Association between serum IgG concentrations and the incidence of infections in patients with chronic lymphocytic leukemia and secondary immunodeficiency under treatment with Privigen.

OBJECTIVE: To investigate the association between serum immunoglobulin G (IgG) concentrations and the incidence of infections in patients with chronic lymphocytic leukemia (CLL) and secondary immunodeficiency receiving treatment with Privigen. MATERIALS AND METHODS: Data was analyzed from a non-interventional study conducted in 31 centers in Germany and 1 in Austria. Adult CLL patients with hypogammaglobulinemia and recurrent infections were allowed to enter the study upon signing informed consent, if a prior decision for treatment with Privigen had been made. All infections requiring an antimicrobial treatment were subject to analysis. Patients were stratified according to their mean post-baseline serum IgG trough levels in a group with lower IgG trough levels (≤ 5.0 g/L), and a group with higher IgG trough levels (> 5.0 g/L). RESULTS: Overall, 89 patients and 840 treatment cycles were analyzed. Up to 11 treatment cycles (average duration 29 days) were documented in each patient. In the group with higher IgG trough levels (> 5.0 g/L, N = 72), significantly fewer infections were observed than in the group with lower IgG trough levels (≤ 5.0 g/L, N = 17), including fewer severe and serious infections. The Privigen dosage was a major determinant of the post-baseline serum IgG levels. Overall tolerability of Privigen was assessed as very good or good in 91% of patients. CONCLUSION: This analysis confirms the association of serum IgG trough levels with the incidence of infections and highlights the importance of careful monitoring of IgG levels during treatment of secondary immunodeficiencies in CLL patients.

Athletic Fear Avoidance in Athletes Receiving Rehabilitation for Sport-Related Concussion: A Preliminary Study.

BACKGROUND: Fear avoidance after musculoskeletal injury is avoiding activity due to fear of pain and contributes to persistent symptoms, depression, and disability. Little is known about fear avoidance for sport (athletic fear avoidance) in athletes with sport-related concussion (SRC). HYPOTHESIS: Athletic fear avoidance after SRC would be elevated at the start of rehabilitation, improve over time, and be associated with postconcussion recovery outcomes. STUDY DESIGN: Observational study. LEVEL OF EVIDENCE: Level 4. METHODS: Athletes in rehabilitation after SRC participated. Testing at initial and discharge visits and 6-month follow-up included Athletic Fear Avoidance Questionnaire (AFAQ), Postconcussion Symptom Scale (PCSS), Profile of Mood States (POMS), and Dizziness Handicap Inventory (DHI). Differences were explored in AFAQ score at initial testing based on sex or age (<18 or ≥18 years). Change in questionnaire scores over time was examined. Association of AFAQ score with other questionnaire scores was determined at each timepoint. RESULTS: A total of 48 athletes participated: 28 completed initial testing only (INITIAL ONLY), and 20 completed all testing (LONGITUDINAL). Across cohorts, the mean (SD) AFAQ score at initial testing was 24.3 (7.6) points, with no significant difference by sex or age. AFAQ, PCSS, POMS, and DHI scores improved in LONGITUDINAL; the effect size was large from initial to discharge testing (1.0, 1.0, 1.0, and 1.2, respectively) and variable from discharge to follow-up testing (0.52, -0.34, -0.08, and 0.02, respectively). AFAQ scores increased from discharge to follow-up in 3 athletes and were consistently above the mean value in 2 athletes. AFAQ score was significantly correlated to the other questionnaire scores at each timepoint (range, r = 0.36-0.75). CONCLUSION: Athletic fear avoidance was elevated at the start of SRC rehabilitation, improved over time in most patients, and was associated with postconcussion symptoms, mood, and disability. CLINICAL RELEVANCE: Athletic fear avoidance may impact recovery after SRC.

A factor analytic comparison of three commonly used depression scales (HAMD, MADRS, BDI) in a large sample of depressed inpatients.

BACKGROUND: Quantifying depression mainly relies on the use of depression scales, and understanding their factor structure is crucial for evaluating their validity. METHODS: This post-hoc analysis utilized prospectively collected data from a naturalistic study of 1014 inpatients with major depression. Confirmatory and exploratory factor analyses were performed to test the psychometric abilities of the Hamilton Depression Rating Scale, the Montgomery Asberg Depression Rating Scale, and the self-rated Beck Depression Inventory. A combined factor analysis was also conducted including all items of all scales. RESULTS: All three scales showed good to very good internal consistency. The HAMD-17 had four factors: an "anxiety" factor, a "depression" factor, an "insomnia" factor, and a "somatic" factor. The MADRS also had four factors: a "sadness" factor, a neurovegetative factor, a "detachment" factor and a "negative thoughts" factor, while the BDI had three factors: a "negative attitude towards self" factor, a "performance impairment" factor, and a "somatic" factor. The combined factor analysis suggested that self-ratings might reflect a distinct illness dimension within major depression. CONCLUSIONS: The factors obtained in this study are comparable to those found in previous research. Self and clinician ratings are complementary and not redundant, highlighting the importance of using multiple measures to quantify depression.

Three-dimensional mapping of sternum fractures from high-energy trauma.

BACKGROUND: Sternum fractures are relatively uncommon injuries, which generally occur as a result of a high-energy mechanism and are often associated with significant concomitant injuries. These injuries may result in decreased quality of life if not properly addressed and yet are rarely operated on. The purpose of this project is to evaluate high-energy sternum fracture patterns using a previously published three-dimensional (3D) computed tomography (CT) reconstruction process to produce fracture frequency maps. METHODS: Patients 18 years and older presenting to a Level I trauma center with sternum fractures due to high-energy trauma between October 2013 and January 2022 were included. A 3D reconstruction and reduction was performed for each sternum using medical image processing software (Materialize NV, Leuven, Belgium). The reconstructions were subsequently overlaid onto a template sternum and normalized using bony landmarks. Fracture lines for each injured sternum were transferred onto the template, creating 3D frequency maps. RESULTS: A total of 120 patients met inclusion criteria. The study population had a uniform age distribution and 57.5% were male. The most common mechanism of injury was motor vehicle collision (64.2%). The breakdown of sternum fractures were isolated sternal body (55.8%), isolated manubrium (31.7%), and combined sternal body and manubrium fractures (12.5%). No xiphoid fractures were observed. Sternal body fractures were a near even mix of transverse (31.7%), oblique (32.9%), and comminuted (35.4%), while 75.5% of manubrium fractures were oblique. The most common associated injuries included rib fractures (80.8%) and traumatic brain injury (61.7%). CONCLUSION: This study presents the fractures from sternum injuries in 3D, and provides insight into reproducible sternum injury patterns that have not previously been analyzed in this format. This fracture mapping technique presents numerous injury patterns simultaneously, such that more frequent morphologies can be appreciated for different patient groups. LEVEL OF EVIDENCE: Diagnostic Tests or Criteria; Level V.

Omega-3 fatty acids in bipolar patients with a low omega-3 index and reduced heart rate variability: the "BIPO-3" trial.

BACKGROUND: Research suggests that a low omega-3 index may contribute to the low heart rate variability and the increased risk of cardiovascular morbidity and mortality in bipolar disorders. However, so far, no intervention trial with EPA and DHA has been conducted in bipolar patients attempting to increase their heart rate variability. METHODS: 119 patients with bipolar disorder according to DSM-IV were screened, with 55 euthymic bipolar patients-owing to inclusion criteria (e.g. low omega-3 index (< 6%), SDNN < 60 ms.)-being enrolled in a randomized, double-blind, 12-week parallel study design with omega-3 fatty acids (4 capsules of 530 mg EPA, 150 mg DHA) or corn oil as a placebo, in addition to usual treatment. Heart rate variability as well as the omega-3 index were measured at baseline and at the endpoint of the study. RESULTS: A total of 42 patients (omega-3: n = 23, corn oil: n = 19) successfully completed the study after 12 weeks. There was a significant increase in the omega-3 index (value at endpoint minus value at baseline) in the omega-3 group compared to the corn oil group (p < 0.0001). However, there was no significant difference in the change of the SDNN (value at endpoint minus value at baseline) between the treatment groups (p = 0.22). In addition, no correlation between changes in SDNN and change in the omega-3 index could be detected in the omega-3 group (correlation coefficient = 0.02, p = 0.94) or the corn oil group (correlation coefficient = - 0.11, p = 0.91). Similarly, no significant differences between corn oil and omega-3 group regarding the change of LF (p = 0.19), HF (p = 0.34) and LF/HF ratio (p = 0.84) could be demonstrated. CONCLUSIONS: In our randomized, controlled intervention trial in euthymic bipolar patients with a low omega-3 index and reduced heart rate variability no significant effect of omega-3 fatty acids on SDNN or frequency-domain measures HF, LF and LF/HF ratio could be detected. Possible reasons include, among others, the effect of psychotropic medication present in our trial and/or the genetics of bipolar disorder itself. Further research is needed to test these hypotheses. Trial registration ClinicalTrials.gov, NCT00891826. Registered 01 May 2009-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT00891826.

Injury-related psychological distress and the association with perceived running ability in injured runners.

OBJECTIVE: Examine injury-related psychological distress and association with perceived running ability in injured runners. DESIGN: Prospective longitudinal study. PARTICIPANTS: Forty-three patients with a running-related injury. MAIN OUTCOME MEASURES: Data collection at initial physical therapy visit and 12-16 weeks later included Optimal Screening for Prediction of Referral and Outcome - Yellow Flag (OSPRO-YF) and Athlete Fear Avoidance Questionnaire (AFAQ) for injury-related psychological distress, and University of Wisconsin Running and Recovery Index (UWRI) for perceived running ability. OSPRO-YF composite score, total yellow flags, and yellow flags in each domain (negative mood, fear-avoidance, positive affect/coping) were calculated. RESULTS: UWRI score and OSPRO-YF composite score and yellow flags significantly improved over time, while AFAQ score and yellow flags in OSPRO-YF negative mood domain did not. AFAQ scores were significantly correlated with UWRI score at baseline, follow-up and change over time, while OSPRO-YF composite score and yellow flags were not. Baseline OSPRO-YF composite score and AFAQ score were not correlated with follow-up UWRI score. CONCLUSIONS: Injury-related psychological distress is elevated when injured runners start rehabilitation, and generally improves; however, negative mood and athletic fear-avoidance may persist. Higher athletic fear-avoidance is associated with lower perceived running ability at the same time point or interval.

Advanced training enhances readiness to return to sport after anterior cruciate ligament reconstruction.

Patients with anterior cruciate ligament reconstruction (ACLR) are often psychologically and physically under-prepared for sports participation. This study compared readiness to return to sport based on completion of advanced training after ACLR. Patients with ACLR who self-selected participation in a 6-week group-format advanced training program (TRAINING) were compared to age- and sex-matched patients who did not participate (NoTRAINING). Each group had 23 participants (14 females). Advanced training consisted of plyometric, strengthening, and agility exercises. Baseline and follow-up testing included psychological measures (Anterior Cruciate Ligament Return to Sport after Injury [ACL-RSI]; Tampa Scale for Kinesiophobia [TSK-11]; Knee Activity Self-Efficacy [KASE]; and fear intensity for the primary fear-evoking task or situation) and a hop test battery. Return to sport criteria were ACL-RSI score ≥70 points and limb symmetry index ≥90% on all hop tests. At follow-up, KASE score was higher in TRAINING than NoTRAINING (92.7 vs. 89.1 points; respectively), but ACL-RSI, TSK-11 and fear intensity scores were not significantly different between groups. Return to sport criteria passing rate was not significantly different between groups at baseline (TRAINING: 13%, NoTRAINING: 30%) or follow-up (TRAINING: 52%, NoTRAINING: 43%); however, the distribution of criteria met at follow-up differed with more patients in TRAINING than NoTRAINING meeting hop test criteria (30% vs. 4%, respectively) and more patients in NoTRAINING than TRAINING failing to meet any criteria (25% vs. 0%, respectively). Advanced training after ACLR facilitated readiness for sport participation by improving confidence and hop performance, but may not have a preferential effect on fear.

PRospective Evaluation of natriuretic peptide-based reFERral of patients with chronic heart failure in primary care (PREFER): a real-world study.

OBJECTIVE: To assess current management practice of heart failure with reduced ejection fraction (HFrEF) in multinational primary care (PC) and determine whether N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP)-guided referral of HFrEF patients from PC to a cardiologist could improve care, defined as adherence to European Society of Cardiology (ESC) guideline-recommended pharmacotherapy. METHODS: PRospective Evaluation of natriuretic peptide-based reFERral of patients with chronic HF in PC (PREFER) study enrolled HFrEF patients from PC considered clinically stable and those with NT-pro-BNP ≥600 pg/mL were referred to a cardiologist for optimisation of HF treatment. The primary outcome of adherence to ESC HF guidelines after referral to specialist was assessed at the second visit within 4 weeks of cardiologist's referral and no later than 6 months after the baseline visit. Based on futility interim analysis, the study was terminated early. RESULTS: In total, 1415 HFrEF patients from 223 PCs from 18 countries in Europe were enrolled. Of these, 1324 (96.9%) were considered clinically stable and 920 (65.0%) had NT-pro-BNP ≥600 pg/mL (mean: 2631 pg/mL). In total, 861 (60.8%) patients fulfilled both criteria and were referred to a cardiologist. Before cardiologist consultation, 10.1% of patients were on ESC guideline-recommended HFrEF medications and 2.7% were on recommended dosages of HFrEF medication (defined as ≥50% of ESC guideline-recommended dose). Postreferral, prescribed HFrEF drugs remained largely unchanged except for an increase in diuretics (+4.6%) and mineralocorticoid receptor antagonists (+7.9%). No significant increase in patients' adherence to guideline-defined drug combinations (11.2% post-referral vs 10.1% baseline) or drug combinations and dosages (3.3% postreferral vs 2.7% baseline) was observed after cardiologist consultation. CONCLUSIONS: PREFER demonstrates substantial suboptimal treatment of HFrEF patients in the real world. Referral of patients with elevated NT-pro-BNP levels from PC to cardiologist did not result in meaningful treatment optimisation for treatments with known mortality and morbidity benefit.

Assessing the links between childhood trauma, C-reactive protein and response to antidepressant treatment in patients with affective disorders.

Adverse Childhood Experiences (ACE) are a well-known risk-factor for depression. Additionally, (high-sensitive) C-reactive Protein (hsCRP) is elevated in subgroups of depressed patients and high following ACE. In this context the literature considers hsCRP and ACE to be associated with treatment resistant depression. With the data being heterogenous, this study aimed to explore the associations of ACE, hsCRP levels and response to antidepressant treatment in uni- and bipolar depression. N = 76 patients diagnosed with uni- or bipolar depression and N = 53 healthy controls were included. Treatment was over 6 weeks in an inpatient psychiatric setting within an observatory study design. Depressive symptoms were assessed by the Montgomery-Asberg Depression Rating Scale (MADRS), ACE were assessed by the Childhood Trauma Questionnaire (CTQ); the body-mass-index (BMI) and hsCRP were measured. HsCRP levels did not differ between the study population and the healthy controls. While the depressive symptoms decreased, the hsCRP levels increased. Sexual abuse was associated with significant higher and emotional abuse with lower levels of hsCRP after 6 weeks. The baseline hsCRP levels and the ACE subgroups did not show significant associations with the treatment response in unipolar depressed patients. The long-lasting effects of specific forms of ACE may have relevant impact on inflammation, supporting hsCRP to be a suitable biomarker. With ACE and hsCRP not showing any significant associations with treatment response in the unipolar depressed subgroup, a more differentiate research concerning biomarkers and treatment regimens is needed when talking about treatment response.

Novel Approaches Identifying Relevant Patient-Reported Outcomes in Patients With Inflammatory Bowel Diseases-LISTEN 1.

Background: Several patient-reported outcomes (PROs) have been established and are widely used in the assessment of patients with inflammatory bowel disease (IBD). However, it has never been investigated which PRO items are experienced by and are considered most relevant for IBD patients. Methods: A review of IBD-related disease scores by a steering committee led to the identification of relevant PRO questions and assignment to 16 different PRO categories (9 symptoms and 7 impacts) that characterize patient's disease burden. In a cross-sectional study, a digital patient survey was carried out to determine the self-reported experience by multiple response, the relevance of these PRO categories by pairwise comparison and the suitability of the respective questions and answer possibilities by yes-or-no-question. Results: Sixty patients with Crohn's disease (CD) (56.7% women; mean age 40.6 years; mean disease duration 12.4 years) and 60 patients with ulcerative colitis (UC) (51.7% women; mean age 37.3 years; mean disease duration 9.0 years) participated in the patient survey. All predefined symptoms and impacts, with the exception of nausea, were experienced by at least 50% of patients. Stool urgency and pain were rated the 2 most important symptoms in CD patients with similar ratings for relevance. Stool urgency was also the most important symptom in patients with UC, followed by stool frequency. Differences in self-reported experience between CD and UC patients were seen for the symptoms of rectal bleeding, pain, and nausea. Most important impact of symptoms in both patient groups were general wellbeing followed by social activities, while sexual activity was the least relevant impact category. Conclusions: Stool urgency was the most relevant and most self-reported symptom for both CD and UC. Relevance and self-reported experience of pain and rectal bleeding differed between the 2 diseases. Therefore, the future collection of PROs should take these disease specificities into consideration.

Injury-Related Fears During the Return-to-Sport Phase of ACL Reconstruction Rehabilitation.

BACKGROUND: Fear of reinjury is common after anterior cruciate ligament reconstruction (ACLR) and often deters a return to preinjury sport participation. A better understanding of injury-related fear is needed to inform rehabilitation strategies. PURPOSE/HYPOTHESIS: The purpose of this study was to (1) identify individual fear-evoking tasks or situations, (2) compare the intensity and amount of change relative to other injury-related fears (reinjury, knee giving way, and knee pain) after completion of a return-to-sport training program, and (3) determine whether standardized questionnaires can identify the intensity of fear for the individual fear-evoking task or situation and for fear of reinjury. The hypothesis was that the task or situation that evokes fear would vary across patients and the intensity of that fear would be higher and show less change after return-to-sport training compared with other injury-related fears. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Participants included 33 patients (15 males; mean age, 18 years) with ACLR who enrolled in a group-format return-to-sport training program. Questionnaires completed before and after return-to-sport training included items to specify fear-evoking tasks or situations, items to rate the intensity of various injury-related fears, the Anterior Cruciate Ligament Return to Sport after Injury scale (ACL-RSI), and the Tampa Scale for Kinesiophobia (TSK-11). RESULTS: The most common fear-evoking task or situation was cutting, followed by contact, jumping, and other. Intensity of fear-evoking task or situation was higher than other injury-related fears, but all fears decreased in intensity after training. The ACL-RSI score better identified the intensity of fear for the individual fear-evoking task or situation and for fear of reinjury than did the TSK-11 score. CONCLUSION: Activities that evoke fear vary across patients, but fear of cutting is common. The intensity of common fears after ACLR decreased after advanced group training, and large effect sizes were seen for nearly all examined fears. Fear of reinjury and intensity of individually feared tasks may be better reflected in the ACL-RSI score than the TSK-11 score.

Update on weight-gain caused by antipsychotics: a systematic review and meta-analysis.

Introduction: Antipsychotic-induced weight-gain (AIWG) is a very important, yet often neglected side-effect in the treatment with first and second generation antipsychotics. AIWG can increase the risk of developing metabolic syndrome, diabetes and cardiovascular disease. Meta-analyzes mostly concentrate on AIWG in schizophrenic and bipolar patients, even though antipsychotics are prescribed off-label across many other diagnostic groups (e.g. anxiety disorders, depression, autistic disorder).Areas covered: Pub Med and Web of Science were systematically searched for RCTs reporting on AIWG with a sample size of ≥ 100 published between 2014 and 2019. All diagnoses and ages were included.Expert opinion: Inclusion criteria were fulfilled by 27 RCTs. All antipsychotics led to significantly more weight-gain (p < .001) and most antipsychotics led to a significantly higher risk for a clinically relevant weight-gain of ≥7% compared to placebo (RR = 2.04). The results support previous findings that weight-gain occurs quickly. To efficaciously and efficiently tackle the problem of AIWG in clinical practice and trials, people at high risk need to be identified by predictive tools enabling the clinician to offer tailored adjunctive therapies (medication and/or lifestyle interventions). Most importantly, weight and metabolic monitoring ought to be consequently implemented in clinical routine in the treatment of any patient with any diagnosis when antipsychotics are prescribed.

What happens with schizophrenia patients after their discharge from hospital? Results on outcome and treatment from a "real-world" 2-year follow-up trial.

Aim of the study was to examine the course of schizophrenia patients within 2 years after discharge. Within a multicenter study of the German Competence Network on Schizophrenia, patients suffering from a schizophrenia spectrum disorder were examined regarding their psychopathological improvement, tolerability, and the treatment regime applied during hospitalization and a 2-year follow-up period. Response, remission, the level of everyday functioning, and relapse were furthermore evaluated during the follow-up period using established definitions for these outcome domains. The psychopharmacological treatment was specifically evaluated in terms of a potential association with relapse. 149 patients were available for analysis, with 65% of the patients being in response, 52% in symptomatic remission, and 64% having a satisfiable everyday functioning 2 years after their discharge from hospital. Despite these favorable outcome rates, 63% of the patients suffered from a relapse within the 2-year follow-up period with 86% of these patients being rehospitalized. Discharge non-responder and non-remitter were twice as likely to relapse during follow-up. A significant decrease of side-effects was observed with negligible rates of extrapyramidal side-effects, sedation, and weight gain during follow-up. Patients receiving treatment with atypical antipsychotics were found to have the lowest risk to relapse (p < 0.0001). The results highlight the natural and unsteady course of schizophrenia in most patients underlining the need to develop more specific treatment strategies ensuring ongoing stability and preventing relapse.

Under temperate climate, the conversion of grassland to arable land affects soil nutrient stocks and bacteria in a short term.

Projected population growth and climate change will make it inevitable to convert neglected and marginal land into productive arable land. We investigate the influence of agricultural management practices on nutrient stocks and soil functions during the conversion of former extensively used grassland to arable land. Effects of grassland removal, tillage, intercropping with faba bean (Vicia faba) and its later incorporation were studied with respect to soil properties and bacterial community structure. Therefore, composite samples were collected with a core sampler from the topsoil (0-20 cm) in (a) the initial grassland, (b) the transitional phase during the vegetation period of V. faba, (c) after ploughing the legume in, and (d) untreated controls. In all samples, nitrate-N, ammonium-N, dissolved organic carbon (DOC) and total nitrogen bound (TNb) were analyzed and comparisons of the bacterial community structure after 16S-amplicon sequencing were performed to assess soil functions. Mineralization after grassland conversion followed by the biological nitrogen fixation of broad beans enhanced the nitrate-N content in bulk soil from 4 to almost 50 µg N g-1dw. Bacterial community structure on phylum level in bulk soil was dominated by Proteobacteria, Actinobacteria, Acidobacteria, Chloroflexi, and Bacteroidetes and remained almost stable. However, alpha and beta-diversity analysis revealed a change of the bacterial composition at the final state of the conversion. This change was primarily driven by increasing abundances of the genera Massilia and Lysobacter, both members of the Proteobacteria, after the decay of the leguminous plant residues. Furthermore, increasing abundances of the family Gaiellaceae and its genus Gaiella fostered this change and were related to the decreasing carbon to nitrogen ratio. In short, gentle management strategies could replace the input of mineral fertilizer with the aim to contribute to future sustainable and intensified production even on converted grassland.

Remission in schizophrenia - What are we measuring? Comparing the consensus remission criteria to a CGI-based definition of remission and to remission in major depression.

BACKGROUND: Despite being recommended for use in clinical trials, the consensus remission criteria were found to leave patients with persisting symptoms, relevant areas of functional impairment and a decreased sense of wellbeing. Therefore, to evaluate the appropriateness of the schizophrenia consensus criteria, a definition of remission based on the Clinical Global Impression Scale (CGI) was developed and remitter subgroups were compared. METHODS: 239 patients with a schizophrenia spectrum disorder were evaluated regarding their remission status after inpatient treatment. Remission in schizophrenia was defined according to the symptom-severity component of the consensus criteria by Andreasen et al. and a CGI based definition was calculated using sensitivity and specificity using receiver operating curves (asymptomatic remitter). Both remitter groups (schizophrenia consensus versus asymptomatic remitters) were compared regarding different clinical variables at discharge as well as the likelihood to relapse within a 1-year follow-up period. Both schizophrenia remitter subgroups were compared to remitters in major depression as a reference value. RESULTS: Following the consensus criteria, 63% of the schizophrenia patients were in remission compared to only 18% following the asymptomatic criterion. The schizophrenia consensus remitters were less likely to be concurrent treatment responders (p < 0.0001), had a significantly greater illness severity (p < 0.0001) and less functioning (p = 0.0358) as well as a significantly greater risk to relapse (p = 0.0174) compared to the schizophrenia asymptomatic remitters as well as the depressed remitters. CONCLUSION: It should be critically re-evaluated if the currently proposed consensus criteria are adequate to measure what is traditionally understood to be remission.

Comparing Schizophrenia Patients With a Predicted High/Low Risk of Nonresponse Receiving Treatment with Ziprasidone and Haloperidol: A Randomized-Controlled Study.

INTRODUCTION: The aim of this double-blind randomized study was to evaluate the response to antipsychotic treatment in schizophrenia patients with predicted high/low risk of nonresponse identified by applying a set of well-established scales and predictors of outcome and to compare efficacy between ziprasidone and haloperidol. METHODS: One hundred twelve schizophrenia patients (ziprasidone: n=54; haloperidol: n=58) were rated weekly on the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), the Global Assessment of Functioning Scale (GAF), the Social and Occupational Functioning Scale (SOFAS), the Simpson-Angus Scale (SAS), and Hillside Akathisia Scale (HAS). RESULTS: Ninety-two patients (82%) were predicted to have a high risk of nonresponse. No significant difference regarding PANSS improvement in this subsample was found comparing ziprasidone and haloperidol (p=0.563). Also, for the total patient sample, no significant difference was found regarding the course of the PANSS total score, GAF (p=0.921), and SOFAS (p=0.658) between ziprasidone and haloperidol. Haloperidol resulted in higher scores on the SAS (p=0.001) and HAS (p=0.011). DISCUSSION: An alarmingly high number of patients were at high risk of nonresponse to antipsychotic treatment.

Platelet-rich plasma in fibrin matrix to augment rotator cuff repair: a prospective, single-blinded, randomized study with 2-year follow-up.

BACKGROUND: Application of autologous platelet-rich plasma in fibrin matrix (PRPFM) improves tendon healing in patients undergoing arthroscopic rotator cuff repair. We performed a prospective, randomized, single-blinded study of 76 patients, with an α level of 5% and power of 80%. MATERIALS AND METHODS: Seventy-six patients were divided into 2 randomized groups. The treatment group underwent arthroscopic rotator cuff repair with PRPFM. The control group did not receive the PRPFM treatment. Patients were evaluated preoperatively and at 6 months and 24 months postoperatively with validated clinical outcome scores, and dynamometer examination. A magnetic resonance imaging scan was performed at 6 months postoperatively. RESULTS: The 2 randomized groups were homogeneous. Western Ontario Rotator Cuff (WORC) scores were not statistically different at any time interval. The WORC scores changed from 1257 to 139 in the control group and from 1106 to 99 in the PRPFM group over the 24-month study period. On the Simple Shoulder Test, improvement over the study period was noted from 45% to 96% in the control group and from 49% to 96% in the PRPFM group. Strength of the supraspinatus at 24 months by dynamometer testing was 99.8% in the control group and 96.3% in the PRPFM group. Infraspinatus strength was 104% in the control group and 103% in the PRPFM group. The secondary outcome of retear occurred at a rate of 19% for the double-row technique and 7.4% for the PRPFM technique at 6 months. All our results were statistically insignificant. CONCLUSIONS: Our results showed no benefit from PRPFM used for rotator cuff repair according to the WORC Index, Simple Shoulder Test, and shoulder strength index.

Examination of Early Functional Recovery After ACL Reconstruction: Functional Milestone Achievement and Self-Reported Function.

BACKGROUND: Few studies have documented early functional recovery after anterior cruciate ligament (ACL) reconstruction. PURPOSE: To quantify the time to early functional milestone achievement and change in function over 12 weeks after ACL reconstruction and to identify demographic characteristic predictors of the outcomes. STUDY DESIGN: Prospective, longitudinal, observational study. LEVEL OF EVIDENCE: Level 4. METHODS: A total of 182 patients (95 females, 87 males; mean ± SD age, 28 ± 12 years; mean ± SD body mass index [BMI], 25 ± 4 kg/m2) who received primary, unilateral, ACL reconstruction were included. Testing occurred before surgery as well as 1, 2, 4, 8, and 12 weeks postsurgery. Outcomes included demographic characteristics, self-reported functional milestone achievements and responses on the Short Musculoskeletal Function Assessment (SMFA) questionnaire. Time to functional milestone achievement was calculated, and patients were categorized into "faster" or "prolonged" recovery groups based on the median value. Longitudinal change in SMFA subscale scores (daily activities and mobility) as well as demographic predictors of functional recovery group assignment and postsurgical change in SMFA subscale scores were examined. RESULTS: Median time for discontinuing narcotic pain medication was 9 days, while that for discontinuing crutches was 15 days. Time to return to work occurred at a median of 11 days, return to school at 7 days, and return to driving at 11 days. Both SMFA subscale scores significantly decreased (improved) over time, with the greatest change occurring between 1 and 4 weeks postsurgery. The demographic predictor of faster functional recovery for discontinuation of narcotic pain medication was surgery with allograft; those for return to work were higher age, male sex, decreasing BMI, and sedentary/light occupational demand; and those for return to driving were higher age, male sex, and surgery on the left side of the body. CONCLUSION: Functional recovery occurs rapidly over the first month after ACL reconstruction for most patients. Nonmodifiable demographic characteristics may influence recovery time for specific functional milestones. CLINICAL RELEVANCE: Results can be used to counsel patients on early functional recovery after ACL reconstruction.

QTc prolongation in short-term treatment of schizophrenia patients: effects of different antipsychotics and genetic factors.

Antipsychotics are effective in treating schizophrenia but may lead to a higher cardiovascular risk due to QTc prolongation. Besides drugs, genetic and clinical factors may contribute to QTc prolongation. The aim of this study is to examine the effect of candidate genes known for QTc prolongation and their interaction with common antipsychotics. Thus, 199 patients were genotyped for nine polymorphisms in KCNQ1, KCNH2, SCN5A, LOC10537879, LOC101927066, NOS1AP and NUBPL. QTc interval duration was measured before treatment and weekly for 5 weeks while being treated with risperidone, quetiapine, olanzapine, amisulpride, aripiprazole and haloperidol in monotherapy. Antipsychotics used in this study showed a different potential to affect the QTc interval. We found no association between KCNH2, KCNQ1, LOC10537879, LOC101927066, NOS1AP and NUBPL polymorphisms and QTc duration at baseline and during antipsychotic treatment. Mixed general models showed a significant overall influence of SCN5A (H558R) on QTc duration but no significant interaction with antipsychotic treatment. Our results do not provide evidence for an involvement of candidate genes for QTc duration in the pathophysiology of QTc prolongation by antipsychotics during short-term treatment. Further association studies are needed to confirm our findings. With a better understanding of these interactions the cardiovascular risk of patients may be decreased.