Non-drug Factors Research Articles

Haemodynamic response to pre-hospital emergency anaesthesia in trauma patients within an urban helicopter emergency medical service.

Pre-hospital emergency anaesthesia is routinely used in the care of severely injured patients by pre-hospital critical care services. Anaesthesia, intubation, and positive pressure ventilation may lead to haemodynamic instability. The aim of this study was to identify the frequency of new-onset haemodynamic instability after induction in trauma patients with a standardised drug regime. A retrospective database analysis was undertaken of all adult patients treated by a physician-led urban pre-hospital care service over a 6-year period. The primary outcome measure was the frequency of new haemodynamic instability following pre-hospital emergency anaesthesia. The association of patient characteristics and drug regimes with new haemodynamic instability was also analysed. A total of 1624 patients were included. New haemodynamic instability occurred in 231 patients (17.4%). Patients where a full-dose regime was administered were less likely to experience new haemodynamic instability than those who received a modified dose regime (9.7% vs 24.8%, p < 0.001). The use of modified drug regimes became more common over the study period (p < 0.001) but there was no change in the rates of pre-existing (p = 0.22), peri-/post-anaesthetic (p = 0.36), or new haemodynamic instability (p = 0.32). New haemodynamic instability within the first 30min following pre-hospital emergency anaesthesia in trauma patients is common despite reduction of sedative drug doses to minimise their haemodynamic impact. It is important to identify non-drug factors that may improve cardiovascular stability in this group to optimise the care received by these patients.

Harnessing placebo: Lessons from psychedelic science.

The randomized controlled trial (RCT) research design assumes that a drug's "specific" effect can be isolated, added, and subtracted from the "nonspecific" effect of context and person. While RCTs are helpful in assessing the added benefit of a novel drug, they tend to obscure the curative potential of extra-pharmacological variables, known as "the placebo effect." Ample empirical evidence suggests that person/context-dependent physical, social, and cultural variables not only add to, but also shape drug effects, making them worth harnessing for patient benefits. Nevertheless, utilizing placebo effects in medicine is challenging due to conceptual and normative obstacles. In this article, we propose a new framework inspired by the field of psychedelic science and its employment of the "set and setting" concept. This framework acknowledges that drug and nondrug factors have an interactive and synergistic relationship. From it, we suggest ways to reintegrate nondrug variables into the biomedical toolbox, to ethically harness the placebo effect for improved clinical care.

Sleep duration and testosterone levels in community older men: results from the West China Health and Aging Trend study.

Sleep duration and testosterone levels in community older men: results from the West China Health and Aging Trend study.

Trends of Clinical Outcomes of Patients with Advanced Hepatocellular Carcinoma Treated with First-Line Sorafenib in Randomized Controlled Trials

Background: Sorafenib has consistently served as the control arm in multiple randomized clinical trials (RCTs) evaluating novel therapies for advanced hepatocellular carcinoma (HCC) for more than a decade. Analyzing trends in clinical outcomes of patients treated with sorafenib for the same indication over time offers the opportunity for unique insight into the evolution of clinical trial conduct and potential non-drug factors impacting outcomes. Methods: We identified RCTs in patients with treatment-naïve advanced HCC where sorafenib was compared to another systemic therapy or placebo. We extracted trial-level demographic, clinicopathologic, and outcome data (overall survival [OS], progression-free survival [PFS], objective response rate [ORR], and duration of therapy). Sample-weighted linear regression was used to identify temporal trends with significance set at p ≤ 0.05. Results: Sixteen RCTs (9 phase III and 7 phase II) enrolling 4,086 patients treated with sorafenib were included in the analysis. Included trials enrolled patients from 2005 to 2019. OS has significantly improved by 4.5 months from 2005 to 2019 (p = 0.048) over time. Thirteen studies provided data on PFS using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, with no significant change over time (p = 0.69). ORR assessed by RECIST 1.1 has significantly improved by 6.0% over time (p = 0.003). Median duration of therapy with sorafenib has decreased by 53% since the enrollment of the first clinical trial in 2005, from 23.1 weeks to 12.2 weeks (p = 0.0037). There was no significant change in patient demographics were identified over time to explain the OS findings. Conclusion: The median OS of patients with advanced HCC treated with sorafenib has improved significantly over 15 years. At the same time, the median duration of therapy with sorafenib has decreased. The reason for these findings was not explained by changing demographics of patients enrolled in these trials and has implications for ongoing clinical trials.

Oscillatory Components of Psychedelic Experience

As humanity has been utilizing psychedelic substances for millennia, much knowledge has already been accumulated about the exploratory potential and therapeutic power of the psychedelic-induced nonordinary states of consciousness (NSC). However, we still have only a limited understanding of the process that unfolds in mind and the brain. Only recently have systematic investigations become possible, as the myths about psychedelics are abating and the legal strictures gradually loosening. With the availability of brain imaging techniques, exciting findings have been made about the associated dynamic brain processes. Our prospective observations of spontaneously generated NSC, major mood disorders, have been elucidating another dynamic aspect, the oscillatory brain processes. The findings indicate that the NSC’s propensity is markedly increased at the peaks of the oscillatory brain activity and that the NSC entirely unfolds when the oscillations exceed their normal range. The observation that neurobiological correlates of experientially opposite NSC, melancholy and mania, appear qualitatively the same is compatible with the concept that the experiential content is emerging from nonlocal consciousness. Psychedelic experiences are triggered by the administration of the psychedelic drug. However, they are influenced by nondrug factors and molded, in particular, by the individual’s mental set and the setting of the session. The transformative process can be utilized psychotherapeutically for healing and profound inner restructuring.

The contribution of non-drug factors to fetal malformation in anti-seizure-medication-treated pregnancy

PurposeTo assess the possible contribution of factors in additional to intrauterine anti-seizure medication (ASM) exposure in the occurrence of fetal malformation in women with ASM-treated epilepsy. ResultsLogistic regression analysis showed that maternal age over 31 years, family histories of fetal malformation, and conception after assisted fertility treatment, and also dosage of valproate, carbamazepine, and topiramate, made statistically significant (P<0.05) contributions to the fetal malformation rate in 2223 pregnancies in Australian women with epilepsy. The malformation rates were lower in pregnancies where the non-ASM-associated contributory factors were not present: statistically significantly so for all ASM-exposed pregnancies, and those pregnancies exposed to the more potent teratogenic drugs. ConclusionIt is important to consider the possible roles of identified, and also possible non-identified, non-ASM factors in relation to the occurrence of fetal malformations in the pregnancies of women with ASM-treated epilepsy.

Pathophysiological mechanisms caused by adverse influence of climatic and geographical factors of the Arctic on human health and technologies of rehabilitation medicine

Adverse conditions in the Arctic North provoke the development of various diseases, primarily cardiovascular and respiratory systems, metabolism. The main etiological factors are hypoxia, low temperatures, geomagnetic storms, desynchronosis, stress, impaired microcirculation, pathogenetic changes in hormonal regulation of metabolic reactions. To develop effective methods of treating diseases provoked by adverse environmental conditions and activities in the Arctic North, as well as their prevention, it is necessary to develop a new strategy for medical support of this problem. As an alternative, it is proposed to use methods of restorative medicine, based on the use of non-drug factors (natural origin and physiotherapy), which have a systemic effect on various functional systems of the body. In this regard, of particular interest are mineral waters used internally, in the form of baths and inhalations, controlled hypoxia, physical activity, reflexology.

Psychedelic therapy for smoking cessation: Qualitative analysis of participant accounts.

Recent pilot trials suggest feasibility and potential efficacy of psychedelic-facilitated addiction treatment interventions. Fifteen participants completed a psilocybin-facilitated smoking cessation pilot study between 2009 and 2015. The aims of this study were as follows: (1) to identify perceived mechanisms of change leading to smoking cessation in the pilot study; (2) to identify key themes in participant experiences and long-term outcomes to better understand the therapeutic process. Participants were invited to a retrospective follow-up interview an average of 30 months after initial psilocybin sessions. Semi-structured interviews were conducted with 12 of the 15 participants. Data were analysed using thematic analysis. Participants reported gaining vivid insights into self-identity and reasons for smoking from their psilocybin sessions. Experiences of interconnectedness, awe, and curiosity persisted beyond the duration of acute drug effects. Participants emphasised that the content of psilocybin experiences overshadowed any short-term withdrawal symptoms. Preparatory counselling, strong rapport with the study team, and a sense of momentum once engaged in the study treatment were perceived as vital additional factors in achieving abstinence. In addition, participants reported a range of persisting positive changes beyond smoking cessation, including increased aesthetic appreciation, altruism, and pro-social behaviour. The findings highlight the value of qualitative research in the psychopharmacological investigation of psychedelics. They describe perceived connections between drug- and non-drug factors, and provide suggestions for future research trial design and clinical applications.

Recent Pharmacokinetic Studies in Combination Therapies for Diabetes and Related Vascular Complications

Combination treatment has been a popular therapeutic strategy in diabetes and related vascular complications. However, the reasonable dosing regimen in combination treatment remains unknown. Nowadays, pharmacokinetics (PK) is becoming a useful approach to reveal the mechanisms of drug-drug interactions (DDIs) and reasonable drug compatibility in combination treatment. This article reviews the pharmacokinetics studies on combination therapies for diabetes and its vascular complications to reveal the mechanisms of reasonable drug compatibility for optimizing drug combination treatment. Relevant articles were identified through the PubMed search (from January 2006 to December 2012) in English and the CNKI and Wan Wei websites in Chinese (from January 2000 to December 2012). Thirty-six articles were identified, including 15 on DDIs, 8 on pharmacological mechanism or metabolic pathways, and 6 on non-drug factors. DDIs studies showed the changes of drug-effect in combination treatment, which could guide physicians to administer anti-hyperglycemic agent in best time and in optimal order. PK studies based on pharmacological mechanism or metabolic pathways revealed reasonable compatibility of fixed-dose combination (FDC). A combination of pharmacokinetics/pharmacodynamics (PK/PD) and population pharmacokinetics (PopPK) and the development of PK/PD models in PK studies were good ways to determine the rational use and treatment effects in combined therapies. There were other 7 PK studies on the compatibility of preparations in Chinese medicine, which also outlined the features of DDIs in herbal drugs. PK studies may be useful to resolve the growing and complex issue of drug combinations to devise reasonable treatment regimens and to make physicians recognize the mechanisms of combined therapies. However, more longterm, comprehensive PK studies on combination therapy should be conducted in future.

Prevalence of and Risk Factors for Lipoatrophy in Patients with HIV Infection in Nigeria.

Background. Although the association between lipoatrophy and highly active antiretroviral therapy (HAART) is well known, other nondrug factors may be associated with lipoatrophy in people living with HIV/AIDS (PLWHA). There are no reports of lipoatrophy from Nigeria, a country with the second largest number of PLWHA. We aimed to determine the prevalence, characteristics, and factors associated with lipoatrophy in a cohort of patients attending the HIV clinic in Lagos University Teaching Hospital, Nigeria. Methods. Two hundred and eighty-eight patients with HIV infection were recruited for the study. The study protocol involved administration of a questionnaire, targeted physical examination (including anthropometric indices and skin fold thickness), and bioelectrical impedance analysis measurements. Lipoatrophy was defined clinically. Results. Lipoatrophy was present in 75 (26.0%) persons. It was associated with lower body circumferences, skin fold thicknesses, and lower % body fat with preservation of skeletal muscle mass (all P < 0.05). Male gender and HAART use were the factors associated with lipoatrophy on multivariate analysis (P < 0.05). Conclusion. Lipoatrophy is frequently encountered in patients with HIV infection in Nigeria, with HAART use conferring an added factor in its development. There is need for more physician and patient awareness of this condition.

Causality assessment: Which is best-expert opinion or RUCAM?

Causality assessment: Which is best-expert opinion or RUCAM?

Role of health education and self-action plan in improving the drug compliance in bronchial asthma.

Background:Considering the prevalence and associated burden of disease due to bronchial asthma, it is mandatory to obtain an optimal control of the disease and to improve outcomes for these patients. But it has been observed that there is very poor adherence to the inhalational therapy which leads to the suboptimal control of the disease.Objectives of the Study:To study the adherence for aerosol therapy in bronchial asthma patients and to assess the impact of health education and self-action plan in improving the compliance to the therapy.Methodology:A prospective study was done in a total of 500 bronchial asthma patients over a period of 2 years. Once included in the study, the patients were followed-up for a total of 12 weeks for calculation of nonadherence to the aerosol therapy. In nonadherent patients, we employed various health education strategies to improve the compliance in these cases.Results:A total of 500 patients of bronchial asthma who were started on aerosol therapy over duration of 2 years were included in the study. At the end of 12 weeks, it was observed that, only 193 patients (38.6%) had regular compliance and 307 patients (61.4%) were noncompliant to aerosol therapy as prescribed for bronchial asthma. Factors that were associated with poor compliance were: Lower educational level status, poor socioeconomic status, cumbersome regimens, dislike of medication, and distant pharmacies. Nondrug factors that reduced the compliance were: Fears about side effects, anger about condition or its treatment, forgetfulness or complacency, and patient's ill attitudes toward health. After employing the various strategies for improving the compliance in these patients, the compliance increased in 176 patients (57.3%) among the earlier defaulted patients, while the remaining 131 patients (42.7%) were found to be noncompliant even after various educational techniques.Conclusion:Noncompliance in asthma management is a fact of life and no single compliance improving strategy probably will be as effective as a good physician-patient relationship. Optimal self-management allowing for optimization of asthma control by adjustment of medications may be conducted by either self-adjustment with the aid of a written action plan or by regular medical review. Individualized written action plans based on peak expiratory flow are equivalent to action plans based on symptoms.

Poor Compliance to Inhaler Therapy in Bronchial Asthma Patients ∼A Prospective Study in General Population

Background: Considering the prevalence and associated burden of disease due to bronchial asthma, it is mandatory to obtain an optimal control of the disease and to improve outcomes for these patients. Asthma control and treatment compliance are widely investigated issues around the world. But it has been observed that there is very poor adherence to the inhalational therapy which leads to the sub-optimal control of the disease. Objectives of the study: To investigate the adherence for anti-asthma inhalational medications in adults with bronchial asthma. Methodology: A prospective study was done in a total of 400 bronchial asthma patients over a period of 2 years. Once included in the study, the patients were followed up for a total of 12 weeks for calculation of non-adherence to the aerosol therapy. Results: A total of 400 patients of bronchial asthma who were started on inhalational therapy were included in the study. At the end of 12 weeks, it was observed that, only 154 patients (38.5%) had regular compliance and 246 patients (61.5%) were non-compliant to aerosol therapy as prescribed for bronchial asthma. Factors that were associated with poor compliance were: lower educational level status, poor socio-economic status, cumbersome regimens, dislike of medication and distant pharmacies. Non-Drug factors that reduced the compliance were: fears about side effects, anger about condition or its treatment, forgetfulness or complacency and patient’s ill attitudes toward health. Conclusion: Noncompliance in asthma management is a fact of life and no single compliance-improving strategy probably will be as effective as a good physician–patient relationship. Optimal self-management allowing for optimization of asthma control by adjustment of medications may be conducted by either self-adjustment with the aid of a written action plan or by regular medical review.

Zopiclone and Prazepam Abuse in a Chronic Migraine Patient

Painful conditions are frequently accompanied by sleep disorders. Here we present the case, never previously reported, of high doses of zopiclone and prazepam abuse in a patient suffering from migraine and insomnia. A 37-year-old female Caucasian patient, nursing degree, with two 7-year-old twin daughters, began to suffer from migraines in her childhood. Migraine worsened and was associated with insomnia after the daughters’ birth. Eight months ago, migraine and insomnia further worsened in conjunction with the prescription of fluoxetine and prazepam as migraine prophylaxis and of zopiclone for insomnia. From that moment, the patient increased the dose of zopiclone up to 20 tablets (150 mg) nightly and prazepam up to 20 tablets (400 mg) daily. As acute migraine treatment she also used ketorolac 1-2 f every day intramuscularly. The patient was hospitalised for withdrawal of medications and to treat migraine. Hair analysis documented the history of this patient and the good progress of the treatment. Zopiclone and prazepam are considered drugs with low abuse potential. However, the final outcome of a drug treatment may be influenced by non-drug factors, such as the patient’s characteristics and the treatment milieu. In fact, in a stressful context, the prescription of zopiclone in a patient vulnerable for migraine triggered abuse of this drug and of prazepam, which was associated with chronification of migraine and analgesics overuse, without relieving insomnia. In prescribing hypnotics and anxiolytics to patients with chronic pain there must therefore be great caution. doi:10.4021/jmc729w

Zopiclone and Prazepam Abuse in a Chronic Migraine Patient

Painful conditions are frequently accompanied by sleep disorders. Here we present the case, never previously reported, of high doses of zopiclone and prazepam abuse in a patient suffering from migraine and insomnia. A 37-year-old female Caucasian patient, nursing degree, with two 7-year-old twin daughters, began to suffer from migraines in her childhood. Migraine worsened and was associated with insomnia after the daughters’ birth. Eight months ago, migraine and insomnia further worsened in conjunction with the prescription of fluoxetine and prazepam as migraine prophylaxis and of zopiclone for insomnia. From that moment, the patient increased the dose of zopiclone up to 20 tablets (150 mg) nightly and prazepam up to 20 tablets (400 mg) daily. As acute migraine treatment she also used ketorolac 1-2 f every day intramuscularly. The patient was hospitalised for withdrawal of medications and to treat migraine. Hair analysis documented the history of this patient and the good progress of the treatment. Zopiclone and prazepam are considered drugs with low abuse potential. However, the final outcome of a drug treatment may be influenced by non-drug factors, such as the patient’s characteristics and the treatment milieu. In fact, in a stressful context, the prescription of zopiclone in a patient vulnerable for migraine triggered abuse of this drug and of prazepam, which was associated with chronification of migraine and analgesics overuse, without relieving insomnia. In prescribing hypnotics and anxiolytics to patients with chronic pain there must therefore be great caution. J Med Cases. 2012;3(5):319-322 doi: https://doi.org/10.4021/jmc729w

Predictors of Depressive Symptomatology Among Rural Stimulant Users

This study examined sociodemographic and drug-related predictors of depressive symptoms among a rural, multistate sample of not-in-treatment stimulant drug users (n = 710). Participants were recruited using respondent-driven sampling in Ohio, Arkansas, and Kentucky. The Patient Health Questionnaire (PHQ-9) was used to measure symptoms of depression. Moderate to severe depressive symptomatology was reported by 43.0% of the sample. Cumulative logistic regression analysis showed that daily and nondaily crack use as well as the daily use of cocaine HCI increased the odds of depressive symptoms. Methamphetamine use had no significant association with depression. The daily use of marijuana, the illicit use of tranquilizers, light/moderate cigarette smoking, and injection drug use also increased the risk of depressive symptoms. Living in Kentucky or Ohio (compared to Arkansas), having unstable living arrangements, and being White, female, and older were related to higher odds of depressive symptoms. These results suggest that a host of drug and nondrug factors need to be considered when addressing depressive symptoms in stimulant users.

Study To Assess Factors Contributing To Compliance Of Aerosol Therapy In Bronchial Asthma.

Objectives of the studyTo study the compliance of aerosol therapy in asthmatics.To know the factors contributing to noncompliance. Methodology:A total of 100 patients were studied. Once included in the study, patient’s follow up was done for one to three months. Percentage compliance on aerosol therapy was calculated. Results: 100 patients of bronchial asthma who were started on aerosol therapy over duration of one year were included in the study. At the end of 3 months it was observed that among 100 patients, only 31 patients (31%) had regular compliance and 69 patients (69%) were non-compliant to aerosol therapy for bronchial asthma. Level of learning status of the individual had an important role for non-compliance, four times daily or multiple drugs, dislike of medication and distant pharmacies. Non-Drug factors include fears about side effects, anger about condition or its treatment, forgetfulness or complacency and attitudes toward ill health. To improve the compliance, whenever there were defaults various strategies were employed, through the patient’s educational techniques, which included verbal praise, interactive communication skills tailoring the medications to the patient’s routine and answering to the family’s worry. This was done by a psychologist. After employing the various strategies of patient’s education, the compliance increased in 23 patients (34.3%) among the earlier defaulted patients, while the remaining 44 patients (65.7%) were found to be noncompliant even after various educational techniques.

Anti-PF4/heparin antibody formation postorthopedic surgery thromboprophylaxis: the role of non-drug risk factors and evidence for a stoichiometry-based model of immunization.

Heparin-induced thrombocytopenia is an antibody-mediated disorder exhibiting variable frequency in different clinical settings. Antibodies recognize PF4/heparin complexes formed at optimal stoichiometric molar ratios. To identify clinical factors influencing risk of anti-PF4/heparin immunization. We performed observational studies and exploratory analyses of the frequency of anti-PF4/heparin antibody formation in 6324 patients who received enoxaparin or fondaparinux in four randomized controlled trials of postorthopedic surgery thromboprophylaxis. Variables included surgery type (knee vs. hip), timing of first anticoagulant dose (pre- vs. postsurgery), circumstances of surgery (elective vs. hip fracture), anticoagulant (enoxaparin vs. fondaparinux) and body-mass index (BMI). We applied a stoichiometry-based model that predicts immunization risk based on expected differences in PF4/anticoagulant ratios in different settings, and specifically used this model to predict the effect of increasing BMI quartiles upon relative risk (RR) of immunization for fondaparinux vs. enoxaparin. Anti-PF4/heparin immunization was more frequent after knee vs. hip surgery (particularly for enoxaparin), and when enoxaparin was given post- rather than pre-elective surgery; however, the opposite occurred with hip fracture surgery, that is, antibody formation was more frequent when enoxaparin or fondaparinux was given presurgery. The RR of immunization for fondaparinux vs. enoxaparin decreased significantly for increasing BMI quartiles, an effect predominantly because of increasing immunization with enoxaparin at increasing BMI quartiles. Several non-drug factors--including type and circumstances of surgery, timing of first anticoagulant dose and BMI--influence risk of anti-PF4/heparin antibody formation, consistent with a stoichiometry-based immunization model of PF4 and anticoagulant ratios occurring during the early peri-operative period.

Factors related to survival and treatment success in invasive candidiasis or candidemia: a pooled analysis of two large, prospective, micafungin trials

Crude and attributable mortality rates in patients with candidemia and invasive candidiasis remain unacceptably high. It is important to reach a more complete understanding of the risk factors underlying poor outcomes in patients with invasive Candida infections. Micafungin therapy has been assessed in two phase 3 trials compared to either liposomal amphotericin B or caspofungin. The availability of this large dataset allows the analyses of non-drug factors associated with survival and treatment success. A multivariate regression analysis was performed on data from the two trials separately and as a pooled analysis (N = 1,070). Analysis outcomes were survival at 42 days post-initiation of therapy and treatment success. For the pooled analysis, treatment success was significantly more likely for candidemia than invasive candidiasis. Both survival and treatment success were significantly less likely for the non-removal of catheter versus removal, Asian-Indians versus Caucasians, APACHE II score >20 to <or=30 and >30 versus <or=20, age >or=70 years versus <50 years, baseline corticosteroids, and persistent neutropenia. Survival was also significantly less likely for treatment in other regions versus North America and for patients with renal failure at baseline. These findings help to define non-antifungal drug factors that may impact survival and treatment success in invasive candidiasis or candidemia.

COMMENTARY: Understanding the Benefits of Pediatric Anti-Retroviral Treatment in Resource-Limited Settings

Access to antiretroviral treatment in resource-limited settings has repeatedly demonstrated reduction in mortality. With more treatment options becoming available, the ability to optimize therapy will depend on population-specific clinical trial data. The role of nondrug factors for optimizing therapy and the potential for drug-related adverse events that are population-specific should not be underestimated.