Exploring measurement tools to optimise hospital physician distribution.

INTRODUCTION: Equitable healthcare delivery is essential and requires resources to be distributed, which include assets and healthcare workers. To date, there is no gold standard for measuring the correct number of physicians to meet healthcare needs. This rapid review aims to explore measurement tools employed to optimise the distribution of hospital physicians, with a focus on ensuring fair resource allocation for equitable healthcare delivery. MATERIALS AND METHODS: A literature search was performed across PubMed, EMBASE, Emerald Insight and grey literature sources. The key terms used in the search include 'distribution', 'method', and 'physician', focusing on research articles published in English from 2002 to 2022 that described methods or tools to measure hospital-based physicians' distribution. Relevant articles were selected through a two-level screening process and critically appraised. The primary outcome is the measurement tools used to assess the distribution of hospital-based physicians. Study characteristics, tool advantages and limitations were also extracted. The extracted data were synthesised narratively. RESULTS: Out of 7,199 identified articles, 13 met the inclusion criteria. Among the selected articles, 12 were from Asia and one from Africa. The review identified eight measurement tools: Gini coefficients and Lorenz curve, Robin Hood index, Theil index, concentration index, Workload Indicator of Staffing Need method, spatial autocorrelation analysis, mixed integer linear programming model and cohortcomponent model. These tools rely on fundamental data concerning population and physician numbers to generate outputs. Additionally, five studies employed a combination of these tools to gain a comprehensive understanding of physician distribution dynamics. CONCLUSION: Measurement tools can be used to assess physician distribution according to population needs. Nevertheless, each tool has its own merits and limitations, underscoring the importance of employing a combination of tools. The choice of measuring tool should be tailored to the specific context and research objectives.

Comparing various cut-offs of aspartate aminotransferase-to-platelet ratio index (APRI) in liver cirrhosis diagnosis among hepatitis C patients in Malaysia.

INTRODUCTION: A major challenge in providing hepatitis C virus (HCV) treatment at primary healthcare clinics is the lack of radiological facilities to guide the decision making of liver cirrhosis (LC). This study aimed to compare the performance of three commonly used cut-offs of the aspartate aminotransferase-to-platelet ratio index (APRI) in diagnosing LC among hepatitis C patients in Malaysia. METHODS: This cross-sectional study was based on the data collected from the Hepatitis C Elimination through Access to Diagnostics (HEAD-Start) study in 25 primary healthcare clinics across three regions of Malaysia. The findings of biochemical tests were used to calculate the APRI for each study participant. Transient elastography was used as a standard reference for the diagnosis of cirrhosis. The area under the receiver operating curve (AUROC) was used to determine the discriminative ability of APRI in both HCV mono-infected and HCV/HIV co-infected patients. The diagnostic performance of APRI at three different cutoffs (>1.0, ≥1.5 and >2.0) were also evaluated. RESULTS: This study included 867 HCV-RNA-positive patients, 158 (16.1%) were co-infected with HIV. For the HCV mono-infected patients, the sensitivity, specificity, positive predictive value (PPV) and negative predictive values (NPV) for the cut-off of >1.0 were 61.8%, 88.7%, 73.8% and 81.9%, and for the cut-off of ≥1.5, 45.6%, 97.0%, 88.7% and 77.6%, respectively. A much lower sensitivity (29.9%) was observed for the cut-off of >2.0. The diagnostic accuracy of APRI at the cut-off of ≥1.5 in the HCV/HIV co-infected patients was relatively suboptimal. CONCLUSION: APRI, with a cut-off of ≥1.5, can more accurately predict LC among hepatitis C patients in Malaysia. However, additional physical examination and laboratory assessment are likely to be required to support the diagnosis, especially in those with HCV/HIV co-infection.

Erratum to "Fragmentation dynamics of single agglomerate-to-wall impaction" [Powder Technology 378 (2021) 561-575, DOI: 10.1016/j.powtec.2020.10.021].

[This corrects the article PMC8724865.].

Local dynamics of pharmaceutical powder fluidization using high speed long distance microscopy and particle image velocimetry.

The local dynamics of fluidized pharmaceutical carrier powders in a turbulent channel flow was studied using particle image velocimetry (PIV) and High-speed, long-distance microscopy (HS-LDM). Four different lactose powders which have been used as a drug carrier in dry powder inhalers were used in this study. These powders have median powder particle diameters ranging between 61 and 121 µm. Air flow velocities ranging between 13.3 m/s and 66.7 m/s were examined. In addition, the effect of grid blockage ratio (ranging from ~25% to ~40% of the area of channel cross-section) was also investigated. Results show that the high-speed, long-distance microscopy (HS-LDM) technique was able to capture the mean velocity of the particles, and the results corresponded well with the PIV measurements. Results from the high-speed, long-distance microscopy (HS-LDM) method also demonstrate that the span of particle velocity closely follows that of the particle size distribution both for cohesive and non-cohesive powders. This study contributes towards an improved understanding of pharmaceutical carrier dynamics in turbulent channel flows and demonstrates how advanced image processing can be used to capture local particle dynamics.

Fragmentation dynamics of single agglomerate-to-wall impaction.

The de-agglomeration characteristics of single agglomerate-wall impaction are examined using high-resolution shadowgraph imaging. Experiments are performed to investigate the effects of constituent particle size (D 50 from 3-7 µ m) and air velocity on the individual size and velocity of de-agglomerated fragments at conditions relevant to dry powder inhalation systems. De-agglomerated fragment area and trajectories were used to differentiate between pseudo-elastic and inelastic collisions during de-agglomeration. Advanced image processing techniques have enabled provision of joint population distributions of fragment area and aspect ratio, which identify a bimodal dispersion of fragments during de-agglomeration. The bimodality is destroyed with increasing air velocity and also generally diminishes with time after impact. The experiment presented forms a platform for the detailed quantitative characterisation of de-agglomeration behaviour and can be useful towards the development and validation of related computational models for pharmaceutical dry powder inhalers.

Pharmacokinetics/pharmacodynamics of antipseudomonal bacteriophage therapy in rats: a proof-of-concept study.

OBJECTIVES: Pan-drug-resistant (PDR) Pseudomonas aeruginosa is one of the three top-priority pathogens identified by the WHO, and bacteriophages have been investigated as an alternative therapy. However, knowledge on the pharmacokinetics/pharmacodynamics (PK/PD) of phage therapy is sparse, limiting its clinical applications. This study aimed to evaluate the PK/PD of the antipseudomonal phage øPEV20 in vivo following intravenous administration. METHODS: Healthy Sprague-Dawley rats were given øPEV20 as a single intravenous bolus of ~6, 9 and 11-log10PFU/rat. Arterial blood was sampled over 72 h. At 72 h, the animals were killed and multiple tissues were harvested for biodistribution studies. A PK model was developed using the importance sampling algorithm and deterministic simulations with a PD model were performed. RESULTS: A three-compartment model with non-linear clearance described the exposure of øPEV20 in blood. Model evaluation indicated that the model was robust and parameter estimates were accurate. The median (standard error) values of model-predicted PK parameters for VC, VP1, VP2, Q1, Q2, Vm and Km were 111 mL/rat (8.5%), 128 mL/rat (4.97%), 180 mL/rat (4.59%), 30.4 mL/h/rat (19.2%), 538 mL/h/rat (4.97%), 4.39 × 1010 PFU/h/rat (10.2%) and 1.64 × 107 PFU/mL/rat (3.6%), respectively. The distribution of øPEV20 was not homogeneous; there was preferential accumulation in the liver and spleen. Deterministic simulations with a PD model confirmed the importance of the host immune system in facilitating phage-mediated bacterial elimination. CONCLUSIONS: We developed a robust PK model to describe the disposition of phages in healthy rats. This model may have significant potential in facilitating future preclinical and clinical PK/PD investigations.

Effect of an upstream grid on the fluidization of pharmaceutical carrier powders.

The influence of grid generated mixing on the fluidization of pharmaceutical carrier powders is studied in a channel-flow experiment using direct high-speed imaging and particle image velocimetry (PIV). Four different lactose powders with mass median diameters that range between 61 µm and 121 µm are used. The degree of powder mixing in the flow as a function of grid position relative to the powder bed and grid area blockage ratios (ranging from ~25% to ~40%) is studied for a range of flow-rates. The study presents comprehensive mappings of how pharmaceutical powders are fluidised under the influence of mixing, by examining powder bed morphology, powder emptying rate, and the local flow-field surrounding the pocket. The use of a grid results in higher evacuation percentages (void fraction) and a faster evacuation rate but is associated with randomized evacuation behaviour as observed from the powder bed morphology. Use of a grid can enable evacuation of powder at lower overall flow-rates, which may have important implications on respiratory drug delivery. PIV results show the trend of mean velocities with the mass median powder diameter and demonstrates how a grid with lower blockage ratio can increase the degree of mixing of the evacuating powder and make the evacuation process more rapid. This study contributes towards a better understanding of fluidization processes as relevant to dry powder inhaler devices and sheds light on how simple design alterations, such as adding an upstream grid, can be incorporated to optimise device effectiveness.

Influence of bariatric surgery on weight reduction and control of chronic disease among obese patients in Malaysia.

INTRODUCTION: This study was designed to determine the influence of bariatric surgery on changes in the body mass index (BMI), and the control of diabetes, hypertension and dyslipidaemia among obese patients in Malaysia. MATERIALS AND METHODS: This was a retrospective cohort study undertaken at a public tertiary care centre in the state of Perak, Malaysia. Information of obese patients who underwent bariatric surgery was obtained from their medical records. The changes in the BMI, HbA1C, systolic and diastolic blood pressure (SBP and DBP), and lipid levels between three months before and after the surgery were assessed. RESULTS: The patients (n=106) were mostly Malay (66.0%), had at least one comorbidity (61.3%), and had a mean age of 40.38±11.75 years. Following surgery, the BMI of the patients was found to reduce by 9.78±5.82kg/m2. For the patients who had diabetes (n=24) and hypertension (n=47), their mean HbA1C, SBP and DBP were also shown to reduce significantly by 2.02±2.13%, 17.19±16.97mmHg, and 11.45±12.63mmHg, respectively. Meanwhile, the mean total cholesterol, triglyceride and low-density lipoprotein levels of those who had dyslipidaemia (n=21) were, respectively, lowered by 0.91±1.18mmol/L, 0.69±1.11mmol/L and 0.47±0.52mmol/L. CONCLUSION: The findings suggest that in addition to weight reduction, bariatric surgery is helpful in improving the diabetes, hypertension and dyslipidaemia control among obese patients. However, a large-scale trial with a control group is required to verify our findings.

Interleukin-28 Polymorphism: Ethnic variations and the response to chronic hepatitis C treatment in Malaysia.

No abstract provided.

Airway geometry, airway flow, and particle measurement methods: implications on pulmonary drug delivery.

INTRODUCTION: The effectiveness of drug delivery to the lungs is inextricably linked to the fundamental interactions that occur between particles and flow in the extrathoracic airway. Research in this field requires time resolved in-vivo and in-vitro measurements of three separate, yet intricately linked parameters: i) airway flow, ii) airway geometry, and iii) drug particle characteristics. A number of recent significant developments have been made in the experimental diagnostic tools used to characterise these parameters. AREAS COVERED: In this review paper, we summarize the key recent findings that have resulted from the implementation of laser and optical diagnostic tools towards characterization of airway flow, extrathoracic airway geometry and drug particle characteristics. These three areas are discussed together, enabling a critical review of the implications of recent experimental findings on likely future developments in drug delivery to the lungs. EXPERT OPINION: Improvements in drug delivery systems will result through implementation of laser and optical based diagnostic methods that can spatially and temporally resolve particle and agglomerate shape, size and dynamic characteristics. Design of inhaler devices must be done in parallel to developing realistic in-vitro upper airway replicas that account for physiological differences between patient groups, as a function of respiratory disease severity.

In vitro evaluation of novel inhalable dry powders consisting of thioridazine and rifapentine for rapid tuberculosis treatment.

Thioridazine is an orally administered antipsychotic drug with potential for treatment of drug-resistant tuberculosis (TB). However, drug-induced adverse cardiac effects have been reported when thioridazine was used at an efficacious oral dose of 200mg/day to treat TB. Pulmonary delivery of thioridazine could be a rational approach to reduce dose-related side effects while enabling high drug concentrations at the primary site of infection. The present study compares in vitro aerosol performance, storage stability, and in vitro antimicrobial activity and cytotoxicity of two inhalable powders composed of thioridazine and a first-line anti-TB drug, rifapentine. Formulation 1 is a combination of amorphous thioridazine and crystalline rifapentine, while Formulation 2 consisted of both drugs as amorphous forms. Both thioridazine-rifapentine formulations were found suitable for inhalation with a total fine particle fraction (<5µm) of 68-76%. The two powders had similar MIC90 to rifapentine alone, being 0.000625µg/mL and 0.005µg/ml against Mycobacterium tuberculosis H37Ra and M. tuberculosis H37Rv, respectively. In contrast, thioridazine alone had a MIC90 of 12.5µg/mL and 500µg/mL, against M. tuberculosis H37Ra and M. tuberculosis H37Rv, respectively, demonstrating no synergistic anti-TB activity. However, thioridazine and rifapentine in a ratio of 1:3 enhanced the killing of M. tuberculosis H37Ra within the human monocyte-derived macrophages (THP-1) compared to the single drug treatments. Both powders showed an acceptable half maximal inhibitory concentration (IC50) of 31.25µg/mL on both THP-1 and human lung epithelial (A549) cells. However, Formulation 1 showed greater chemical stability than Formulation 2 after three months of storage under low humidity (vacuum) at 20±3°C. In conclusion, we have demonstrated a novel inhalable powder consisted of amorphous thioridazine and crystalline rifapentine (Formulation 1) with a good aerosol performance, potent anti-TB activity and storage stability, which deserves further in vivo investigations.

In Vitro Evaluation of Inhalable Verapamil-Rifapentine Particles for Tuberculosis Therapy.

Recent studies have demonstrated that efflux pumps of Mycobacterium tuberculosis (M. tb) provide a crucial mechanism in the development of drug resistant to antimycobacterial drugs. Drugs that inhibit these efflux pumps, such as verapamil, have shown the potential in enhancing the treatment success. We therefore hypothesized that the combined inhaled administration of verapamil and a first-line rifamycin antibiotic will further improve the treatment efficacy. An inhalable dry powder consisting of amorphous verapamil and crystalline rifapentine with l-leucine as an excipient was produced by spray drying. The in vitro aerosol characteristic of the powder, its microbiological activity and stability were assessed. When the powder was dispersed by an Osmohaler, the total fine particle fraction (FPFtotal, wt % of particles in aerosol <5 µm) of verapamil and rifapentine was 77.4 ± 1.1% and 71.5 ± 2.0%, respectively. The combination drug formulation showed a minimum inhibitory concentration (MIC90) similar to that of rifapentine alone when tested against both M. tb H37Ra and M. tb H37Rv strains. Importantly, the combination resulted in increased killing of M. tb H37Ra within the infected macrophage cells compared to either verapamil or rifapentine alone. In assessing cellular toxicity, the combination exhibited an acceptable half maximal inhibitory concentration (IC50) values (62.5 µg/mL) on both human monocytic (THP-1) and lung alveolar basal epithelial (A549) cell lines. Finally, the powder was stable after 3 months storage in 0% relative humidity at 20 ± 3 °C.

Using pictograms to assist caregivers in liquid medication administration: a systematic review.

WHAT IS KNOWN AND OBJECTIVE: It has been reported that more than 80% of out-of-hospital medication errors among the young children involve liquid formulations. The usefulness of pictorial aids to improve communication of medication instructions has not been extensively investigated for child health. The objective of this study was to determine the effectiveness of pictorial aids used to assist caregivers in the administration of liquid medications. METHODS: MEDLINE, CINAHL, PsycINFO, ScienceDirect, Scopus and the Cochrane Library were searched for articles published up to February 2015. Studies that used pictorial aids with liquid medications and measured at least one of the following outcomes were included: dosing accuracy, comprehension of medication instructions, recall of information and adherence of caregivers. Two authors independently selected studies, extracted data and assessed methodological quality of studies using the Cochrane Collaboration's tool. RESULTS AND DISCUSSION: Five experimental studies (four hospital based and one community based) with a total of 962 participants were included. A wide range of liquid formulations were studied, including both prescription and over-the-counter medications. The existing findings suggest that pictographic interventions reduced dosing errors, enhanced comprehension and recall of medication instructions and improved adherence of caregivers. Incorporating pictorial aids into verbal medication counselling or text-based instructions was more beneficial than using the single approach alone. Mixed results were identified for the relationship between health literacy of caregivers and effectiveness of pictorial aids. WHAT IS NEW AND CONCLUSION: The evidence remains limited due to the small number of studies found and variations in methodological quality. This review suggests that pictorial aids might be potential interventions, but more high-quality studies are needed to support the routine use of any pictogram-based materials with liquid medications in the clinical settings.

Dense packings of spheres in cylinders: simulations.

We study the optimal packing of hard spheres in an infinitely long cylinder, using simulated annealing, and compare our results with the analogous problem of packing disks on the unrolled surface of a cylinder. The densest structures are described and tabulated in detail up to D/d=2.873 (ratio of cylinder and sphere diameters). This extends previous computations into the range of structures which include internal spheres that are not in contact with the cylinder.

A critical view on lactose-based drug formulation and device studies for dry powder inhalation: which are relevant and what interactions to expect?

Many years of research have not led to a profound knowledge of the mechanisms involved in the formulation and dispersion of carrier based mixtures for inhalation. Although it is well understood that the mixing is a key process in DPI carrier based formulation, there remains a limited understanding of how blending processes affect in-process material properties and the resulting distribution of the drug in the final dosage form. A great number of variables are considered relevant to the interfacial forces in adhesive mixtures, but their effects have mostly been investigated individually, without taking account of the influence they may have on each other. Interactions may be expected and without proper choices made and definitions given for all the variables involved, conclusions from studies on adhesive mixtures are of less relevance. By varying any of the variables that are not subject of the study, an opposite effect may be obtained. Currently, there is a strong focus on exploring techniques for the characterisation of drug and carrier surface properties that are believed to have an influence on the interparticulate forces in adhesive mixtures. For a number of surface properties it may be questioned whether they are really the key parameters to investigate however. Their orders of magnitude are subordinate to the effects they are supposed to have on the drug-to-carrier forces. Therefore, they seem rather indicators of other variability and their influence may be dominated by other effects. Finally, the relevance of inhaler design is often ignored. By using powerful inhalers, the effect of many variables of current concern may become less relevant. Carrier properties that are considered disadvantageous at present may even become desirable when a more appropriate type of dispersion force is applied. This can be shown for the effect of carrier surface rugosity when inertial separation forces are applied instead of the more widely applied lift and drag forces. Therefore, inhaler design should be taken into consideration when evaluating studies on adhesive mixtures. It should also become an integral part of powder formulation for inhalation.

Phyllotactic description of hard sphere packing in cylindrical channels.

We develop a simple analytical theory that relates dense sphere packings in a cylinder to corresponding disk packings on its surface. It applies for ratios R=D/d (where d and D are the diameters of the hard spheres and the bounding cylinder, respectively) up to R=1+1/sin(π/5). Within this range the densest packings are such that all spheres are in contact with the cylindrical boundary. The detailed results elucidate extensive numerical simulations by ourselves and others by identifying the nature of various competing phases.

Muscle coordination is key to the power output and mechanical efficiency of limb movements.

The purpose of this study was to determine which features of muscle mechanics and muscle coordination affect the power output from a limb during locomotion. Eight subjects were tested while cycling at maximum exertion for 25 min on a stationary dynamometer. Cadence and load were varied to span a range of power outputs and myoelectric activity was measured from 10 muscles in the leg. Cycle-by-cycle variations in muscle coordination, cadence and power output were observed and the EMG intensity across all muscles was used as an estimate of the metabolic cost for each cycle. Data for the cycles at greatest power output were separated into three groups: maximum power, 80% power but lower EMG intensity and 80% power and higher EMG intensity. Torque-angular velocity relations were determined for the ankle and knee joints. During cycling at maximum power output the ankle joint was not extending at the velocity necessary for maximum power output; thus, maximum limb power occurs when some of the individual muscles cannot be generating maximum power output. Increases in EMG intensity occurred with no increase in power output from the limb: these corresponded to decreases in the efficiency and changes in coordination. Increases in power were achieved that were not matched by equivalent increases in EMG intensity, but did occur with changes in coordination. It is proposed that the power output from the limb is limited by the coordination pattern of the muscles rather than the maximum power output from any one muscle itself.

Characterisation and aerosolisation of mannitol particles produced via confined liquid impinging jets.

Mannitol particles, produced by spray drying (SD), have been used commercially (Aridol) in bronchial provocation test. In this study, we propose an alternative method to produce inhalable mannitol powders. The elongated mannitol particles (number median length 4.0microm, and axial ratio of 3.5) were prepared using a confined liquid impinging jets (CLIJs) followed by jet milling (JM). Spray dried and jet milled raw mannitol particles were compared in an attempt to assess the performance of the particles produced by the new method. Aerosol performance of the three different powders (CLIJ, SD, and JM) was relatively poor (fine particle fraction or FPF(loaded) below 15%) when dispersed by the Rotahaler. Dispersion through the Aeroliser led to better aerosol performance of the CLIJ mannitol (FPF(loaded) 20.3%), which is worse than the JM (FPF(loaded) 30.3%) and SD mannitol particles (FPF(loaded) 45.7%) at 60 L/min, but comparable (FPF(loaded) 40.0%) with those of the JM (FPF(loaded) 40.7%) and SD (FPF(loaded) 45.5%) powders at 100L/min. Hence, the optimum use of these elongated mannitol particles can be achieved at increased air flow with a more efficient inhaler. In addition to crystallinity, morphology, and particle size distribution, the surface energies of these powders were measured to explain the differences in aerosol performance. A major advantage of using the CLIJ method is that it can be scaled up with a good yield as the precipitate can be largely collected and recovered on a filter, compared with spray drying which has a low collection efficiency for fine particles below 2microm.