[Benefits and harms of cannabis-based medicines from the viewpoint of patients with chronic pain and their physicians : A cohort study in three pain centers of the German federal state Saarland]. / Nutzen und Schaden von Cannabisarzneimitteln aus Sicht von Patienten mit chronischen Schmerzen und ihren Ärzten : Eine Kohortenstudie in drei saarländischen Schmerzzentren.

BACKGROUND: There are no studies available that have simultaneously assessed the benefits and harms of cannabis-based medicines from the viewpoint of patients and their physicians. METHODS: All chronic pain patients at three pain centres in the German federal state of Saarland who had received at least one prescription of cannabis-based medicines (CbMs) in the past from the study centre were included in a cross-sectional study from January 1 to December 31, 2021. Patients and their physicians completed a self-developed questionnaire separately. RESULTS: All 187 contacted patients participated in the study. Since the start of CbM therapy, 44.9% of patients reported to be much or very much, 43.3% to be moderately and 8.0% to be slightly improved overall. A total of 2.7% reported no change and 1.1% a moderate deterioration of overall wellbeing. From the patients' point of view, the symptoms most frequently reported to have substantially improved were sleep problems (36.4%), muscle tension (25.1%) and appetite problems (22.1%). The most frequent bothersome side effects were sweating (6.4%), concentration problems (4.2%) and nausea (4.1%). Physicians noted substantial pain relief in 60.7%, improvement of sleep in 65.7% and of mental well-being in 34.3%. A complete cessation of opioids was achieved in 64.7%, of anticonvulsants in 57.9% and of antidepressants in 60% of patients that had received these medications before the start of CbM therapy. CONCLUSIONS: CbMs can contribute to a clinically relevant reduction in pain, sleep problems and muscle tension and can improve daily functioning in carefully selected and supervised patients with chronic pain. CbM can contribute to the reduction or complete cessation of other pain medications (antidepressants, anticonvulsants, opioids).

Integrative medicine during the intensive phase of chemotherapy in pediatric oncology in Germany: a randomized controlled trial with 5-year follow up.

BACKGROUND: Integrative medicine is used frequently alongside chemotherapy treatment in pediatric oncology, but little is known about the influence on toxicity. This German, multi-center, open-label, randomized controlled trial assessed the effects of complementary treatments on toxicity related to intensive-phase chemotherapy treatment in children aged 1-18 with the primary outcome of the toxicity sum score. Secondary outcomes were chemotherapy-related toxicity, overall and event-free survival after 5 years in study patients. METHODS: Intervention and control were given standard chemotherapy according to malignancy & tumor type. The intervention arm was provided with anthroposophic supportive treatment (AST); given as anthroposophic base medication (AMP), as a base medication for all patients and additional on-demand treatment tailored to the intervention malignancy groups. The control was given no AMP. The toxicity sum score (TSS) was assessed using NCI-CTC scales. RESULTS: Data of 288 patients could be analyzed. Analysis did not reveal any statistically significant differences between the AST and the control group for the primary endpoint or the toxicity measures (secondary endpoints). Furthermore, groups did not differ significantly in the five-year overall and event-free survival follow up. DISCUSSION: In this trial findings showed that AST was able to be safely administered in a clinical setting, although no beneficial effects of AST between group toxicity scores, overall or event-free survival were shown.

[Progressive muscle relaxation in postoperative pain therapy]. / Progressive Muskelrelaxation in der postoperativen Schmerztherapie.

BACKGROUND: Early and optimal treatment of postoperative pain based on a multimodal treatment concept is very important so that subsequent chronification can be avoided. OBJECTIVES: This study investigated the influence of progressive muscle relaxation on the sensation of pain and the need for analgesics after orthopedic interventions. MATERIALS AND METHODS: This nonrandomized pilot study tested 104 patients in the Clinic of Orthopedics at the Saarland University Medical Center in Homburg, Germany. The patients underwent total endoprosthesis (TEP) of the or the knee or spine surgery (laminectomy), and they had the option of choosing to use the technique of progressive muscle relaxation. All patients completed a questionnaire on the first, fourth, and ninth postoperative day. Data were collected on the maximum and minimum intensity of pain, duration of strong pain, length of hospital stay, and use of pain medication. These were compared by means of t tests for the group with progressive muscle relaxation and the group without progressive muscle relaxation. RESULTS: No significant difference was observed between the two groups regarding pain sensation analgesic dosage. There was a tendency for the length of hospital stay to be shorter in the group with progressive muscle relaxation. CONCLUSION: The positive effect of progressive muscle relaxation cannot be confirmed on the basis of the study data. Owing to the varying study design and implementation as well as the inclusion of heterogeneous patient groups, no conclusion can be drawn at present regarding the effectiveness of progressive muscle relaxation in common practice; therefore, further research is necessary.

[Cannabis-based medicines for chronic pain: indications, selection of drugs, effectiveness and safety : Experiences of pain physicians in Saarland]. / Cannabispräparate bei chronischen Schmerzen: Indikationen, Präparateauswahl, Wirksamkeit und Sicherheit : Erfahrungen der saarländischen Schmerztherapeuten.

BACKGROUND: There are uncertainties among physicians with respect to the indications, selection of drugs, effectiveness and safety of cannabis-based medicines for chronic pain. METHODS: All statutory health insurance pain physicians in Saarland were asked to complete a self-developed questionnaire assessing their experiences with cannabis-based medicines, which they prescribed between 10 March 2017 and 30 November 2018 for adult patients with chronic cancer and non-cancer pain. RESULTS: All statutory health insurance pain physicians participated in the survey and 13 out of 20 reported having prescribed cannabis-based medicines. The most frequent reasons for prescriptions in 136 patients (1.9% of the patients of the institutions) were failure of established treatment (73%) and desire of the patient (63%). In 35% of patients the type of pain was nociceptive, in 34% neuropathic, in 29% nociceptive and neuropathic and in 13% nociplastic. Dronabinol was prescribed for 95% of the patients and 71% were responders (clinically relevant reduction of pain or of other symptoms). In 29% of patients treatment was terminated due to either a lack of efficacy or adverse events. CONCLUSION: Statutory health insurance pain physicians in Saarland were reluctant to prescribe cannabis-based medicines. Dronabinol was effective and well-tolerated in the majority of the highly selected patients.

Photobiomodulation therapy in breast cancer-related lymphedema: a randomized placebo-controlled trial.

BACKGROUND: The aim of our study was to examine the effects of photobiomodulation therapy (PBMT) in the treatment of breast cancer-related lymphedema using a compactly designed treatment regime consisting of eight therapy sessions in combination with a cluster laser device covering a total area size of 78.54 cm² over the axillary. METHODS: Forty patients with unilateral lymphedema were enrolled in this double-blind, placebo-controlled trial in order to evaluate effects of PBMT on lymphedema-related pain, quality of life, grip strength and limb volume difference. Subjects received irradiation for ten minutes per session using a cluster laser covering a beam area of 78.54 cm². The applied energy was 384 Joules resulting in an energy density of 4.89 J/cm². RESULTS: Post-treatment, a 50% reduction in median pain scores and an increase in mean quality of life were observed. Mean grip strength was persistently higher after eight sessions of PBMT compared with pretreatment; however, no statistically significant intergroup differences (P > 0.05) were found over the time course. CONCLUSION: PBMT using a compactly designed treatment regime in combination with a cluster laser device did not significantly improve quality of life, pain scores, grip strength and limb volume over the time course.

Severe cyanide poisoning from an alternative medicine treatment with amygdalin and apricot kernels in a 4-year-old child.

BACKGROUND: The use of complementary and alternative medicine (CAM) is widespread in children with cancer and is poorly regulated. PATIENTS AND METHODS: Case report. RESULTS: We describe a case of severe cyanide poisoning arising from CAM use. A severely agitated, encephalopathic, unresponsive 4-year-old boy (initial Glasgow Coma Scale of 3) with a history of metastatic ependymoma was brought to our emergency department by ambulance services. Initial blood gas analysis demonstrated severe metabolic/lactic acidosis. On detailed questioning of the parents, the use of CAM including intravenous and oral "vitamin B 17" (amygdalin) and oral apricot kernel was reported. After administering sodium thiosulfate, rapid improvement in his medical condition with complete recovery without need for further intensive care treatment was seen. Serum cyanide level was markedly elevated. CONCLUSIONS: Cyanide poisoning can be the cause of severe encephalopathy in children receiving CAM treatment with substances containing cyanogenic glycosides.

Differences in use of complementary and alternative medicine between children and adolescents with cancer in Germany: a population based survey.

BACKGROUND: Use of complementary and alternative medicine (CAM) in children with cancer is common and probably increasing. However, data concerning differences between children and adolescents focusing on prevalence, reasons for use/non-use, costs, adverse effects, and socio-demographic factors are lacking. PROCEDURE: A population-based survey over a 1 year period with 497 participants was conducted. RESULTS: Of the 457 respondents (92%) 322 were children and 135 adolescents (>16 years of age) with malignancies. 31% reported CAM use from the time when being diagnosed, compared to an overall lifetime prevalence rate of 41% before cancer diagnosis. Among CAM users the most prevalent therapies were homeopathy, massage, anthroposophic medicine, acupuncture, and Bach flowers. The main reasons for use were to reduce therapy-related side effects, to strengthen the immune system, to achieve physical stabilization and to increase healing chances. Socio-demographic factors associated with CAM use were higher parental education and higher family income. A majority of CAM users (97%) would recommend CAM use. Most users (78%) informed a physician about CAM use. Side effects were rarely reported (5%), minor and self-limiting. CONCLUSIONS: The high prevalence rates seem to represent the parental or patients needs for additional treatment perceived as successful and devoid of side-effects. Clinical care and the physician-patient relation would profit from an enhanced understanding of CAM and a greater candidness towards the parental needs. Safety and efficacy - especially of CAM with high prevalence rates - should be studied in rigorous basic and clinical research.

Headache in children: update on complementary treatments.

Complementary and alternative medicine (CAM) is widely used by both physicians and patients with primary headache syndromes. Despite a considerable number of articles addressing CAM in primary headache syndromes, the overall evidence for CAM is still poor. The aim of this review was to give an overview of the current evidence of the main alternative therapies used in the treatment of primary headache syndromes of childhood. MEDLINE and Cochrane Library were systematically searched for articles dealing with complementary and alternative treatment or prophylaxis of headache and migraine published within the past 20 years.

Cannabis use disorder in patients with chronic pain: overestimation and underestimation in a cross-sectional observational study in 3 German pain management centres.

ABSTRACT: There are concerns that cannabis use disorder (CUD) may develop in patients with chronic pain prescribed medical cannabis (MC). The criteria for CUD according to the Statistical Manual for Mental Disorders Version 5 (DSM-5) were not developed for the identification of patients using cannabis for therapeutic reasons. In addition, some items of CUD might be attributed to the desire of the patient to relieve the pain. Therefore, alternative strategies are needed to identify the true prevalence of CUD in persons with chronic pain being treated with MC. The prevalence of CUD in patients with chronic pain according to the DSM-5 criteria was assessed using an anonymous questionnaire in 187 consecutive patients attending 3 German pain centres in 2021. Questionnaires were rated as follows: (1) all criteria included, (2) removal of items addressing tolerance and withdrawal, and (3) removal of positive items if associated with the desire to relieve pain. Abuse was assessed by self-report (use of illegal drugs and diversion and illegal acquisition of MC) and urine tests for illegal drugs. Physicians recorded any observation of abuse. Cannabis use disorder according to the DSM-5 criteria was present in 29.9%, in 13.9% when items of tolerance and withdrawal were removed, and in 2.1% when positive behaviour items were removed. In 10.7%, at least 1 signal of abuse was noted. Urine tests were positive for nonprescribed drugs (amphetamines and tranquilizer) in 4.8% of subjects. Physicians identified abuse in 1 patient. In this study, the DSM-5 criteria overestimated and physicians underestimated the prevalence of CUD in patients prescribed MC for chronic pain.

Melatonin does not influence sleep deprivation electroencephalogram recordings in children.

UNLABELLED: The electroencephalogram (EEG) is an essential diagnostic tool in children with epilepsy. The recording of a sleep EEG can increase the yield of EEG recordings in certain epileptic syndromes. The primary aim of this study was to assess the influence of melatonin on EEG recording (quality, EEG characteristics) and to assess its efficacy to induce sleep. Children with epilepsy or non-epileptic neurological patients requiring sleep deprivation EEG studies were enrolled into this prospective study at a tertiary University Hospital study. Sequential recording of sleep deprivation EEGs both with and without prior administration of melatonin was performed. A total of 50 patients (27 with epilepsy, 23 non-epileptic neurological patients) were included in this study (median age 9.5 years; range 1-18 years; male 28). The quality and EEG characteristics (abnormal findings, depth of sleep) were not affected by the use of melatonin. In total, 92 of 100 EEGs were successfully performed without significant differences between the two groups (six failures with melatonin, two failures without melatonin; p = 0.289). CONCLUSIONS: We conclude that melatonin does not alter the quality of sleep EEG studies in children with epilepsy or suspected epilepsy. Melatonin does not increase the rate of successfully performed EEG studies in sleep-deprived children.

Postoperative Pain Therapy with Laser Acupuncture after Cesarean Section under Spinal Anesthesia: A Double-Blinded, Randomized, Placebo-Controlled Trial.

PURPOSE: The aim of our prospective, randomized, double-blind, placebo-controlled study was to investigate the effect of laser acupuncture on postoperative pain in women undergoing cesarean section. METHODS: 99 women (mean age 32 ± 5 years) scheduled for cesarean section under spinal anesthesia at Saarland University Hospital Medical Center, Homburg (Germany) were enrolled in this trial after giving written consent. Patients were randomized in two groups receiving a course of 3 treatments over 3 days with either active or placebo laser. Each acupuncture session treated Di-4 and Shen-men of both hands and ears. Primary outcome was defined as the pain severity at rest measured by Numeric Rating Scale (NRS) on the first postoperative day. Secondary outcome measures included analgesic consumption, time to mobilization, and length of stay. Treatment occurred on the operation day and on the following 2 days. Data were collected by a standardized questionnaire. RESULTS: From 95 included patients, 80 were analyzed. No statistical difference between both groups were observed for pain severity at rest on the first postoperative day after cesarean section (Mann-Whitney U test, p = 0.850, verum group [mean ± standard deviation]: 3.3 ± 2.1 vs. placebo group: 3.2 ± 1.9). Secondary outcome measures regarding analgesic consumption showed no difference in NSAID or opioid between treatment and placebo group. Laser acupuncture showed no effect on time to mobilization and length of stay. CONCLUSION: Our study could not demonstrate significant effects by the application of laser acupuncture on postoperative pain in women undergoing cesarean section.

Sudden unexpected death in epilepsy in children.

Sudden unexpected death in epilepsy (SUPEP) is the commonest cause of seizure-related mortality in people with intractable epilepsy. The incidence of SUDEP varies in different epilepsy populations, with lower rates in population-based studies, higher in referral populations and clinical trials of adjunct drugs for complex partial epilepsy, and highest rates for surgical series. Certain risk factors for SUDEP have been identified, with seizure activity being one of the strongest risk factor for SUDEP. Suspected underlying mechanisms include cardiac dysrhythmias, seizure-related apnoea and postictal respiratory arrest. Prevention of SUDEP has centred on seizure control, and SUDEP incidence has been reduced by epilepsy surgery in some studies. In this review, we present epidemiological data, and discuss risk factors and underlying pathophysiological mechanisms that are associated with SUDEP in children.

The role of vasopressin and terlipressin in catecholamine-resistant shock and cardio-circulatory arrest in children: review of the literature.

INTRODUCTION: Arginine-vasopressin (AVP) and terlipressin (TP) are used as rescue drugs for states of shock and cardio-circulatory failure. METHODS: Review to assess AVP/TP as a rescue therapy in children with catecholamine-resistant shock or cardio-circulatory arrest. RESULTS: A total of 31 reports were included (428 patients); sixteen articles were case series, 10 case reports, 3 clinical evaluation studies, one study was a non-blind RCT while one study was a multicentre double-blind RCT. The most common indication for either drug was catecholamine-refractory septic shock (12 reports). Commonly reported responses following AVP/TP administration were a rapid increase in blood pressure, an increase in urine output, and a decrease in serum lactate. In most reports, AVP and TP led to the reduction of catecholamines. The cumulative mortality rate remained high (188/428; 43.9%) despite the use of AVP/TP. CONCLUSIONS: No firm recommendations on the use of AVP/TP in children with severe forms of cardio-circulatory failure can be issued.

Wishes and Needs at the End of Life­Communication Strategies, Counseling, and Administrative Aspects.

BACKGROUND: Managing the last phase of life properly, i.e., taking care that a patient's wishes are respected at the end of life and beyond, is very important and can relieve the patient and his or her family of unnecessary burdens. METHODS: This review is based on guidelines, reviews, meta-analyses, selected publications, and the authors' own experiences from everyday clinical practice. RESULTS: Most patients want frank information from their physicians about their condition at all times over the course of their treatment, from the moment of diagnosis to the end of their life. This has no lasting adverse effects, but rather enables patients to take decisions that are appropriate to their stage of disease. Early integration in palliative care can improve patients' quality of life, symptom control, and mood. In helping to manage the last phase of life, the physician often serves as a provider of impulses, or else determines which other types of professional should counsel or support the patient. Patients should be enabled to issue directives that reflect their wishes, as well as to choose representatives who are allowed to speak for them. Consideration should also be given to the patient's emotional legacy, e.g., letters or video messages with personal content. CONCLUSION: In the care of patients with life-limiting diseases, more attention should be paid to the management of the last phase of life. Palliative-care physicians can take over this task from other medical disciplines, and early integration in palliative care is recommended.

Agreement of invasive versus non-invasive blood pressure in preterm neonates is not dependent on birth weight or gestational age.

PURPOSE: Blood pressure constitutes an important parameter in the assessment of the cardiovascular status in preterm infants. Invasive arterial blood pressure (IBP) is considered the 'gold-standard', but non-invasive blood pressure (NIBP) is used frequently in preterm infants. The aim of this prospective study was to compare mean IBP and mean NIBP arterial blood pressure measurements in three subsets of preterm infants (>1500 g; 1000-1500 g, and <1000 g, and >31 weeks, 28-31 weeks, and <28 weeks of gestation). METHODS: Prospective, simultaneous assessment of both IBP and NIBP measurements in 50 preterm neonates at 6, 12, 18, 24 h after birth in a tertiary University centre. RESULTS: Mean gestational age was 26.7 +/- 2.2 (24-32) in group I (n= 18), 29.6 +/- 2.0 (27-34) in group II (n= 19) and 32.2 +/- 1.9(30-36) weeks in group III (n= 13), respectively; mean birth weight was 777 +/- 161 (495-995), 1251 +/- 154 (1010-1490) and 2010 +/- 332 (1590-2550) g. Mean IBP and mean NIBP increased significantly during the first 24 h of life in all three sub-groups (P < 0.01); IBP and NIBP measurements were significantly correlated, and showed good agreement, irrespective of birth weight and gestational age. CONCLUSIONS: Although IBP monitoring is considered the 'gold standard', NIBP values showed good agreement with those obtained invasively irrespective of gestational age and birth weight. We conclude that NIBP monitoring constitutes an important parameter in the assessment of the cardiovascular status even in extremely low birth weight infants.

Electroencephalogram in children with minor traumatic brain injury.

BACKGROUND: Mild traumatic brain injury (MTBI) is one of the most frequent causes for hospitalisation in childhood. Because of different guidelines in the management the diagnostic approach varies substantially. Apart from neuroimaging studies (CT, MRI, sonography) an electroencephalogram (EEG) is often performed without any evidence-based data supporting its use. METHODS: Retrospective analysis of 150 children with MTBI (age 0-16 years), who were admitted to the Children's Hospital of the University of Saarland from January 2006 to December 2007. RESULTS: Mean age was 4.3 (SD 3.6) years: 55.3% were boys. The most common mechanisms of injury were: Minor fall <1 m of height (60%) and fall >1.5 m of height (10%). The most common symptoms were: one or more episodes of vomiting (60%), somnolence (26.7%) and headache (12.7%). On 118 patients an EEG was performed; 106 (89.8%) were normal, 11 (9.3%) pathological and 1 (0.9%) invalid because of artefacts. The pathological EEGs showed focal findings with localised slowing in nine cases, spike-wave complexes in one case and general slowing in one case. Of the 11 patients with pathological EEG, two had a CT scan, two a MRI and two had cranial sonography; all the neuro-imaging was normal. None of the children required neurosurgical intervention, had a negative outcome or showed persistent symptoms. CONCLUSION: The routine performance of an EEG after MTBI in children is not indicated because in most of the cases it is unrevealing, and may lead to unnecessary diagnostic procedures. Instead, children with MTBI should be closely monitored for possible clinical complications and neurological deterioration.

Safety Considerations in Cannabinoid-Based Medicine.

Cannabinoids are a diverse class of chemical compounds that are increasingly recognized as potential therapeutic options for a range of conditions. While many studies and reviews of cannabinoids focus on efficacy, safety is much less well reported. Overall assessment of the safety of cannabinoid-based medicines is confounded by confusion with recreational cannabis use as well as different study designs, indications, dosing, and administration methods. However, clinical studies in registered products are increasingly available, and this article aims to discuss and clarify what is known regarding the safety profiles of cannabinoid-based medicines, focusing on the medical and clinical safety evidence and identifying areas for future research. The two most well-studied cannabinoids are Δ9-tetrahydrocannabinol (THC), or its synthetic variants (dronabinol, nabilone), and cannabidiol (CBD). Across diverse indications, dizziness and fatigue are generally the most common adverse events experienced by patients receiving THC or combined THC and CBD. Patients receiving THC may experience adverse cognitive effects and impairment in psychomotor skills, with implications for driving and some occupations, while CBD may help to lower the psychotropic effects of THC when used in combination. Studies on dependency and addiction in a medical context are limited, but have shown inconsistent findings regarding misuse potential. Generally, the recommended route of administration is oral ingestion, as smoking medicinal cannabinoid products potentially releases mutagenic and carcinogenic by-products. There are several potential drug-drug interactions and contraindications for cannabinoid-based medicines, which physicians should account for when making prescribing decisions. The available evidence shows that, as with any other class of pharmaceuticals, cannabinoid-based medicines are associated with safety risks which should be assessed in the context of potential therapeutic benefits. Each patient should be assessed on an individual basis and physicians must rely on informed, evidence-based decision-making when determining whether a cannabinoid-based medicine could be an appropriate treatment option.

Mechanisms of disease/hypothesis: neurogenic left ventricular dysfunction and neurogenic pulmonary oedema.

BACKGROUND: Acute onset of cardiovascular dysfunction may be the result of insults to the central nervous and autonomic system. Several cerebral regions (insular cortex, lateral, hypothalamus, and brain stem) have been identified as part of the "central autonomic network". The brain stem plays an integral role in controlling and mediating autonomic tone. PATIENT AND METHODS: Case reports. RESULTS: These two case reports demonstrate the intimate connectivity between the cardiovascular/pulmonary system and the central nervous system in a 13-year-old girl with occipital angiomatosis, but no history of heart disease who developed profound left ventricular dysfunction and pulmonary oedema following pontine haemorrhage, and in a 5-year-old girl who developed severe pulmonary oedema after suffering from status epilepticus. CONCLUSIONS: The two case reports suggest that cardiovascular dysfunction secondary to central nervous insults and neurogenic pulmonary oedema are not two separate clinical entities, but may very well encompass two different presentations of central autonomic disturbances.