Risk Of Long-term Use Research Articles

Cardiovascular risk with long-term use of proton pump inhibitors: myth or reality. A review

Proton pump inhibitors (PPIs) are the most effective drugs for treating acid-related diseases. In recent decades, the use of PPIs has increased exponentially. From gastroenterological practice, PPIs are being actively introduced into other specialties, in particular in cardiology and rheumatology, where they are used to protect the mucous membrane of the gastrointestinal tract and prevent gastrointestinal bleeding during long-term antithrombotic therapy and long-term use of non-steroidal anti-inflammatory drugs. For a long time, PPIs were considered completely safe drugs for both short-term and long-term use. However, modern clinical guidelines note that when prescribing PPIs in large doses for a long period, the possibility of side effects should be taken into account. In recent years, a number of foreign reviews have been published that examine the relationship between PPIs and a number of diseases/conditions, including the question of a possible association of PPI use with an increased risk of cardiovascular complications, but note the inconsistency of these data. We searched the PubMed and Scopus information databases for publications on the safety of PPI use, including sources up to 12/01/2023. In this review, we examined the possible cardiovascular risk of long-term use of PPIs. Analysis of publications, despite a number of contradictions, allows us to conclude that the cardiovascular risk with long-term use of PPIs is real and must be taken into account when prescribing PPIs for a long period and to comorbid/multimorbid patients.

Supplement Use and Increased Risks of Cancer: Unveiling the Other Side of the Coin.

There is a rising trend in the consumption of dietary supplements, especially among adults, with the purpose of improving health. While marketing campaigns tout the potential health benefits of using dietary supplements, it is critical to evaluate the potential harmful effects associated with these supplements as well. The majority of the scarce research on the potential harmful effects of vitamins focuses on the acute or chronic toxicities associated with the use of dietary supplements. Quality research is still required to further investigate the risks of long-term use of dietary supplements, especially the risk of developing cancers. The present review concentrates on studies that have investigated the association between the risk of developing cancers and associated mortality with the risk of dietary supplements. Such an association has been reported for several vitamins, minerals, and other dietary supplements. Even though several of these studies come with their own shortcomings and critics, they must draw attention to further investigate long-term adverse effects of dietary supplements and advise consumers and healthcare providers to ponder the extensive use of dietary supplements.

Psychedelics and cognitive function: A systematic review

Introduction: With the progressive advancement of clinical and experimental trials aimed at investigating the pharmacotherapeutic potential of psychedelic substances, there is also the development of other conceptions of use, not only for the treatment of psychiatric disorders, but also for the improvement of emotional/cognitive functions. Objective: The present study is a systematic review of investigations aimed at evaluating the effects of psychedelics on cognitive functions in healthy volunteers. Methods: A search was performed in PubMed database, using the search terms “psychedelics and cognitive enhancement” and “psychedelics and cognitive performance”. Results and conclusions: Of the experimental studies analyzed, only forty-six (46) met the inclusion criteria. The results obtained showed that 3,4-methylenedioxy-methamphetamine (MDMA) was the most studied drug, with eighteen (18) articles. Fourteen (14) articles were published with psilocybin. Lysergic acid diethylamide (LSD) ranked third, with six (6) articles; other two (2) studies focused on investigating the beverage ayahuasca, and another (1) its psychoactive-containing molecule: dimethyltryptamine (DMT). Eight (8) studies investigated the effects of other psychedelic drugs, like S-ketamine, mescaline, 3,4-methylenedioxy-amphetamine (MDE), and ibogaine. Although there were no serious adverse effects resulting from the use of the investigated psychedelic drugs, rigorous assessment of the potential risks of long-term use and of the advantages of the continuous use of these drugs through neuropsychological assessments are still warranted.

Long-Term Use of Benzodiazepines and Benzodiazepine-Related Drugs: A Register-Based Danish Cohort Study on Determinants and Risk of Dose Escalation.

The authors investigated the frequency and determinants of long-term use and risk of dose escalation of benzodiazepines and benzodiazepine-related drugs (benzodiazepine receptor agonists, or BZRAs). All adults ages 20-80 years living in Denmark on January 1, 2000 (N=4,297,045) were followed for redeemed prescriptions of BZRAs in the Danish National Prescription Registry from January 1, 2000, to December 31, 2020. For each drug class, we calculated long-term use for more than 1 or 7 years, and dose escalation measured as increase in dose to a level above the recommended level. Associations were examined using logistic regression. The authors identified 950,767 incident BZRA users, of whom 15% and 3% became long-term users for more than 1 or 7 years, respectively. These percentages were highest for individuals who initiated Z-drugs (17.8% and 4%). Among the 5% of BZRA users who had at least 3 years of continuous use, there was no indication of dose escalation, as the median dose remained relatively stable. However, 7% (N=3,545) of BZRA users escalated to doses above the recommended level. Psychiatric comorbidity, especially substance use disorder, was associated with higher risk of long-term use and dose escalation. A limited portion of the population that received BZRA prescriptions were classified as continuous users, and only a small proportion of this group escalated to doses higher than those recommended in clinical guidelines. Thus, this study does not, under the current regulations, support the belief that BZRA use frequently results in long-term use or dose escalation.

Examining Adult Patients' Success with Discontinuing Long-term Benzodiazepine Use: a Qualitative Study.

Little is known about patients' experiences with benzodiazepine (BZD) discontinuation, which is thought to be challenging given the physiological and psychological dependence and accompanying potential for significant withdrawal symptoms. The marked decline in BZD prescribing over the past decade in the US Department of Veterans Affairs healthcare system presents an important opportunity to examine the experience of BZD discontinuation among long-term users. Examine the experience of BZD discontinuation among individuals prescribed long-term BZD treatment to identify factors that contributed to successful discontinuation. Descriptive qualitative analysis of semi-structured interviews conducted between April and December of 2020. A total of 21 Veterans who had been prescribed long-term BZD pharmacotherapy (i.e., > 120days of exposure in a 12-month period) and had their BZD discontinued. We conducted semi-structured interviews with Veteran participants to learn about their BZD use and the process of discontinuation, with interviews recorded and transcribed verbatim. Data were deductively and inductively coded and coded text entered into a matrix to identify factors that contributed to successful BZD discontinuation. The mean age of interview participants was 63.0years (standard deviation 3.9); 94.2% were male and 76.2% were white. Of 21 participants, only 1 had resumed BZD treatment (prescribed by a non-VA clinician). Three main factors influenced success with discontinuation: (1) participants' attitudes toward BZDs (e.g., risks of long-term use, perceived lack of efficacy, potential for dependence); (2) limited withdrawal symptoms; and (3) effective alternatives, either from their clinician (e.g., medication, psychotherapy) or identified by participants. BZD discontinuation after long-term use is relatively well tolerated, and participants appreciated reducing their medication exposure, particularly to one associated with physical dependence. These findings may help reduce both patient and clinician anxiety related to BZD discontinuation.

Health professionals' views on discontinuation of long-term antidepressants: a systematic review and thematic synthesis.

Long-term antidepressant use, much longer than recommended by guidelines, may cause harmful effects and generate unnecessary costs. To investigate health professionals (HPs) views of long-term antidepressant discontinuation and their barriers and facilitators. Systematic review and meta-synthesis. We included studies that used qualitative data collection and had data on HPs perceptions on (dis)continuing AD use. The review searched nine database sources until May 2022. Study quality was assessed using the CASP checklist and the COREQ criteria. A thematic synthesis was performed. Thirteen studies were included in the review. Nine studies were of GPs' perspectives, one study of psychiatrists', and three of a mix of HPs. Barriers and facilitators to discontinuing long-term AD yielded eight themes, ordered chronologically according to the considerations that HPs make when they review a long-term AD: perception of AD use, fears, HP role and responsibility, HPs attitude towards discontinuation, HPs confidence regarding ability to stop AD, perceived patient readiness to stop, support from relatives and support from other HP. Deprescribing long-term AD is a difficult and complex process for HPs. The review found evidence that the barriers far outweigh the facilitators. More education on the lack of evidence for the long-term effect of AD and the risks of long-term use, guidance on managing long-term use, and support for HPs and patients is needed to increase long-term AD discontinuation. Further research from an HP perspective other than GPs is required and should also explore how HPs can be supported in managing discontinuation ADs.

Association between Initial Opioid Prescription and Patient Pain with Continued Opioid Use among Opioid-Naïve Patients Undergoing Elective Surgery in a Large American Health System.

There is growing concern about the over-prescription of opioids and the risks of long-term use. This study examined the relationship between initial need (pre-operative, post-operative, and discharge pain) and dosage of opioids in the first prescription after surgery with continued opioid use through opioid refills over 12 months, while considering patient-level characteristics. A total of 9262 opioid-naïve patients underwent elective surgery, 7219 of whom were prescribed opioids following surgery. The results showed that 17% of patients received at least one opioid refill within one year post-surgery. Higher initial opioid doses, measured in morphine milligram equivalent (MME), were associated with a greater likelihood of continued use. Patients receiving a dose greater than 90 MME were 1.57 times more likely to receive a refill compared to those receiving less than 90 MME (95% confidence interval: 1.30-1.90, p < 0.001). Additionally, patients who experienced pain before or after surgery were more likely to receive opioid refills. Those experiencing moderate or severe pain were 1.66 times more likely to receive a refill (95% confidence interval: 1.45-1.91, p < 0.001). The findings highlight the need to consider surgery-related factors when prescribing opioids and the importance of developing strategies to balance the optimization of pain management with the risk of opioid-related harms.

Risk Factors for Chronic Prescription Opioid Use in Multiple Sclerosis

ObjectiveTo characterize patterns of prescription opioid use among individuals with multiple sclerosis (MS) and identify risk factors associated with chronic use. DesignRetrospective longitudinal cohort study examining US Department of Veterans Affairs electronic medical record data of Veterans with MS. The annual prevalence of prescription opioid use by type (any, acute, chronic, incident chronic) was calculated for each study year (2015-2017). Multivariable logistic regression was used to identify demographics and medical, mental health, and substance use comorbidities in 2015-2016 associated with chronic prescription opioid use in 2017. SettingUS Department of Veterans Affairs, Veteran's Health Administration. ParticipantsNational sample of Veterans with MS (N=14,974). Main Outcome MeasureChronic prescription opioid use (≥90 days). ResultsAll types of prescription opioid use declined across the 3 study years (chronic opioid use prevalence=14.6%, 14.0%, and 12.2%, respectively). In multivariable logistic regression, prior chronic opioid use, history of pain condition, paraplegia or hemiplegia, post-traumatic stress disorder, and rural residence were associated with greater risk of chronic prescription opioid use. History of dementia and psychotic disorder were both associated with lower risk of chronic prescription opioid use. ConclusionDespite reductions over time, chronic prescription opioid use remains common among a substantial minority of Veterans with MS and is associated with multiple biopsychosocial factors that are important for understanding risk for long-term use.

Comparative renal risk of long-term use of beta-lactams in combination with vancomycin across the continuum of care.

Data are controversial regarding nephrotoxicity risk with vancomycin plus piperacillin-tazobactam (VPT) compared to vancomycin alone or in combination with other beta-lactams (BLs) in acute care use. Furthermore, data are lacking on the incidence of acute kidney injury (AKI) with long-term use of VPT including outpatient parenteral antimicrobial therapy (OPAT). This retrospective study included 826 adult patients on an intravenous vancomycin plus BL for ⩾2 weeks, including cefepime, piperacillin/tazobactam, ertapenem, or meropenem, from August 2017 to January 2022. The primary outcome was incidence of AKI. Univariate and multivariable Cox proportional hazard regression analyses were conducted to adjust for confounding variables. A secondary analysis based on the propensity score (PS)-matched cohort was performed. AKI occurred in 14.4% of patients in the VPT group (n = 15/104) compared to 5.5% in the other BL group (n = 40/722) (p < 0.001). Average time to AKI from start of combination therapy was 9.4 (1.7-12.0) days in the VPT group and 10.9 (5-22.7) days in the other BL group (p = 0.20). The median duration of vancomycin and BL in the overall cohort was approximately 1 month. Beyond BL selection, patient characteristics were not associated with AKI other than the receipt of concomitant acyclovir [hazard ratio (HR) 2.48 (95% confidence interval (CI): 1.33-4.65), p = 0.004]. In the PS-matched cohort, AKI occurred in 14.4% of patients in the VPT group (n = 15/104) and 5.3% in the other BL group (n = 11/208) (p = 0.006). Receipt of VPT [HR: 2.55 (1.36-4.78), p = 0.004] and acyclovir [HR: 2.38 (1.19-4.74), p = 0.014) remained significantly associated with AKI in the multivariable model. Clinicians should exercise caution when using VPT for >2 weeks, including in the OPAT setting, even when no renal dysfunction is observed during the initial week of combination therapy.

Chronic Dysphagia in Patients Treated with Head and Neck Intensity-Modulated Radiotherapy: Incidence, Risk Factors and Implications

<h3>Purpose/Objective(s)</h3> Late dysphagia after head and neck radiotherapy is an important driver of poor quality-of-life. We aimed to identify risk factors associated with long-term gastrostomy tube (g-tube) dependence in patients with head and neck squamous cell carcinoma treated with definitive or postoperative radiotherapy. <h3>Materials/Methods</h3> A retrospective cohort analysis of patients with head and neck squamous cell carcinoma treated with definitive or adjuvant intensity-modulated radiotherapy was performed. Patients with locoregional or distance recurrence were excluded from the analysis. G-tube dependence was used as a surrogate marker for late dysphagia, and its placement and removal from initial presentation to last follow-up was tracked. The risk of g-tube dependence from years one through five was calculated, and factors associated with 1- and 2-year g-tube use were analyzed with multivariable logistic regression. <h3>Results</h3> Our analytic cohort consisted of 421 survivors with head and neck squamous cell cancer treated from 2001 to 2018. A total of 210 patients required a g-tube with 80, 124, and 13 g-tubes placed before, during, and after radiotherapy, respectively. The median follow-up of the entire cohort was 4 years (IQR 3-5), with 314, 222, and 124 patients at-risk in years 3, 4 and 5. The Kaplan-Meier g-tube dependence rate at 1 and 2 years after radiotherapy were 11% and 6%, respectively, and 5%, 3% and 2% at three, four and five years, respectively. On multivariable regression analysis on 1-year g-tube dependence, history of depression or anxiety (odds ratio, OR, 95% confidence interval, CI, 3.86 [1.47, 10.3]), clinical T3/T4 stage (3.75 [1.60, 9.30]), clinical N2 or N3 stage (3.66 [1.03, 14.4]), baseline swallowing impairment to both solids and liquids (11.1 [3.22, 41.8]), and intra-treatment weight loss greater than 10% (3.75 [1.51, 9.81]) were significant predictors. A total of 390 patients had adequate follow-up data for the 2-year analysis. On multivariable analysis, age (1.06 [1.00, 1.14]), clinical N2/N3 stage (15.2 [1.72, 393]), and baseline swallowing impairment to both solids and liquids (95% confidence interval: 41.5 [5.59, 551]) were significantly associated with increased odds of 2-year g-tube dependence. Definitive vs. adjuvant treatment was not significantly associated with 1 or 2-year g-tube dependence. Out of 22 patients with g-tube dependence at two years after radiotherapy, only six (27%) patients had a known tube removal in the years to follow. <h3>Conclusion</h3> The overall incidence of prolonged g-tube dependence is low but not trivial, and the vast majority of patients with dependence at two years remained dependent permanently. We have identified a cohort at highest risk for long-term use, for whom early interventions should be targeted since late removal becomes progressively more unlikely.

Insights into patient characteristics and documentation of the use of sedative-hypnotic/anxiolytics in primary care: a retrospective chart review study

BackgroundDespite the known safety risks of long-term use of sedative-hypnotic/anxiolytic medications, there has been limited guidance for the safe and effective use of their chronic use in a primary care clinic setting. Understanding the characteristics of patients who receive sedative-hypnotic/anxiolytic medication and the clinical documentation process in primary care is the first step towards understanding the nature of the problem and will help inform future strategies for clinical research and practice.ObjectivesCharacterize patients who received a sedative-hypnotic/anxiolytic prescription in primary care, and (2) gain an understanding of the clinical documentation of sedative-hypnotic/anxiolytic indication and monitoring in electronic medical records (EMR).MethodsA random selection of patients who received a prescription for a benzodiazepine or Z-drug hypnotic between January 2014 and August 2016 from four primary care clinics in Winnipeg were included. Data was collected retrospectively using the EMR (Accuro®). Patient variables recorded included sex, age, comorbidities, medications, smoking status, and alcohol status. Treatment variables included drug type, indication, pattern of use, dose, adverse events, psychosocial intervention, tapering attempts, social support, life stressor, and monitoring parameters for sedative-hypnotic use. Demographic and clinical characteristics were described using descriptive statistics.ResultsRecords from a sample of 200 primary care patients prescribed sedative-hypnotic/anxiolytics were analyzed (mean age 55.8 years old, 61.5% ≥ 65 years old, 61.0% female). Long-term chronic use (≥ 1 year) of a sedative-hypnotic/anxiolytic agent was observed in 29.5% of the sample. Zopiclone (30.7%) and lorazepam (28.7%) were the most common agents prescribed. Only 9.5% of patients had documentation of a past tapering attempt of their sedative-hypnotic/anxiolytic. The most common indications for sedative-hypnotic/anxiolytic use recorded were anxiety (33.0%) and sleep (18.0%), but indication was undetermined for 57.0% of patients. Depression (33.5%) and falls (18.5%) were reported by patients after the initiation of these agents.ConclusionsA higher proportion of females and users 65 years and older received a prescription for a sedative-hypnotic/anxiolytic, consistent with previous studies on sedative-hypnotic use. We found inconsistencies in the documentation surrounding sedative-hypnotic/anxiolytic use. The indication for their use was unclear in a large number of patients. These findings will help us understand the state of the problem in primary care and inform future strategies for clinical research.

Strategies aimed at preventing long-term opioid use in trauma and orthopaedic surgery: a scoping review

BackgroundLong-term opioid use, which may have significant individual and societal impacts, has been documented in up to 20% of patients after trauma or orthopaedic surgery. The objectives of this scoping review were to systematically map the research on strategies aiming to prevent chronic opioid use in these populations and to identify knowledge gaps in this area.MethodsThis scoping review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist. We searched seven databases and websites of relevant organizations. Selected studies and guidelines were published between January 2008 and September 2021. Preventive strategies were categorized as: system-based, pharmacological, educational, multimodal, and others. We summarized findings using measures of central tendency and frequency along with p-values. We also reported the level of evidence and the strength of recommendations presented in clinical guidelines.ResultsA total of 391 studies met the inclusion criteria after initial screening from which 66 studies and 20 guidelines were selected. Studies mainly focused on orthopaedic surgery (62,1%), trauma (30.3%) and spine surgery (7.6%). Among system-based strategies, hospital-based individualized opioid tapering protocols, and regulation initiatives limiting the prescription of opioids were associated with statistically significant decreases in morphine equivalent doses (MEDs) at 1 to 3 months following trauma and orthopaedic surgery. Among pharmacological strategies, only the use of non-steroidal anti-inflammatory drugs and beta blockers led to a significant reduction in MEDs up to 12 months after orthopaedic surgery. Most studies on educational strategies, multimodal strategies and psychological strategies were associated with significant reductions in MEDs beyond 1 month. The majority of recommendations from clinical practice guidelines were of low level of evidence.ConclusionsThis scoping review advances knowledge on existing strategies to prevent long-term opioid use in trauma and orthopaedic surgery patients. We observed that system-based, educational, multimodal and psychological strategies are the most promising. Future research should focus on determining which strategies should be implemented particularly in trauma patients at high risk for long-term use, testing those that can promote a judicious prescription of opioids while preventing an illicit use, and evaluating their effects on relevant patient-reported and social outcomes.

Treatment of cystic fibrosis related bone disease

The advent of highly effective CFTR modulator therapies has slowed the progression of pulmonary complications in people with cystic fibrosis. There is increased interest in cystic fibrosis bone disease (CFBD) due to the increasing longevity of people with cystic fibrosis. CFBD is a complex and multifactorial disease. CFBD is a result of hypomineralized bone leading to poor strength, structure and quality leading to susceptibility to fractures. The development of CFBD spans different age groups. The management must be tailored to each group with nuance and based on available guidelines while balancing therapeutic benefits to risks of long-term use of bone-active medication. For now, the mainstay of treatment includes bisphosphonates. However, the long-term effects of bisphosphonate treatment in people with CF are not fully understood. We describe newer agents available for osteoporosis treatment. Still, the lack of data behooves trials of monoclonal antibodies treatments such as Denosumab and Romozosumab and anabolic bone therapy such as teriparatide and Abaloparatide. In this review, we also summarize screening and non-pharmacologic treatment of CFBD and describe the various options available for the pharmacotherapy of CFBD. We address the prospect of CFTR modulators on bone health while awaiting long-term trials to describe the effects of these medications on bone health.

Analgesic use in adolescents with patellofemoral pain or Osgood-Schlatter Disease: a secondary cross-sectional analysis of 323 subjects.

The prevalence of pain medication use for adolescent knee pain and factors associated with use are not well understood. This study aimed to determine the self-reported use of pain medication for knee pain and identify factors associated with use in adolescents (age 10-19) with longstanding knee symptoms. In this exploratory cross-sectional study, we performed a secondary analysis of data previously collected in 323 adolescents with longstanding knee pain. Factors associated with pain medication use were assessed using multivariable logistic regressions. Analyses were repeated with stratification by age, sex, sport participation frequency, knee pain duration, and knee pain intensity. Among 323 adolescents (mean age 14.4±2.5, 73% female), 84% had patellofemoral pain, (peri- or retro-patellar pain during loaded bending of the knee) and 16% had Osgood-Schlatter Disease (apophysitis with swelling and localized pain at the tibial tuberosity). Twenty-one percent (95% CI 16-25%) of adolescents reported pain medication use for their knee pain, with no difference in usage between those≤ vs. > 15 years of age (21%, 95% CI 16-27% vs. 20%, 95% CI 13-29%). Adolescents with patellofemoral pain reported greater usage than their counterparts with Osgood-Schlatter Disease (22%, 95% CI 17-28% vs. 12%, 95% CI 4.5-24.3%). The most consistent factor associated with use was knee-related symptoms, observed in both the overall (OR 0.97, 95% CI 0.94-0.99) and stratified analyses (ORs ranged from 0.89 to 0.96). Approximately one in five adolescents with longstanding knee pain reported pain medication use, particularly in adolescents with patellofemoral pain. Knee-related symptoms most consistently associated with the use of pain medications in this population. Future longitudinal studies with data collected at multiple time-points are needed to validate these findings. Self-reported pain medication use is common in adolescents with longstanding knee pain, even though whether pharmacological therapy is the best pain management option at this young age is debatable. Reliance on pain medication at an early age could potentially hamper the development of healthy pain coping strategies and increase the risk of dependence and misuse later in life. Future studies should assess the safety, efficacy, and risks of long-term use of pain medications for adolescent knee pain.

New Persistent Opioid Use After Surgery: A Risk Factor for Opioid Use Disorder?

New Persistent Opioid Use After Surgery: A Risk Factor for Opioid Use Disorder?

Evolution of biofilm-forming pathogenic bacteria in the presence of nanoparticles and antibiotic: adaptation phenomena and cross-resistance

BackgroundTreatment of bacterial biofilms are difficult and in many cases, expensive. Bacterial biofilms are naturally more resilient to antimicrobial agents than their free-living planktonic counterparts, rendering the community growth harder to control. The present work described the risks of long-term use of an important alternative antimicrobial, silver nanoparticles (NAg), for the first time, on the dominant mode of bacterial growth.ResultsNAg could inhibit the formation as well as eradicating an already grown biofilm of Pseudomonas aeruginosa, a pathogen notorious for its resilience to antibiotics. The biofilm-forming bacterium however, evolved a reduced sensitivity to the nanoparticle. Evidence suggests that survival is linked to the development of persister cells within the population. A similar adaptation was also seen upon prolonged exposures to ionic silver (Ag+). The persister population resumed normal growth after subsequent passage in the absence of silver, highlighting the potential risks of recurrent infections with long-term NAg (and Ag+) treatments of biofilm growth. The present study further observed a potential silver/antibiotic cross-resistance, whereby NAg (as well as Ag+) could not eradicate an already growing gentamicin-resistant P. aeruginosa biofilm. The phenomena is thought to result from the hindered biofilm penetration of the silver species. In contrast, both silver formulations inhibited biofilm formation of the resistant strain, presenting a promising avenue for the control of biofilm-forming antibiotic-resistant bacteria.ConclusionThe findings signify the importance to study the nanoparticle adaptation phenomena in the biofilm mode of bacterial growth, which are apparently unique to those already reported with the planktonic growth counterparts. This work sets the foundation for future studies in other globally significant bacterial pathogens when present as biofilms. Scientifically based strategies for management of pathogenic growth is necessary, particularly in this era of increasing antibiotic resistance.Graphic abstract

Solid fuel use, socioeconomic indicators and risk of cardiovascular diseases and all-cause mortality: a prospective cohort study in a rural area of Sichuan, China.

Estimates indicate that household air pollution caused by solid fuel burning accounted for about 1.03 million premature mortalities in China in 2016. In the country's rural areas, more than half the population still relies on biomass fuels and coals for cooking and heating. Understanding the health impact of indoor air pollution and socioeconomic indicators is essential for the country to improve its developmental targets. We aimed to describe demographic and socioeconomic characteristics associated with solid fuel users in a rural area in China. We also estimated the risk of cardiovascular disease and all-cause mortality in association with solid fuel use and described the relationship between solid fuel use, socioeconomic status and mortality. We also measured the risk of long-term use, and the effect of ameliorative action, on mortality caused by cardiovascular disease and other causes. We used the China Kadoorie Biobank (CKB) site in Pengzhou, Sichuan, China. We followed a cohort of 55 687 people over 2004-13. We calculated the mean and standard deviation among subgroups classified by fuel use types: gas, coal, wood and electricity (central heating additionally for heating). We tested the mediation effect using the stepwise method and Sobel test. We used Cox proportional models to estimate the risk of incidences of cardiovascular disease and mortality with survival days as the time scale, adjusted for age, gender, socioeconomic status, physical measurements, lifestyle, stove ventilation and fuel type used for other purposes. The survival days were defined as the follow-up days from the baseline survey till the date of death or 31 December 2013 if right-censored. We also calculated the absolute mortality rate difference (ARD) between the exposure group and the reference group. The study population had an average age of 51.0, and 61.9% of the individuals were female; 64.8% participants (n = 35 543) cooked regularly and 25.4% participants (n = 13 921) needed winter heating. With clean fuel users as the reference group, participant households that used solid fuel for cooking or heating both had a higher risk of all-cause mortality: hazard ratio (HR) for: cooking, 1.11 [95% confidence interval (CI) 1.02, 1.26]; heating, 1.34 (95% CI 1.16, 1.54). Solid fuel used for winter heating was associated with a higher risk of mortality caused by cerebrovascular disease: HR 1.64 (95% CI 1.12, 2.40); stroke: HR 1.70 (95% CI 1.13, 2.56); and cardiovascular disease: HR 1.49 (95% CI 1.10, 2.02). Low income and poor education level had a significant correlation with solid fuel used for cooking: odds ratio (OR) for income: 2.27 (95% CI 2.14, 2.41); education: 2.34 (95% CI 2.18, 2.53); and for heating: income: 2.69 (95% CI 2.46, 2.97); education: 2.05 (95% CI 1.88, 2.26), which may be potential mediators bridging the effects of socioeconomic status factors on cardiovascular disease and all-cause mortality. Solid fuel used for cooking and heating accounted for 42.4% and 81.1% of the effect of poor education and 55.2% and 76.0% of the effect of low income on all-cause mortality, respectively. The risk of all-cause mortality could be ameliorated by stopping regularly cooking and heating using solid fuel or switching from solid fuel to clean fuels: HR for cooking: 0.90 (95% CI 0.84, 0.96); heating: 0.76 (95% CI 0.64, 0.92). Our study reinforces the evidence of an association between solid fuel use and risk of cardiovascular disease and all-cause mortality. We also assessed the effect of socioeconomic status as the potential mediator on mortality. As solid fuel use was a major contributor in the effect of socioeconomic status on cardiovascular disease and all-cause mortality, policies to improve access to clean fuels could reduce morbidity and mortality related to poor education and low income.

Modelling Salinity and Sodicity Risks of Long-Term Use of Recycled Water for Irrigation of Horticultural Crops

Long-term use of recycled water (RW) for irrigation in arid and semiarid regions usually changes the soil solution composition and soil exchange characteristics, enhancing the risk for salinity and sodicity hazards in soils. This modelling study focuses on developing alternative management options that can reduce the potentially harmful impacts of RW use on the irrigation of wine grapes and almonds. The multicomponent UNSATCHEM add-on module for HYDRUS-1D was used to evaluate the impact of long-term (2018–2050) use of irrigation waters of different compositions: good-quality low-salinity (175 mg/L) water (GW), recycled water with 1200 mg/L salinity (RW), blended water of GW and RW in the 1:1 proportion (B), and monthly (Alt1) and half-yearly (Alt6) alternate use of GW and RW. The management options include different levels of annual gypsum applications (0, 1.7, 4.3, and 8.6 t/ha soil) to the calcareous (Cal) and hard red-brown (HRB) soils occurring in the Northern Adelaide Plain (NAP) region, South Australia. Additional management scenarios involve considering different leaching fractions (LF) (0.2, 0.3, 0.4, and 0.5) to reduce the salinity build-up in the soil. A new routine in UNSATCHEM to simulate annual gypsum applications was developed and tested for its applicability for ameliorating irrigation-induced soil sodicity. The 1970–2017 period with GW irrigation was used as a warmup period for the model. The water quality was switched from 2018 onwards to reflect different irrigation water qualities, gypsum applications, and LF levels. The data showed that the GW, B, Alt1, and Alt6 irrigation scenarios resulted in lower soil solution salinity (ECsw) than the RW irrigation scenario, which led to increased ECsw values (4.1–6.6 dS/m) in the soil. Annual gypsum applications of 1.7, 4.3, and 8.6 t/ha reduced pH, SAR, and ESP in both soils and reduced the adverse impacts of irrigation, especially in surface soils. A combination of water blending or cyclic water use with 3.8 t/ha annual gypsum applications showed promise for the SAR and ESP control. Additionally, irrigation with RW, a 0.2 LF, and annual gypsum applications limited the harmful salinity impacts in the soils. However, in the RW irrigation scenario, ECsw and ESP at the bottom of the crop root zone (90–120 cm depth) in the HRB soil were still higher than the wine grape and almond salinity thresholds. Thus, annual amendment applications, combined with the long-term use of blended water or cyclic use of RW and GW, represent a sustainable management option for crop production at the calcareous and hard red-brown soils.

The Role of Cannabidiol in Neurological Disorders.

Cannabis has been used for both recreational and medicinal purposes for more than 4 millennia. Cannabis has been studied in various medical disorders including neurological disorders. There are well-known risks of long-term use of cannabis, including low motivation, lowered cognitive capabilities, and diminished IQ and brain mass. Cannabinoids are compounds in cannabis that are known to have therapeutic potential. The most abundant chemicals in cannabinoids are delta-9-tetrahydrocannabinol and cannabidiol. Delta-9-tetrahydrocannabinol has psychotropic effects that limits its use as a pharmacotherapeutic agent. Cannabidiol is a nonpsychotropic chemical and therefore has become a compound of interest for clinical researchers to study its therapeutic potential. This article reviews the efficacy and safety of cannabidiol in various neurological disorders in humans.

Deprescribing benzodiazepines: Do Brazilian package inserts address this issue?

OBJECTIVE: To analyze the presence and quality of content on drug deprescribing in Brazilian package inserts for benzodiazepine drugs. METHODS: Documentary study where we analyzed data on deprescribing extracted from electronic package inserts of drugs containing benzodiazepines; these documents were available at the Brazilian Health Surveillance Agency website. Our search was performed independently by 2 researchers who used the following keywords: “deprescription,” “withdrawal,” and “tapering.” The deprescribing plan, when presented by the package insert, was compared to deprescribing protocols for benzodiazepines found in the literature. Moreover, we assessed the presence of guidance on the maximum length of treatment and risks of long-term use. RESULTS: We found 12 package inserts for benzodiazepines and 100% of them suggested gradual withdrawal; only 1 (8.33%) suggested a systematized deprescribing plan. One document (8.33%) did not offer guidance on maximum treatment duration. Eleven (91.67%) had the information on long-term use possibly causing dependence or tolerance, and 1 (8.33%) did not describe the risks of continuous use. CONCLUSIONS: It is known that benzodiazepines should be withdrawn in a gradual and schematized manner, but package inserts do not currently bring this information in detail. It is of utmost importance that health professionals be educated on their conduct, hence the necessity for updating medication package inserts.