Evaluating the prospective utility of pharmacogenetics reporting among Canadian Armed Forces personnel receiving pharmacotherapy: a preliminary assessment towards precision psychiatric care.

Pharmacological interventions for treating posttraumatic stress disorder in Canadian Armed Forces (CAF) members and Veterans often achieve modest results. The field of pharmacogenetics, or the study of how genes influence an individual's response to different medications, offers insight into how prior knowledge of gene-drug interactions may potentially improve the trial-and-error process of drug selection in pharmacotherapy, thereby improving treatment effects and remission rates. Given the relative recency of pharmacogenetics testing and sparse research in military samples, we used pharmacogenetics testing in a small pilot group (n=23) of CAF members and Veterans who were already engaged in pharmacotherapy for a service-related mental health condition to better understand the associated opportunities and challenges of pharmacogenetics testing in this population. Our preliminary evaluation involved: (1) reporting the prevalence of pharmacogenetics testing 'bin' status according to participants' reports ('green', 'yellow' or 'red'; intending to signal 'go', 'caution' or 'stop', regarding the potential for gene-drug interactions); (2) calculating the percentage of currently prescribed psychotropic medications that were assessed and included in the reports; (3) evaluating whether prescribers used pharmacogenetics testing information according to clinical notes and (4) collecting informal feedback from participating psychiatrists. While pharmacogenetics testing appeared to provide valuable information for a number of clients, a major limitation was the number of commonly prescribed medications not included in the reports.

Recurrence and return to duty following patellar instability events in military personnel.

INTRODUCTION: Military service members experience patellar dislocations at a rate 10 times that of civilians. The purpose of this study was to determine the return to duty rate of active duty military personnel following first-time or recurrent patellar dislocation. Secondary goals were to identify patient variables and radiographic parameters associated with recurrent instability and requiring medical separation from military service. METHODS: The Military Health System Data Repository was used to identify all active-duty military personnel who sustained a patellar dislocation between 2013 and 2018. Medical records were searched for patient variables including demographics, clinical findings, radiographic findings, treatment, adverse outcomes and military disposition. Patient variables associated with recurrent instability and undergoing medical separation were determined using univariate analysis and multivariate logistic regression. A total of 207 patients met inclusion and exclusion criteria. RESULTS: Following patellar instability event, 30% of the cohort underwent surgical treatment. Fourteen per cent (29 of 207) underwent medical separation from military service. Regardless of treatment, 9% (18 of 207) experienced recurrent dislocation and 3% (6 of 207) experienced recurrent instability without dislocation. On multivariate analysis, none of the studied patient variables were associated with recurrent instability or medical separation. CONCLUSIONS: Among military personnel, return to duty rates are similar to return to sport rates in civilians. This study demonstrates no difference in risk of recurrent instability or medical separation based on anatomical factors, which is useful during shared decision-making regarding treatment options and goals.

A phase II open-label trial of avelumab plus axitinib in previously treated non-small-cell lung cancer or treatment-naïve, cisplatin-ineligible urothelial cancer.

BACKGROUND: We hypothesized that avelumab plus axitinib could improve clinical outcomes in patients with advanced non-small-cell lung cancer (NSCLC) or urothelial carcinoma (UC). PATIENTS AND METHODS: We enrolled previously treated patients with advanced or metastatic NSCLC, or untreated, cisplatin-ineligible patients with advanced or metastatic UC. Patients received avelumab 800 mg every 2 weeks (Q2W) and axitinib 5 mg orally two times daily. The primary endpoint was objective response rate (ORR). Immunohistochemistry was used to assess programmed death-ligand 1 (PD-L1) expression (SP263 assay) and the presence of CD8+ T cells (clone C8/144B). Tumor mutational burden (TMB) was assessed by whole-exome sequencing. RESULTS: A total of 61 patients were enrolled and treated (NSCLC, n = 41; UC, n = 20); 5 remained on treatment at data cut-off (26 February 2021). The confirmed ORR was 31.7% in the NSCLC cohort and 10.0% in the UC cohort (all partial responses). Antitumor activity was observed irrespective of PD-L1 expression. In exploratory subgroups, ORRs were higher in patients with higher (≥median) CD8+ T cells in the tumor. ORRs were higher in patients with lower TMB (

Developing a platform for Fresnel diffractive radiography with 1 µm spatial resolution at the National Ignition Facility.

An x-ray Fresnel diffractive radiography platform was designed for use at the National Ignition Facility. It will enable measurements of micron-scale changes in the density gradients across an interface between isochorically heated warm dense matter materials, the evolution of which is driven primarily through thermal conductivity and mutual diffusion. We use 4.75 keV Ti K-shell x-ray emission to heat a 1000 µm diameter plastic cylinder, with a central 30 µm diameter channel filled with liquid D2, up to 8 eV. This leads to a cylindrical implosion of the liquid D2 column, compressing it to ∼2.3 g/cm3. After pressure equilibration, the location of the D2/plastic interface remains steady for several nanoseconds, which enables us to track density gradient changes across the material interface with high precision. For radiography, we use Cu He-α x rays at 8.3 keV. Using a slit aperture of only 1 µm width increases the spatial coherence of the source, giving rise to significant diffraction features in the radiography signal, in addition to the refraction enhancement, which further increases its sensitivity to density scale length changes at the D2/plastic interface.

Why are US military personnel prescribed transdermal fentanyl patches?

INTRODUCTION: Transdermal fentanyl is a continuous release opioid delivery system intended for use in opioid-tolerant patients requiring around-the-clock opioid therapy. The purpose of this study is to identify the most common indications for transdermal fentanyl prescriptions in active duty US military personnel, and determine whether these prescriptions meet US Food and Drug Administration (FDA) labelling. METHODS: Active duty US military personnel initiating transdermal fentanyl therapy with prescriptions filled at Military Health System pharmacies between 2015 and 2019 were identified in the Military Data Repository. Electronic health records were searched for patient demographic information, clinical information and prescription data. A total of 225 patients with complete data were identified. RESULTS: The most common reason for transdermal fentanyl initiation was chronic non-cancer musculoskeletal pain. Among patients with non-cancer pain, 36% received their initial prescription from an internal medicine/primary care provider, and 35% did not meet published US FDA criteria for opioid tolerance prior to treatment initiation. There was an 81% decrease in patients initiating therapy between 2015 and 2019. CONCLUSIONS: While a substantial minority of transdermal fentanyl prescriptions to US military personnel did not meet FDA guidelines on appropriate use, the overall number of prescriptions fell dramatically over the study period. This suggests that automated profile review or additional targeted policies to limit transdermal fentanyl prescribing are unnecessary at this time.

Total hip and knee arthroplasty after lower extremity amputation in a military population.

INTRODUCTION: The military includes lower extremity amputees requiring arthroplasty; however, there is little literature on this population. The primary aim of this study was to report demographics and clinical factors in amputees who undergo total hip or knee arthroplasty (THA/TKA) in the Military Health System (MHS). Second, patient-reported outcome measures (PROMs) are reported. METHODS: The Military Data Repository was queried for patients with lower extremity amputations and TKA or THA between 1 October 2014 and 12 October 2020. The medical records were reviewed and patients were contacted to complete PROMs. Mean follow-up for TKA and THA was 5.5 and 2.5 years, respectively. RESULTS: Nineteen TKAs (76%) and eight THAs (28%) were performed in 25 patients. Mean age of TKA and THA patients at the time of arthroplasty was 57 years old. A majority of TKA (68%) and THA (57%) patients underwent amputations secondary to trauma. Nearly all TKAs were performed on the contralateral side to the amputation (95%), while half of THAs were performed on the ipsilateral side (50%). Two THAs (29%) were revised due to periprosthetic fractures, whereas six TKAs (32%) were revised or reoperated on due to infection. Ten TKA patients completed PROMs. The mean score on Knee Osteoarthritis Outcome Score for Joint Replacement (KOOS JR) was 41.8 and Patient-Reported Outcomes Measurement Information System Global-10 (PROMIS-10) was 41.6 (Global Physical Health) and 49.6 (Global Mental Health). CONCLUSIONS: Most TKAs were performed on the contralateral limb, suggesting increased demand on the joint. The most common indication for amputation and post-TKA complication was trauma and infection, respectively. KOOS JR may not accurately capture the outcomes of this population, or they simply do worse. However, PROMIS-10 scores were similar to the non-amputee population, suggesting that the PROMIS-10 may be more useful than the KOOS JR.

UPPER ARM CONTOURING - A NARRATIVE REVIEW.

Disfigurement of upper arms is a common esthetic problem. All soft tissues contribute with skin and subcutaneous adipose tissue as the major targets of medical intervention. This narrative review describes the complex pathogenesis of upper arm ptosis and its classification. Surgical and non-surgical methods to improve upper arm contour are discussed. With the broad spectrum of available treatments, a tailored approach is possible to address the individual patient's needs.

PIGMENTED NODULAR CYSTIC HIDRADENOMA OF THE ANKLE.

Solid-cystic hidradenoma is a benign cutaneous tumor that is most commonly found in the head, neck, trunk, and upper extremity regions of patients in the middle to older aged groups. Presentation on lower extremities and in particular on the foot is uncommon. Nodular hidradenomas represent a dermatological pitfall, being difficult to differentiate from basal cell carcinoma and melanoma. We report on a 53-year-old male patient with a pigmented nodular hidradenoma on his ankle that was surgically removed. We discuss histopathology and differential diagnosis of this eccrine tumor of skin. This is the second reported case in the English literature.

LONG-PULSED ND:YAG LASER TO TREAT TELANGIECTASIA OF THE NOSE: A COMPREHENSIVE 5-YEAR SINGLE CENTER STUDY.

Telangiectases of the nose are of esthetic concern and treatment is warranted. The study provides the results of 5 years of treatment of telangiectases of the nose region with the long-pulsed Nd:YAG 1,064 nm laser. A retrospective analysis was conducted in patients of Fitzpatrick skin type II-V. Exclusion criteria were patients with a previous history of treatment of the nose region, pregnant or lactating patients or patients with unrealistic expectations regarding the treatment risks, limitations and results. Standardized photographs were obtained before each session and at least 2 months after the last treatment session. A long-pulsed Nd:YAG 1,064 nm laser was used with a spot size of 2.5mm, fluence of 100 - 175 J/cm2, pulse duration of up to 135ms and repetition rate of 2-4 Hz. The follow-up ranged from 2 months to 5 years. The number of laser sessions varied from 1 to 5 monthly. Assessment was made by comparing pre-treatment and post-treatment photographs by two independent specialists and also by the patients' own assessment. All patients presented improvement of the vascular alterations. Evaluation of independent specialists as well as the evaluation of the patients themselves showed a high degree of satisfaction with the treatment. The treatment presented only few transitory side effects. Treatment of telangiectasia on the nose skin with the long-pulsed Nd:YAG 1,064 nm laser demonstrated to be safe and effective even in darker pigmented skin. The major limitation of this study is its retrospective nature.

[Paradigm shift in understanding hyaluronic acid filler effects]. / Paradigmenwechsel im Verständnis der Wirkung von Hyaluronsäurefillern.

Hyaluronic acid (hyaluron; HA) is an important constituent of the extracellular matrix and has an age-dependent decrease in tissue concentration. While natural HA is rapidly degraded, filler cross-linked HA achieve a half-life of 6-12 months. Such fillers enjoy increasing popularity in esthetic medicine and are versatile tools. Although HA fillers can activate fibroblasts it is of minor importance for long-term results. Fillers are injected into subcutaneous adipose tissue. Their interaction with somatic stem cells and mature adipocytes has gained increasing interest. Cross-linked HA can indeed support proliferation of pre-adipocytes, stimulate their differentiation into mature adipocytes and protect the mature cells from senescence, apoptosis and lipolysis. This view offers a new perspective on the development of future fillers for esthetic medicine.

[Complications after laser treatment of facial vascular lesions]. / Komplikationen nach Laserbehandlung vaskulärer Veränderungen des Gesichts.

Laser technology represents a major advance in the treatment of vascular changes. Excellent knowledge combined with technological advances in new laser sources form the basis of this safe and effective option in many acquired or congenital vascular changes on the face. With regard to the different laser sources, the pulsed dye laser (PDL) has the best efficacy-to-safety ratio. This type of laser remains the gold standard for vascular lesions. Neodymium-doped yttrium aluminium garnet (Nd: YAG) lasers and diode lasers, among others, as well as intensed pulsed light (IPL), play an important role in addressing vascular changes in the face. Good knowledge of the laser approach to vascular lesions and technological progress have led to safety features that seek to minimize side effects. These advances mainly include the introduction of cooled tips, cooling devices and cooling systems, changes in pulse duration, and the introduction of different wavelengths, among others. However, undesirable side effects can still occur. Although these are mostly discrete and resolve spontaneously, some complications can be serious and difficult to manage. Therefore, the prevention and early management of complications are all the more important in the treatment of vascular changes on the face.

Magnetic ordering and structural distortion in a PrFeAsO single crystal studied by neutron and x-ray scattering.

We report the magnetic ordering and structural distortion in PrFeAsO crystals, the basis compound for one of the oxypnictide superconductors, using high-resolution x-ray diffraction, neutron diffraction, and x-ray resonant magnetic scattering (XRMS). We find the structural tetragonal-to-orthorhombic phase transition at TS=147K, the AFM phase transition of the Fe moments at TFe=72K, and the Pr AFM phase transition at TPr=21K. Combined high-resolution neutron diffraction and XRMS show unambiguously that the Pr moments point parallel to the longer orthorhombic a axis and order antiferromagnetically along the a axis but ferromagnetically along the b and c directions in the stripelike AFM order. The temperature-dependent magnetic order parameter of the Pr moments shows no evidence for a reorientation of moments.

IMPROVEMENT OF HYPERTROPHIC SCARS WITH INTRALESION INJECTIONS OF HYALURONIDASE.

In contrast to intra-urine wounds, extra-uterine wounds will heal with a scar. A number of conservative and surgical methods have been developed, aiming at improving unsightly and hypertrophic scars. The authors report on their experience with intralesional injection of the enzyme hyaluronidase to improve hypertrophic scars. Hyaluronidase produces low-molecular weight fragments during digestion of high-molecular weight hyaluronic acid. These fragments are known to stimulate angiogenesis and to activate mesenchymal stem cells. The manuscript presents a clinical review of series of patients with hypertrophic scars, mainly resulted from tumor resection, who were treated by this technique.

GIANT PEDUNCULATED TUMORS OF SKIN.

The clinical appearance of a skin tumor is of major importance for clinical diagnosis of both benign and malignant neoplasias. Pedunculated growth pattern is unusual to exceptionally rare, depending on a tumor type. A necessary prerequisite for pedunculated growth is a well vascularized stem. We provide a review on large and giant pedunculated tumors of skin to serve as an additional guidance for the clinicians to avoid diagnostic errors and mistreatment. The knowledge of unusual growth pattern of cutaneous neoplasia is an essential not only in outpatient care, but also in care of hospital-admitted patients.

Magnetic-field effects on the fragile antiferromagnetism in YbBiPt.

We present neutron-diffraction data for the cubic-heavy-fermion YbBiPt that show broad magnetic diffraction peaks due to the fragile short-range antiferromagnetic (AFM) order persist under an applied magnetic-field H . Our results for H ⊥ [ 1 ¯ 1 0 ] and a temperature of T = 0.14 1 K show that 1 2 , 1 2 , 3 2 ) magnetic diffraction peak can be described by the same two-peak line shape found for µ 0 H = 0 T below the Néel temperature of T N = 0.4 K . Both components of the peak exist for µ 0 H ≲ 1.4 T , which is well past the AFM phase boundary determined from our new resistivity data. Using neutron-diffraction data taken at T = 0.13 ( 2 ) K for H ∥ 0 0 1 taken at or 1 1 0 , we show that domains of short-range AFM order change size throughout the previously determined AFM and non-Fermi liquid regions of the phase diagram, and that the appearance of a magnetic diffraction peak at 1 2 , 1 2 , 1 2 at µ 0 H ≈ 0.4 T signals canting of the ordered magnetic moment away from 1 1 1 . The continued broadness of the magnetic diffraction peaks under a magnetic field and their persistence across the AFM phase boundary established by detailed transport and thermodynamic experiments present an interesting quandary concerning the nature of YbBiPt's electronic ground state.

HYPERCALCEMIA DUE TO POLYMETHYLMETHACRYLATE INJECTIONS? (LITERATURE REVIEW AND CASE REPORTS).

Hypercalcemia is a common feature of malignancy, bone metabolic conditions and granulomatous disorders. In the latter, hypercalcemia is usually calcitriol-related. As eventual association of silicone and polymethylmethacrylate (PMMA) injections with granulomatous disease and hypercalcemia the condition has become an issue of recent interest. Authors report on two cases of calcitriol-related hypercalcemia where PMMA injections had been previously administered. The association, even though intriguing, requires additional confirmation by follow-up studies.

Using controlled disorder to probe the interplay between charge order and superconductivity in NbSe2.

The interplay between superconductivity and charge-density wave (CDW) in 2H-NbSe2 is not fully understood despite decades of study. Artificially introduced disorder can tip the delicate balance between two competing long-range orders, and reveal the underlying interactions that give rise to them. Here we introduce disorder by electron irradiation and measure in-plane resistivity, Hall resistivity, X-ray scattering, and London penetration depth. With increasing disorder, the superconducting transition temperature, Tc, varies non-monotonically, whereas the CDW transition temperature, TCDW, monotonically decreases and becomes unresolvable above a critical irradiation dose where Tc drops sharply. Our results imply that the CDW order initially competes with superconductivity, but eventually assists it. We argue that at the transition where the long-range CDW order disappears, the cooperation with superconductivity is dramatically suppressed. X-ray scattering and Hall resistivity measurements reveal that the short-range CDW survives above the transition. Superconductivity persists to much higher dose levels, consistent with fully gapped superconductivity and moderate interband pairing.

VITamin D and OmegA-3 TriaL (VITAL) bone health ancillary study: clinical factors associated with trabecular bone score in women and men.

We investigated the association of clinical variables with TBS at baseline in the bone health sub-cohort of the VITamin D and OmegA-3 TriaL (VITAL). Lower TBS was associated with female sex, aging, BMI ≥ 25 kg/m2, SSRI use, high alcohol intake, and presence of diabetes; there was a trend towards significance between lower TBS and history of fragility fractures. INTRODUCTION: We investigated whether TBS differs by sex, race, body mass index (BMI), and other clinical variables. METHODS: The VITamin D and OmegA-3 TriaL (VITAL) is determining effects of vitamin D3 and/or omega-3 fatty acid (FA) supplements in reducing risks of cancer and cardiovascular disease. In the VITAL: Effects on Bone Structure/Architecture ancillary study, effects of these interventions on bone will be investigated. Here, we examine the associations of clinical risk factors with TBS assessments at baseline in the bone health sub-cohort, comprised of 672 participants (369 men and 303 women), mean (± SD) age 63.5 ± 6.0 years; BMI ≤ 37 kg/m2, no bisphosphonates within 2 years or other bone active medications within 1 year. RESULTS: TBS was greater in men than women (1.311 vs. 1.278, P < 0.001) and lower with elevated BMIs (P < 0.001), higher age (P = 0.004), diabetes (P = 0.008), SSRI use (P = 0.044), and high alcohol intake (P = 0.009). There was a trend for history of fragility fractures (P = 0.072), and lower TBS. TBS did not vary when analyzed by race, smoking, history of falls, and multivitamin or caffeine use. CONCLUSIONS: Lower TBS was associated with female sex, aging, BMI ≥ 25 kg/m2, SSRI use, alcohol use, and presence of diabetes; there was a trend between lower TBS and history of fragility fractures. TBS may be useful clinically to assess structural changes that may be associated with fractures among patients who are overweight or obese, those on SSRIs, or with diabetes. Ongoing follow-up studies will clarify the effects of supplemental vitamin D3 and/or FA's on TBS and other bone health measures. TRIAL REGISTRATION: NCT01747447.

UNILATERAL FRONTALIS MUSCLE PARALYSIS: MANAGEMENT WITH BOTULINUM TOXIN A (CASE REPORTS).

Unilateral frontalis muscle palsy is a debilitating disease with a heterogeneous etiology. Congenital or acquired unilateral paralysis of the frontalis muscle causes ipsilateral brow ptosis and contralateral hypermobility of the non-paralytic frontalis muscle, resulting in a bizarre asymmetry and emotional embarrassment. We present five patients with unilateral frontal muscle paralysis, two males and three females, aged between 32 and 68, treated with botulinum toxin A injection to the contralateral (non-affected) side. A total dose between 10 to 30 U botulinum toxin A (onabotulinum or incobotulinum toxin A) successfully improve symmetry and facial esthetics without any adverse events. Botulinum toxin A is an alternative to facial palsy surgery but may also be used as an adjunct after the surgical procedure to optimize the outcome.

KERATOACANTHOMA OF THE UPPER LIP: REVIEW OF THE LITERATURE AND REPORT OF CASE WITH CENTRAL UPPER LIP RECONSTRUCTION.

Keratoakanthoma (KA) is a common non-melanoma skin tumor of sun-exposed skin. Recently it has been classified as a highly differentiated squamous cell carcinoma, based on the evidence of local destruction, tissue invasion and malignant transformation with metastatic spread described in the medical literature. Lower lip KA is not uncommon on lower lip, and quite rare on upper lip. The authors present a case of 78-year-old Caucasian male patient with a rapidly growing keratotic tumor of the central region of upper lip. After complete surgical excision, single-stage reconstruction of the defect was performed by modified Goldstein's bilateral advancement myocutaneous vermilion flap. The histologic examination confirmed KA with excision margins within healthy tissue. Healing was unremarkable and functional and esthetic outcomes were very good. KA of the upper lip is a rare tumor that warrants complete surgical excision. Reconstruction of the central part of the upper lip is a challenge, but bilateral advancement myocutaneous vermilion flap resulted in good outcome.