Search

Currently, there is a renewed interest in treatments with medical cannabis and cannabinoids. Based on an increasing number of publications over the last decades that permitted new insights into mechanisms, efficacy and safety of cannabinoids, the use of cannabinergic medications is authorised in an increasing number of European and non-European countries. The alleviation of chronic, painful conditions is, since thousands of years, one of the primary reasons for the use of cannabis. Depending on the country, a wide range of medicinal cannabis preparations are available:ranging from defined cultivars of medical cannabis, mainly varying in their THC:CBD ratio, that are inhaled or taken as whole plant extracts,to highly purified single cannabinoids, such as delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD),or mixtures of two enriched extracts, standardised to a 1:1 ratio of THC:CBD (nabiximols). Although conflicting opinions continue to exist, the majority of reviews in the past concluded that medical cannabis and cannabinoids play a significant role in the management of pain. Surprisingly, systematic studies to date do not support an "entourage effect" of the other plant constituents of cannabis (mainly terpenoids) in treatment of chronic pain. An emerging cannabinoid is CBD which is the only cannabinergic medication available at present that does not cause the typical "cannabis high"; it is not a "controlled substance". However, despite years of research, there is either no study or no well-conducted, head-to-head, comparison available between different cannabis cultivars, between pure cannabinoids, and between pure cannabinoids and extracts. It remains unanswered which is the optimal treatment approach.

Background Transcatheter aortic valve implantation (TAVI) is an established treatment for patients with severe aortic stenosis and high to intermediate surgical risk. However, the proximity of the conduction system to the prosthesis landing zone bears the risk of atrioventricular conduction disorders. The underlying pathophysiology is not fully understood. Objective The purpose of this study was to characterize the impact of TAVI on the conduction system as assessed by simultaneous electrophysiological testing. Methods AH and HV intervals and QRS duration were measured using a quadripolar His catheter and surface electrocardiogram in 108 patients at baseline (BL), after balloon predilation (timepoint 1 [T1]), after implantation of the valve prosthesis (T2), and after postdilation, if deemed necessary (T3). Results Between BL and T2, significant increases of HV interval and QRS duration were observed, with a mean delta of +12.4 ms and +32.7 ms, respectively. Both balloon predilation and valve implantation had an impact on infranodal conduction. No significant increase of AH intervals was documented. The increase of QRS duration led to left bundle branch block (LBBB) in 57 patients (52.8%). Implantation depth positively correlated with QRS prolongation (ρ = 0.21, P = .042) but not with changes of AH or HV interval (ρ = –0.03, P = .762; and ρ = 0.15, P = .130, respectively). Conclusion Electrophysiological testing during TAVI shows impairment of infranodal atrioventricular conduction by balloon predilation and valve implantation. This impairment is positively correlated with valve implantation depth and results in an increase of QRS duration with mainly LBBB pattern on surface electrocardiogram.

Background: Pancreatic cancer ranks among the deadliest solid tumors. When patients complain about symptoms, the tumor has already spread in the majority of cases to neighbouring tissues and organs with limited possibilities for surgical interventions. In a very recent population-based study which included a total of 36,453 patients with pancreatic ductal adenocarcinoma, median overall survival was only 3.8 months. A growing number of articles suggest potential anticancer benefits of cannabinoids, in particular of cannabidiol (CBD). This is the first time that treatment experiences with CBD are described in patients with pancreatic cancer. Case Series: A total of nine consecutive patients with pancreatic cancer received CBD. All but two received standard chemotherapy in addition, two patients only CBD. CBD was usually administered in an oral daily dose of 400mg. The mean overall survival of these nine patients was 11.5 months (median 11 months). Conclusion: Overall survival seems to be about two times longer than reported in the population-based study mentioned above.

Background: Glioblastoma multiforme (GBM) is a relatively rare type of brain tumour with an incidence rate around 6 per 100,000. Even with the widely practiced combination of radiotherapy with adjuvant temozolomide, the median overall survival remains low with just 13.5 to 16 months after diagnosis. Patients and Methods: We retrospectively reviewed the survival of a cohort of 15 consecutive, unselected patients with histopathologically confirmed glioblastoma multiforme (GBM) who received CBD (400 to 600 mg orally per day) in addition to standard therapy (maximum resection of the tumour followed by radio-chemotherapy). Results: Of 15 patients, seven (46.7%) are now living for at least 24 months, and four (26.7%) for at least 36 months. This is more than twice as long as has been previously reported in the literature. The mean overall survival is currently 24.2 months (median 21 months). Conclusion: CBD is a well supported co-medication and seems to prolong the survival of patients with glioblastoma multiforme.

Patients with symptomatic, drug-refractory atrial fibrillation (AF) are frequently treated with catheter ablation. Cryo-ablation has been established as an alternative to radiofrequency ablation but long-term outcome data are still limited. This study aimed at elucidating the influence of the left atrial volume index (LAVI), derived from cardiac computed tomography (cCT) data, on the long-term outcome of ablation-naive AF patients, after their first cryo-ablation. 415 patients (n = 290 [69.90%] male, 60.00 [IQR: 53.00 to 68.00] years old) who underwent a cCT and subsequent cryo-ablation index procedure were included in this single centre retrospective data analysis. A composite end point was defined (AF on electrocardiogram and/or electric cardioversion and/or re-do). Patients were closely followed for a year and then contacted for long-term follow-up after a median of 53.00 months (IQR: 34.50 to 73.00). Statistical analyses of the outcome and predictors of AF recurrence were conducted. In 224 patients (53.98%) no evidence of AF recurrence could be found. LAVI differed significantly between the positive and adverse (AF recurrence) outcome group (49.96 vs 56.07 ml/m2, p

Transcatheter aortic valve replacement (TAVR) has been shown to be a valid treatment option for patients with significant symptomatic aortic valve stenosis and high surgical risk. Rupture of the aortic root is a rare but life-threatening complication that occurs in approximately 1% of procedures and usually manifests as an acute complication at the time of valve implantation; however, physicians should be aware of a potentially subacute onset, since early recognition and immediate management are crucial. While many potential causes have been described, it is currently unknown which combinations will lead to its occurrence. Accurate preprocedural assessment of the aortic annulus and its adjacent structures as well as adequate sizing of the prosthetic valve are important steps to prevent rupture of the device landing zone.

Grade IV glioblastoma multiforme is a deadly disease, with a median survival of around 14 to 16 months. Maximal resection followed by adjuvant radiochemotherapy has been the mainstay of treatment since many years, although survival is only extended by a few months. In recent years, an increasing number of data from in vitro and in vivo research with cannabinoids, particularly with the non-intoxicating cannabidiol (CBD), point to their potential role as tumour-inhibiting agents. Herein, a total of nine consecutive patients with brain tumours are described as case series; all patients received CBD in a daily dose of 400 mg concomitantly to the standard therapeutic procedure of maximal resection followed by radiochemotherapy. By the time of the submission of this article, all but one patient are still alive with a mean survival time of 22.3 months (range=7-47 months). This is longer than what would have been expected.

Catheter-based ablation of nerves in the adventitia of renal arteries (renal artery denervation [RAD]) using radiofrequency energy can reduce blood pressure (BP) in patients with resistant arterial hypertension (RAH). Occurrence of renal artery stenosis after RAD is still an important concern. We systematically investigated the renal artery anatomy using magnetic resonance imaging (MRI) or computed tomography (CT) angiography in a consecutive series of patients 6 months after RAD. Patients with RAH were treated by RAD after exclusion of secondary causes of hypertension. RAH was defined by a mean systolic office BP160 mm Hg. Renal artery imaging was performed 6 months after RAD by MRI angiography. In case of any contraindication for MRI, a CT angiography was performed. The primary end point was the incidence of significant renal artery stenosis (≥70% lumen diameter reduction). RAD was performed in 76 patients, and evaluation of renal artery anatomy by MRI (n = 66; 87%) or CT angiography (n = 10; 13%) was performed in all patients 6 months after RAD. We found no renal artery stenosis but 2 cases of new nonsignificant stenosis (50% TO 69% lumen diameter reduction). In responders, mean systolic office BP reduction was -30 mm Hg (p0.001) and mean systolic 24-hour BP reduction was -18 mm Hg (p0.001). In conclusion, the incidence of significant renal artery stenosis 6 months after RAD seems to be very low. However, late-onset development of nonsignificant renal artery narrowing cannot be excluded in some patients and should be anticipated in the case of RAH relapse or worsening of renal function after successful RAD.

Background Renal denervation (RDN) is a promising treatment option in addition to medical antihypertensive treatment in patients suffering from resistant hypertension. Despite the growing interest in RDN, the negative result of the Symplicity HTN-3 trial led to a debate on the efficacy of RDN. Methods We systematically investigated the effects of RDN, evaluated by 24-hr ambulatory blood pressure measurements (ABPM), in a consecutive series of patients with resistant hypertension, which was defined by a mean office systolic blood pressure (SBP) >160 mm Hg (>150 mm Hg in patients with diabetes). Patients with a mean 24-hr SBP of less than 130 mm Hg at baseline were classified as pseudo-resistant, while all other patients were classified as true-resistant. After six months, we analyzed the response rates in true-resistant and in pseudo-resistant patients, respectively, by the means of 24-hr ABPM. Thereby, patients with a reduction of more than 5 mm Hg in 24-hr SBP were classified as responders. Results RDN was performed in 106 patients. By 24-hr ABPM, 20 patients (18.9%) were classified as pseudo-resistant patients. In this cohort, we only found two responders (response rate 10%) six months after RDN. By contrast, in true-resistant patients, the response rate was almost 60% and the mean BP reduction was −18.6/−9 mm Hg in 24-hr ABPM. Conclusions We found a significant BP reduction in almost 60% of patients with true-resistant hypertension, but only in 10% in patients with pseudo-resistant hypertension. According to our results, patient selection seems to be crucial for acceptable response rates after RDN. © 2015 Wiley Periodicals, Inc.

Background The sympathetic nervous system is an important factor in hypertension. In patients suffering from resistant hypertension, transfemoral renal sympathetic denervation (RDN) reduces office blood pressure (BP) values. Hypothesis Ambulatory BP measurement (ABPM) is a better predictor than office BP of cardiovascular morbidity and mortality. We thus believe that ABPM should be added to the systematic evaluation and follow-up protocol when treating patients with resistant hypertension with RDN. Therefore, we evaluated the effect of RDN on mean 24-hour BP by the use of ABPM. Methods Patients with resistant hypertension (office systolic BP >160 mm Hg, or >150 mm Hg in patients with diabetes) have been treated with RDN. Ambulatory BP measurement was performed at baseline and at 3 and 6 months after RDN. Patients with a 24-hour systolic BP reduction of ≥5 mm Hg were classified as responders. Results Of 86 patients initially enrolled in the study, 5 had to be excluded from the analysis because of

Amyotrophic lateral sclerosis (ALS, also called Charcot disease, Lou Gehrig disease), is a progressive, neurodegenerative disease caused by the degeneration of motor neurons in the brain and spinal cord. There is no cure. This report describes a case of motor neuron disease with typical weakness in one leg, one hand and the tongue. Despite of treatment with riluzole, symptoms progressed relatively fast. Therefore, the patient decided to take cannabidiol (CBD, 2 × 200 mg/day) as co-medication, which was started 8 weeks after riluzole, and increased to a daily dose of 2 × 300 mg. Within 6 weeks, the impaired function of the right hand and foot reversed almost completely and dysphagia partially. Improvement was maintained for about 10 weeks, when again a slow progression of dysarthria and dysphagia was observed. Eighteen months after onset, speech is almost completely lost, and dysphagia also progressed. However, symptoms of the limbs (weakness, fasciculation, atrophy) worsened much less. It is concluded, that Co-medication with CBD may be able to slow down the progression of some but not all symptoms of motor neuron disease.

Whereas in-stent restenosis (ISR) is widely discussed after coronary stenting procedures, this phenomenon is a considerable problem after interventional treatment of carotid artery stenosis as well. We sought to quantify ISR rate and to identify important respective risk factors in our cohort. We retrospectively analyzed data of our carotid artery stenting database comprising 1165 angiographically successful interventional procedures during the last 19 years. Significant ISR was assessed by Doppler ultrasound and defined as a flow velocity exceeding 300 cm/s representing a lumen narrowing >70%. Examinations were performed the day after intervention, at follow-up visits 1, 6 and 12 months after index hospitalization and once a year afterwards. Thirty-nine patients (3.4%) developed a significant ISR > 70% during the follow-up period (median 19.6 months, IQR 5.1–49.6 months). In 13 of them, restenosis was caused by a mechanical collapse (stent crush) of the implanted stent. All patients with significant ISR were free of neurological events during follow-up and 31 patients underwent a stent-in-stent implantation. We found a shorter stent length, a narrower stent diameter, performance of post-dilatation as well as stent type to significantly influence development of ISR. ISR > 70% after carotid artery stenting is a rare finding also during long-term follow-up. Especially in patients treated with balloon-expandable stents, post-dilatation reduced ISR significantly. As ISR was rare and clinically benign, this technique seems to remain a good therapy option in patients with significant carotid artery stenosis.

Coronary anomalies are rare congenital abnormalities and are often associated with complex congenital heart diseases and manifest in infancy or childhood. Single coronary artery arising from the sinus of Valsalva supplying the entire heart is one of these congenital anomalies. The prevalence is reported to be approximately 0.3 to 2.0% of the general population, mostly clinically asymptomatic and with good prognosis. However, in some cases this anomaly can present as acute coronary syndrome in adults. Literature reports of patients with both a single coronary artery and an acute coronary syndrome are sparse, and percutaneous coronary interventions in such cases are technically challenging. We report a case of a patient with a single coronary artery suffering from an acute coronary syndrom who underwent complex bifurcational percutaneous intervention and provide a review of the literature.

Rational Homeostasis of vascular barriers depends upon sphingosine 1-phosphate (S1P) signaling via the S1P1 receptor. Accordingly, S1P1 competitive antagonism is known to reduce vascular barrier integrity with still unclear pathophysiological consequences. This was explored in the present study using NIBR-0213, a potent and selective S1P1 competitive antagonist. Results NIBR-0213 was tolerated at the efficacious oral dose of 30 mg/kg BID in the rat adjuvant-induced arthritis (AiA) model, with no sign of labored breathing. However, it induced dose-dependent acute vascular pulmonary leakage and pleural effusion that fully resolved within 3–4 days, as evidenced by MRI monitoring. At the supra-maximal oral dose of 300 mg/kg QD, NIBR-0213 impaired lung function (with increased breathing rate and reduced tidal volume) within the first 24 hrs. Two weeks of NIBR-0213 oral dosing at 30, 100 and 300 mg/kg QD induced moderate pulmonary changes, characterized by alveolar wall thickening, macrophage accumulation, fibrosis, micro-hemorrhage, edema and necrosis. In addition to this picture of chronic inflammation, perivascular edema and myofiber degeneration observed in the heart were also indicative of vascular leakage and its consequences. Conclusions Overall, these observations suggest that, in the rat, the lung is the main target organ for the S1P1 competitive antagonism-induced acute vascular leakage, which appears first as transient and asymptomatic but could lead, upon chronic dosing, to lung remodeling with functional impairments. Hence, this not only raises the question of organ specificity in the homeostasis of vascular barriers, but also provides insight into the pre-clinical evaluation of a potential safety window for S1P1 competitive antagonists as drug candidates.

Acute graft rejection in patients after heart transplantation can cause arrhythmias and acute angina pectoris with electrocardiographic ST-segment elevation. We report a case of a 53-year old female patient who had undergone cardiac transplantation 8 years previously. She developed bradycardia with co-existent ST-segment elevation caused by a histologically proven acute graft rejection. After administration of methylprednisolone and immune absorption leading to initial clinical improvement, the patient died unexpectedly. The reasons remain unclear, but a degeneration of the conduction system as well as impaired blood flow in the right coronary caused by cellular and humoral rejection most likely have both contributed.

Instent- restenosis is a major issue after all intravascular interventional treatments applying stents. We retrospectively analyzed data from our center with respect to instent-restenosis rates in patients who had undergone carotid artery stenting (CAS) at our department. We retrospectively

In this article, we report on a 22-year-old patient with myocardial infarction, which was the initial manifestation of polycythaemia vera. The awareness of myeloproliferative disorders as possible underlying disease - especially in young patients presenting with myocardial infarction - is crucial for clinical management, as a missed diagnosis can worsen the patient's further prognosis.

CAS has emerged as an alternative to carotid endarterectomy for the treatment of significant carotid artery stenosis. We investigated if the side of the stenosis treated has an influence on the neurological outcome of our patients. CAS was performed in 1124 patients at our center. The left carotid artery (group L) was intervened in 557 and the right carotid artery (group R) in 567 patients. Data of both patient groups were analyzed with respect to the total rate of peri-interventional ischemic cerebral events, defined as transient ischemic attacks, minor and major strokes, respectively. The total peri-interventional ischemic cerebral event rate was 10.1% in group L and 6.7% in group R (p = 0.042), respectively. The routine use of a filter wire resulted in a significant reduction of complication rates in group L (from 14.7 to 7.1%; p = 0.005) but not in group R (from 7.8 to 6.0%; p = 0.505). Ischemic cerebral events did not differ between group L and R, when only patients in whom a filter wire was used were analyzed (7.1% in group L and 6.0% in group R, p = 0.174). Peri-interventional ischemic cerebral complication rates in patients undergoing CAS differ with respect to the side treated. This may be due to a more frequent plaque mobilization caused by the guiding catheter.

We studied the immunomodulating effect of withdrawal of immunosuppression with cyclosporin A (CsA) in 42 patients with leukemic relapse of chronic myelogenous leukemia (CML) (n = 24), acute myeloid leukemia (AML) (n = 13) and acute lymphoblastic leukemia (ALL) (n = 5) after allogeneic unmanipulated bone marrow (BMT) or peripheral blood stem cell transplantation (PBSCT). Response to CsA withdrawal was monitored molecularly by the polymerase chain reaction for elimination of CML cells containing the bcr-abl messenger RNA (mRNA) transcript (n = 24), or mll-af4 mRNA transcript characteristic of leukemic cells with a 11q23 chromosomal abnormality (n = 1). Rapid tapering of CsA resulted in subsequent achievement of cytogenetic remission in 11 of 14 CML patients (79%) who relapsed in early disease phase (n = 9 cytogenetic relapse, n = 2 hematological relapse) after a median of 57 days. Three of 13 AML patients and one of five ALL patients achieved complete remission. CsA withdrawal was accompanied by the development of acute graft-versus-host disease (GVHD) grade II in most of the 24 patients with CML. Two patients who achieved remission of AML or ALL died from severe GVHD grade III-IV. We calculated a probability of 84% for achieving and remaining in remission with early relapse of CML 4 years after relapse post BMT, whereas patients with AML have only a probability of about 10% of achieving and remaining in remission after 3 years. Patients with advanced CML and ALL had no chance of achieving and remaining in remission in the same time period.

Background: Multiple sclerosis (MS) is an autoimmune disorder characterized by inflammatory, demyelinating lesions in the central nervous system. Open studies an

Summary Background Multiple sclerosis is an autoimmune disorder characterised by the repeated occurrence of demyelinating lesions within the central nervous system. Uncontrolled studies and experimental evidence suggest beneficial effects of repeated administration of intravenous immunoglobulin (IVIg) by immunomodulating mechanisms and induction or remyelination. We aimed to investigate the efficacy of IVIg in a randomised double-blind multicentre study. Methods Patients with relapsing-remitting multiple sclerosis were randomly assigned a monthly dose of IVIg (0·15–0·2 g/kg bodyweight) or placebo. Duration of treatment was 2 years. The primary outcome measures were the effect of treatment on clinical disability—measured by the absolute change in Kurtzke's expanded disability status scale (EDSS) score—and the proportion of patients with improved, stable, or worse clinical disability (⩾ 1·0 grade on EDSS score). Findings Of the 243 patients screened, 150 met our eligibility criteria and were randomly assigned to IVIg or placebo. Before the start of treatment two patients in the placebo group dropped out, so there were 75 patients in the IVIg group and 73 in the placebo group. Intention-to-treat analysis showed that IVIg treatment had a beneficial effect on the course of clinical disability. The EDSS score decreased in the IVIg-treated patients and increased in the placebo group (−0·23 [95% CI −0·43 to −0·03] vs 0·12 [−0·13 to 0·37], p=0·008). In the IVIg group, the numbers of patients with improved, stable, or worse clinical disability were 23 (31%), 40 (53%), and 12 (16%) compared with ten (14%), 46 (63%), and 17 (23%) in the placebo group. Side-effects were reported in three (4%) IVIg-treated patients and in four (5%) placebo-group patients, but were not directly linked to study medication.

Department within a pharmaceutical company which is responsible for collecting and processing of adverse reaction reports.

syn. drug monitoring, pharmacoepidemiology involves the collection of clinical data on marketed medicines, primarily on drug safety (incidence of esp. rare side effects, new hazards, specific risk factors, risk/benefit analysis) but also on unexpected benefits, and their scientific evaluation or cost/benefit aspects, and to evaluate if drugs are prescribed as directed; often the approach is retrospective which might then cause severe bias; surveillance can be “pasive”, i.e. spontaneous reporting of ADRs to National Authority, Event Monitoring, ICSR, or “active/”solicited”“, i.e. as studies by industry or academic institutions (safety follow-up, ph IV, observational st., “sentinel” sites, prescription-event monitoring, …); true PMS technique should tap the results of field use of a medicine without disturbing prescribing decision or patient selection; for marketing, PMS provides therefore information on the performance of the drug in general use, often on the base of automated record linkage rather than in data sheet use, and may be an alternative to megatrials or long-term follow-up; in some EC member states, e.g. Austria, Belgium, France, Germany, Ireland, PMS studies may be a condition of marketing approval (restricted marketing authorisation) and required by health authorities (post-approval research)

a notification from a health professional regarding a patient with a disorder that is suspected to be drug-related; → see also adverse reaction, EudraVigilance, expedited reporting.

Unused or returned medication is usually destroyed either by the sponsor or by the hospital pharmacy; for drug accountability reasons this process has to be documented with date, quantity, and identification of drugs incl. the batch number.

ICH: “An adverse reaction, the nature or severity of which is not consistent with the information included in the company Core Safety Information; → see also listed adverse drug reaction.

Drug which may be sold at any shop without supervision from a pharmacist or a doctor (UK); → see also controlled drug, gras-list, pharmacy drug, prescription only medicine.

In some countries (e.g. Japan) guidelines for monitoring prescription drugs, new chemical entities, new indications, combinations of drugs, routes of administration, dosages a.s.o. exist, which make it necessary for companies to establish a dedicated postmarketing surveillance management department, appoint suitable educated and trained staff, and designate a manager responsible for forwarding relevant information to the national health authority.

(Immortalised) foetal cells can be transplanted into damaged tissue and effect repair; research concentrates e.g., on diseases of the central nervous system, namely Parkinson’s disease, stroke, Huntington’s chorea.

ICH: “any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment”; any undesirable experience occurring to a subject during a clinical treatment, whether or not considered related to the (investigational) product(s); expected AE = event which is already known from previous experiences and described in the investigator’s brochure or package insert; techniques to evaluate AEs are e.g.: case control studies, post-marketing surveillance programmes, prescriptionevent monitoring, prescription-sequence analyses etc.; when an AE has been assessed (→ see standardised assessment of causality) and there are reasonable grounds for the suspicion that it is causally related to the (investigational) drug(s), it must be considered as an adverse drug reaction; for regulatory reporting purposes, if an event is spontaneously reported, even if the relationship is unknown or unstated, it meets the definition of an ADR; → see also adverse experience, adverse reaction, blinding, concomitant event, incident, medical device reporting, pharmacovigilance, rule of three, safety update report, significant adverse event, unexpected adverse event.

According to the EC guidelines on good clinical practice (III) “patients/healthy volunteers taking part in a clinical trial should be satisfactorily insured against any injury caused by the trial”; usual maximal sums are in the order of € 500,000.00 per patient or of € 10,000,000.00 per trial respectively; → see also clinical trial compensation guidelines, indemnification, insurance, product liability.

Retrospective study which investigates, from outcome to exposure, potential associations between a drug and adverse events or, more generally, between a variable and the onset of a disease; a study in which patients who already have a certain condition are compared to people who do not. E.g: lung cancer patients are asked how much they smoked in the past; answers are then compared with a sample of the general population; c.c.s. are often the design of choice when outcome is rare and when random sampling is therefore far less efficient than selection by outcome; the use of a drug by patients with a specific disease (“cases”) is compared with that of a group of patients without the disease but otherwise similar (the “controls”); if use is higher among cases than controls, then it may be possible to infer an association between the drug and the disease; example: subjects suffering from lung cancer are selected as “cases” and another group of non-diseased subjects as the “controls”; than the frequency of smokers in both groups is determined in order to clarify a relationship between smoking habits and lung cancer (in a cohort study one would draw a sample of smokers and nonsmokers and compare the frequency of lung cancer)

For reporting results of cancer treatment the following definitions (WHO) of objective response are used (separately!): (I) measurable disease: complete response (CR) = disappearance of all known disease, determined by 2 observations not less than 4 weeks apart; partial r. (PR)= 50% or more decrease in total tumour size of the lesions which have been measured to determine the effect of therapy by 2 observations not less than 4 weeks apart (there can be no appearance of new lesions or progression of any lesion); no change (NC)= 50% decrease in total tumour size cannot be established nor has a 25% increase in the size of one or more measurable lesions been demonstrated; progressive disease (PD)= 25% or more increase in the size of one or more measurable lesions, or the appearance of new lesions; (II) unmeasurable disease: complete r. (CR) = complete disappearance of all known disease for at least 4 weeks; partial r. (PR) = estimated decrease in tumour size of 50% or more for at least 4 weeks; no change (NC) = no significant change for at least 4 weeks; this includes stable disease, estimated decrease of less than 50%, and lesions with estimated increase of less than 25%; progressive disease (PD) = appearance of any new lesion not previously identified or estimated increase of 25% or more in existent lesions

syn. GP trial, usually a multicentre trial, done in general practice or other non-hospital units.

Bayesian based approach for assessing drug-induced illness; the goal is to calculate the posterior odds in favor of a particular drug being the cause of the adverse event; the posterior odds are calculated by considering 6 assessment subsets: “prior odds” as background epidemiological and clinical trials information, and 5 other dealing with case-specific information of possible differential diagnostic value (“likelihood ratios”); → see also adverse drug reaction, standardized assessment of causality (SAC).

List of pharmaceutical products deemed absolutely necessary for treatment of patients; issued by national governments (non-listed products may be banned!), but also by the who.

FDA: “The sponsor shall notify FDA and all participating investigators in a written investigational new drug (IND) s.r. of any adverse experience associated with use of the drug that is both serious and unexpected. Such notification shall be made as soon as possible and in no event later than 10 working days after the sponsor’s initial receipt of the information … The sponsor shall also notify the FDA by telephone of any unexpected fatal or life threatening experience associated with the use of the drug in the clinical studies conducted under the IND no later than 3 working days (5 for trials conducted outside the US) after receipt of the information …”; → see also investigational drug.

Class of new therapeutics planned for the treatment of viral infections, autoimmune disease, endocrine disease and cancers; AS-ODNs are small synthetic molecules of single-stranded DNA that suppress gene expression by binding to RNA templates in a sequence-specific manner, thus suppressing gene expression, mRNA translation and therefore the production of disease-causing proteins; → see gene therapy, ribozyme.

ICH: “An unsolicited communication to a company, regulatory authority or other organisation that describes an adverse medical reaction in a patient given one or more medicinal products and which does not derive from a study or any organised data collection scheme”; → see also individual case safety report.

syn. Core Safety Profile; ICH: “All relevant safety information contained in the Company Core Data Sheet prepared by the marketing authorisation holder (MAH) and which the MAH requires to be listed in all countries where the company markets the drug, except when the local regulatory authority specifically requires a modification. It is the reference information by which listed and unlisted are determined for the purpose of periodic reporting for marketed products, but not by which expected and unexpected are determined for expedited reporting”; → see also see Company Core Data Sheet, listed adverse drug reaction, unlisted adverse drug reaction.

Classification of heart failure; I = no limitation of physical activity; II = slight limitation of physical activity; III = marked limitation of physical activity; IV = inability to carry out any physical activity without discomfort.

Patients lost to a clinical trial without knowing the reasons; sometimes also used to describe the total number of patients lost, i.e. not finishing a particular clinical trial (premature termination; the FDA (Clinical Guidance Document, 1994) suggests that loss to follow-up should be less than 20%; → see also drop-out, withdrawal.

Information on pharmaceutical products, such as patient package inserts or e.g. the annually published Physician’s Desk Reference; → see also patient information leaflet.

Middleman in the insurancebased US health system; acts like a loss-adjuster on behalf of the insurance company or employer, to control and optimise the healthcare expenditure of the insured.