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PCOM Library / Archive for "Hot Topics in Research"

Category: Hot Topics in Research

Hot Topics: Mothers with Anti-Vaccine Friends and Family Delay Babies’ Shots

katheride Hot Topics in Research, Pediatrics

Vaccine Education During Pregnancy and Timeliness of Infant Immunization
Veerasingam P, Grant CC, Chelimo C, et al. Vaccine education during pregnancy and timeliness of infant immunization. Pediatrics. 2017. doi: 10.1542/peds.2016-3727

OBJECTIVES: Pregnant women routinely receive information in support of or opposing infant immunization. We aimed to describe immunization information sources of future mothers’ and determine if receiving immunization information is associated with infant immunization timeliness.

METHODS: We analyzed data from a child cohort born 2009–2010 in New Zealand. Pregnant women (N = 6822) at a median gestation of 39 weeks described sources of information encouraging or discouraging infant immunization. Immunizations received by cohort infants were determined through linkage with the National Immunization Register (n = 6682 of 6853 [98%]). Independent associations of immunization information received with immunization timeliness were described by using adjusted odds ratios (ORs) and 95% confidence intervals (CIs).

RESULTS: Immunization information sources were described by 6182 of 6822 (91%) women. Of these, 2416 (39%) received information encouraging immunization, 846 (14%) received discouraging information, and 565 (9%) received both encouraging and discouraging information. Compared with infants of women who received no immunization information (71% immunized on-time), infants of women who received discouraging information only (57% immunized on time, OR = 0.49, 95% CI 0.38–0.64) or encouraging and discouraging information (61% immunized on time, OR = 0.51, 95% CI 0.42–0.63) were at decreased odds of receiving all immunizations on time. Receipt of encouraging information only was not associated with infant immunization timeliness (73% immunized on time, OR = 1.00, 95% CI 0.87–1.15).

CONCLUSIONS: Receipt, during pregnancy, of information against immunization was associated with delayed infant immunization regardless of receipt of information supporting immunization. In contrast, receipt of encouraging information is not associated with infant immunization timeliness.

Hot Topics: Cardiovascular Event Risk Lowered by Reducing Inflammation Alone

katheride Cardiology, Hot Topics in Research

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017. http://dx.doi.org/10.1056/NEJMoa1707914.

BACKGROUND

Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved.

METHODS

We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death.

RESULTS

At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31).

CONCLUSIONS

Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.)

Hot Topics: Combination of Traditional and New Drugs Effective for Esophageal Cancer

katheride Hot Topics in Research, Oncology

Inhibition of pRB pathway differentially modulates apoptosis in esophageal cancer cells
Soletti RC, Biasoli D, Rodrigues NALV, et al. Inhibition of pRB pathway differentially modulates apoptosis in esophageal cancer cells. Translational Oncology. 2017;10(5):726-733. doi: http://dx.doi.org/10.1016/j.tranon.2017.06.008.
Esophageal cancer is the sixth most common cause of cancer-related death worldwide. Current chemotherapy regimens include a combination of 5-fluorouracil (5-FU) and cisplatin, but more efficient therapy strategies are needed to increase 5-year survival. Alterations in the signaling pathway of the tumor suppressor gene Rb-1, which encodes a phosphoprotein (pRB) that negatively regulates the G1/S transition of the cell cycle, are present in 70% of all tumors, but its role in esophageal cancer is still unclear. Most of these are alterations leading to up-regulation of the activity of cyclin-dependent kinases (CDKs) to phosphorylate pRB, which suggests that keeping the wild type pRB phosphorylated might be advantageous. Besides proliferation, pRB also regulates apoptosis induced by tumor necrosis factor-alpha (TNF-α) and DNA-damage. We investigated the status of phosphorylation of pRB along esophageal tumorigenesis stages, as well as whether hyperphosphorylation of pRB could suppress apoptosis induced by cisplatin, 5-FU, or TNF-α in esophageal cancer cells. pRB phosphorylation increased progressively from normal esophageal tissue to metaplasia and adenocarcinoma, suggesting that pRB phosphorylation increases along esophageal tumor stages. When RB-1 was knocked down or CDK inhibitors reduced the levels of phosphorylated pRB, opposite apoptotic effects were observed, depending on the combination of drugs tested: whereas TNF-α- and cisplatin-induced apoptosis increased, 5-FU-induced apoptosis decreased. Taken together, these data suggest that pRB plays a role in esophageal adenocarcinoma and that, depending on the type of anti-cancer treatment, combining CDK inhibitors and chemotherapy has the potential to increase the sensitivity of esophageal cancer cells to cell death.

Hot Topic: Cannabis May Ease Neuropathic Pain

katheride Hot Topics in Research, Neurology

The effects of cannabis among adults with chronic pain and an overview of general harms: A systematic review
Nugent SM, Morasco BJ, O’Neil ME, al e. The effects of cannabis among adults with chronic pain and an overview of general harms: A systematic review. Annals of Internal Medicine. doi: 10.7326/M17-0155

Background: Cannabis is increasingly available for the treatment of chronic pain, yet its efficacy remains uncertain.
Purpose: To review the benefits of plant-based cannabis preparations for treating chronic pain in adults and the harms of cannabis use in chronic pain and general adult populations.
Data Sources: MEDLINE, Cochrane Database of Systematic Reviews, and several other sources from database inception to March 2017.
Study Selection: Intervention trials and observational studies, published in English, involving adults using plant-based cannabis preparations that reported pain, quality of life, or adverse effect outcomes.
Data Extraction: Two investigators independently abstracted study characteristics and assessed study quality, and the investigator group graded the overall strength of evidence using standard criteria.
Data Synthesis: From 27 chronic pain trials, there is low-strength evidence that cannabis alleviates neuropathic pain but insufficient evidence in other pain populations. According to 11 systematic reviews and 32 primary studies, harms in general population studies include increased risk for motor vehicle accidents, psychotic symptoms, and short-term cognitive impairment. Although adverse pulmonary effects were not seen in younger populations, evidence on most other long-term physical harms, in heavy or long-term cannabis users, or in older populations is insufficient.
Limitation: Few methodologically rigorous trials; the cannabis formulations studied may not reflect commercially available products; and limited applicability to older, chronically ill populations and patients who use cannabis heavily.
Conclusion: Limited evidence suggests that cannabis may alleviate neuropathic pain in some patients, but insufficient evidence exists for other types of chronic pain. Among general populations, limited evidence suggests that cannabis is associated with an increased risk for adverse mental health effects.

 

Hot Topic: Mind-Body Therapies Dramatically Reduce Pain in Hospital Patients

katheride Hot Topics in Research, Neurology, Psychology and Psychiatry

Randomized Controlled Trial of Brief Mindfulness Training and Hypnotic Suggestion for Acute Pain Relief in the Hospital Setting
Garland EL, Baker AK, Larsen P, et al. Randomized controlled trial of brief mindfulness training and hypnotic suggestion for acute pain relief in the hospital setting. Journal of General Internal Medicine. 2017. https://doi.org/10.1007/s11606-017-4116-9.
Background
Medical management of acute pain among hospital inpatients may be enhanced by mind-body interventions.
Objective
We hypothesized that a single, scripted session of mindfulness training focused on acceptance of pain or hypnotic suggestion focused on changing pain sensations through imagery would significantly reduce acute pain intensity and unpleasantness compared to a psychoeducation pain coping control. We also hypothesized that mindfulness and suggestion would produce significant improvements in secondary outcomes including relaxation, pleasant body sensations, anxiety, and desire for opioids, compared to the control condition.
Methods
This three-arm, parallel-group randomized controlled trial conducted at a university-based hospital examined the acute effects of 15-min psychosocial interventions (mindfulness, hypnotic suggestion, psychoeducation) on adult inpatients reporting “intolerable pain” or “inadequate pain control.” Participants (N = 244) were assigned to one of three intervention conditions: mindfulness (n = 86), suggestion (n = 73), or psychoeducation (n = 85).
Key Results
Participants in the mind-body interventions reported significantly lower baseline-adjusted pain intensity post-intervention than those assigned to psychoeducation (p < 0.001, percentage pain reduction: mindfulness = 23%, suggestion = 29%, education = 9%), and lower baseline-adjusted pain unpleasantness (p < 0.001). Intervention conditions differed significantly with regard to relaxation (p < 0.001), pleasurable body sensations (p = 0.001), and desire for opioids (p = 0.015), but all three interventions were associated with a significant reduction in anxiety (p < 0.001).
Conclusions
Brief, single-session mind-body interventions delivered by hospital social workers led to clinically significant improvements in pain and related outcomes, suggesting that such interventions may be useful adjuncts to medical pain management.

Hot Topics: Oral Bacteria Can Help Determine Time of Death

katheride Forensic Medicine and Pathology, Hot Topics in Research

Dynamics of the oral microbiota as a tool to estimate time since death
Adserias-Garriga J, Quijada NM, Hernandez M, Rodríguez Lázaro D, Steadman D, Garcia-Gil L. Dynamics of the oral microbiota as a tool to estimate time since death. Mol Oral Microbiol. http://dx.doi.org/10.1111/omi.12191.
The oral cavity harbors one of the most diverse microbiomes in the human body. It has been shown to be the second most complex in the body after the gastrointestinal tract. Upon death, the indigenous microorganisms lead to the decomposition of the carcass. Therefore, the oral cavity and gastrointestinal tract microbiomes play a key role in human decomposition. The aim of the present study is to monitor the microbiome of decaying bodies on a daily basis and to identify signature bacterial taxa, that can improve postmortem interval estimation. Three individuals (one male and two female) donated to the University of Tennessee Forensic Anthropology Center for the W.M. Bass Donated Skeletal Collection were studied. Oral swab samples were taken daily throughout the different stages of cadaveric putrefaction. DNA was extracted and analyzed by next-generation sequencing techniques. The three cadavers showed similar overall successional changes during the decomposition process. Firmicutes and Actinobacteria are the predominant phyla in the fresh stage. The presence of Tenericutes corresponds to bloat stage. Firmicutes is the predominant phylum in advanced decay, but the Firmicutes community is a different one from the predominant Firmicutes of the fresh stage. This study depicts the thanatomicrobiome successional changes in the oral cavity, and highlights its potential use in forensic cases as a quantitative and objective approach to estimate postmortem interval, from an ecological rationale.

Hot Topics: Customized 3-D Models Effectively Train Children’s Surgeons

katheride Hot Topics in Research, Pediatrics, Surgery

Patient-specific 3D models aid planning for triplane proximal femoral osteotomy in slipped capital femoral epiphysis
Cherkasskiy L, Caffrey JP, Szewczyk AF, et al. Patient-specific 3D models aid planning for triplane proximal femoral osteotomy in slipped capital femoral epiphysis. J Child Orthop. 2017;11(2):147-153. https://doi.org/10.1302/1863-2548-11-170277.
Purpose
Slipped capital femoral epiphysis (SCFE) can result in a complex three-dimensional (3D) deformity of the proximal femur. A three-plane proximal femoral osteotomy (TPFO) has been described to improve hip mechanics. The purpose of this study was to evaluate the benefits of using 3D print technology to aid in surgical planning.
Patients and Methods
Fifteen children treated with TPFO for symptomatic proximal femoral deformity due to SCFE were included in this study. Ten patients were treated by a single surgeon with (model group, n = 5) or without (no-model group, n = 5) a 3D model for pre-operative planning, and compared with patients treated by two senior partners without the use of a model (senior group, n = 5) to evaluate for a learning curve. Peri-operative data including patient body mass index (BMI), surgical time and fluoroscopy time were recorded.
Results
Children in all three groups had similar BMIs at the time of the TPFO. Post-operative radiographic parameters were equally improved in all three groups. On average, surgical time decreased by 45 minutes and 38 minutes, and fluoroscopy time decreased by 50% and 25%, in the model group compared with the no-model and senior groups, respectively.
Conclusions
Patient-specific 3D models aid in surgical planning for complex 3D orthopaedic deformities by enabling practice of osteotomies. Results suggest that 3D models may decrease surgical time and fluoroscopy time while allowing for similar deformity correction. These models may be especially useful to overcome steep learning curves for complex procedures or in trainee education through mock surgical procedures.

Hot Topics: Anti-Statin Internet Trend Could Threaten Lives

katheride Cardiology, Hot Topics in Research

Statin Denial: An Internet-Driven Cult With Deadly Consequences
Nissen SE. Statin Denial: An Internet-Driven Cult With Deadly Consequences. Ann Intern Med. doi: 10.7326/M17-1566
The reduction in cardiovascular morbidity and mortality during the past 3 decades represents one of the great triumphs of contemporary medicine. In 1987, the age-adjusted mortality rate in the U.S. population for cardiovascular disease was 357 in 100 000, decreasing to 167 in 100 000 by 2014 (1). Although precisely gauging the relative contributions of various public health measures to the decline in cardiovascular morbidity and mortality is impossible, most critical observers consider the introduction of statins in 1987 to be one of the keys to this success. According to the Centers for Disease Control and Prevention, the prevalence of elevated low-density lipoprotein cholesterol levels (>4.1 mmol/L [160 mg/dL], >3.4 mmol/L [130 mg/dL], and >2.6 mmol/L [100 mg/dL] for low-, medium-, and high-risk persons, respectively) declined from 59% to 28% between 1980 and 2010 (2). Average low-density lipoprotein cholesterol levels decreased from 3.3 mmol/L (129 mg/dL) in 1988 to 1994 to 3.0 mmol/L (116 mg/dL) in 2007 to 2010.

Hot Topics: Monthly Injections Could Replace Pills for HIV Treatment

katheride Hot Topics in Research, Infectious Disease

Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial
Margolis DA, Gonzalez-Garcia J, Stellbrink H, et al. Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial. The Lancet. http://dx.doi.org/10.1016/S0140-6736(17)31917-7.
Summary
Background
Cabotegravir and rilpivirine are antiretroviral drugs in development as long-acting injectable formulations. The LATTE-2 study evaluated long-acting cabotegravir plus rilpivirine for maintenance of HIV-1 viral suppression through 96 weeks.
Methods
In this randomised, phase 2b, open-label study, treatment-naive adults infected with HIV-1 initially received oral cabotegravir 30 mg plus abacavir–lamivudine 600–300 mg once daily. The objective of this study was to select an intramuscular dosing regimen based on a comparison of the antiviral activity, tolerability, and safety of the two intramuscular dosing regimens relative to oral cabotegravir plus abacavir–lamivudine. After a 20-week induction period on oral cabotegravir plus abacavir–lamivudine, patients with viral suppression (plasma HIV-1 RNA <50 copies per mL) were randomly assigned (2:2:1) to intramuscular long-acting cabotegravir plus rilpivirine at 4-week intervals (long-acting cabotegravir 400 mg plus rilpivirine 600 mg; two 2 mL injections) or 8-week intervals (long-acting cabotegravir 600 mg plus rilpivirine 900 mg; two 3 mL injections) or continued oral cabotegravir plus abacavir–lamivudine. Randomisation was computer-generated with stratification by HIV-1 RNA (<50 copies per mL, yes or no) during the first 12 weeks of the induction period. The primary endpoints were the proportion of patients with viral suppression at week 32 (as defined by the US Food and Drug Administration snapshot algorithm), protocol-defined virological failures, and safety events through 96 weeks. All randomly assigned patients who received at least one dose of study drug during the maintenance period were included in the primary efficacy and safety analyses. The primary analysis used a Bayesian approach to evaluate the hypothesis that the proportion with viral suppression for each long-acting regimen is not worse than the oral regimen proportion by more than 10% (denoted comparable) according to a prespecified decision rule (ie, posterior probability for comparability >90%). Difference in proportions and associated 95% CIs were supportive to the primary analysis. The trial is registered at ClinicalTrials.gov, number NCT02120352.
Findings
Among 309 enrolled patients, 286 were randomly assigned to the maintenance period (115 to each of the 4-week and 8-week groups and 56 to the oral treatment group). This study is currently ongoing. At 32 weeks following randomisation, both long-acting regimens met primary criteria for comparability in viral suppression relative to the oral comparator group. Viral suppression was maintained at 32 weeks in 51 (91%) of 56 patients in the oral treatment group, 108 (94%) of 115 patients in the 4-week group (difference 2·8% [95% CI −5·8 to 11·5] vs oral treatment), and 109 (95%) of 115 patients in the 8-week group (difference 3·7% [−4·8 to 12·2] vs oral treatment). At week 96, viral suppression was maintained in 47 (84%) of 56 patients receiving oral treatment, 100 (87%) of 115 patients in the 4-week group, and 108 (94%) of 115 patients in the 8-week group. Three patients (1%) experienced protocol-defined virological failure (two in the 8-week group; one in the oral treatment group). Injection-site reactions were mild (3648 [84%] of 4360 injections) or moderate (673 [15%] of 4360 injections) in intensity and rarely resulted in discontinuation (two [<1%] of 230 patients); injection-site pain was reported most frequently. Serious adverse events during maintenance were reported in 22 (10%) of 230 patients in the intramuscular groups (4-week and 8-week groups) and seven (13%) of 56 patients in the oral treatment group; none were drug related.
Interpretation
The two-drug combination of all-injectable, long-acting cabotegravir plus rilpivirine every 4 weeks or every 8 weeks was as effective as daily three-drug oral therapy at maintaining HIV-1 viral suppression through 96 weeks and was well accepted and tolerated.

Hot Topics: Transcriptional Regulator CTCF Found Essential in Immune Response

katheride Biomedical Sciences, Hot Topics in Research

CTCF orchestrates the germinal centre transcriptional program and prevents premature plasma cell differentiation
Pérez-Garcí­a A, Marina-Zárate E, Álvarez-Prado ÁF, Ligos JM, Galjart N, Ramiro AR. CTCF orchestrates the germinal centre transcriptional program and prevents premature plasma cell differentiation. Nature Communications. 2017;8:16067. http://dx.doi.org/10.1038/ncomms16067.
In germinal centres (GC) mature B cells undergo intense proliferation and immunoglobulin gene modification before they differentiate into memory B cells or long-lived plasma cells (PC). GC B-cell-to-PC transition involves a major transcriptional switch that promotes a halt in cell proliferation and the production of secreted immunoglobulins. Here we show that the CCCTC-binding factor (CTCF) is required for the GC reaction in vivo, whereas in vitro the requirement for CTCF is not universal and instead depends on the pathways used for B-cell activation. CTCF maintains the GC transcriptional programme, allows a high proliferation rate, and represses the expression of Blimp-1, the master regulator of PC differentiation. Restoration of Blimp-1 levels partially rescues the proliferation defect of CTCF-deficient B cells. Thus, our data reveal an essential function of CTCF in maintaining the GC transcriptional programme and preventing premature PC differentiation.