What proportion of patients with chronic noncancer pain are prescribed an opioid medicine? Systematic review and meta-regression of observational studies

Guidelines now discourage opioid analgesics for chronic noncancer pain because the benefits frequently do not outweigh the harms. We aimed to determine the proportion of patients with chronic noncancer pain who are prescribed an opioid, the types prescribed and factors associated with prescribing. Database searches were conducted from inception to 29 October 2018 without language restrictions. We included observational studies of adults with chronic noncancer pain measuring opioid prescribing. Opioids were categorized as weak (e.g. codeine) or strong (e.g. oxycodone). Study quality was assessed using a risk of bias tool designed for observational studies measuring prevalence. Individual study results were pooled using a random‐effects model. Meta‐regression investigated study‐level factors associated with prescribing (e.g. sampling year, geographic region as per World Health Organization). The overall evidence quality was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria. Of the 42 studies (5,059,098 participants) identified, the majority (n = 28) were from the United States of America. Eleven studies were at low risk of bias. The pooled estimate of the proportion of patients with chronic noncancer pain prescribed opioids was 30.7% (95% CI 28.7% to 32.7%, n = 42 studies, moderate‐quality evidence). Strong opioids were more frequently prescribed than weak (18.4% (95% CI 16.0–21.0%, n = 15 studies, low‐quality evidence), versus 8.5% (95% CI 7.2–9.9%, n = 15 studies, low‐quality evidence)). Meta‐regression determined that opioid prescribing was associated with year of sampling (more prescribing in recent years) (P = 0.014) and not geographic region (P = 0.056). Opioid prescribing for patients with chronic noncancer pain is common and has increased over time

The potential savings of using thiazides as the first choice antihypertensive drug: cost-minimisation analysis

BACKGROUND: All clinical practice guidelines recommend thiazides as a first-choice drug for the management of uncomplicated hypertension. Thiazides are also the lowest priced antihypertensive drugs. Despite this, the use of thiazides is much lower than that of other drug-classes. We wanted to estimate the potential for savings if thiazides were used as the first choice drug for the management of uncomplicated hypertension. METHODS: For six countries (Canada, France, Germany, Norway, the UK and the US) we estimated the number of people that are being treated for hypertension, and the proportion of them that are suitable candidates for thiazide-therapy. By comparing this estimate with thiazide prescribing, we calculated the number of people that could switch from more expensive medication to thiazides. This enabled us to estimate the potential drug-cost savings. The analysis was based on findings from epidemiological studies and drug trials, and data on sales and prescribing provided by IMS for the year 2000. RESULTS: For Canada, France, Germany, Norway, the UK and the US the estimated potential annual savings were US$13.8 million, US$37.4 million, US$72.2 million, US$10.7 million, US$119.7 million and US$433.6 million, respectively. CONCLUSIONS: Millions of dollars could be saved each year if thiazides were prescribed for hypertension in place of more expensive drugs. Our calculations are based on conservative assumptions. The potential for savings is likely considerably higher and may be more than US$1 billion per year in the US

Abnormal salience signaling in schizophrenia: the role of integrative beta oscillations

Aberrant salience attribution and cerebral dysconnectivity both have strong evidential support as core dysfunctions in schizophrenia. Aberrant salience arising from an excess of dopamine activity has been implicated in delusions and hallucinations, exaggerating the significance of everyday occurrences and thus leading to perceptual distortions and delusional causal inferences. Meanwhile, abnormalities in key nodes of a salience brain network have been implicated in other characteristic symptoms, including the disorganization and impoverishment of mental activity. A substantial body of literature reports disruption to brain network connectivity in schizophrenia. Electrical oscillations likely play a key role in the coordination of brain activity at spatially remote sites, and recent, evidence implicates beta band oscillations in long-range integrative processes. We used magnetoencephalography (MEG) and a task designed to disambiguate responses to relevant from irrelevant stimuli to investigated beta oscillations in nodes of a network implicated in salience detection and previously shown to be structurally and functionally abnormal in schizophrenia. Healthy participants, as expected, produced an enhanced beta synchronisation to behaviourally relevant, as compared to irrelevant, stimuli, while patients with schizophrenia showed the reverse pattern: a greater beta synchronisation in response to irrelevant than to relevant stimuli. These findings not only support both the aberrant salience and disconnectivity hypotheses, but indicate a common mechanism that allows us to integrate them into a single framework for understanding schizophrenia in terms of disrupted recruitment of contextually appropriate brain networks

Has primary care antimicrobial use really been increasing? Comparison of changes in different prescribing measures for a complete geographic population 1995-2014

Objectives To elucidate how population trends in total antimicrobials dispensed in the community translate into individual exposure. Methods Retrospective, population-based observational study of all antimicrobial prescribing in a Scottish region in financial years 1995, 2000 and 2005–14. Analysis of temporal changes in all antimicrobials and specific antimicrobials measured in: WHO DDD per 1000 population; prescriptions per 1000 population; proportion of population with ≥1 prescription; mean number of prescriptions per person receiving any; mean DDD per prescription. Results Antimicrobial DDD increased between 1995 and 2014, from 5651 to 6987 per 1000 population [difference 1336 (95% CI 1309–1363)]. Prescriptions per 1000 fell (from 821 to 667, difference –154, –151 to –157), as did the proportion prescribed any antimicrobial [from 39.3% to 30.8% (–8.5, –8.4 to –8.6)]. Rising mean DDD per prescription, from 6.88 in 1995 to 10.47 in 2014 (3.59, 3.55–3.63), drove rising total DDD. In the under-5s, every measure fell over time (68.2% fall in DDD per 1000; 60.7% fall in prescriptions per 1000). Among 5–64 year olds, prescriptions per 1000 were lowest in 2014 but among older people, despite a reduction since 2010, the 2014 rate was still higher than in 2000. Trends in individual antimicrobials provide some explanation for overall trends. Conclusions Rising antimicrobial volumes up to 2011 were mainly due to rising DDD per prescription. Trends in dispensed drug volumes do not readily translate into information on individual exposure, which is more relevant for adverse consequences including emergence of resistance.PostprintPeer reviewe

Validating the Johns Hopkins ACG Case-Mix System of the elderly in Swedish primary health care

BACKGROUND: Individualbased measures for comorbidity are of increasing importance for planning and funding health care services. No measurement for individualbased healthcare costs exist in Sweden. The aim of this study was to validate the Johns Hopkins ACG Case-Mix System's predictive value of polypharmacy (regular use of 4 or more prescription medicines) used as a proxy for health care costs in an elderly population and to study if the prediction could be improved by adding variables from a population based study i.e. level of education, functional status indicators and health perception. METHODS: The Johns Hopkins ACG Case-Mix System was applied to primary health care diagnoses of 1402 participants (60–96 years) in a cross-sectional community based study in Karlskrona, Sweden (the Swedish National study on Ageing and Care) during a period of two years before they took part in the study. The predictive value of the Johns Hopkins ACG Case-Mix System was modeled against the regular use of 4 or more prescription medicines, also using age, sex, level of education, instrumental activity of daily living- and measures of health perception as covariates. RESULTS: In an exploratory biplot analysis the Johns Hopkins ACG Case-Mix System, was shown to explain a large part of the variance for regular use of 4 or more prescription medicines. The sensitivity of the prediction was 31.9%, whereas the specificity was 88.5%, when the Johns Hopkins ACG Case-Mix System was adjusted for age. By adding covariates to the model the sensitivity was increased to 46.3%, with a specificity of 90.1%. This increased the number of correctly classified by 5.6% and the area under the curve by 11.1%. CONCLUSION: The Johns Hopkins ACG Case-Mix System is an important factor in measuring comorbidity, however it does not reflect an individual's capability to function despite a disease burden, which has importance for prediction of comorbidity. In this study we have shown that information on such factors, which can be obtained from short questionnaires increases the probability to correctly predict an individual's use of resources, such as medications

Naproxen affects multiple organs in fish but is still an environmentally better alternative to diclofenac

The presence of diclofenac in the aquatic environment and the risks for aquatic wildlife, especially fish, have been raised in several studies. One way to manage risks without enforcing improved wastewater treatment would be to substitute diclofenac (when suitable from a clinical perspective) with another non-steroidal anti-inflammatory drug (NSAID) associated with less environmental risk. While there are many ecotoxicity-studies of different NSAIDs, they vary extensively in set-up, species studied, endpoints and reporting format, making direct comparisons difficult. We previously published a comprehensive study on the effects of diclofenac in the three-spined stickleback (Gasterosteus aculeatus). Our present aim was to generate relevant effect data for another NSAID (naproxen) using a very similar setup, which also allowed direct comparisons with diclofenac regarding hazards and risks. Sticklebacks were therefore exposed to naproxen in flow-through systems for 27 days. Triplicate aquaria with 20 fish per aquarium were used for each concentration (0, 18, 70, 299 or 1232 mu g/L). We investigated bioconcentration, hepatic gene expression, jaw lesions, kidney and liver histology. On day 21, mortalities in the highest exposure concentration group unexpectedly reached >= 25 % in all three replicate aquaria, leading us to terminate and sample that group the same day. On the last day (day 27), the mortality was also significantly increased in the second highest exposure concentration group. Increased renal hematopoietic hyperplasia was observed in fish exposed to 299 and 1232 mu g/L. This represents considerably higher concentrations than those expected in surface waters as a result of naproxen use. Such effects were observed already at 4.6 mu g/L in the experiment with diclofenac (lowest tested concentration). Similar to the responses to diclofenac, a concentration-dependent increase in both relative hepatic gene expression of c7 (complement component 7) and jaw lesions were observed, again at concentrations considerably higher than expected in surface waters. Naproxen bioconcentrated less than diclofenac, in line with the observed effect data. An analysis of recent sales data and reported concentrations in treated sewage effluent in Sweden suggest that despite higher dosages used for naproxen, a complete substitution would only be expected to double naproxen emissions. In summary, naproxen and diclofenac produce highly similar effects in fish but the environmental hazards and risks are clearly lower for naproxen. Hence, if there are concerns for environmental risks to fish with diclofenac, a substitution would be advisable when naproxen presents an adequate alternative from a clinical point-of-view