[Short paths to diagnosis with artificial intelligence: systematic literature review on diagnostic decision support systems]. / Kurze Wege zur Diagnose mit künstlicher Intelligenz ­ systematische Literaturrecherche zu "diagnostic decision support systems".

BACKGROUND: Rare diseases are often recognized late. Their diagnosis is particularly challenging due to the diversity, complexity and heterogeneity of clinical symptoms. Computer-aided diagnostic aids, often referred to as diagnostic decision support systems (DDSS), are promising tools for shortening the time to diagnosis. Despite initial positive evaluations, DDSS are not yet widely used, partly due to a lack of integration with existing clinical or practice information systems. OBJECTIVE: This article provides an insight into currently existing diagnostic support systems that function without access to electronic patient records and only require information that is easily obtainable. MATERIALS AND METHODS: A systematic literature search identified eight articles on DDSS that can assist in the diagnosis of rare diseases with no need for access to electronic patient records or other information systems in practices and hospitals. The main advantages and disadvantages of the identified rare disease diagnostic support systems were extracted and summarized. RESULTS: Symptom checkers and DDSS based on portrait photos and pain drawings already exist. The degree of maturity of these applications varies. CONCLUSION: DDSS currently still face a number of challenges, such as concerns about data protection and accuracy, and acceptance and awareness continue to be rather low. On the other hand, there is great potential for faster diagnosis, especially for rare diseases, which are easily overlooked due to their large number and the low awareness of them. The use of DDSS should therefore be carefully considered by doctors on a case-by-case basis.

Treating pain in patients with Ehlers-Danlos syndrome : Multidisciplinary management of a multisystemic disease.

BACKGROUND: The clinical picture of people with Ehlers-Danlos syndromes (EDS) is complex and involves a variety of potential causes of pain. This poses major challenges to patients and healthcare professionals alike in terms of diagnosis and management of the condition. OBJECTIVES: The aim of the article was to provide an overview of the specific pain management needs of patients with EDS and address their background. MATERIAL AND METHODS: A selective literature search was performed to highlight the current state of research on pain management in EDS patients. RESULTS: Affected patients require multimodal pain management considering their individual needs, disease-specific features, and comorbidities. CONCLUSION: Medical awareness and evidence need to be further improved to enhance the medical care situation of these patients with complex needs.

[Neuropathic pain as a symptom in autonomic neuropathies and other rare diseases : Small fiber neuropathy: its recognition, diagnosis, and treatment]. / Neuropathische Schmerzen als Symptom bei autonomen Neuropathien und anderen seltenen Erkrankungen : Kleinfaserneuropathie erkennen, diagnostizieren und behandeln.

BACKGROUND: Neuropathic pain is difficult to diagnose and treat. Small fiber neuropathy (SFN) flies under the radar of nerve conduction studies. OBJECTIVES: The importance of a structured patient history and physical examination in the context of neuropathic pain is emphasized. Describing SFN as an important cause, the authors consider rare but partially treatable differential diagnoses. They conclude that autonomic symptoms are frequently associated, often presenting with diverse symptoms. METHODS: A selective literature research to present SFN symptoms as well as differential diagnostic and therapeutic steps in the context of SFN and rare diseases focusing on the autonomic nervous system. RESULTS: Neuropathic pain significantly reduces quality of life. To shorten the time until diagnosis and to initiate therapy, the authors recommend a structured patient history including sensory plus and minus symptoms and non-specific autonomic signs. If the initial search for the cause is not successful, rare causes such as treatable transthyretin (ATTR) amyloidosis and Fabry's disease or autoimmune causes should be considered, particularly in the case of progressive and/or autonomic symptoms. CONCLUSION: The diagnosis and therapy of rare SFN requires interdisciplinary collaboration and, in many cases, a referral to specialized centers to achieve the best patient care.

Cluster-Analytic Identification of Clinically Meaningful Subtypes in MCAS: The Relevance of Heat and Cold.

BACKGROUND: Mast cell activation syndrome (MCAS) is a clinically heterogeneous disease with allergy-like symptoms and abdominal complaints. Its etiology is only partially understood and it is often overlooked. AIMS: The aim of this study was to identify subgroups of MCAS patients to facilitate diagnosis and allow a personalized therapy. METHODS: Based on data from 250 MCAS patients, hierarchical and two-step cluster analyses as well as association analyses were performed. The data used included data from a MCAS checklist asking about symptoms and triggers and a set of diagnostically relevant laboratory parameters. RESULTS: Using a two-step cluster analysis, MCAS patients could be divided into three clusters. Physical trigger factors were particularly decisive for the classification as they showed remarkable differences between the three clusters. Cluster 1, labeled high responders, showed high values for the triggers heat and cold, whereas cluster 2, labeled intermediate responders, presented with high values for the trigger heat and low values for cold. The third cluster, labeled low responders, did not react to thermal triggers. The first two clusters showed more divers clinical symptoms especially with regard to dermatological and cardiological complaints. Subsequent association analyses revealed relationships between triggers and clinical complaints: Abdominal discomfort is mainly triggered by histamine consumption, dermatological discomfort by exercise, and neurological symptoms are related to physical exertion and periods of starvation. The reasons for the occurrence of cardiological complaints are manifold and triggers for respiratory complaints still need better identification. CONCLUSION: Our study identified three distinct clusters on the basis of physical triggers, which also differ significantly in their clinical symptoms. A trigger-related classification can be helpful in clinical practice for diagnosis and therapy. Longitudinal studies should be conducted to further understand the relationship between triggers and symptoms.

Evaluation of a tryptase depletion index for better pathologic identification of mast cell activation syndrome.

BACKGROUND: Laboratory evidence supporting diagnosis of the prevalent condition of mast cell activation syndrome (MCAS) currently includes elevated levels in blood or urine of mediators relatively specific to mast cells (MCs) and/or increased numbers of MCs in luminal gastrointestinal (GI) tract tissues. However, identification of elevated mediators is technically challenging and expensive, and controversy persists regarding the normal ranges of numbers/counts of MCs in various GI tract segments, let alone challenges in determining how many of the visualized MCs are activated. To aid diagnosis of MCAS, we developed a potential new approach for the pathologist to identify the extent of GI tract MC activation easily and inexpensively. PARTICIPANTS AND METHODS: Visualization of MCs in gastrointestinal biopsies from 251 patients vs. 95 controls using antibodies against CD117 and tryptase; MC counting per mm2; calculation of the difference between the CD117-positive MCs (identifying all MCs) vs. tryptase-positive MCs (identifying non-activated tryptase-containing MCs), which we define as the tryptase depletion index (TDI). RESULTS: Mean total MC counts did not differ significantly between patients and controls, but mean TDIs differed significantly. Non-overlapping confidence intervals at the 99.9% level identified cut-offs of TDIs between patients vs. controls of 26, 45 and 32 MCs/mm2 in gastric antrum, duodenum, and colon, respectively. CONCLUSIONS: The TDI may discriminate between MCAS patients vs. controls. If this preliminary work can be independently confirmed, the TDI may become a useful additional minor diagnostic criterion for MCAS.

Exploring different stakeholders' perspectives on ward rounds in paediatric oncology: a qualitative study.

RATIONAL/AIMS AND OBJECTIVES: Ward rounds are a core routine for interprofessional communication and clinical care planning: Health care professionals and patients meet regularly and it encourages patients to actively participate. In paediatric oncology, the long treatment process, the serious diagnosis, and involvement of both patients and their parents in shared-decision-making require specific ward round skills. Despite its high value for patient-centred care, a universal definition of ward round is lacking. Little is known about attitudes and expectations of different participants towards a 'good' ward round. This study aims to capture experiences and expectations of different stakeholders to better understand ward round needs in paediatric oncology and serve as a basis to improve future ward rounds. METHOD: Semi-structured interviews were conducted with patients, parents, nurses and medical doctors of a paediatric oncology ward until theoretical saturation (13 interviews). A standardised qualitative analysis using the phenomenological framework defined by Colaizzi was used to identify important aspects in the interviews. RESULTS: Three major themes were identified in the interviews: [1] Structure and Organisation; [2] Communication; [3] Education. Further analysis revealed 23 categories and elucidated several opportunities and unmet needs recognized by stakeholders: Ward round functions in comforting families in stressful situations, and relationship building. Interviewees expressed their concerns about missing structures. Families pleaded for smaller ward round teams and layperson language. Health care professionals underscored the lack of ward round training. Paediatric patients stated that ward round scared them without proper explanation. All interviewees emphasized the need for professionalization of the ward round in the setting of paediatric oncology. CONCLUSION: This study gives important insights into ward round functions and organisational requirements. It addresses special challenges for ward round participants in paediatric oncology, such as consideration of the emotional aspect of cancer treatment or the limits of shared decision making. Furthermore, this study underscores the great significance of ward rounds in paediatric oncology, with an emphasis on communication and relationship-building. Although performed universally, ward rounds are poorly explored or evaluated. This structured analysis synthesizes important expectations of different WR stakeholders, revealing opportunities of improvement and stressing the need for guidelines, training, and preparation.

Risk factors for pressure ulcers in adult patients: A meta-analysis on sociodemographic factors and the Braden scale.

AIMS AND OBJECTIVES: Providing the first meta-analysis of risk factors for pressure ulcer development in adult patients. BACKGROUND: Pressure ulcers remain a serious health complication for patients and nursing staff. However, there is a lack of statistical evidence for risk factors as previous research did not include any quantitative synthesis. DESIGN: Meta-analysis, using PRISMA guidelines. METHODS: Studies from PubMed, Embase, CINAHL Complete, Web of Science, Cochrane Library, and other reviews and sources were screened and checked against the inclusion criteria. The risk of bias was evaluated using a slightly modified QUIPS tool. Data regarding population, design, statistical analysis and risk factors were extracted. Meta-analysis with comparable studies was conducted for age, sex, and Braden scale. The sub-group analysis was used to account for heterogeneity. RESULTS: 28 studies with 570,162 patients were entered in meta-analysis. Older age and a low total Braden scale score increased the risk for pressure ulcers. All subscales excluding 'moisture' reached significance in meta-analysis based only on few studies, however, limiting overall evidence. Male sex achieved mixed results, too. CONCLUSION: The first meta-analytic analysis shows evidence for age and Braden scale as risk factors for pressure ulcer development. Limitations regarding study quality and heterogeneity must be considered, highlighting the need for unifying certain conditions in risk factor research. RELEVANCE TO CLINICAL PRACTICE: Patients at risk for new pressure ulcers can be identified by their total Braden score and age, whereas the latter is also connected to deeper pressure ulcers. Nurses and health personnel should pay great attention to patients in older age and undergo specific training to utilise and evaluate the Braden scale effectively, if necessary.

[Postoperative pain experience after proximal femur fracture in dementia]. / Postoperatives Schmerzerleben nach proximaler Femurfraktur bei Demenz.

BACKGROUND: The present study aimed to assess the postoperative pain experience in cognitive deficit patients with special reference to sensory or affective pain quality. METHODS: Nineteen patients with normal cognition up to cognitive impairments according to the DemTect screening-tool were studied regarding their postoperative pain experience after proximal femur fracture. The numerical rating scale (NRS), the cognitive DemTect questionnaire, the pain sensation questionnaire (SES), and a quantitative sensory test (QST) were used as examination instruments. RESULTS: The mean ± SD age of the patients was 83.8 ± 10.0 years. Of the 19 patients, 6 (31.6%) had normal cognitive abilities. In 4 patients (21.1%) there were indications of mild cognitive impairments, and in 9 patients (47.4%) the suspicions of the presence of dementia arose. The mean postoperative pain intensity (NRS) was 4.0 (1.6). With comparable analgesic therapy, the reported pain intensities did not differ between the three patient groups with different cognitive impairments and the first three postoperative treatment days. There were no statistically significant differences between the groups for the sensory or affective total scores of the pain sensation scale. The QST parameters deep pain (PPT), superficial mechanical pain after needle stimulation (MPT), and the superficial sensitivity to light touch stimuli (MDT) showed a significantly increased sensitivity of the operated side. For the sensation of vibration (VDT) no differences between operated and healthy extremities could be proven. DISCUSSION: The postoperative pain experience does not differ between patients with normal and limited cognition. The quantitative sensory testing showed mechanical hyperalgesia in the operated area. The study points to the importance of adequate postoperative pain management even in those with dementia.

Development of Care Pathway for Assessment and Treatment of Fatigue in Palliative Care.

Objectives: Fatigue is a frequent and burdensome symptom in patients with advanced disease in palliative care. However, it is under-assessed and undertreated in clinical practice, even though many treatment options have been identified in systematic reviews. Care pathways with defined and standardised steps have been recommended for effective management in the clinical setting. This paper describes a care pathway for managing fatigue in palliative care patients. This study aims to develop a care pathway with detailed guidance for screening, assessment, diagnosis, and treatment of fatigue in palliative care patients. Material and methods: A collaborative effort of multidisciplinary clinicians participated in constructing the care pathway. The care pathway was developed using the following steps: (a) Developing an intervention; (b) piloting and feasibility; (c) evaluating the intervention; (d) reporting; and (e) implementation. This paper covers the first step, which includes the evidence base identification, theory identification/development, and process/outcomes modeling. A literature search was conducted to understand the extent of the fatigue problem in the palliative care setting and identify existing guidelines and strategies for managing fatigue. Consistent recommendations emanating from the included papers were then contributed to a care pathway. Patient representatives and palliative care professionals provided feedback on the draft. Results: The care pathway address the following care processes: (1) Screening for the presence of fatigue; (2) assessment to evaluate the severity of fatigue; (3) diagnostic procedure, including history, physical examination, and laboratory finding; (4) therapeutic management pathway for clinical decision-making; and (5) valuation of treatment effect, using questionnaires, diaries and physical activity monitoring with body-worn sensors. Conclusion: The development of a care pathway will help to implement regular and structured assessment, diagnosis, and treatment of fatigue for healthcare professionals treating palliative care patients. Reviewing the pathway with a multidisciplinary expert group and field testing the pathway will be the next steps toward implementation.

Significance of anger suppression and preoccupied attachment in social anxiety disorder: a cross-sectional study.

BACKGROUND: There is evidence for the relevance of attachment style and anger expression for the manifestation of social anxiety disorder (SAD). METHOD: In a cross-sectional study 321 individuals with social anxiety disorder (41% men, age 38.8 ± 13.9) were compared with 94 healthy controls (37% men, age 35.8 ± 15.1) on several questionnaires (Attachment Styles Questionnaire, State Trait Anger Inventory, Social Phobia Inventory, Beck Depression Inventory). RESULTS: Individuals with SAD showed moderate-sized reduced levels of secure and large-sized increased levels of fearful and preoccupied attachment style compared to healthy controls (all p < 0.001) as well as small-sized increased levels of trait anger (p = 0.03) and moderate-sized increased levels of anger-in (p < 0.001). Attachment style and anger regulation could predict 21% (R2 = 0.21, p < 0.001) of the extent of social anxiety (SPIN) in SAD; secure (ß = - 0.196, p < 0.01) and preoccupied attachment style (ß = 0.117, p < 0.05), as well as anger-in (ß = 0.199, p < 0.01) were significant cross-sectional predictors. Further analysis revealed that the relationship between preoccupied attachment and social anxiety is partially mediated by anger-in. CONCLUSION: Study findings confirm the relevance of preoccupied attachment style and anger suppression for social anxiety. Disentangling the role of anger regulation in early attachment patterns has significant therapeutic implications in SAD.

Fatigue in advanced disease associated with palliative care: A systematic review of non-pharmacological treatments.

BACKGROUND: Fatigue is a common complaint reported by patients with advanced disease, impacting their daily activities and quality of life. The pathophysiology is incompletely understood, and evidence-based treatment approaches are needed. AIM: This systematic review aims to evaluate the efficacy of non-pharmacological interventions as treatment for fatigue in advanced disease. DESIGN: The review design follows the Cochrane guidelines for systematic reviews of interventions. DATA SOURCES: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, PubMed, ClinicalTrials.gov and a selection of journals up to February 28th 2019, for randomised controlled trials (RCTs) investigating the effect of non-pharmacological treatments for fatigue in advanced disease associated with palliative care. Further potentially relevant studies were identified from the reference lists in relevant reviews, and in studies considered for this review. RESULTS: We screened 579 publications; 15 met the inclusion criteria, with data from 1179 participants: 815 were treated with physical exercise, 309 with psycho-educational therapy and 55 with an energy restoration approach. Sources of potential bias included lack of description of blinding and allocation concealment methods, and small study sizes. Physical exercise as treatment for fatigue in patients with advanced cancer was supported by moderate-quality evidence. CONCLUSION: Physical exercise should be considered as a measure to reduce fatigue in patients with advanced cancer, but data on other advanced diseases is lacking. Due to the differences between studies, no clear recommendations can be made with respect to the best type of physical therapy. Restoration exercise and psycho-educational therapy are promising treatment options, although further research is needed.

Multidisciplinary management and outcome in pancreatic cancer patients treated with high-intensity focused ultrasound.

Introduction: High-intensity focused ultrasound (HIFU) for pancreatic cancer is a growing therapeutic field which has been proven to reduce cancer pain and provide a local tumor control additionally to standard palliative care. However, less is known about the multidisciplinary and especially anesthesiological management of HIFU treatment although an interdisciplinary approach is crucial for treatment success.Material and methods: Anesthesiological and radiological records of 71 HIFU-treated pancreatic cancer patients were analyzed with regard to the following items: intervention time, sonication time, total energy, anesthesia time, peri-interventional medication, body temperature maximum and minimum, pain scores before and 1 day, 6 weeks and 3 months after intervention, peri-interventional complications. Effects on pain scores were estimated with a mixed panel data model. Bivariate associations between interventional variables were examined with the Spearman's correlation.Results: HIFU treatment was performed without major adverse events. Peri-procedural hyperthermia >37.5 °C occurred in 2 patients, hypothermia <35 °C in 8 cases. Interventional variables did not correlate significantly with pain scores, opioid dose, nor body temperature. 85.5% of patients experienced significant early pain relief within the first week after intervention. Post-interventional pain relief is associated with morphine equivalent opioid dose (p = 0.025) and treatment time (p = 0.040).Conclusion: While HIFU can be considered safe and effective treatment option, procedure-associated pain and temperature management represent challenges for the interdisciplinary HIFU intervention team. Especially short-term pain relief depends on the combined effort of the radiologist and anesthesiologist.

Quality of life in patients with midgut NET following peptide receptor radionuclide therapy.

OBJECTIVES: There is convincing evidence that peptide receptor radionuclide therapy (PRRT) using 177Lu-DOTATATE compared to octreotide therapy has a positive effect on overall survival and progression-free survival in midgut neuroendocrine tumors (NET). The current study analyzed health-related quality of life (QoL) in patients undergoing PRRT with a special focus on differences in functional performance. MATERIALS AND METHODS: In our study, 70 patients (39 men or 31 female) suffering from midgut NET were included, with a mean age of 64.2 years. Functional performance was assessed by the index of the Eastern Cooperative of Oncology Group (ECOG). Thirty-three patients (47%) showed ECOG 0, 31 patients (44%) ECOG 1, and six patients (9%) ECOG 2. Health-related QoL was assessed by the EORTC QLQ-C30 questionnaire filled in at baseline and 3 months after each PRRT cycle. RESULTS: The median cumulative administered activity was 27.4 GBq. Global health status significantly improved compared to baseline status after 1st (p = 0.05), 2nd (p = 0.004), and 3rd (p = 0.04) treatment cycle. Analyzing specific aspects of QoL, emotional functioning significantly improved after 1st and 2nd treatment cycle (both p < 0.001) as well as after 3rd cycle (p = 0.001). With regard to cognitive functioning, there was a significant improvement after 1st and 2nd treatment cycle (p = 0.003 and p = 0.05 respectively). With regard to alleviation of somatic symptoms, a significant reduction in pain and diarrhea was observed after the 2nd cycle (p = 0.038) and 3rd cycle (p = 0.036). Furthermore, changes in QoL in relation to functional performance status as assessed by ECOG were analyzed. There were no significant differences with regard to QoL alterations between patients with high (ECOG 0 or 1) and moderate performance status. CONCLUSION: Our study confirmed an equally positive effect of PRRT on quality of life in midgut NET patients with high or moderate functional status in terms of increasing global health, functional status, and alleviating symptoms.

Clinical Effectiveness and Potential Survival Benefit of US-Guided High-Intensity Focused Ultrasound Therapy in Patients with Advanced-Stage Pancreatic Cancer.

PURPOSE: Pancreatic cancer (PaC) is a life-limiting tumor with a wide range of incapacitating symptoms such as cancer pain in more than 80 % of patients. This prospective interventional study addresses the clinical effectiveness of ultrasound-guided high-intensity focused ultrasound (HIFU) treatment for patients with advanced-stage PaC, including pain perception, tumor size and survival benefit. MATERIALS AND METHODS: 50 patients with late-stage PaC underwent HIFU. Clinical assessment included evaluation of tumor volume by imaging and pain burden (pain severity, pain sensation, interference with daily activities) using the Brief Pain Inventory at baseline and follow-up. Median overall survival, progression-free survival and time to local progression were estimated using Kaplan-Meier analysis. RESULTS: In 84 % of patients, significant early relief of cancer-induced abdominal pain was achieved by HIFU independent of metastatic status; it persisted during follow-up. Tumor volume reduction was 37.8 ±â€Š18.1 % after 6 weeks and 57.9 ± 25.9 % after 6 months. 21 % of HIFU-treated patients had local tumor progression with a median time of 14.4 months from intervention. The median overall survival and progression-free survival were 16.2 and 16.9 months from diagnosis and 8.3 and 6.8 months from intervention. CONCLUSION: In patients with advanced pancreatic cancer and otherwise limited treatment options, HIFU resulted in significant early and long-lasting pain relief and tumor size reduction over time independent of metastatic status. Clinical data suggest an additional potential survival benefit.

[Cannabis and cannabinoids in palliative care]. / Cannabis und Cannabinoide in der Palliativversorgung.

Cannabis and cannabinoids are discussed as a potential treatment for a broad spectrum of diseases and symptoms. This article presents current evidence for the use of cannabis and cannabinoids in palliative care and delivers background information. For this purpose recent literature was examined and evaluated. The authors focused on a systematic review and meta-analysis of cannabinoids in palliative care by Mücke et al.Overall, there is no high-quality evidence for the use of cannabis and cannabinoids in palliative care. Cannabinoids may be considered as a therapeutic attempt in the treatment of cancer pain and weight gain in patients with HIV as well as other symptoms (such as nausea and loss of appetite) if established treatments fail.Further studies involving more patients are needed to evaluate the therapeutic potential of cannabis and cannabinoids. However, special conditions in the field of palliative care make it difficult to carry out high-quality studies.

Improving quality of life in patients with pancreatic neuroendocrine tumor following peptide receptor radionuclide therapy assessed by EORTC QLQ-C30.

INTRODUCTION: Neuroendocrine tumors (NETs) have proven to be appropriate neoplasms for peptide receptor radionuclide therapy (PRRT), as the majority of these slow-growing malignancies overexpress somatostatin receptors. The aim of this study was to evaluate changes in quality of life (QoL) of patients with P-NET following PRRT. METHODS: Sixty-eight patients with P-NET (31 female, mean age 61.4 y) underwent PRRT: 12 with NET of grade 1, 40 of grade 2, 8 of grade 3 (grade non-available n = 8). Prior to treatment, 39 patients showed ECOG 0, 26 patients ECOG 1, and three patients ECOG 2. Clinical assessment included evaluation of QoL and symptom changes using a standardized questionnaire (EORTC QLQ-C30) and was performed at baseline and every three months following each therapy cycle up to 12 months. Primary analysis compared QoL at baseline and after the fourth treatment cycle (N = 53). RESULTS: Up to four treatment cycles PRRT were performed for each patient. The median cumulative administered activity was 28.2 GBq. Primary analysis revealed that compared to baseline QoL was significantly improved revealing increased global health status (p = 0.008) and social functioning (p = 0.049) at the end of the study. Furthermore, fatigue and appetite loss showed a significant improvement after the last PRRT cycle (fatigue: p = 0.029, appetite loss p = 0.015). Sub-analyses showed that QoL was improved revealing increased global health status (3 months after first, second, and third treatment cycle p = 0.048, p = 0.002, and p < 0.001, respectively), emotional functioning (3 months after first-third cycle p = 0.003, p = 0.049, and p = 0.001, respectively) and social functioning (3 months after the first and second p < 0.001, and after the third cycle p = 0.015, respectively). Furthermore, some symptoms were significantly alleviated compared with baseline: fatigue (after first-third cycle p = 0.026, p = 0.050, and p = 0.008, respectively), nausea and vomiting (after first and second cycle p = 0.006 and p = 0.001, respectively), dyspnea (after third cycle p = 0.025), appetite loss (after first-third cycle p = 0.010, p = 0.001, and p = 0.009, respectively), constipation (after first-third cycle p = 0.050, p = 0.003, and p = 0.060, respectively). CONCLUSION: PRRT is an effective treatment of P-NET improving QoL of patients in terms of increasing global health and mitigation of physical complaints.

An elementary quantum network of single atoms in optical cavities.

Quantum networks are distributed quantum many-body systems with tailored topology and controlled information exchange. They are the backbone of distributed quantum computing architectures and quantum communication. Here we present a prototype of such a quantum network based on single atoms embedded in optical cavities. We show that atom-cavity systems form universal nodes capable of sending, receiving, storing and releasing photonic quantum information. Quantum connectivity between nodes is achieved in the conceptually most fundamental way-by the coherent exchange of a single photon. We demonstrate the faithful transfer of an atomic quantum state and the creation of entanglement between two identical nodes in separate laboratories. The non-local state that is created is manipulated by local quantum bit (qubit) rotation. This efficient cavity-based approach to quantum networking is particularly promising because it offers a clear perspective for scalability, thus paving the way towards large-scale quantum networks and their applications.

Cannabis-based medicines for chronic neuropathic pain in adults.

BACKGROUND: This review is one of a series on drugs used to treat chronic neuropathic pain. Estimates of the population prevalence of chronic pain with neuropathic components range between 6% and 10%. Current pharmacological treatment options for neuropathic pain afford substantial benefit for only a few people, often with adverse effects that outweigh the benefits. There is a need to explore other treatment options, with different mechanisms of action for treatment of conditions with chronic neuropathic pain. Cannabis has been used for millennia to reduce pain. Herbal cannabis is currently strongly promoted by some patients and their advocates to treat any type of chronic pain. OBJECTIVES: To assess the efficacy, tolerability, and safety of cannabis-based medicines (herbal, plant-derived, synthetic) compared to placebo or conventional drugs for conditions with chronic neuropathic pain in adults. SEARCH METHODS: In November 2017 we searched CENTRAL, MEDLINE, Embase, and two trials registries for published and ongoing trials, and examined the reference lists of reviewed articles. SELECTION CRITERIA: We selected randomised, double-blind controlled trials of medical cannabis, plant-derived and synthetic cannabis-based medicines against placebo or any other active treatment of conditions with chronic neuropathic pain in adults, with a treatment duration of at least two weeks and at least 10 participants per treatment arm. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data of study characteristics and outcomes of efficacy, tolerability and safety, examined issues of study quality, and assessed risk of bias. We resolved discrepancies by discussion. For efficacy, we calculated the number needed to treat for an additional beneficial outcome (NNTB) for pain relief of 30% and 50% or greater, patient's global impression to be much or very much improved, dropout rates due to lack of efficacy, and the standardised mean differences for pain intensity, sleep problems, health-related quality of life (HRQoL), and psychological distress. For tolerability, we calculated number needed to treat for an additional harmful outcome (NNTH) for withdrawal due to adverse events and specific adverse events, nervous system disorders and psychiatric disorders. For safety, we calculated NNTH for serious adverse events. Meta-analysis was undertaken using a random-effects model. We assessed the quality of evidence using GRADE and created a 'Summary of findings' table. MAIN RESULTS: We included 16 studies with 1750 participants. The studies were 2 to 26 weeks long and compared an oromucosal spray with a plant-derived combination of tetrahydrocannabinol (THC) and cannabidiol (CBD) (10 studies), a synthetic cannabinoid mimicking THC (nabilone) (two studies), inhaled herbal cannabis (two studies) and plant-derived THC (dronabinol) (two studies) against placebo (15 studies) and an analgesic (dihydrocodeine) (one study). We used the Cochrane 'Risk of bias' tool to assess study quality. We defined studies with zero to two unclear or high risks of bias judgements to be high-quality studies, with three to five unclear or high risks of bias to be moderate-quality studies, and with six to eight unclear or high risks of bias to be low-quality studies. Study quality was low in two studies, moderate in 12 studies and high in two studies. Nine studies were at high risk of bias for study size. We rated the quality of the evidence according to GRADE as very low to moderate.Primary outcomesCannabis-based medicines may increase the number of people achieving 50% or greater pain relief compared with placebo (21% versus 17%; risk difference (RD) 0.05 (95% confidence interval (CI) 0.00 to 0.09); NNTB 20 (95% CI 11 to 100); 1001 participants, eight studies, low-quality evidence). We rated the evidence for improvement in Patient Global Impression of Change (PGIC) with cannabis to be of very low quality (26% versus 21%;RD 0.09 (95% CI 0.01 to 0.17); NNTB 11 (95% CI 6 to 100); 1092 participants, six studies). More participants withdrew from the studies due to adverse events with cannabis-based medicines (10% of participants) than with placebo (5% of participants) (RD 0.04 (95% CI 0.02 to 0.07); NNTH 25 (95% CI 16 to 50); 1848 participants, 13 studies, moderate-quality evidence). We did not have enough evidence to determine if cannabis-based medicines increase the frequency of serious adverse events compared with placebo (RD 0.01 (95% CI -0.01 to 0.03); 1876 participants, 13 studies, low-quality evidence).Secondary outcomesCannabis-based medicines probably increase the number of people achieving pain relief of 30% or greater compared with placebo (39% versus 33%; RD 0.09 (95% CI 0.03 to 0.15); NNTB 11 (95% CI 7 to 33); 1586 participants, 10 studies, moderate quality evidence). Cannabis-based medicines may increase nervous system adverse events compared with placebo (61% versus 29%; RD 0.38 (95% CI 0.18 to 0.58); NNTH 3 (95% CI 2 to 6); 1304 participants, nine studies, low-quality evidence). Psychiatric disorders occurred in 17% of participants using cannabis-based medicines and in 5% using placebo (RD 0.10 (95% CI 0.06 to 0.15); NNTH 10 (95% CI 7 to 16); 1314 participants, nine studies, low-quality evidence).We found no information about long-term risks in the studies analysed.Subgroup analysesWe are uncertain whether herbal cannabis reduces mean pain intensity (very low-quality evidence). Herbal cannabis and placebo did not differ in tolerability (very low-quality evidence). AUTHORS' CONCLUSIONS: The potential benefits of cannabis-based medicine (herbal cannabis, plant-derived or synthetic THC, THC/CBD oromucosal spray) in chronic neuropathic pain might be outweighed by their potential harms. The quality of evidence for pain relief outcomes reflects the exclusion of participants with a history of substance abuse and other significant comorbidities from the studies, together with their small sample sizes.