Could it have been predicted? A retrospective analysis of the last year of life for people who died whilst in an intermediate care centre.

Objectives: Intermediate care centres (ICCs) exist in the UK to bridge between acute hospital and home for those with rehabilitation needs. A national study shows 25% of ICC in-patients died within a year of admission. High quality end-of-life care includes early conversations with a person and their loved ones about what matters to them; timely identification of those who are likely to be nearing the end of their life is key. Methods: This retrospective quantitative review of 98 patient notes reviewed deaths in one NHS trust, comparing 50 deaths in the acute hospital and 48 in the ICC. Data included frailty score, previous hospital admissions, specialist palliative input and conversations between professionals, patients and their loved ones. Supportive and Palliative Care Indicators Tool (SPICT) scores were used to identify those likely to have a poor prognosis. Results: Results showed statistically significant differences between the groups. The ICC cohort were older with higher clinical frailty scores. They were less likely to have previous hospital admissions but more likely to have poor prognostic features on final admission. Despite this, the possibility of deterioration was discussed them less frequently than the acute hospital cohort, and fewer saw the Palliative care team. Conclusion: This data suggests support is needed in ICCs to recognise those likely to be nearing end-of-life. One challenge is patients are more likely to be seen as 'well' in a rehabilitation focused environment. This paper suggests a 'proactive approach' trial using SPICT for ongoing assessment of ICC in-patients supporting identification of a deteriorating person and avoid missed opportunities for key conversations.

The aetiology of fracture and nonunion in the hook of the hamate.

Fractures of the hook of the hamate are traditionally thought to be caused by direct trauma. A review of the anatomy and function of the hamate hook suggests that fracture is more likely as a result of a fatigue response that develops in the hook from repetitive load applied by the adjacent deep flexor tendons. Additional vascular compromise, from direct pressure of the tendons on critical local vessels, reduces blood flow leading to both mechanical and vascular effects that create pathological osseous change and weakening. These changes are likely to predispose to stress fracture and nonunion in repetitive gripping activities and are consistent with radiological findings.

Systematic review and QSPR analysis of chemical penetration through the nail to inform onychomycosis candidate selection.

Recalcitrant nail plate infections can be life-long problems because localizing antifungal agents into infected tissues is problematic. In this systematic review, guided by the SPIDER method, we extracted chemical nail permeation data for 38 compounds from 16 articles, and analyzed the data using quantitative structure-property relationships (QSPRs). Our analysis demonstrated that low-molecular weight was essential for effective nail penetration, with <120 g/mol being preferred. Interestingly, chemical polarity had little effect on nail penetration; therefore, small polar molecules, which effectively penetrate the nail, but not the skin, should be set as the most desirable target chemical property in new post-screen onychomycosis candidate selections.

Revision of Failed Nonanatomic Extensor Retinacular Stabilization of the Unstable ECU Tendon: Surgical Technique and Case Series.

Nonanatomic surgical stabilization of the unstable extensor carpi ulnaris (ECU) tendon (where the subluxing tendon is re-routed away from the bony groove in the distal ulna) utilizes a flap of extensor retinaculum to create a new retaining sheath that will stabilize the tendon during forearm rotation movements. When this surgery fails, the extensor retinaculum tissue does not regenerate with sufficient structural strength to be used again. Previously, a different approach has then been needed for revision surgery, often using more complex surgical techniques with a substantially greater impact on recovery. We describe a highly reliable yet simple method of using local soft tissue to adequately restabilize the subluxing ECU tendon in cases where an extensor retinacular flap has already been used. We report the results of this technique in 4 patients, all of whom returned to jobs/hobbies where ECU instability was a considerable functional risk.

Laser-cutting: A novel alternative approach for point-of-care manufacturing of bespoke tablets.

A novel subtractive manufacturing method to produce bespoke tablets with immediate and extended drug release is presented. This is the first report on applying fusion laser cutting to produce bespoke furosemide solid dosage forms based on pharmaceutical-grade polymeric carriers. Cylindric tablets of different sizes were produced by controlling the two-dimensional design of circles of the corresponding diameter. Immediate and extended drug release patterns were achieved by modifying the composition of the polymeric matrix. Thermal analysis and XRD indicated that furosemide was present in an amorphous form. The laser-cut tablets demonstrated no significant drug degradation (<2%) nor the formation of impurities were identified. Multi-linear regression was used to quantify the influences of laser-cutting process parameters (laser energy levels, scan speeds, and the number of laser applications) on the depth of the laser cut. The utility of this approach was exemplified by manufacturing tablets of accurate doses of furosemide. Unlike additive or formative manufacturing, the reported approach of subtractive manufacturing avoids the modification of the structure, e.g., the physical form of the drug or matrix density of the tablet during the production process. Hence, fusion laser cutting is less likely to modify critical quality attributes such as release patterns or drug contents. In a point-of-care manufacturing scenario, laser cutting offers a significant advantage of simplifying quality control and a real-time release of laser-cut products such as solid dosage forms and implants.

Identification of traits underpinning good breadmaking performance of wheat grown with reduced nitrogen fertilisation.

BACKGROUND: Nitrogen fertiliser is the major input and cost for wheat production, being required to support the development of the canopy to maximise yield and for the synthesis of the gluten proteins that are necessary for breadmaking. Consequently, current high-yielding cultivars require the use of nitrogen fertilisation levels above the yield optimum to achieve the grain protein content needed for breadmaking. This study aimed to reduce this requirement by identifying traits that allow the use of lower levels of nitrogen fertiliser to produce wheat for breadmaking. RESULTS: A range of commercial wheat genotypes (cultivars) were grown in multiple field trials (six sites over 3 years) in the UK with optimal (200 kg Ha-1 ) and suboptimal (150 kg Ha-1 ) application of nitrogen. Bulked grain samples from four sites per year were milled and white flours were baked using three types of breadmaking process. This identified five cultivars that consistently exhibited good breadmaking quality when grown with the lower nitrogen application. Chemical and biochemical analyses showed that the five cultivars were characterised by exhibiting grain protein deviation (GPD) and high dough elasticity. CONCLUSIONS: It is possible to develop novel types of wheat that exhibit good breadmaking quality by selecting for GPD and high dough strength. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

In-Silico Modelling of Transdermal Delivery of Macromolecule Drugs Assisted by a Skin Stretching Hypobaric Device.

OBJECTIVES: To develop a simulation model to explore the interplay between mechanical stretch and diffusion of large molecules into the skin under locally applied hypobaric pressure, a novel penetration enhancement method. METHODS: Finite element method was used to model the skin mechanical deformation and molecular diffusion processes, with validation against in-vitro transdermal permeation experiments. Simulations and experimental data were used together to investigate the transdermal permeation of large molecules under local hypobaric pressure. RESULTS: Mechanical simulations resulted in skin stretching and thinning (20%-26% hair follicle diameter increase, and 21%-27% skin thickness reduction). Concentration of dextrans in the stratum corneum was below detection limit with and without hypobaric pressure. Concentrations in viable epidermis and dermis were not affected by hypobaric pressure (approximately 2 µg [Formula: see text] cm-2). Permeation into the receptor fluid was substantially enhanced from below the detection limit at atmospheric pressure to up to 6 µg [Formula: see text] cm-2 under hypobaric pressure. The in-silico simulations compared satisfactorily with the experimental results at atmospheric conditions. Under hypobaric pressure, satisfactory comparison was attained when the diffusion coefficients of dextrans in the skin layers were increased from [Formula: see text] 10 µm2 [Formula: see text] s-1 to between 200-500 µm2 [Formula: see text] s-1. CONCLUSIONS: Application of hypobaric pressure induces skin mechanical stretching and enlarges the hair follicle. This enlargement alone cannot satisfactorily explain the increased transdermal permeation into the receptor fluid under hypobaric pressure. The results from the in-silico simulations suggest that the application of hypobaric pressure increases diffusion in the skin, which leads to improved overall transdermal permeation.

Lung Cancer in Young Adults: A Single-Center Experience.

OBJECTIVE: This single-center retrospective review examines the unique characteristics of young patients (ages 18 to 40 years) who were diagnosed as having non-small-cell lung cancer (NSCLC) at Markey Cancer Center, the only National Cancer Institute-designated cancer center in the state of Kentucky. METHODS: This retrospective study examines adult patients with NSCLC who were between ages 18 and 40 at diagnosis. Patients diagnosed between 2012 and 2018 were included. The final cohort consisted of 35 patients. The data collected included patient demographic information, tumor topography, clinical stage, cell type, treatment information/dates, metastasis, and survival data. RESULTS: In total, 36 of 3246 total NSCLC cases treated at Markey Cancer Center from 2012 to 2018 were diagnosed in adults aged 18 to 40 (1.11%); 35 of these 36 patients were included in our cohort. The majority (22; 62.86%) presented at an advanced stage of disease (stage III or IV). Furthermore, our cohort consisted of a strong majority of female patients (24; 68.57%). The most common histological type was adenocarcinoma (14; 40.00%). The 5-year survival rate was 47% (standard error 9%). CONCLUSIONS: Lung cancer is rare in young patients; when present, often it presents at the advanced stage. Despite many diagnostic tools and treatment modalities available, long-term survival remains poor. Our experience showed a small proportion of patients with NSCLC aged 18 to 40 at diagnosis; among this unique patient population, there is a predominance of smokers, women, adenocarcinoma, and advanced disease.

Needleless administration of advanced therapies into the skin via the appendages using a hypobaric patch.

Advanced therapies are commonly administered via injection even when they act within the skin tissue, and this increases the chances of off-target effects. Here we report the use of a skin patch containing a hypobaric chamber that induces skin dome formation to enable needleless delivery of advanced therapies directly into porcine, rat, and mouse skin. Finite element method modeling showed that the hypobaric chamber in the patch opened the skin appendages by 32%, thinned the skin, and compressed the appendage wall epithelia. These changes allowed direct delivery of an H1N1 vaccine antigen and a diclofenac nanotherapeutic into the skin. Fluorescence imaging and infrared mapping of the skin showed needleless delivery via the appendages. The in vivo utility of the patch was demonstrated by a superior immunoglobulin G response to the vaccine antigen in mice compared to intramuscular injection and a 70% reduction in rat paw swelling in vivo over 5 h with diclofenac without skin histology changes.

Tiotropium treatment for bronchiectasis: a randomised, placebo-controlled, crossover trial.

BACKGROUND: Tiotropium via the HandiHaler device is an established long-acting, anticholinergic bronchodilator that prevents exacerbations and improves lung function in patients with chronic obstructive pulmonary disease. We hypothesised that tiotropium would reduce pulmonary exacerbations and improve lung function in patients with stable bronchiectasis and airflow limitation, and assessed the effect of tiotropium on these outcomes. METHODS: In a randomised, double-blind, two-period crossover trial, we recruited adult patients from three hospitals in New Zealand. Patients were excluded if they had a smoking history of >20 pack-years. Patients were assigned to either the tiotropium-placebo or placebo-tiotropium sequence in a 1:1 ratio, using randomly permuted blocks stratified by centre. Participants and investigators were masked to treatment allocation. Eligible patients received tiotropium 18 µg via HandiHaler daily for 6 months followed by 6 months of placebo, or vice versa, with a washout period of 4 weeks. The primary end-point was rate of event-based exacerbations during the 6-month period. Primary analyses were carried out in an intention-to-treat set. RESULTS: 90 patients were randomly assigned and 85 completed both treatment cycles. The rate of exacerbations was 2.17 per year under the tiotropium treatment and 2.27 per year under placebo (rate ratio 0.96, 95% CI 0.72-1.27; p=0.77). Tiotropium, compared with placebo, improved forced expiratory volume in 1 s by 58 mL (95% CI 23-92 mL; p=0.002). Adverse events were similar under both treatments. CONCLUSIONS: Tiotropium via HandiHaler over 6 months significantly improved lung function but not frequency of exacerbations. Further research is required to understand the clinical context and significance of these findings.

Sputum procalcitonin: a potential biomarker in stable bronchiectasis.

Sputum procalcitonin is elevated in exacerbations of bronchiectasis. The primary aim of this study was to investigate whether sputum procalcitonin levels are higher in patients with stable bronchiectasis than in healthy controls. We also assessed differences in procalcitonin levels in spontaneously expectorated and induced sputum samples and their repeatability 1 week later. Participants included were aged over 18 years and either had radiologically confirmed bronchiectasis or were healthy controls. Patients with bronchiectasis were clinically stable for at least 6 weeks and had spontaneous and induced sputum collected at visit 1 and again 7 days later. Only induced sputum samples were collected from healthy controls during visit 1. Sputum procalcitonin concentrations in sputum were measured. In total, 30 patients with bronchiectasis and 15 healthy controls were enrolled in this observational study. In the pooled data from visit 1 and 2, the geometric mean procalcitonin level in induced sputum was significantly higher in the bronchiectasis group than in the healthy control group (1.5 ng·mL-1, 95% CI 1.0-2.1 ng·mL-1 versus 0.4 ng·mL-1, 95% CI 0.2-0.9 ng·mL-1; mean ratio 3.6, 95% CI 1.5-8.6; p=0.006). Mean procalcitonin level was higher in spontaneous sputum than in induced sputum at visit 1 (1.8 ng·mL-1, 95% CI 1.2-2.7 ng·mL-1 versus 1.1 ng·mL-1, 95% CI 0.7-1.8 ng·mL-1) and visit 2 (1.5 ng·mL-1, 95% CI 1.0-2.5 ng·mL-1 versus 1.2 ng·mL-1, 95% CI 0.8-1.6 ng·mL-1; p=0.001). Repeating spontaneous and induced sputum procalcitonin levels 1 week later produced similar concentrations (p=0.29, intraclass correlation coefficient (ICC)=0.76 and p=0.72, ICC=0.70, respectively). Sputum procalcitonin is increased in patients with stable bronchiectasis and has potential as a biomarker of airway inflammation and infection in bronchiectasis.

Microbial population dynamics and evolutionary outcomes under extreme energy limitation.

Microorganisms commonly inhabit energy-limited ecosystems where cellular maintenance and reproduction is highly constrained. To gain insight into how individuals persist under such conditions, we derived demographic parameters from a collection of 21 heterotrophic bacterial taxa by censusing 100 populations in an effectively closed system for 1,000 d. All but one taxon survived prolonged resource scarcity, yielding estimated times to extinction ranging over four orders of magnitude from 100 to 105 y. Our findings corroborate reports of long-lived bacteria recovered from ancient environmental samples, while providing insight into mechanisms of persistence. As death rates declined over time, lifespan was extended through the scavenging of dead cells. Although reproduction was suppressed in the absence of exogenous resources, populations continued to evolve. Hundreds of mutations were acquired, contributing to genome-wide signatures of purifying selection as well as molecular signals of adaptation. Consistent ecological and evolutionary dynamics indicate that distantly related bacteria respond to energy limitation in a similar and predictable manner, which likely contributes to the stability and robustness of microbial life.

Investigating how amine structure influences drug-amine ion-pair formation and uptake via the polyamine transporter in A549 lung cells.

Transiently associating amines with therapeutic agents through the formation of ion-pairs has been established both in vitro and in vivo as an effective means to systemically direct drug delivery to the lung via the polyamine transport system (PTS). However, there remains a need to better understand the structural traits required for effective PTS uptake of drug ion-pairs. This study aimed to use a structurally related series of amine counterions to investigate how they influenced the stability of theophylline ion-pairs and their active uptake in A549 cells. Using ethylamine (mono-amine), ethylenediamine (di-amine), spermidine (tri-amine) and spermine (tetra-amine) as counterions the ion-pair affinity was shown to increase as the number of protonated amine groups in the counterion structure increased. The mono and diamines generated a single hydrogen bond and the weakest ion-pair affinities (pKFTIR: 1.32 ± 0.04 and 1.43 ± 0.02) whereas the polyamines produced two hydrogen bonds and thus the strongest ion-pair affinities (pKFTIR: 1.93 ± 0.05 and 1.96 ± 0.04). In A549 cells depleted of endogenous polyamines using α-difluoromethylornithine (DFMO), the spermine-theophylline uptake was significantly increased (p < 0.05) compared to non-amine depleted cells and this evidenced the active PTS sequestering of the ion-pair. The mono-amine and di-amine failed to enhance theophylline uptake in these A549 cells, but the tri-amine and tetra-amine both almost doubled the theophylline uptake into the cells when compared to the uptake of free drug. As the data indicated that polyamines with at least 3 amines were required to form ion-pairs that could enhance A549 cell uptake, it suggested that at least two amines were required to physically stabilise the ion-pair and one to interact with the PTS.

The concept and use of the neoadjuvant rectal score as a composite endpoint in rectal cancer.

There is no universally accepted instrument to use as a validated surrogate endpoint for overall survival in phase 2 and phase 3 multimodal rectal cancer trials using chemoradiotherapy. Efforts are hampered by the inaccuracy of clinical TNM staging, the variability of indications for neoadjuvant treatment, and diverse definitions of tumour regression grade. Pathological complete response is commonly used, but fails to capture information from the majority of patients. The neoadjuvant rectal score categorises response and downstaging from the entire trial population to identify whether or not a novel treatment group in a chemoradiation trial is superior by predicting overall survival outcomes. Additionally, the neoadjuvant rectal score assesses the difference between initial clinical and pathological T stage and the presence or absence of nodal involvement after treatment. The neoadjuvant rectal score has been conceptually, but incompletely, statistically validated by two independent trial datasets. However, a fundamental weakness of the score is that no preoperative phase 3 trials in locally advanced rectal cancer in the past 20 years have provided a significant benefit in overall survival to statistically validate the neoadjuvant rectal score as a surrogate endpoint for overall survival. We review the robustness, practical value, applicability, generalisability, advantages, and disadvantages of the neoadjuvant rectal score as a surrogate endpoint for overall survival and recommend how this score could be improved and be acceptable as a standard endpoint in studies investigating neoadjuvant chemotherapy and chemoradiation in patients with rectal cancer.

Numerical analysis of the strain distribution in skin domes formed upon the application of hypobaric pressure.

BACKGROUND: Suction cups are widely used in applications such as in measurement of mechanical properties of skin in vivo, in drug delivery devices or in acupuncture treatment. Understanding mechanical response of skin under hypobaric pressure is of great importance for users of suction cups. The aim of this work is to predict the hypobaric pressure induced 3D stretching of the skin. METHODS: Experimental skin tensile tests were carried out for mechanical property characterization. Both linear elasticity and hyperelasticity parameters were determined and implemented in Finite Element modelling. Skin suction tests were performed in both experiments and FEM simulations for model validation. 3D skin stretching is then visualized in detail in FEM simulations. RESULTS: The simulations showed that the skin was compressed consistently along the thickness direction, leading to reduced thickness. At the center of the dome, the radial and angular strain decreases from the top surface to the bottom surface, although always in tension. Hyperelasticity modelling showed superiority over linear elasticity modelling while predicting the strain distribution because the stretch ratio reaches values exceeding the initial linear elastic stage of the stress-strain curve for skin. CONCLUSION: Hyperelasticity modelling is an effective approach to predict the 3D strain distribution, which paves a way to accurately design safe commercial products that interface with the skin.

New Zealand COPD Guidelines: Quick Reference Guide.

The purpose of the Asthma and Respiratory Foundation of New Zealand's COPD Guidelines: Quick Reference Guide is to provide simple, practical, evidence-based recommendations for the diagnosis, assessment, and management of chronic obstructive pulmonary disease (COPD) in clinical practice. The intended users are health professionals responsible for delivering acute and chronic COPD care in community and hospital settings, and those responsible for the training of such health professionals.

Revascularization of intermittent claudicants leads to more chronic limb-threatening ischemia and higher amputation rates.

BACKGROUND: There is an increasing incidence of peripheral arterial disease (PAD). The most common symptomatic presentation of PAD is intermittent claudication (IC), reproducible leg pain with ambulation. The progression of symptoms beyond IC is rare, and a nonprocedural approach of smoking cessation, supervised exercise therapy, and best medical therapy can mitigate progression of IC. Despite the lack of limb- or life-threatening sequelae of IC, invasive treatment strategies of IC have experienced rapid growth. Within our health care system, PAD is treated by multiple disciplines with varying practice patterns, providing an opportunity to investigate the progression of IC based on treatment strategy. This study aims to compare PAD progression and amputation in patients with IC with and without revascularization. METHODS: This institutional review board-approved, single institute retrospective study reviewed all patients with an initial diagnosis of IC between June 11, 2003, and April 24, 2019. Revascularization was defined as endovascular or open. Time to chronic limb-threatening ischemia (CLTI) diagnosis and amputation were stratified by revascularization status using the Kaplan-Meier method. The association between revascularization status and each of CLTI progression and amputation using multivariable Cox regression, adjusting for demographic and clinical potential confounding variables was assessed. RESULTS: We identified 1051 patients who met the inclusion criteria. Of these patients, 328 had at least one revascularization procedure and 723 did not. The revascularized group was younger than the nonrevascularized group (60.3 years vs 62.1 years; P = .013). There was no significant difference in sex or comorbidities in the two groups other than a higher rate of diabetes mellitus type 2 (32.3% vs 16.3%; P < .001) and COPD (4.3% vs 1.7%; P = .017) in the revascularized group. Multivariable Cox regression found revascularization of patients with IC to be significantly associated with the progression to CLTI (hazard ratio, 2.9; 95% confidence interval, 2.0-4.2) and amputation (hazard ratio, 4.5; 95% confidence interval, 2.2-9.5). These findings were also demonstrated in propensity-matched cohorts of 218 revascularized and 340 nonrevascularized patients. CONCLUSIONS: Revascularization of patients with IC is associated with an increased rate of progression to CLTI and increased amputation rates. Given these findings, further studies are required to identify which, if any, patients with IC benefit from revascularization procedures.

Nanomaterials fusing with the skin: Alpha-tocopherol phosphate delivery into the viable epidermis to protect against ultraviolet radiation damage.

Vitamin E (alpha tocopherol, α-T) is an important skin antioxidant, but its penetration into the viable epidermis, where it acts, is very limited. This study investigated if phosphorylating α-tocopherol (α-TP) to form a provitamin, improved its interactions with skin, its passage into the tissue, and thus its ability to protect the skin from ultraviolet radiation (UVR) damage. At pH 7.4, when the α-TPO4-1 microspecies predominated in solution, dynamic light scattering measurements showed that α-TP formed nanoaggregates with a median hydrodynamic diameter of 9 nm (Critical aggregation constant, CAC, - 4.2 mM). At 9.0 when the α-TPO4-2 microspecies predominated there was no aggregation. The passage of α-TP nanoaggregates through regenerated cellulose membranes was significantly slower than the α-TP monomers (at pH 9) suggesting that aggregation slowed diffusion. However, a lotion formulation containing the nanoaggregates delivered more α-TP into the skin compared to the formulation containing the monomers. In addition, the nanosized α-TP aggregates delivered 8-fold more active into the stratum corneum (SC) (252.2 µg/cm2 vs 29.5 µg/cm2) and 4 fold more active into the epidermis (85.1 µg/cm2 vs 19 µg/cm2, respectively, p < 0.05) compared to α-T. Langmuir subphase injection studies at pH 7.4 (surface pressure 10 mN m-1) showed that the α-TP nanoaggregates more readily fused with the SC compared to the monomers and the membrane compression studies demonstrated that α-TP fluidised the SC lipids. Together the fusion with the SC and its fluidisation were proposed as the causes of the better α-TP penetration into the skin, which enhanced potential of α-TP to protect from UVR-induced skin damage compared to α-T.

Quality and use of unlicensed vitamin D preparations in primary care in England: Retrospective review of national prescription data and laboratory analysis.

AIM: To evaluate the type (licensed vs unlicensed) and cost of preparations used to fulfil vitamin D prescriptions in England over time, and to compare measured vitamin D content of selected vitamin D preparations against labelled claim. METHODS: Retrospective analysis of vitamin D prescription data in primary care in England (2008-2018). Laboratory analysis of 13 selected vitamin D preparations. RESULTS: Alongside a rise in the number of oral licensed colecalciferol preparations from 0 to 27 between 2012 and 2018, the proportion of vitamin D prescriptions in which licensed vitamin D preparations were supplied increased from 11.8 to 54.2%. However, the use of unlicensed food supplements (dose strength 400-50 000 IU) remained high, accounting for 39.7% of vitamin D prescriptions in 2018. The two licensed preparations showed mean (±SD) vitamin D content of 90.9 ± 0.7% and 90.5 ± 3.9% of the labelled claimed amount, meeting the British Pharmacopeia specification for licensed medicines (90-125% of labelled claim). The 11 food supplements showed vitamin D content ranging from 41.2 ± 10.6% to 165.3 ± 17.8% of the labelled claim, with eight of the preparations failing to comply with the food supplement specification (80-150% of labelled claim). CONCLUSIONS: Despite the increasing availability of quality assured licensed preparations, food supplements continued to be used interchangeably with licensed preparations to fulfil vitamin D prescriptions. Food supplements, manufactured under less stringent quality standards, showed wide variations between measured and declared vitamin D content, which could lead to the risk of under- and over-dosing.