Single-stage total hip arthroplasty after failed fixation of proximal femoral fractures: an increased risk for periprosthetic joint infections?

BACKGROUND: Higher complication rates have been reported for total hip arthroplasty (THA) after osteosynthesis of proximal femur fractures (PFF). This study evaluated the infection risk for conversion of internal fixation of PFF to THA by a single-staged procedure in the absence of clear infection signs. METHODS: Patients undergoing a one-staged conversion to THA (2013-2018) after prior internal fixation of the proximal femur were included. Preoperative diagnostics with laboratory results, hip aspirations as well as intraoperative microbiology and sonication were assessed. Postoperative complications were recorded as well as patient demographics, duration between initial and conversion to THA, explanted osteosynthesis and implanted THA. RESULTS: Fifty-eight patients (24 male/34 female, 62.8 ± 14.5 years) were included with a mean time of 3.8 ± 7.5 years between internal fixation and conversion to THA (45 cementless, 3 cemented, 3 hybrid and 7 hybrid inverse THAs). Preoperative mean blood level CRP was 8.36 ± 14 mg/l (reference value < 5 mg/l) and leukocyte count was 7.11 ± 1.84^3/µl (4.5-10.000^3/µl). Fifty patients had intraoperative microbiological diagnostics, with either swabs in 86.2% and/or sonication in 29.3%. Positive microbiological results were recorded in 10% (5 of 50 patients), with pathogens identified being mainly Staphylococcus. Complications after conversion occurred in 9.6% including a postoperative low-grade infection rate of 5.8% after a mean of 2.5 years. CONCLUSION: This study found a positive microbiological test result in 10% of a one-stage conversion of PFF fixation to THA. Moreover, we found a high infection rate (5.8%) for early postoperative periprosthetic joint infection. Interestingly, CRP has not been proven to be an adequate parameter for low-grade infections or occult colonized implants. Therefore, we recommend a comprehensive pre- and intraoperative diagnostic including hip aspiration, swabs and sonication when considering one-staged revision.

[Periprosthetic fractures of the acetabulum: osteosynthesis]. / Periprothetische Frakturen des Acetabulums: Osteosynthese.

In most cases periprosthetic fractures of the acetabulum are complex injuries and are extremely challenging for the treating medical team. Over the years the frequency of this overall rare entity has increased due to demographic changes. In recent years several treatment algorithms were published and provided the possibility of developing standardized treatment concepts. The classification of the fractures and a dedicated preoperative strategy are highly important for the quality of patient-centered care. In the literature the frequency of intraoperative fractures was initially given as 0.4%; however, several studies have been published in which a far higher rate of intraoperative fractures was detected by computed tomography (CT), often referred to as so-called occult fractures. The causes are multifactorial and there is significant association with whether cement-free press-fit acetabular cups were used or cemented forms. In approximately 75% of the cases a low energy impact was the cause of the fracture. In these patients systemic processes, such as osteoporotic alterations of the bony substance or the possible presence of low-grade infections should be considered. This article gives an overview of the diagnostics, planning, challenges and osteosynthetic treatment options for periprosthetic fractures of the acetabulum.

Trends in fracture development of the upper extremity in Germany-a population-based description of the past 15 years.

BACKGROUND: Recent studies investigating fracture development in Germany are not available especially with regard to demographic change. The primary aim of this study was to report trends in fracture development of the upper extremity in Germany between 2002 and 2017 and to evaluate changes over time. METHODS: Evaluating inpatient data from the German National Hospital Discharge Registry (International Classification of Diseases, ICD-10) between 2002 and 2017. Total count, incidences and percentage changes of the following fracture localizations were analysed: proximal humerus, distal humerus, proximal ulna, proximal radius, ulna diaphysis (including Monteggia lesion) and distal radius. Ten age groups for men and women were formed: 35-44, 45-54, 55-64, 65-74; 75-84; 85-90, and > 90 (years). RESULTS: The total count of proximal humeral fractures increased from 40,839 (2002, men/women 9967/30,872) to 59,545 (2017, men/women 14,484/45,061). Distal humeral fractures increased from 5912 (2002, men/women 1559/4353) to 6493 (2017, men/women1840/4653). The total count of forearm fractures increased from 68,636 (2002, men/women 17,186/51,450) to 89,040 (2017, men/women 20,185/68,855). Women were affected in 70-75% of all cases with rising incidences among nearly every age group in female patients. CONCLUSION: Total count of nearly every evaluated fracture increased. Also, incidences increased especially in the older female age groups. Fracture development already seems to reflect demographic changes in Germany.

[Combined posterior and anterior cruciate ligament reconstruction : Arthroscopic treatment with the GraftLink® system]. / Kombinierte Rekonstruktion des hinteren und vorderen Kreuzbandes : Arthroskopische Versorgung mit dem GraftLink®-System.

OBJECTIVE: Simultaneous arthroscopic reconstruction of the anterior and/or posterior cruciate ligament (ACL/PCL) using the GraftLink® system (Arthrex) to obtain stable treatment and good functional results. The transplant is protected by the safety belt like biomechanical GraftLink® principle, which is used to secure the intraoperatively obtained stability in the long term. INDICATIONS: ACL, PCL, or combined cruciate ligament rupture, especially multiligament injuries. Revision ACL and PCL reconstruction. CONTRAINDICATIONS: Preoperative fixed posterior tibial subluxation. Reduced range of motion (ROM) with an extension lag (extension/flexion 0­0-120° preoperatively required). Complex regional pain syndrome. High-grade atrophy of the quadriceps femoris muscle and osseous deformities. SURGICAL TECHNIQUE: Supine position with mobile leg and possible flexion of at least 120° allowing antegrade femoral bone tunnel replacement. Retrograde tunnel placement (e. g. using a retrocutter) is recommended in case of less than 120° knee flexion. Thigh tourniquet. Staging arthroscopy. Cruciate ligament reconstruction is realized by anatomic tunnel placement for the ACL/PCL using the GraftLink®. Recommended sequence of reconstruction: 1. tibial PCL tunnel, 2. femoral ACL tunnel, 3. femoral PCL tunnel, 4. tibial ACL tunnel. Hybrid fixation is recommended. Portals: High anteromedial, high anterolateral, posteromedial, posterolateral, small subvastus incision. POSTOPERATIVE MANAGEMENT: Combined cruciate ligament replacement: Gradual load and ROM increase in the PCL track. After postoperative week 5, increasing load up to full weight bearing, with extension/flexion 0­0-90° after week 7. Down training of the PCL track after week 13. Contact and competitive sports after 1 year. RESULTS: The GraftLink® system allows restoration of knee joint stability with good functional results. The procedure is especially suitable for complex situations like after knee dislocation with ACL and PCL reconstruction in 1 or 2 steps.

[Trochanteric and subtrochanteric fractures]. / Per- und subtrochantäre Femurfrakturen.

Proximal femoral fractures are one of the most common fractures, particularly in older people. The most common cause is a falling event due to dizziness and gait insecurity. In most cases prompt surgical treatment is necessary to achieve early mobilization and to reduce the risk of mortality. The aim is a stable osteosynthesis and patient-centered care. A great variety of implants are available for this purpose. Furthermore, perioperative management is important to prevent further problematic events, such as delirium, reoccurrence of falling events and to diagnose and adequately treat a pre-existing osteoporosis.

[Periprosthetic Acetabulum Fractures]. / Periprothetische Azetabulumfrakturen.

In contrast to periprosthetic fractures of the femur, periprosthetic fractures of the acetabulum are rare complications - both primary fractures and fractures in revision surgery. This topic is largely under-reported in the literature; there are a few case reports and no long term results. Due to an increase in life expectancy, the level of patients' activity and the number of primary joint replacements, one has to expect a rise in periprosthetic complications in general and periprosthetic acetabular fractures in particular. This kind of fracture can be intra-, peri- or postoperative. Intraoperative fractures are especially associated with insertion of cementless press-fit acetabular components or revision surgery. Postoperative periprosthetic fractures of the acetabulum are usually related to osteolysis, for example, due to polyethylene wear. There are also traumatic fractures and fractures missed intraoperatively that lead to some kind of insufficiency fracture. Periprosthetic fractures of the acetabulum are treated conservatively if the implant is stable and the fracture is not dislocated. If surgery is needed, there are many possible different surgical techniques and challenging approaches. That is why periprosthetic fractures of the acetabulum should be treated by experts in pelvic surgery as well as revision arthroplasty and the features specific to the patient, fracture and prosthetic must always be considered.

Once-monthly paliperidone palmitate in recently diagnosed and chronic non-acute patients with schizophrenia.

OBJECTIVE: To explore the treatment response, tolerability and safety of once-monthly paliperidone palmitate (PP1M) in non-acute patients switched from oral antipsychotics, stratified by time since diagnosis as recently diagnosed (≤3 years) or chronic patients (>3 years). RESEARCH DESIGN AND METHODS: Post hoc analysis of a prospective, interventional, single-arm, multicentre, open-label, 6-month study performed in 233 recently diagnosed and 360 chronic patients. MAIN OUTCOME MEASURES: The proportion achieving treatment response (defined as ≥20% improvement in Positive and Negative Syndrome Scale [PANSS] total score from baseline to endpoint) and maintained efficacy (defined as non-inferiority in the change in PANSS total score at endpoint [Schuirmann's test]). RESULTS: 71.4% of recently diagnosed and 59.2% of chronic patients showed a ≥20% decrease in PANSS total score (p = 0.0028 between groups). Changes in PANSS Marder factors, PANSS subscales, and the proportion of patients with a Personal and Social Performance scale (PSP) total score of 71-100 were significantly greater in recently diagnosed compared with chronic patients. PP1M was well tolerated, presenting no unexpected safety findings. CONCLUSION: These data show that recently diagnosed patients treated with PP1M had a significantly higher treatment response and improved functioning, as assessed by the PSP total score, than chronic patients.

New insights into the protein aggregation pathology in myotilinopathy by combined proteomic and immunolocalization analyses.

INTRODUCTION: Myofibrillar myopathies are characterized by progressive muscle weakness and impressive abnormal protein aggregation in muscle fibers. In about 10 % of patients, the disease is caused by mutations in the MYOT gene encoding myotilin. The aim of our study was to decipher the composition of protein deposits in myotilinopathy to get new information about aggregate pathology. RESULTS: Skeletal muscle samples from 15 myotilinopathy patients were included in the study. Aggregate and control samples were collected from muscle sections by laser microdissection and subsequently analyzed by a highly sensitive proteomic approach that enables a relative protein quantification. In total 1002 different proteins were detected. Seventy-six proteins showed a significant over-representation in aggregate samples including 66 newly identified aggregate proteins. Z-disc-associated proteins were the most abundant aggregate components, followed by sarcolemmal and extracellular matrix proteins, proteins involved in protein quality control and degradation, and proteins with a function in actin dynamics or cytoskeletal transport. Forty over-represented proteins were evaluated by immunolocalization studies. These analyses validated our mass spectrometric data and revealed different regions of protein accumulation in abnormal muscle fibers. Comparison of data from our proteomic analysis in myotilinopathy with findings in other myofibrillar myopathy subtypes indicates a characteristic basic pattern of aggregate composition and resulted in identification of a highly sensitive and specific diagnostic marker for myotilinopathy. CONCLUSIONS: Our findings i) indicate that main protein components of aggregates belong to a network of interacting proteins, ii) provide new insights into the complex regulation of protein degradation in myotilinopathy that may be relevant for new treatment strategies, iii) imply a combination of a toxic gain-of-function leading to myotilin-positive protein aggregates and a loss-of-function caused by a shift in subcellular distribution with a deficiency of myotilin at Z-discs that impairs the integrity of myofibrils, and iv) demonstrate that proteomic analysis can be helpful in differential diagnosis of protein aggregate myopathies.

Paliperidone palmitate in non-acute patients with schizophrenia previously unsuccessfully treated with risperidone long-acting therapy or frequently used conventional depot antipsychotics.

PALMFlexS, a prospective multicentre, open-label, 6-month, phase IIIb interventional study, explored tolerability, safety and treatment response in adults (n = 231) with non-acute but symptomatic schizophrenia switching to flexibly dosed paliperidone palmitate (PP) after unsuccessful treatment with risperidone long-acting injectable therapy (RLAT) or conventional depot antipsychotics (APs). Treatment response was measured by change in Positive and Negative Syndrome Scale (PANSS) total score from baseline (BL) to last-observation-carried-forward (LOCF) endpoint (EP). Safety and tolerability assessments included Extrapyramidal Symptom Rating Scale (ESRS) total score and treatment-emergent adverse events. Significant reductions in mean PANSS total score were observed for all groups (-7.5 to -10.6; p ⩽ 0.01 [BL to LOCF EP]). After switching to PP, more than 50% of all patients achieved ⩾20% and one-third of RLAT-treated patients even achieved ⩾50% improvement in PANSS total score. Across groups, there were significant improvements (p < 0.05) in symptom severity as measured by Clinical Global Impression-Severity (CGI-S; trend for improvement with RLAT; p = 0.0568), subjective well-being, medication satisfaction, and patient functioning with PP. PP was generally well tolerated. Clinically relevant benefits were observed in non-acute patients with schizophrenia switched from RLAT or conventional depot APs to PP.

Schizophrenia through the carers' eyes: results of a European cross-sectional survey.

Schizophrenia is a serious mental disorder affecting approximately 29 million people worldwide. The ideal treatment and care of patients with schizophrenia should be provided by a multidisciplinary 'team' involving psychiatrists, nurses and other healthcare professionals, together with carers and patients. In light of the key role carers play in the care of patients with schizophrenia, the present survey was designed to assess the opinions of family members and friends of patients with schizophrenia across Europe and to ascertain their attitudes towards the illness, medication and adherence to medication. Among carers participating in this survey, there was widespread awareness of the issues involved in supporting patients with schizophrenia and the importance of their role in improving poor adherence to medication. Three differences in opinion emerged between the views of carers and psychiatrists; psychiatrists rely more on the patient themselves when assessing adherence than carers would recommend; in contrast to psychiatrists, many carers believe the illness itself contributes to non-adherence; two thirds of carers think that schizophrenia medication damages health (higher than estimated by psychiatrists). The findings from the present survey, taken together with the results from the Adherencia Terapéutica en la Esquizofrenia surveys of psychiatrists and nurses, support the need for a collaborative approach to the issue of treatment nonadherence. In particular, healthcare professionals should recognize the valuable contribution that family carers can make to improve treatment adherence and consequently clinical outcomes for patients with schizophrenia. Schizophrenia carries a significant burden for families providing care. The Adherencia Terapéutica en la Esquizofrenia (ADHES) carers' survey was designed to assess the opinions of family and friends of patients with schizophrenia across Europe and ascertain their attitudes towards the illness, medication and adherence to medication. A questionnaire-based cross-sectional survey of 138 carers across 16 European countries. Interpretation of results was based on a descriptive comparison of responses. Carers recognized the importance of medication to help patients get better (76%) and improve their quality of life (76%) and relationships (74%). Sixty-seven per cent believed medication damages general health. Sixty-five per cent reported that treatment adherence was a burden for patients. Thirty-eight per cent indicated that it was a daily struggle to get patients to take their medication. Fifty per cent perceived that medication administered every few weeks rather than daily was quite/very important. Ninety-three per cent agreed on the importance of family support to boost adherence, with education and information deemed important for families and patients. Carers rely less on the patient themselves when assessing adherence than psychiatrists. The burden faced by carers and patients in taking medication provides an opportunity for healthcare professionals to provide support in a multidisciplinary 'team' involving psychiatrists, nurses and carers.

Clinical effectiveness and resource utilization of paliperidone ER for schizophrenia: Pharmacoepidemiologic International Longitudinal Antipsychotic Registry (PILAR).

OBJECTIVE: To document prescribing patterns in clinical practice and assess long-term outcomes related to initiation of paliperidone ER and other oral antipsychotics among patients with schizophrenia in a naturalistic setting. RESEARCH DESIGN AND METHODS: An international, non-interventional, naturalistic study of adult patients (≥18 years) with schizophrenia. Patients were assigned to the relevant treatment group (paliperidone ER or 'all other oral antipsychotics') after switching to, or initiating, oral antipsychotic treatment. Retrospective 12 month data collection was followed by 12 month prospective data collection, with 3-monthly assessments. The primary endpoint was time to all-cause discontinuation of new medication. Secondary endpoints included Clinical Global Impression-Severity (CGI-S) score, Clinical Global Impression-Schizophrenia (CGI-SCH) score, Personal and Social Performance (PSP) score, health-related quality of life (HR-QoL) and quality of sleep, evaluation of healthcare resource utilization and patient's treatment satisfaction. RESULTS: A total of 4051 patients were included in the intent-to-treat (ITT) analysis set. All-cause study discontinuation rates were comparable between the paliperidone ER group (16.8%) and the 'all other oral antipsychotics' group (15.5%). There was no difference in the time to discontinuation of newly initiated antipsychotic treatments between paliperidone ER and 'all other oral antipsychotics' groups. Paliperidone ER was associated with greater improvements from baseline to endpoint in both the PSP scale score (+14.2 vs +13.1, p = 0.041) and the physical component of quality of life (SF-12 Physical scores; +3.9 vs +2.9, p = 0.003) compared to 'all other oral antipsychotics'. Improvements in mean CGI-S score, CGI-SCH score, HR-QoL, quality of sleep and daytime drowsiness, as well as patients' treatment satisfaction were comparable between treatment groups. The incidence of adverse events was comparable between groups. CONCLUSIONS: This study provides valuable data on the prescribing habits and treatment outcomes associated with use of paliperidone ER in everyday clinical practice, and supports previous findings of the favorable functional improvement and treatment satisfaction associated with paliperidone ER. CLINICAL TRIAL REGISTRATION: NCT00696813; R076477SCH4015 (Register of German Association of Research-based Pharmaceutical Companies [VFA] http://www.vfa.de/de/arzneimittel-forschung/datenbanken-zu-arzneimitteln/nisdb).

Differential proteomic analysis of abnormal intramyoplasmic aggregates in desminopathy.

Desminopathy is a subtype of myofibrillar myopathy caused by desmin mutations and characterized by protein aggregates accumulating in muscle fibers. The aim of this study was to assess the protein composition of these aggregates. Aggregates and intact myofiber sections were obtained from skeletal muscle biopsies of five desminopathy patients by laser microdissection and analyzed by a label-free spectral count-based proteomic approach. We identified 397 proteins with 22 showing significantly higher spectral indices in aggregates (ratio >1.8, p<0.05). Fifteen of these proteins not previously reported as specific aggregate components provide new insights regarding pathomechanisms of desminopathy. Results of proteomic analysis were supported by immunolocalization studies and parallel reaction monitoring. Three mutant desmin variants were detected directly on the protein level as components of the aggregates, suggesting their direct involvement in aggregate-formation and demonstrating for the first time that proteomic analysis can be used for direct identification of a disease-causing mutation in myofibrillar myopathy. Comparison of the proteomic results in desminopathy with our previous analysis of aggregate composition in filaminopathy, another myofibrillar myopathy subtype, allows to determine subtype-specific proteomic profile that facilitates identification of the specific disorder. BIOLOGICAL SIGNIFICANCE: Our proteomic analysis provides essential new insights in the composition of pathological protein aggregates in skeletal muscle fibers of desminopathy patients. The results contribute to a better understanding of pathomechanisms in myofibrillar myopathies and provide the basis for hypothesis-driven studies. The detection of specific proteomic profiles in different myofibrillar myopathy subtypes indicates that proteomic analysis may become a useful tool in differential diagnosis of protein aggregate myopathies.

Criteria and suspension levels in diagnostic radiology.

The EC (European Council) Directive on radiation protection of patients requires that criteria for acceptability of equipment in diagnostic radiology, nuclear medicine and radiotherapy be established throughout the member states. This study reviews the background to this requirement and to its implementation in practice. It notes and considers parallel requirements in the EC medical devices directive and International Electrotechnical Commission standards that it is also important to consider and that both sets of requirements should ideally be harmonised due to the global nature of the equipment industry. The study further reviews the types of criteria that can be well applied for the above purposes, and defines qualitative criteria and suspension levels suitable for application. Both are defined and relationships with other acceptance processes are considered (including acceptance testing at the time of purchase, commissioning and the issue of second-hand equipment). Suspension levels are divided into four types, A, B, C and D, depending on the quality of evidence and consensus they are based on. Exceptional situations involving, for example, new or rapidly evolving technology are also considered. The publication and paper focuses on the role of the holder of the equipment and related staff, particularly the medical physics expert and the practitioner. Advice on how the criteria should be created and implemented is provided for these groups and how this might be coordinated with the supplier. Additional advice on the role of the regulator is provided.

Can abundant colloid exclude oncocytic (Hürthle cell) carcinoma in thyroid fine needle aspiration? Cytohistological correlation of 127 oncocytic (Hürthle cell) lesions.

OBJECTIVE: The objective of the present study was to find out whether the presence or absence of certain cytological features can exclude oncocytic (Hürthle cell) carcinoma in thyroid fine needle aspiration (FNA) to minimize unnecessary surgery. METHODS: Over a 17-year period, 127 hypercellular, oncocyte-exclusive, lymphocyte-absent aspirates obtained via ultrasound-guided FNA with on-site assessment had histology slides for review. The presence or absence of six cytological features (microfollicular arrangement, discohesive single cells, small cell dysplasia, large cell dysplasia, transgressing blood vessels and colloid) and one histological feature (macrofollicular component) were determined for each case independently by two cytopathologists. RESULTS: Histology showed 12 (9.4%) cases of Hashimoto thyroiditis, 23 (18.1%) oncocytic adenomatoid nodules in nodular goitre, 66 (52.0%) oncocytic adenomas and 26 (20.5%) oncocytic carcinomas (13 minimally invasive without angioinvasion, six minimally invasive with angioinvasion, seven widely invasive). Histologically, a macrofollicular component was present in seven of 26 (26.9%) oncocytic carcinomas, including one case with abundant thin colloid. A microfollicular arrangement, discohesive single cells, small cell dysplasia, large cell dysplasia and transgressing vessels were present in oncocytic carcinoma, oncocytic adenoma and oncocytic adenomatoid nodules in nodular goitre. CONCLUSIONS: A macrofollicular component is frequently present in oncocytic carcinoma, oncocytic adenoma and oncocytic adenomatoid nodules in nodular goitre. None of the cytological features studied, including abundant colloid, can exclude oncocytic carcinoma. Oncocytic carcinoma can only be excluded by thorough histological examination of thyroidectomy specimens. A molecular marker is needed to triage oncocytic lesions in thyroid FNA.

Seizure and cognitive outcomes in children and adolescents with epilepsy treated with topiramate.

This 12-week open label study explored cognitive and seizure outcomes of 53 children treated with topiramate (TPM). The digit symbol test and verbal learning memory test were administered at baseline and study endpoint. Topiramate was started either in monotherapy or add-on therapy. Overall, 57% of children experienced a ≥50% seizure reduction, 36% became seizure free and cognitive testing revealed no significant changes during TPM therapy. Due to the heterogeneity of the study population, post hoc analyses were added to compare patients in initial or conversion to TPM monotherapy as well as patients who continued add-on therapy. Verbal learning memory test parameters showed neither significant differences within any subgroup comparing baseline with endpoint nor significant differences between described subgroups except for one finding. The digit symbol test revealed no differences between each subgroup between baseline and endpoint. Comparing pre-post differences, TPM monotherapy was associated with better cognitive outcomes than treatment in add-on therapy. These results have to be interpreted with caution given the short study duration and the heterogeneity of the study population. Despite these limitations, our overall results suggest that treatment with topiramate is associated with improved seizure control without significant changes in cognitive functions at the low doses tested.

Does oral antipsychotic pre-treatment influence outcome of a switch to long-acting injectable risperidone in patients with schizophrenia?

INTRODUCTION: The objective of this open-label study was to evaluate treatment benefits of risperidone long-acting injectable (RLAI) in patients with schizophrenia following direct transition from oral risperidone (RIS) compared with transition from other oral second generation antipsychotics. METHODS: Stable in- or outpatients (n=206) receiving RIS or OQAZ (olanzapine, quetiapine, amisulpride, ziprasidone) were transitioned to RLAI for 12 weeks. The primary outcome was the between-group treatment difference in change in PANSS total score from baseline to endpoint. Secondary outcomes included health-related quality-of-life and therapeutic alliance. RESULTS: Mean between-group difference in the change in PANSS total score from baseline to endpoint was -6.1 (CI: -17.6, 5.4), suggesting greater improvement in OQAZ than RIS patients. Due to the pre-specified non-inferiority margin of 5.1, it could not be concluded that OQAZ pre-treatment results in an at least non-inferior PANSS reduction versus RIS pre-treatment. Patient satisfaction with medication and change in quality-of-life subscores showed advantages for OQAZ patients. DISCUSSION: Compared to RIS pre-treatment, clinically stable patients with schizophrenia who are pre-treated with OQAZ might draw a stronger clinical benefit from direct transition to RLAI.

Establishing remission and good clinical functioning in schizophrenia: predictors of best outcome with long-term risperidone long-acting injectable treatment.

OBJECTIVE: To measure symptomatic and functional remission in patients treated with risperidone long-acting injectable (RLAI). METHODS: Stable patients with psychotic disorders requiring medication change were switched to open-label RLAI in the switch to risperidone microspheres (StoRMi) trial. In this post-hoc analysis of the trial extension, follow-up was or=6 months occurred at some point during treatment in 33% of patients; predictors included comorbid disease, country, baseline symptom severity, baseline functioning, type of antipsychotic before switching, and duration of untreated psychosis. Best outcome occurred in 21% of patients; predictors included baseline symptom severity, baseline functioning, country, schizophrenia type, and early positive treatment course. CONCLUSIONS: One in three patients with stable schizophrenia switching to RLAI experienced symptomatic remission, with combined symptomatic, functional, and quality-of-life remission in one in five patients. Symptomatic remission was predicted by better baseline symptom severity and country of origin, with a significantly greater likelihood of remission occurring among patients in Estonia/Slovenia compared with Portugal. Relapse was predicted by higher mode doses of RLAI, additional use of psychoactive medications, male gender, and country of origin, with relapse occurring most frequently in France and least frequently in Portugal. RLAI dose, additional use of psychoactive medications, and country of origin predicted best outcome, with best outcome occurring most frequently in Estonia/Slovenia and least frequently in Portugal.

Effectiveness of low dose of topiramate following rapid titration in multiply handicapped children and difficult-to-treat epilepsy.

This prospective, observational, single arm, monocentric study explored efficacy and tolerability outcomes of rapid oral initiation of topimarate in children with difficult to treat epilepsy. The study population consisted of 19 multiply handicapped children (mean age 4.4 years, range 0.6-15.3 years). The observation period was 12 weeks and included 7 visits. The mean initial dose of topiramate was 1.1 mg/kg body weight/d (range: 0.66-2.67 mg/kg/d) following rapid titration. The mean final dose was 3.3 mg/kg/d (range 0.5-6.7 mg/kg/d). An at least 50% reduction of seizure frequency compared to baseline was observed in 9 of 19 patients (47.4%). Six patients (31.6%) had a slight reduction of seizure frequency (<50%) and 4 patients (21.1%) experienced an increase of seizure frequency. A total number of 29 adverse events were documented in 17 of 19 patients. Most frequently captured were fatigue (26.3% of patients), decreased appetite (15.8%) and psychiatric disturbances (15.8%). No serious adverse events were reported. These data might suggest that in certain clinical circumstances rapid dose escalation with topiramate followed by a low maintenance dose might be a good therapeutic option for pediatric patients with difficult to treat epilepsy.