Altered gastric emptying in the head-injured patient: relationship to feeding intolerance

Most patients with moderate to severe head injury initially do not tolerate enteral feedings postinjury. This intolerance is more prolonged than that found in patients suffering other types of trauma. The authors prospectively evaluated 12 patients with moderate to severe head injury (Glasgow Coma Scale score between 4 and 10) throughout their hospitalization for liquid gastric emptying as a possible mechanism for intolerance to enteral feeding. During Week 1, the majority of patients displayed a delay in gastric emptying. Patients also displayed an abnormal biphasic response (gastric emptying faster than normal during the early stage but prolonged later). By Week 2, many patients still had delayed and abnormal biphasic responses to gastric emptying. By Week 3, an improvement was observed with the majority of patients exhibiting rapid gastric emptying, but delays and abnormal biphasic responses were still seen. Patients who initially had rapid or normal gastric emptying tolerated full-strength full-rate feedings significantly earlier compared with those who experienced delayed gastric emptying (8.5 +/- 0.5 days vs. 13.7 +/- 3.2 days, p less than 0.001). All patients tolerated full-strength full-rate feedings by Day 16 postinjury (range 7 to 16 days) except the two patients who displayed delayed gastric emptying for prolonged periods of time (mean 25 days). This is the first study to longitudinally evaluate gastric emptying following head injury. The authors suggest that patients with moderate to severe head injury often experience alterations in gastric emptying which may affect their ability to tolerate enteral feedings.     

Day 1 serum lactate values in preterm infants less than 32 weeks gestation

Base deficit and serum lactate concentrations may be important prognostic indicators in preterm infants. We sought to (1) determine the relationship between day 1 serum lactate values and base deficit and (2) determine the relationship between day 1 biochemical parameters and adverse outcome in preterm infants <32 weeks. This was a retrospective study of all patients less than 32 weeks gestation admitted to neonatal intensive care unit over a 6-month period. All blood gases performed during the first 24 h post delivery were analysed. Adverse outcome was defined as death, severe (grade 3 or 4) intraventricular haemorrhage or periventricular leukomalaica on cranial ultrasonography. Patients were excluded if there was a known lethal malformation or cardiac defect. Seventy-two infants had a total of 473 lactate levels performed in the first 24 h. Mean (SD) gestational age was 29 (2.3) weeks, mean (SD) birth weight 1.28 (0.42) kg. Mean (SD) lactate values in first 6 h was 4.63 (3.69), at 12 h 3.08 (2.6), at 18 h 2.47 (2.68) and 2.08 (2.74) mmol/l at 24 h. There was a strong correlation between lactate values and base deficit values (R value 0.8, p < 0.01). Mean base deficit values at 6 h were 5.9 (4.5), at 12 h 3.8 (3.9), at 18 h 3.6 (3.1) and at 24 h 4.1 (3.8) mmol/l. A single lactate value greater than 5.6 mmol/l had a sensitivity of 100% and specificity of 85% of identifying adverse outcome. Persistently elevated or worsening lactates were associated with adverse outcome. There is a strong correlation between lactate values and base deficit on day 1 of life. Serial lactate measurements greater than 5.6 mmol/l predict adverse outcome and may aid the clinician in bedside decision making.     

Efficacy of "high-intensity" blue-light and "standard" daylight phototherapy for non-haemolytic hyperbilirubinaemia

We report our clinical experience with phototherapy in 3802 infants; 3629 were exposed to "standard" daylight phototherapy and 173 to "high-intensity" blue-light phototherapy. High-intensity blue-light phototherapy was twice as effective as standard daylight phototherapy in decreasing bilirubin concentrations. No failures occurred with high-intensity phototherapy compared with an overall failure rate of 1.84/1000 with daylight lamps; these cases were transferred to high-intensity phototherapy with prompt response. Rebound after cessation of phototherapy was greater in those exposed to high-intensity blue light with a significantly greater number requiring a second exposure. However, the incidence was still low. No third exposure was required in any infant. Nursing of infants under high-intensity blue light was more difficult and inconvenient as was clinical monitoring. The light also caused more stress on the nursing and medical personnel. However, the infants tolerated both types of phototherapy equally well. High-intensity blue-light phototherapy would seem to be the treatment of choice for infants with rapidly increasing or very high bilirubin levels, as well as in those not responding adequately to daylight phototherapy.     

The moderating effects of intellectual development on core symptoms of autism and PDD-NOS in toddlers and infants

Little research has been conducted on whether deficits in developmental functioning affect the range of core symptoms for autism spectrum disorders (ASD). This study represents a first attempt to determine whether developmental level has an effect on the expression of ASD symptoms in infants and toddlers. Eight hundred and fifty-three infants were evaluated with respect to the nature and extent of their ASD symptoms and developmental functioning. Young children with autism displayed a higher number of symptoms than those with PDD-NOS on all three domains of impairment (social, communication, repetitive behaviors). As expected, children without an ASD evinced far fewer symptoms than both these groups. Developmental level was not found to be a moderator for expression of ASD symptoms for the entire sample, or individual diagnostic groups. Higher developmental level was associated with lower severity of evinced ASD symptoms in the sample.     

Managing community acquired pneumonia in the elderly – the next generation of pharmacotherapy on the horizon

Introduction: Community acquired pneumonia (CAP) is associated with high rates of morbidity and mortality, especially among the elderly. Antibiotic treatment for CAP in the elderly is particularly challenging for many reasons, including compliance issues, immunosuppression, polypharmacy and antimicrobial resistance. There are few available antibiotics that are able to address these concerns.

Areas covered: After a systematic review of the current literature, we describe seven novel antibiotics that are currently in advanced stages of development (phase 3 and beyond) and show promise for the treatment of CAP in those over the age of 65. These antibiotics are: Solithromycin, Pristinamycin, Nemonaxacin, Lefamulin, Omadacycline, Ceftobiprole and Delafloxacin. Using a novel conceptual framework designed by the present authors, known as the ‘San Antonio NIPS model’, we evaluate their strengths and weaknesses based on their ability to address the unique challenges that face the elderly.

Expert opinion: All seven antibiotics have potential value for effective utilization in the elderly, but to varying degrees based on their NIPS model score. The goal of this model is to reorganize a clinician’s focus on antibiotic choices in the elderly and bring attention to a seldom discussed topic that may potentially become a health-care crisis in the next decade.     

The pharmacologic management of multiple myeloma in older adults

Introduction: Multiple myeloma is a disease predominately affecting older adults. Pivotal to treating older adults is understanding their physiologic differences compared to younger subjects and how the complexity of therapies has an impact upon this patient population.

Areas covered: Herein, the authors address the efficacy of chemotherapy regimens, decision-making for older adults, chemotherapy-associated toxicity and the approach to management. This review focuses on the complex treatment of older multiple myeloma patients and management of treatment-related adverse events.

Expert opinion: Balancing efficacy and managing toxicity is a challenge for older myeloma patients. This group is more susceptible to treatment toxicities due to a higher incidence of pre-existing comorbidities and underlying diminished physiologic reserve. Intensive therapies such as autologous hematopoietic cell transplant (AHCT), however, still should be considered for all multiple myeloma patients, including older adults. The continued development of novel therapies and increased use of multi-drug regimens has changed the treatment paradigms yet understanding the complexity of the aging adult in the context of various drugs is warranted.     

Associations of context-specific sitting time with markers of cardiometabolic risk in Australian adults

Background

High volumes of sitting time are associated with an elevated risk of type 2 diabetes and cardiovascular disease, and with adverse cardiometabolic risk profiles. However, previous studies have predominately evaluated only total sitting or television (TV) viewing time, limiting inferences about the specific cardiometabolic health impacts of sitting accumulated in different contexts. We examined associations of sitting time in four contexts with cardiometabolic risk biomarkers in Australian adults.

Methods

Participants (n?=?3429; mean?±?SD age 58?±?10 years) were adults without clinically diagnosed diabetes or cardiovascular disease from the 2011–2012 Australian Diabetes, Obesity and Lifestyle (AusDiab) study. Multiple linear regressions examined associations of self-reported context-specific sitting time (occupational, transportation, TV-viewing and leisure-time computer use) with a clustered cardiometabolic risk score (CMR) and with individual cardiometabolic risk biomarkers (waist circumference, BMI, resting blood pressure, triglycerides, HDL- and LDL-cholesterol, and fasting and 2-h post-load plasma glucose).

Results

Higher CMR was significantly associated with greater TV-viewing and computer sitting time (b [95%CI]?=?0.07 [0.04, 0.09] and 0.06 [0.03, 0.09]), and tended to be associated with higher occupational and transport sitting time (0.01 [??0.01, 0.03] and 0.03 [??0.00, 0.06]), after adjustment for potential confounders. Furthermore, keeping total sitting time constant, accruing sitting via TV-viewing and computer use was associated with significantly higher CMR (0.05 [0.02, 0.08] and 0.04 [0.01, 0.06]), accruing sitting in an occupational context was associated with significantly lower CMR (??0.03 [??0.05, ??0.01]), while no significant association was seen for transport sitting (0.00 [??0.03, 0.04]). Results varied somewhat between the respective biomarkers; however, higher sitting time in each domain tended to be associated detrimentally with individual biomarkers except for fasting glucose (non-significant associations) and systolic blood pressure (a beneficial association was observed). Overall, associations were stronger for TV-viewing and computer use, and weaker for occupational sitting.

Conclusions

Higher context-specific sitting times tended to be detrimentally associated, albeit modestly, with CMR and several cardiometabolic risk biomarkers. There was some evidence suggesting that the context in which people sit is relevant above and beyond total sitting time. Methodological issues notwithstanding, these findings may assist in identifying priorities for sitting-reduction initiatives, in order to achieve optimal cardiometabolic health benefits.

     

High potency inhibition of hERG potassium channels by the sodium-calcium exchange inhibitor KB-R7943

BACKGROUND AND PURPOSE

KB-R7943 is an isothiourea derivative that is used widely as a pharmacological inhibitor of sodium–calcium exchange (NCX) in experiments on cardiac and other tissue types. This study investigated KB-R7943 inhibition of hERG (human ether-à-go-go-related gene) K⁺ channels that underpin the cardiac rapid delayed rectifier potassium current, I_Kr.

EXPERIMENTAL APPROACH

Whole-cell patch-clamp measurements were made of hERG current (I_hERG) carried by wild-type or mutant hERG channels and of native rabbit ventricular I_Kr. Docking simulations utilized a hERG homology model built on a MthK-based template.

KEY RESULTS

KB-R7943 inhibited both I_hERG and native I_Kr rapidly on membrane depolarization with IC₅₀ values of ∼89 and ∼120 nM, respectively, for current tails at −40 mV following depolarizing voltage commands to +20 mV. Marked I_hERG inhibition also occurred under ventricular action potential voltage clamp. I_hERG inhibition by KB-R7943 exhibited both time- and voltage-dependence but showed no preference for inactivated over activated channels. Results of alanine mutagenesis and docking simulations indicate that KB-R7943 can bind to a pocket formed of the side chains of aromatic residues Y652 and F656, with the compound''s nitrobenzyl group orientated towards the cytoplasmic side of the channel pore. The structurally related NCX inhibitor SN-6 also inhibited I_hERG, but with a markedly reduced potency.

CONCLUSIONS AND IMPLICATIONS

KB-R7943 inhibits I_hERG/I_Kr with a potency that exceeds that reported previously for acute cardiac NCX inhibition. Our results also support the feasibility of benzyloxyphenyl-containing NCX inhibitors with reduced potential, in comparison with KB-R7943, to inhibit hERG.     

Acceptability of a hypothetical group B strep vaccine among pregnant and recently delivered women

Objective

Group B Streptococcus (GBS) causes significant infant morbidity and mortality. Promising GBS vaccines are currently in clinical trials. Because GBS vaccines would be the first to specifically target pregnant women, we sought to assess acceptability of a hypothetical GBS vaccine.

Study design

We performed an internet survey among currently pregnant or recently delivered women receiving care at one of 9 Ob/Gyn practices in Colorado. Vaccine acceptability was assessed using questions based on constructs from the Health Belief Model. Multivariable analyses assessed the characteristics associated with GBS vaccine acceptability during the current/recent pregnancy.

Results

The response rate was 50% (n = 231). While 78% agreed that a GBS vaccine would be a good way to protect newborns, 90% and 83% agreed, respectively, that they worried generally about the safety and effectiveness of new vaccines. Moreover, 39% believed it is generally dangerous for pregnant women to get vaccines. Seventy nine percent ‘definitely’ or ‘probably’ would have gotten a GBS vaccine in their most recent pregnancy if available. The most influential factors associated with this outcome were a strong belief in the vaccine's benefits (adjusted odds ratio [AOR] 6.37, 95% confidence interval [CI] 2.01–20.16), and low perceived barriers to vaccination (AOR 0.11, 95% CI (0.03–0.37)).

Conclusion

A GBS vaccine may be acceptable to pregnant women but would benefit from strong provider support and education about the risks and consequences of GBS infection and the benefits to vaccination.