evaluated as a continuous variable, KMT2E expression retained association with poor remission rate (OR: 10·3, 95% CI: 2·49-43·2; P=0·001) and shorter survival (HR: 0·17, 95% IC: 0·05-0·53; P=0·002), while the association with DFS was of marginal significance (HR: 1·01; 95% CI: 0·99-1·02; P=0·06). In summary, low KMT2E expression may predict poor outcome in APL patients.

Impact of Technique on Cushing Disease Outcome Using Strict Remission Criteria

Cushing disease (CD) constitutes a challenging condition for the pituitary surgeon. Given the variety of factors affecting outcomes in CD, it is uncertain whether the newer endoscopic technique improves the results of surgery. A review was conducted of CD cases at our institution between 2000 and 2010. Analysis was done to: determine if surgical technique had an effect on outcome, identify the predictors of outcome and provide details of failed cases. Remission was defined as normal postoperative 24-hour urinary free cortisol (24-h UFC), suppression of morning serum cortisol to <50 nmol/L after 1mg of dexamethasone or being dependent on steroid replacement. Forty-two patients met our inclusion criteria. Average follow-up period was 33 months. There were 15 macroadenomas and 27 microadenomas. Seventeen patients had an endoscopic transsphenoidal surgery and twenty-five patients had a microscopic transsphenoidal procedure. Long-term overall remission was achieved in 26 (62%) patients. There was no significant difference in remission rates between the two techniques (p value 0.757). Patient's subjective symptomatic improvement and drop of morning serum cortisol in the postoperative period to less than 100 nmol/L correlated with long-term remission (p value 0.0031 and 0.0101, respectively) while repeat surgery was the only predictor of the lack of postoperative remission (p value 0.0008). Revision surgery predicted poor remission rate for CD. Within the power of our study size, there was no difference in outcome between the endoscopic and microscopic approaches. Surgical outcomes should be reviewed in association with remission criteria used in a study.

Obesity and reduction of the response rate to anti–tumor necrosis factor α in rheumatoid arthritis: An approach to a personalized medicine

Obesity is a mild, long-lasting inflammatory disease and, as such, could increase the inflammatory burden of rheumatoid arthritis (RA). The study aim was to determine whether obesity represents a risk factor for a poor remission rate in RA patients requiring anti-tumor necrosis factor α (anti-TNFα) therapy for progressive and active disease despite treatment with methotrexate or other disease-modifying antirheumatic drugs. Patients were identified from 15 outpatient clinics of university hospitals and hospitals in Italy taking part in the Gruppo Italiano di Studio sulle Early Arthritis network. Disease Activity Score in 28 joints (DAS28), body mass index (BMI; categorized as <25, 25-30, and >30 kg/m(2) ), acute-phase reactants, IgM rheumatoid factor, and anti-cyclic citrullinated peptide antibody values were collected. DAS28 remission was defined as a score of <2.6 lasting for at least 3 months. Six hundred forty-one outpatients with longstanding RA receiving anti-TNFα blockers (adalimumab, n = 260; etanercept, n = 227; infliximab, n = 154), recruited from 2006-2009 and monitored for at least 12 months, were analyzed. The mean ± SD DAS28 at baseline was 5.6 ± 1.4. A BMI of >30 kg/m(2) was recorded in 66 (10.3%) of 641 RA patients. After 12 months of anti-TNFα treatment, a DAS28 of <2.6 was noted in 15.2% of the obese subjects, in 30.4% of the patients with a BMI of 25-30 kg/m(2) , and in 32.9% of the patients with a BMI of <25 kg/m(2) (P = 0.01). The lowest percentage of remission, which was statistically significant versus adalimumab and etanercept (P = 0.003), was observed with infliximab. Obesity represents a risk factor for a poor remission rate in patients with longstanding RA treated with anti-TNFα agents. A personalized treatment plan might be a possible solution.

Late-Life Depression Not a Unified Syndrome

Back to table of contents Previous article Next article Clinical & Research NewsFull AccessLate-Life Depression Not a Unified SyndromeAaron LevinAaron LevinSearch for more papers by this authorPublished Online:6 Jul 2012https://doi.org/10.1176/pn.47.13.psychnews_47_13_12-bAbstract“Geriatric depression is a hypothesis, not a syndrome,” George Alexopoulos, M.D., postulated at a symposium on geriatric psychiatry at APA’s 2012 annual meeting in Philadelphia in May.Alexopoulos, a professor of psychiatry at Weill-Cornell Medical College in New York and founder and director of the Weill-Cornell Institute of Geriatric Psychiatry, has spent a career exploring the complexities of late-life depression.Elderly patients who present with late-onset depression exhibit a different constellation of symptoms than older people whose depression first appeared when they were young, said Alexopoulos.In general, late-onset patients appear to have higher rates of dementia, cognitive dysfunction, or structural brain abnormalities, he said.That is because when depression starts late in life, it often occurs in people with vascular disease or severe vascular risk factors, he said. Rapid changes occur once vascular disease begins, including psychomotor retardation, apathy, lack of guilt and insight, disproportionate disability, and executive dysfunction.The last of these has been the focus of much research attention, said Alexopoulos. Poor abstract thinking, difficulty planning, and perseveration leave patients messy and disorganized.“They don’t get better executive function even if you treat their depression,” he said. “So we have hypothesized that there is a form of depression with executive dysfunction characterized by periventricular white-matter hyperintensities.”Research shows that depressed patients who remit have similar volumes of hyperintensities as controls, while nonremitters have higher volumes, suggesting a different etiology or disease course.Individuals with the s-allele of the 5-HTTLPR gene also demonstrated increased white-matter hyperintensities and poorer remission rates, leading Alexopoulos to speculate that the s-allele’s influence on poor remission may be associated with microstructural lesions in the prefrontal cortex.In some ways, this syndrome resembles medial frontal lobe syndrome and has a poor response to serotonin antidepressants, he said.In addition, the cognitive control network (including the anterior cingulate cortex and the dorsolateral prefrontal cortex) has been thought of as a structure remote from emotional events, but that may not be true, he suggested. The network is impaired in elderly patients and may cause a poor response to antidepressant drugs, although not to psychotherapy.“Depressed patients with executive dysfunction respond well to problem-solving therapy,” he said.Alexopoulos suggests the following etiology for late-onset depression among the elderly: vascular changes produce repair responses and inflammation, triggering a cascade of events leading to a predisposition for depression that is expressed in frontolimbic compromise, either alone or in response to neurobiological responses associated with stress that lead to mechanisms mediating depression.With that in mind, he has tested several therapies, although so far without definitive outcomes, he said.One trial of the anti-inflammatory antibiotic minocycline in six patients who had failed at least one antidepressant had mixed results. Two showed an excellent response, three were considered “good,” and one regressed.Prevention studies have proved equally ambiguous. Trials of cholinesterase inhibitors, NMDA inhibitors, and statins have yet to show benefit, he said.Taken together, the research leads Alexopoulos to state cautiously where the field stands at present and where it must go to find useful treatments.“Vascular depression is not a syndrome,” he said. “It is a hypothesis about etiology and pathogenesis that has served as the conceptual basis for developing studies with testable hypotheses.” ISSUES NewArchived

Extended Transsternal Thymectomy for Myasthenia Gravis: a Report of 19 Consecutive Cases

Background : Thymectomy is considered as an effective therapeutic option for patients with myasthenia gravis (MG). This study reports the experience of our centre’s investigation into the efficacy and the safety of the procedure and the influence of different pre-operative factors on the surgical outcome.Methods : A retrospective chart review/interview was made of 19 consecutive patients who underwent extended transsternal thymectomy for MG from 1992 to 2003. The severity of the disease was determined according to the Osserman Classification. Efficacy was measured by determining the change in clinical status, the rate of remission during follow-up, and the reduction in medication requirements after thymectomy. Complete remission (CR) was defined as asymptomatic off medication for 6 months. The CR rate was calculated using the Kaplan-Meyer method. Results : The mean age of the patients at surgery was 34 years (range, 9–63) and 78.9% were female. Mean length of follow up was 86 months (range, 24–163). The overall complication rate was 10.6% (1 episode of atrial fibrillation and a left recurrent laryngeal nerve palsy that resolved after the first postoperative month). There was no operative mortality. The mean hospital stay was 9.4 days (range, 5–23). The crude CR rate was 32% (n = 6). The Kaplan-Meier estimate of CR was 42% at 6 years. Age, gender, duration of symptoms, thymic histology, Osserman stage and the presence of thymoma were not identified as prognostic variables. The average daily dose of Medrol® and Mestinon® decreased significantly between the pre-operative period and the last follow-up (Medrol®, p = 0.0081; Mestinon®, p = 0.0013).Conclusions : Transsternal thymectomy for MG is safe and effective. It benefits patients with MG at all stages. Patients with thymoma are not associated with poorer remission rates. Complete responses are durable, as the CR rate remains stable over time.

Remission Rates for Depression in STAR*D Study

Back to table of contents Previous article Next article Letters to the EditorFull AccessRemission Rates for Depression in STAR*D StudyRobert Hierholzer M.D.,Robert Hierholzer M.D.Search for more papers by this author,Published Online:1 Jul 2006AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: The less than spectacular remission rates for depression recently reported in The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (1) will likely be of no surprise to experienced clinicians. I, for one, am relieved to find that the frustratingly poor remission rates that I’ve witnessed for many years among my depressed patients (most of whom are characterized by features associated in the study with lower remission rates) are in accord with a well-designed effectiveness study such as STAR*D. The STAR*D study is a welcome change from the era of efficacy studies in which patients like mine were largely excluded. The “real world” findings of the STAR*D study pose thought-provoking questions concerning how we think about and promote treatments for depression. Much of the current promotional and educational literature on depression is infused with the more optimistic response (not remission) figures derived from older antidepressant efficacy studies. Certainly, much of the promotional literature emanating from the pharmaceutical industry seems to promise better results with antidepressants than those obtained in STAR*D. I doubt that any pharmaceutical company would want it to be said that their antidepressant appears to be “only sufficient for a minority of patients, particularly high functioning, well-educated women with few comorbid psychiatric or medical problems” ( 2 , p. 6). Even information from an APA informational website (www.healthyminds.org) on the treatment of depression, although no doubt technically accurate, seems to gloss over the unpleasant realities of the limitations in our treatments: “between 80%–90% of people with depression eventually respond well to treatment.” We don’t serve anyone well by overselling what we have to offer. My clinical sense is that “real world” patients are often perplexed when they don’t rapidly achieve a spectacular response from their medication, whatever it is. It is worth debating when our desire to impart hope becomes downright misleading to patients and their families and when overly optimistic pronouncements about the effectiveness of our treatments undercut our pleas for additional funding to study a wide range of treatment interventions for depression and other mental disorders, especially those interventions that may lack the financial backing of industry. Obviously, this initial report from the STAR*D study is not the end of the matter, and it is important to note that the report suggests interventions that might yield higher remission rates (1) . I look forward to subsequent publications from STAR*D that will, hopefully, help us to better educate the public about what to expect from medications and what best to do when our patients are not among the minority who fully remit with the first medication that they try. Fresno, Calif.

Remission Rates for Depression in STAR*D Study

Back to table of contents Previous article Next article Letters to the EditorFull AccessRemission Rates for Depression in STAR*D StudyRobert Hierholzer M.D.,Robert Hierholzer M.D.Search for more papers by this author,Published Online:1 Jul 2006AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: The less than spectacular remission rates for depression recently reported in The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (1) will likely be of no surprise to experienced clinicians. I, for one, am relieved to find that the frustratingly poor remission rates that I’ve witnessed for many years among my depressed patients (most of whom are characterized by features associated in the study with lower remission rates) are in accord with a well-designed effectiveness study such as STAR*D. The STAR*D study is a welcome change from the era of efficacy studies in which patients like mine were largely excluded. The “real world” findings of the STAR*D study pose thought-provoking questions concerning how we think about and promote treatments for depression. Much of the current promotional and educational literature on depression is infused with the more optimistic response (not remission) figures derived from older antidepressant efficacy studies. Certainly, much of the promotional literature emanating from the pharmaceutical industry seems to promise better results with antidepressants than those obtained in STAR*D. I doubt that any pharmaceutical company would want it to be said that their antidepressant appears to be “only sufficient for a minority of patients, particularly high functioning, well-educated women with few comorbid psychiatric or medical problems” ( 2 , p. 6). Even information from an APA informational website (www.healthyminds.org) on the treatment of depression, although no doubt technically accurate, seems to gloss over the unpleasant realities of the limitations in our treatments: “between 80%–90% of people with depression eventually respond well to treatment.” We don’t serve anyone well by overselling what we have to offer. My clinical sense is that “real world” patients are often perplexed when they don’t rapidly achieve a spectacular response from their medication, whatever it is. It is worth debating when our desire to impart hope becomes downright misleading to patients and their families and when overly optimistic pronouncements about the effectiveness of our treatments undercut our pleas for additional funding to study a wide range of treatment interventions for depression and other mental disorders, especially those interventions that may lack the financial backing of industry. Obviously, this initial report from the STAR*D study is not the end of the matter, and it is important to note that the report suggests interventions that might yield higher remission rates (1) . I look forward to subsequent publications from STAR*D that will, hopefully, help us to better educate the public about what to expect from medications and what best to do when our patients are not among the minority who fully remit with the first medication that they try. Fresno, Calif.

The impact of substance use disorders on clinical outcome in 643 patients with first‐episode psychosis

Studies investigating the impact of comorbid substance use disorders (SUD) in psychosis have tended to focus on cross-sectional data, with few studies examining the effects of substance use course on clinical outcome. The main aim of the present study was to assess the impact of baseline SUD and course of SUD on remission of positive symptoms. The Early Psychosis Prevention and Intervention Centre admitted 786 first-episode psychosis (FEP) patients between 1998 and 2000. Data on SUD and clinical outcome were collected from patients' medical records (MR) of 643 patients who met inclusion criteria. Lifetime prevalence of SUD was 74%, with 62% having a SUD at baseline. This reduced to 36% in those patients who completed 18 months of treatment at the EPPIC program. A Cox regression analysis indicated that a decrease or cessation of substance use significantly increased the probability of remission, whilst persistent SUD substantially reduced the likelihood. In addition, patients who reduced use appeared to have better outcomes at 18 months than those patients who had never used substances. Baseline SUD was not found to have any significant influence on symptom remission. Patients presenting with FEP have high rates of SUD. Effective management of psychosis within a specialized service is associated with reductions in SUD over the course of treatment, although persistent substance use is associated with non-compliance, treatment drop-out and poor remission rates. As such, young people with FEP and comorbid substance use should be offered integrated treatment that addresses both disorders.

Remission in Depressed Geriatric Primary Care Patients: A Report From the PROSPECT Study

This study compared time to first remission for elderly depressed patients in primary care for practices that implemented a care management model versus those providing usual care. In addition, it sought to identify risk factors for nonremission that could guide treatment planning and referral to care managers or specialists. Prevention of Suicide in Primary Care Elderly: Collaborative Trial (PROSPECT) data were analyzed. Participants were older patients (> or =60 years) selected following screening of 9,072 randomly identified primary care patients. The present analysis examined patients with major depression and a 24-item Hamilton Depression Rating Scale score of 18 or greater who were followed for at least 4 months (N=215). Primary care practices were randomly assigned to offer the PROSPECT intervention or usual care. The intervention consisted of services of trained care managers, who offered algorithm-based recommendations to physicians and helped patients with treatment adherence over 18 months. First remission occurred earlier and was more common among patients receiving the intervention than among those receiving usual care. For all patients, limitations in physical and emotional functions predicted poor remission rate. Patients experiencing hopelessness were more likely to achieve remission if treated in intervention practices. Similarly, the intervention was more effective in patients with low baseline anxiety. Longitudinal assessment of depression, hopelessness, anxiety, and physical and emotional functional limitations in depressed older primary care patients is critical. Patients with prominent symptoms or impairment in these areas may be candidates for care management or mental health care, since they are at risk for remaining depressed and disabled.