Physical measures and biomarker collection in health surveys: Propensity to participate

Population-based surveys have long been a key tool for health researchers, policy makers and program managers. The addition of bio-measures, including physical measures and specimen collection, to self-reported health and health behaviors can increase the value of the research for health sciences. At the same time, these bio-measures are likely to increase the perceived burden and intrusiveness to the respondent. Relatively little research has been reported on respondent willingness to participate in surveys that involve physical measures and specimen collection and whether there is any associated non-response bias.This paper explores the willingness of respondents to participate in surveys that involve physical measures and biomarkers. A Census-balanced sample of nearly 2000 adults from a national mobile panel of persons residing in the U.S. were interviewed. Willingness to participate in six specific bio-measures was assessed. The survey finds a high correlation in the willingness of respondents to participate among these specific bio-measures. This suggests there is a general propensity towards (and against) bio-measures among potential respondents, despite some differences in willingness to participate in the more sensitive, intrusive or burdensome biomarkers. This study finds the general propensity to participate in bio-measures is correlated with a number of key measures of health and illness. This suggests that the inclusion of biomarkers in health surveys may introduce some bias in key measures that need to be balanced against the value of the additional information.     

Does Postoperative Showering or Bathing of a Surgical Site Increase the Incidence of Infection? A Systematic Review of the Literature

Infection is one of the many postoperative complications a surgeon must attempt to control during the perioperative period. Surgeons have used a variety of modalities to prevent surgical site infection and have adhered to a variety of protocols. It has been common for foot and ankle surgeons to recommend that a patient keep the surgical incision covered and dry and to instruct the patient to avoid bathing and showering until the sutures have been removed. Surgeons have theorized that this will reduce contamination of the surgical site and help to prevent infection. We questioned the evidence basis for this practice and undertook a systematic review of electronic databases and other relevant sources regarding the incidence of infection when patients had been allowed to wet their surgical incision site by showering or bathing before suture removal. Nine studies involving 2150 patients met our inclusion criteria. No increased incidence of infection was found in the patients allowed to shower or bathe as a part of their normal daily hygiene before suture removal compared with those who were instructed to keep the site dry until suture removal.     

Bioequivalence and Food Effect of Dapagliflozin/Saxagliptin/Metformin Extended-release Fixed-combination Drug Products Compared With Coadministration of the Individual Components in Healthy Subjects

PurposeFixed-combination drug products (FCDPs) for patients with type 2 diabetes mellitus (T2DM) may show efficacy comparable to their individual components (ICs) while improving adherence to treatment. This study evaluated the bioequivalence and safety of 2 dapagliflozin/saxagliptin/metformin extended-release (XR) FCDPs relative to their ICs: saxagliptin and dapagliflozin/metformin XR.MethodsThis randomized, open-label, single-dose, single-center crossover study was conducted in 84 healthy subjects aged 18–55 years. The primary objective was to evaluate the fed-state bioequivalence of a dapagliflozin 5-mg/saxagliptin 2.5-mg/metformin 1000-mg XR FCDP and a dapagliflozin 10-mg/saxagliptin 5-mg/metformin 1000-mg XR FCDP relative to the ICs. Secondary objectives included the evaluation of the effect of food on the pharmacokinetic (PK) parameters of saxagliptin, dapagliflozin, and metformin in both FCDPs and characterization of the PK parameters of the active metabolite of saxagliptin, 5-hydroxy saxagliptin, in healthy subjects. PK parameters (AUC_0–∞, AUC_0–t, and C_max) were used to assess the bioequivalence of the 2 FCDPs with their ICs. The C_max and AUC_0–t of the study drugs were compared between female and male subjects to assess sex differences in exposure. Safety and tolerability of both FCDPs and ICs were also assessed with adverse events, vital signs (systolic and diastolic blood pressures and pulse rate), 12-lead ECG, physical examinations, and laboratory assessments.FindingsBoth dapagliflozin/saxagliptin/metformin XR FCDPs were bioequivalent to their ICs. For the dapagliflozin 5-mg/saxagliptin 2.5-mg/metformin 1000-mg XR FCDP, the 90% CI for the geometric mean ratio of dapagliflozin C_max was slightly above the 80%–125% bioequivalence limit, which is unlikely to be clinically relevant. Food delayed the absorption of the study drugs in both FCDPs, which is unlikely to have a clinically relevant impact on efficacy. In both cohorts, exposure was higher in female subjects compared with male subjects, potentially due to the lower body weight of the female subjects. The safety profile and tolerability of the FCDPs were similar to those of their ICs, and no deaths or serious adverse events were reported.ImplicationsThese data support the use of the dapagliflozin/saxagliptin/metformin XR FCDP in patients with T2DM. ClinicalTrials.gov identifier: NCT03169959.     

Reports of Injury Risks and Reasons for Choice of Sleep Environments for Infants and Toddlers

Objective

Compare mothers’ reports of injuries for infants and toddlers sleeping with crib-bumpers/mesh-liners/no-barriers and reasons for these sleep environment choices.

Methods

A cross-sectional survey of mothers subscribing to a parenting magazine and using crib bumpers (n?=?224), mesh liners (n?=?262), and no barriers (n?=?842). Analyses of four possible injuries (face-covered, climb-out/fall, slat-entrapment, hit-head) including multivariate logistic regression adjusted for missing data/demographics and Chi squared analyses of reasons for mothers’ choices.

Results

Maternal reports of finding infants/toddlers with face covered had 3.5 times higher adjusted odds (aOR) for crib bumper versus mesh liner use. Breathing difficulties and wedgings were reported for infants/toddlers using crib bumpers but not mesh liners. Climb-outs/falls showed no significant difference in aORs for crib bumpers versus no-barriers and mesh liners versus no barriers. Reports of slat-entrapment were less likely for mothers using crib bumpers and mesh liners than using no barrier (aOR?=?.28 and .32). Reports of hit-heads were less likely for crib bumpers vs no barrier (aOR?=?.38) with no significant difference between mesh liners versus no barrier use. Mothers using crib bumpers and mesh liners felt their choice prevented slat-entrapment (89%, 91%); 93.5% of crib bumper users felt their choice prevented hit-heads. Significantly more mesh liner than crib bumper users chose them because “There is no suffocation risk” (64.1% vs. 40.6%), while 83.6% of no-barrier users chose them because “I was concerned about suffocation risk.”

Conclusions for Practice

Mothers appeared to be more concerned about preventing minor risks than suffocation. Understanding reasons for mothers’ use of barriers/no-barriers is important in tailoring counseling for mothers with infants/toddlers.

     

Effect of constant light on rhythmic gastric functions in fasting rats

The effects of four weeks of continuous illumination (LL), a subacute stress, on gastric mucosal endogenous aggressive and defensive factors were studied. Young male Sprague-Dawley rats were used with two different illumination regimens: LL and 12 hr light/12 hr dark (LD). At the end of three to four weeks of either regimen of illumination, gastric acid secretion, pepsin secretion, mucus secretion, and potential difference (PD) were studied. All gastric parameters, except mucus secretion, were significantly reduced by LL. The reduction in acid secretion (13.3%) was not significant after Bonferroni correction for the fourt tests Pepsin secretion and PD were 27.9% and 24.6% less, respectively. These differences were significant after Bonferroni correction. The LD rats showed significant circadian rhythms for acid, mucus, and pepsin secretion. The LL rats showed significant rhythmicity for these same parameters with period lengths different from 24 hr. Gross inspection of the gastric mucosa indicated that 69.8% of the LL rats had lesion scores of 1.0 or higher, while none of the LD rats had scores above 0.5.The authors acknowledge the Salt Lake Veterans Administration Medical Center, Department of Research, for support of this study.     

Validation of 64Cu-ATSM damaging DNA via high-LET Auger electron emission

Radioactive copper (II) (diacetyl-bis N4-methylthiosemicarbazone) (Cu-ATSM) isotopes were originally developed for the imaging of hypoxia in tumors. Because the decay of a ⁶⁴Cu atom is emitting not only positrons but also Auger electrons, this radionuclide has great potential as a theranostic agent. However, the success of ⁶⁴Cu-ATSM internal radiation therapy would depend on the contribution of Auger electrons to tumor cell killing. Therefore, we designed a cell culture system to define the contributions to cell death from Auger electrons to support or refute our hypothesis that the majority of cell death from ⁶⁴Cu-ATSM is a result of high-LET Auger electrons and not positrons or other low-LET radiation. Chinese hamster ovary (CHO) wild type and DNA repair–deficient xrs5 cells were exposed to ⁶⁴Cu-ATSM during hypoxic conditions. Surviving fractions were compared with those surviving gamma-radiation, low-LET hadron radiation, and high-LET heavy ion exposure. The ratio of the D₁₀ values (doses required to achieve 10% cell survival) between CHO wild type and xrs5 cells suggested that ⁶⁴Cu-ATSM toxicity is similar to that of high-LET Carbon ion radiation (70 keV/μm). γH2AX foci assays confirmed DNA double-strand breaks and cluster damage by high-LET Auger electrons from ⁶⁴Cu decay, and complex types of chromosomal aberrations typical of high-LET radiation were observed after ⁶⁴Cu-ATSM exposure. The majority of cell death was caused by high-LET radiation. This work provides strong evidence that ⁶⁴Cu-ATSM damages DNA via high-LET Auger electrons, supporting further study and consideration of ⁶⁴Cu-ATSM as a cancer treatment modality for hypoxic tumors.     

Influence of dietary status and diabetes on aortic acyl-CoA hydrolase activity.

We have postulated that the accelerated snythesis of cholesteryl ester in atherosclerotic microsomes may result in part from decreased acyl-CoA hydrolase activity in arterial tissue, because acyl-CoA is a common substrate for both reactions. We have now investigated the influence of nutritional status, type of diet, and diabetes on the acyl-CoA hydrolase activity of otherwise normal aortic microsomes. Fasting rabbits for 16 hr diminished the acyl-CoA hydrolase activity approximately 30%. The activity of this aortic microsomal enzyme in rats maintained on a high-carbohydrate diet for 5 weeks was comparable to the activity observed on a high fat (olive oil) diet. The type of fat in the diet influences the acyl-CoA hydrolase activity: oils containing 77% oleic acid (high-oleic safflower oil) and containing 70% linoleic acid (conventional safflower oil) lowered the aortic microsomal acyl-CoA hydrolase activity in comparison to a more saturated fat (cocoa butter). Aortic preparations of rats made diabetic by streptozotocin exhibited higher acyl-CoA hydrolase activity than the normal. The results show that conditions associated with human atherogenesis (diabetes and saturated fat diet) increase rather than suppress the activity of this arterial enzyme in normal arterial tissues of the rat.     

African American Renal Transplant Recipients (RTR) Require Higher Tacrolimus Doses to Achieve Target Levels Compared to White RTR: Does Clotrimazole Help?

The number of African Americans (AAs) on the kidney waiting list is increasing in the United States. Several studies showed that AAs are at higher risk for rejection and graft loss. Because of genetic polymorphisms, AAs may metabolize calcineurin inhibitors faster than Caucasian (C) individuals. The goal of this study is to evaluate the tacrolimus (TAC) dose required to reach therapeutic levels and to assess the impact of clotrimazole on TAC metabolism in AAs compared to C patients. One hundred forty-two AA renal transplant recipients (RTRs) were compared to 309 C RTRs. Demographics were similar in both groups. Induction therapy and maintenance immunosuppression were similar in both groups and included TAC, mycophenolate acid (MPA), and steroids. The goal in all RTRs was to maintain a 12-hour trough level of 10 to 15 ng/mL in the first 3 months, 8 to 10 ng/mL for the first year, and 5 to 8 ng/mL thereafter. To achieve these levels, AA RTRs require a significantly higher dosage of TAC compared to C patients (5.9 ± 2.9 vs 3.6 ± 2 mg/d, respectively, P < .0001). By multivariate analysis, TAC dose requirements were not affected by age, gender, MPA or prednisone dose, diabetes, and renal function. Adding clotrimazole (CTM) to the RTR regimen significantly reduced the TAC dose requirements in all RTRs. When CTM was used, the TAC dose requirement was not statistically significantly different between AA and C patients (2.6 ± 1.2 mg/d vs 1.8 ± 1.5 mg/d, P = .07). We conclude that AAs required a higher TAC dose to reach the desired trough level in RTRs compared to C RTRs. The use of CTM eliminates the need for higher doses of TAC in AA RTRs. Thus, CTM may aid AA RTRs in achieving therapeutic TAC levels while reducing drug costs.     

Relationship of Frontal Plane Rotation of First Metatarsal to Proximal Articular Set Angle and Hallux Alignment in Patients Undergoing Tarsometatarsal Arthrodesis for Hallux Abducto Valgus: A Case Series and Critical Review of the Literature

Rotation of the first metatarsal, as a component of hallux abducto valgus, is rarely discussed and is not addressed as a component of most hallux valgus corrective procedures. We believe frontal plane rotation of the first metatarsal to be an integral component of hallux abducto valgus deformity (the “third plane of deformity”) and believe de-rotation is necessary for complete deformity correction. We observed the change in angular measurements commonly used in the evaluation of hallux valgus deformity in patients who underwent a modified lapidus procedure. We measured the intermetatarsal angle, hallux abductus angle, proximal articular set angle, and tibial sesamoid position on weightbearing radiographs of 25 feet in 24 patients who had undergone tarsal metatarsal corrective arthrodesis and lateral capsular release. Specific attention was given to reduction of the frontal plane rotation of the first metatarsal during correction. Our results showed a change in the angular measurements observed by 4 investigators as follows. The mean change in the intermetatarsal angle was 10.1° (p < .0001). The mean change in the hallux abductus angle was 17.8° (p < .0001). The mean change in the proximal articular set angle was 18.7° (p < .0001). The mean change in the tibial sesamoid position was 3.8 (p < .0001). Also, a consistent valgus, or everted position of the first metatarsal, was noted as a component of the hallux abducto valgus deformity in our patient population and was corrected by varus rotation or inversion of the metatarsal. We also reviewed the current literature related to anatomic changes in the first ray in the patient with hallux valgus deformity and reviewed our hypothesis regarding the reduction in the proximal articular set angle, which we believe to be related to frontal plane rotation of the first metatarsal, resulting in a radiographic artifact.