Nevin Manimala

Pain. 2021 Apr 7. doi: 10.1097/j.pain.0000000000002298. Online ahead of print.

ABSTRACT

The net effects of prescribing initiatives that encourage dose reductions are uncertain. We examined whether rapid dose reduction after high dose chronic opioid treatment (COT) associates with suicide, overdose, or other opioid-related adverse events. This retrospective cohort study included Oregon Medicaid recipients with high-dose COT. Claims were linked with prescription data from the Prescription Drug Monitoring Program (PDMP) and death data from vital statistics, 2014 to 2017. Participants were placed into four mutually exclusive dose trajectory groups following the high-dose COT period, and Cox proportional hazard models were used to examine the effect of dose changes on patient outcomes in the following year. Of the 14,596 high-dose COT patients, 4,191 (28.7%) abruptly discontinued opioid prescriptions, 1,648 (11.3%) reduced opioid dose prior to discontinuing, 6,480 (44.4%) had a dose reduction but never discontinued, and 2,277 (15.6%) had a stable or increasing dose. Discontinuation, whether abrupt (adjusted hazard ratio (aHR) 3.63; 95% CI 1.42-9.25) or with dose reduction (aHR 4.47, 95% CI 1.68-11.88) significantly increased risk of suicide compared to those with stable or increasing dose. In contrast, discontinuation or dose reduction reduced the risk of overdose compared to those with a stable or increasing dose (aHR 0.36 – 0.62, 95% CI 0.20 – 0.94). Patients with an abrupt discontinuation were more likely to overdose on heroin (vs. prescription opioids) than patients in other groups (p<0.0001). Our study suggests that patients on COT require careful risk assessment and supportive interventions when considering opioid discontinuation or continuation at a high dose.

PMID:33863865 | DOI:10.1097/j.pain.0000000000002298

Pain. 2021 Apr 8. doi: 10.1097/j.pain.0000000000002287. Online ahead of print.

ABSTRACT

Because chronic chronic pain has been poorly represented in the International statistical classification of diseases and related health problems (ICD) despite its significant contribution to the burden of disease worldwide, the International Association for the Study of Pain (IASP) developed a classification of chronic pain that was included in the ICD-11 version as ‘MG30’ and approved by the World Health Assembly in 2019. The objective of this field test was to determine its properties. A web-based survey using the WHO-FiT platform recruited 177 health-care professionals from all WHO regions. Following a training on coding chronic pain hosted by the IASP website, participants evaluated 18 diagnostic codes (lines) of the 2017 frozen version of the ICD-11 and 12 vignettes (cases) describing chronic pain conditions. Correctness, ambiguity and perceived difficulty of the coding were compared between the ICD-11 and the ICD-10 and the applicability of the morbidity rules for the ICD-11 verified. In the line coding, 43.0% of correct chronic pain diagnoses assigned with the ICD-10 contrasted with 63.2% with the ICD-11. Especially in cases in which the chronic pain is regarded as the symptom of an underlying disease, the ICD-11 (63.5%) commanded more correct diagnoses than the ICD-10 (26.8%). The case coding was on average 83.9% accurate, only in 1.6% of cases any difficulty was perceived. The morbidity rules were applied correctly in 74.1% of cases. From a coding perspective, the ICD-11 is superior to the ICD-10 in every respect, offering better accuracy, difficulty and ambiguity in coding chronic pain conditions.

PMID:33863861 | DOI:10.1097/j.pain.0000000000002287

Pediatrics. 2021 Apr 16:e20201500. doi: 10.1542/peds.2020-1500. Online ahead of print.

ABSTRACT

BACKGROUND: In preterm infants who require mechanical ventilation (MV), volume-targeted ventilation (VTV) modes are associated with lower rates of bronchopulmonary dysplasia compared with pressure-limited ventilation. Bronchopulmonary dysplasia rates in our NICU were higher than desired, prompting quality improvement initiatives to improve MV by increasing the use of VTV.

METHODS: We implemented and tested interventions over a 3-year period. Primary outcomes were the percentage of conventional MV hours when any-VTV mode was used and the percentage of conventional MV hours when an exclusively VTV mode was used. Exclusively VTV modes were modes in which all breaths were volume targeted. We evaluated outcomes during 3 project periods: baseline (May 2016-December 2016); epoch 1 (December 2016-October 2018), increasing the use of any-VTV mode; and epoch 2 (October 2018-November 2019), increasing the use of exclusively VTV modes.

RESULTS: Use of any-VTV mode increased from 18 694 of 22 387 (83%) MV hours during baseline to 72 846 of 77 264 (94%) and 58 174 of 60 605 (96%) MV hours during epochs 1 and 2, respectively (P < .001). Use of exclusively VTV increased from 5967 of 22 387 (27%) during baseline to 47 364 of 77 264 (61%) and 46 091 of 60 605 (76%) of all conventional MV hours during epochs 1 and 2, respectively (P < .001). In statistical process control analyses, multiple interventions were associated with improvements in primary outcomes. Measured clinical outcomes were unchanged.

CONCLUSIONS: Quality improvement interventions were associated with improved use of VTV but no change in measured clinical outcomes.

PMID:33863843 | DOI:10.1542/peds.2020-1500

Genome Res. 2021 Apr 16. doi: 10.1101/gr.266049.120. Online ahead of print.

ABSTRACT

Extreme phenotypic diversity, a history of artificial selection, and socioeconomic value make domestic dog breeds a compelling subject for genomic research. Copy number variation (CNV) is known to account for a significant part of inter-individual genomic diversity in other systems. However, a comprehensive genome-wide study of structural variation as it relates to breed-specific phenotypes is lacking. We have generated whole genome CNV maps for more than 300 canids. Our data set extends the canine structural variation landscape to more than 100 dog breeds, including novel variants that cannot be assessed using microarray technologies. We have taken advantage of this data set to perform the first CNV-based genome-wide association study (GWAS) in canids. We identify 96 loci that display copy number differences across breeds, which are statistically associated with a previously compiled set of breed-specific morphometrics and disease susceptibilities. Among these, we highlight the discovery of a long-range interaction involving a CNV near MED13L and TBX3, which could influence breed standard height. Integration of the CNVs with chromatin interactions, long noncoding RNA expression, and single nucleotide variation highlights a subset of specific loci and genes with potential functional relevance and the prospect to explain trait variation between dog breeds.

PMID:33863806 | DOI:10.1101/gr.266049.120

Genome Res. 2021 Apr 16. doi: 10.1101/gr.270033.120. Online ahead of print.

ABSTRACT

The members of the tribe Brassiceae share a whole-genome triplication (WGT), and one proposed model for its formation is a two-step pair of hybridizations producing hexaploid descendants. However, evidence for this model is incomplete, and the evolutionary and functional constraints that drove evolution after the hexaploidy are even less understood. Here, we report a new genome sequence of Crambe hispanica, a species sister to most sequenced Brassiceae. Using this new genome and three others that share the hexaploidy, we traced the history of gene loss after the WGT using the Polyploidy Orthology Inference Tool (POInT). We confirm the two-step formation model and infer that there was a significant temporal gap between those two allopolyploidizations, with about a third of the gene losses from the first two subgenomes occurring before the arrival of the third. We also, for the 90,000 individual genes in our study, make parental subgenome assignments, inferring, with measured uncertainty, from which of the progenitor genomes of the allohexaploidy each gene derives. We further show that each subgenome has a statistically distinguishable rate of homoeolog losses. There is little indication of functional distinction between the three subgenomes: the individual subgenomes show no patterns of functional enrichment, no excess of shared protein-protein or metabolic interactions between their members, and no biases in their likelihood of having experienced a recent selective sweep. We propose a “mix and match” model of allopolyploidy, in which subgenome origin drives homoeolog loss propensities but where genes from different subgenomes function together without difficulty.

PMID:33863805 | DOI:10.1101/gr.270033.120

CMAJ Open. 2021 Apr 16;9(2):E413-E423. doi: 10.9778/cmajo.20200067. Print 2021 Apr-Jun.

ABSTRACT

BACKGROUND: Canada lags behind other countries with respect to wait times for specialist physician and allied health professional consultations. We conducted a systematic review to assess the effects of a single-entry model on waiting time, referral volume and the satisfaction of patients and health care providers.

METHODS: We searched MEDLINE, Embase, Cochrane CENTRAL and CINAHL databases from inception to December 2019. We included studies from countries in the Organisation for Economic Co-operation and Development that reported on the effects of a single-entry model on the time between referral to first assessment by a specialist physician or allied health professional, termed wait time 1 (WT1). Patient volume and the satisfaction of providers and patients were secondary outcomes. We conducted a narrative synthesis using descriptive statistics.

RESULTS: Of the 4637 citations identified, 17 met the eligibility criteria, and we included 10 of these in the final analysis. All of the included studies reported an absolute reduction in WT1 after implementation of the single-entry model. The average percent reduction in WT1 across specialties was greatest for surgical referrals (57%) and urgent internal medicine referrals (40%). Higher initial WT1 was associated with a greater absolute reduction in WT1 after implementation of the single-entry model (p = 0.002). Patient and provider satisfaction with the single-entry model was high in all studies. The effect estimates from all included studies were at high risk of bias.

INTERPRETATION: Single-entry models were associated with an absolute reduction in time from referral from primary care to consultation. These models represent a promising option to improve access to a range of health services, but there is a need for rigorous prospective evaluations to inform policy.

PROSPERO REGISTRATION: CRD42018100395.

PMID:33863800 | DOI:10.9778/cmajo.20200067

Eur Respir J. 2021 Apr 16:2004656. doi: 10.1183/13993003.04656-2020. Online ahead of print.

ABSTRACT

RATIONALE: Patients with concomitant features of asthma and chronic obstructive pulmonary disease (COPD) have a heavy disease burden.

OBJECTIVES: Using data collected prospectively in the European Community Respiratory Health Survey, we compared the risk factors, clinical history, and lung function trajectories from early adulthood to the late sixties of middle aged subjects having asthma+COPD (n=179), past (n=263) or current (n=808) asthma alone, COPD alone (n=111), or none of these (n=3477).

METHODS: Interview data and prebronchodilator FEV₁ and FVC were obtained during three clinical examinations in 1991-1993, 1999-2002, and 2010-2013. Disease status was classified in 2010-2013, when the subjects were aged 40-68, according to the presence of fixed airflow obstruction (postbronchodilator FEV₁/FVC below the lower limit of normal), a lifetime history of asthma, and cumulative exposure to tobacco or occupational inhalants. Previous lung function trajectories, clinical characteristics, and risk factors of these phenotypes were estimated.

MAIN RESULTS: Subjects with asthma+COPD reported maternal smoking (28.2%) and respiratory infections in childhood (19.1%) more frequently than subjects with COPD alone (20.9 and 14.0%, respectively). Subjects with asthma+COPD had an impairment of lung function at age 20 that tracked over adulthood, and more than half of them had asthma onset in childhood. Subjects with COPD alone had the highest lifelong exposure to tobacco smoking and occupational inhalants, and they showed accelerated lung function decline during adult life.

CONCLUSIONS: The coexistence between asthma and COPD seems to have its origins earlier in life compared to COPD alone. These findings suggest that prevention of this severe condition, which is typical at older ages, should start in childhood.

PMID:33863744 | DOI:10.1183/13993003.04656-2020

Turk J Med Sci. 2021 Apr 17. doi: 10.3906/sag-2011-323. Online ahead of print.

ABSTRACT

BACKGROUND/AIM: Physical exercise is a state of physiological stress that requires adaptation of the organism to physical activity. Glycogen is an important and essential energy source for muscle contraction. Skeletal muscle and liver are two important glycogen stores and the energy required to maintain exercise in rodents are provided by destruction of this glycogen depot. In this study, the effects of endogenous opioid peptide antagonism at the central nervous system level on tissue glycogen content after exhaustive exercise were investigated.

MATERIALS AND METHODS: Rats had intracerebroventricularly (icv) received nonspecific opioid peptide receptor antagonist, naloxone (50 ?g/10 ?l in saline) and ?-opioid receptor-selective antagonist naltrindole (50 ?g/10 ?l in saline) and then exercised till exhaustion. After exhaustion, skeletal muscle, heart, and liver were excised immediately.

RESULTS: Both opioid peptide antagonists decreased glycogen levels in skeletal muscle. Although in soleus muscle, this decrease was not statistically significant (p>0.05) but in gastrocnemius muscle, it was significant in the icv naloxone administered group compared with control (p<0.05). Heart glycogen levels increased significantly in both naloxone and naltrindole groups compared to control and sham-operated groups (p<0.05). Heart glycogen levels were higher in the naloxone group than naltrindole (p<0.05). Liver glycogen levels were elevated significantly with icv naloxone administration compared with the control group (p<0.05). Glycogen levels in the naloxone group was also significantly higher than the naltrindole group (p<0.05).

CONCLUSION: Our findings indicate that icv administered opioid peptide antagonists may play a role in glycogen metabolism in peripheral tissues such as skeletal muscle, heart, and liver.

PMID:33862670 | DOI:10.3906/sag-2011-323

Turk J Med Sci. 2021 Apr 17. doi: 10.3906/sag-2004-307. Online ahead of print.

ABSTRACT

BACKGROUND/AIM: Tuberculosis is a public health problem that still remains significant. For prevention, diagnosis and treatment on tuberculosis more effective novel biomarkers are needed. MicroRNAs can regulate innate and adaptive immune responses, alter host-pathogen interactions and affect progression of diseases. The relationship between microRNA expression and active pulmonary tuberculosis (APT) has not been investigated in Turkish population yet. We aimed to test the potential diagnostic value of some microRNAs whose levels were previously reported to be altered in APT patients.

MATERIALS AND METHODS: Using two different references (U6 and miR-93), we compared the expression levels of potentially important microRNAs in serum of APT patients with healthy individuals using quantitative polymerase chain reaction (qPCR).

RESULTS: miR-144 expression level was down-regulated in APT patients when either U6 or miR-93 was used for normalization. When data was normalized with miR-93, a statistically significant decrease in miR-125b (0.8 fold) and miR-146a (0.7 fold) expression levels were observed, while no differences were detected for U6. Receiver operating characteristic suggested that miR-144 may be a candidate biomarker for discriminating APT patients and controls (p <0.05) both for U6 and miR-93.

CONCLUSION: These findings suggest that miR-144 can have potential as a biomarker for APT. Using a single reference may be misleading in evaluation of microRNA expression. U6 and miR-93 can be used in combination as reference for normalization of serum microRNA expression data.

PMID:33862668 | DOI:10.3906/sag-2004-307

Thorac Cardiovasc Surg. 2021 Apr 16. doi: 10.1055/s-0041-1727150. Online ahead of print.

ABSTRACT

BACKGROUND: Due to its very aggressive nature and low survival chances, the metastasized urothelium carcinoma poses a challenge in regard to therapy. The gold-standard chemotherapy is platinum based. The therapy options are considered controversial, including new systemic therapies. In this respect, surgical therapies, as already established for pulmonary metastases of other tumor entities play an increasingly important role. The consumption of nicotine is a risk factor not only for urothelium carcinoma but also for a pulmonary carcinoma. Thus, we examined the frequency of a second carcinoma in this cohort.

METHODS: We retrospectively examined patients who had a differential diagnosis of pulmonary metastases, as well as those patients who underwent a surgery due to pulmonary metastases of a urothelium carcinoma between 1999 and 2015.

RESULTS: A total of 139 patients came to our clinic with the differential diagnosis of pulmonary metastases of a urothelium carcinoma. The most common diagnosis was pulmonary carcinoma (53%). Thirty-one patients underwent surgeries due to pulmonary metastases of a urothelium carcinoma. The median survival was 53 months and the 5-year survival was 51%. With the univariate analysis, only the relapse-free interval of more than 10 months was statistically significant (p < 0.001).

CONCLUSION: There is a high coincidence of urothelial carcinoma and lung carcinoma. A histological confirmation should be endeavored. Selected patients undergoing a pulmonary metastasis resection have a survival advantage during the multimodal treatment of pulmonary metastasized urothelial carcinomas. For a definitive recommendation, randomized trials including a uniform multimodal therapy regimen and higher numbers of patients are necessary.

PMID:33862636 | DOI:10.1055/s-0041-1727150