Comorbidity clusters in patients with rheumatoid arthritis identify a patient phenotype with a favourable prognosis.

OBJECTIVES: We aimed to cluster patients with rheumatoid arthritis (RA) based on comorbidities and then examine the association between these clusters and RA disease activity and mortality. METHODS: In this population-based study, residents of an eight-county region with prevalent RA on 1 January 2015 were identified. Patients were followed for vital status until death, last contact or 31 December 2021. Diagnostic codes for 5 years before the prevalence date were used to define 55 comorbidities. Latent class analysis was used to cluster patients based on comorbidity patterns. Standardised mortality ratios were used to assess mortality. RESULTS: A total of 1643 patients with prevalent RA (72% female; 94% white; median age 64 years, median RA duration 7 years) were studied. Four clusters were identified. Cluster 1 (n=686) included patients with few comorbidities, and cluster 4 (n=134) included older patients with 10 or more comorbidities. Cluster 2 (n=200) included patients with five or more comorbidities and high prevalences of depression and obesity, while cluster 3 (n=623) included the remainder. RA disease activity and survival differed across the clusters, with cluster 1 demonstrating more remission and mortality comparable to the general population. CONCLUSIONS: More than 40% of patients with prevalent RA did not experience worse mortality than their peers without RA. The cluster with the worst prognosis (<10% of patients with prevalent RA) was older, had more comorbidities and had less disease-modifying antirheumatic drug and biological use compared with the other clusters. Comorbidity patterns may hold the key to moving beyond a one-size-fits-all perspective of RA prognosis.

A Brownian quasi-crystal of pre-assembled colloidal Penrose tiles.

Penrose's pentagonal P2 quasi-crystal1-4 is a beautiful, hierarchically organized multiscale structure in which kite- and dart-shaped tiles are arranged into local motifs, such as pentagonal stars, which are in turn arranged into various close-packed superstructural patterns that become increasingly complex at larger length scales. Although certain types of quasi-periodic structure have been observed in hard and soft matter, such structures are difficult to engineer, especially over large areas, because generating the necessary, highly specific interactions between constituent building blocks is challenging. Previously reported soft-matter quasi-crystals of dendrimers5, triblock copolymers6, nanoparticles7 and polymeric micelles8 have been limited to 12- or 18-fold symmetries. Because routes for self-assembling complex colloidal building blocks9-11 into low-defect dynamic superstructures remain limited12, alternative methods, such as using optical and directed assembly, are being explored13,14. Holographic laser tweezers15 and optical standing waves16 have been used to hold microspheres in local quasi-crystalline arrangements, and magnetic microspheres of two different sizes have been assembled into local five-fold-symmetric quasi-crystalline arrangements in two dimensions17. But a Penrose quasi-crystal of mobile colloidal tiles has hitherto not been fabricated over large areas. Here we report such a quasi-crystal in two dimensions, created using a highly parallelizable method of lithographic printing and subsequent release of pre-assembled kite- and dart-shaped tiles into a solution-dispersion containing a depletion agent. After release, the positions and orientations of the tiles within the quasi-crystal can fluctuate, and these tiles undergo random, Brownian motion in the monolayer owing to frequent collisions between neighbouring tiles, even after the system reaches equilibrium. Using optical microscopy, we study both the equilibrium fluctuations of the system at high tile densities and also the 'melting' of the pattern as the tile density is lowered. At high tile densities we find signatures of a five-fold pentatic liquid quasi-crystalline phase, analogous to a six-fold hexatic liquid crystal. Our fabrication approach is applicable to tiles of different sizes and shapes, and with different initial positions and orientations, enabling the creation of two-dimensional quasi-crystalline systems (and other systems that possess multiscale complexity at high tile densities) beyond those of current self- or directed-assembly methods18-20. We anticipate that our approach for generating lithographically pre-assembled monolayers could be extended to create three-dimensional Brownian systems of fluctuating particles with custom-designed shapes through holographic lithography21,22 or stereolithography23.

Low Recurrence of Instability and Satisfying Patient-Reported Outcomes Following Various Surgical Treatments of Reverse Hill-Sachs Lesions in the Setting of Posterior Instability: A Systematic Review.

PURPOSE: To systematically review the literature and report the outcomes of various surgical treatments for reverse Hill-Sachs lesions (RHSL) in the setting of posterior shoulder instability. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. All studies assessing outcomes of surgical treatment of RHSL from inception to January 2023 were identified in PubMed, Embase, and Cochrane Library. Inclusion criteria consisted of studies reporting outcomes, minimum mean 1-year follow-up, and minimum Level IV evidence. Outcomes were assessed using Forest plots with random effects models using R software. RESULTS: A total of 29 studies consisting of 291 patients were included with a mean age of 42 years (range 16-88 years), 87% male gender, and mean follow-up of 4.5 years. The mean size of impacted or affected cartilage was 35%, and time from injury to surgery was mean 15 weeks. Nearly all studies were Level IV evidence, and quality of studies was low. Random effect models were performed, and data are presented as range. A low incidence of instability was noted for all surgical techniques with good patient-reported outcome measures. Most studies reported outcomes of the modified McLaughlin procedure (13 studies, 126 patients) with overall Constant-Murley Score of 65 to 92. Trends were seen towards better Constant-Murley Score and external rotation with a shorter delay between injury, and when arthroscopic and joint preserving treatments were performed. CONCLUSIONS: This systematic review showed low rates of instability recurrence, reproducible range of motion, and favorable patient-reported outcome measures were reported following all treatments for RHSLs with posterior instability. There was a significant association between better outcomes and a shorter delay between injury and surgery. The level of evidence is limited, given the small and retrospective studies which can be explained by the rarity of these injuries. LEVEL OF EVIDENCE: Level IV; systematic review of Level III and IV studies.

Taylor Dispersion-Induced Phase Separation for the Efficient Characterisation of Protein Condensate Formation.

Biomolecular condensates have emerged as important structures in cellular function and disease, and are thought to form through liquid-liquid phase separation (LLPS). Thorough and efficient in vitro experiments are therefore needed to elucidate the driving forces of protein LLPS and the possibility to modulate it with drugs. Here we present Taylor dispersion-induced phase separation (TDIPS), a method to robustly measure condensation phenomena using a commercially available microfluidic platform. It uses only nanoliters of sample, does not require extrinsic fluorescent labels, and is straightforward to implement. We demonstrate TDIPS by screening the phase behaviour of two proteins that form biomolecular condensates in vivo, PGL-3 and Ddx4. Uniquely accessible to this method, we find an unexpected re-entrant behaviour at very low ionic strength, where LLPS is inhibited for both proteins. TDIPS can also probe the reversibility of assemblies, which was shown for both α-synuclein and for lysozyme, relevant for health and biotechnology, respectively. Finally, we highlight how effective inhibition concentrations and partitioning of LLPS-modifying compounds can be screened highly efficiently.

Structural elucidation of polydopamine facilitated by ionic liquid solvation.

Minimal understanding of the formation mechanism and structure of polydopamine (pDA) and its natural analogue, eumelanin, impedes the practical application of these versatile polymers and limits our knowledge of the origin of melanoma. The lack of conclusive structural evidence stems from the insolubility of these materials, which has spawned significantly diverse suggestions of pDA's structure in the literature. We discovered that pDA is soluble in certain ionic liquids. Using these ionic liquids (ILs) as solvents, we present an experimental methodology to solvate pDA, enabling us to identify pDA's chemical structure. The resolved pDA structure consists of self-assembled supramolecular aggregates that contribute to the increasing complexity of the polymer. The underlying molecular energetics of pDA solvation and a macroscopic picture of the disruption of the aggregates using IL solvents have been investigated, along with studies of the aggregation mechanism in water.

A hospital-based independent domestic violence advisor service: demand and response during the Covid-19 pandemic.

BACKGROUND AND AIM: Recent UK policy has focussed on improving support for victims of domestic violence and abuse (DVA), in healthcare settings. DVA victims attending hospital are often at highest risk of harm, yet DVA support in hospitals has been inadequate. A targeted service supporting high risk DVA victims, was implemented at a hospital Trust in North West England. The service was provided by Independent Domestic Violence Advisors (IDVAs). This paper assesses the activity in the hospital-based IDVA service during the COVID-19 pandemicand addresses the research questions: What was the demand for the service? How did the service respond? What facilitated this response? METHODS: A mixed-methods study was undertaken. Quantitative data on referrals to the service were examined using simple descriptive statistics and compared to other DVA services. Semi-structured interviews were undertaken with IDVAs and other hospital staff involved with the service and the data subjected to thematic analysis. RESULTS: The quantitative analysis showed that referrals dropped at the start of lockdown, then increased and continued to rise; the qualitative findings reiterated this pattern. Referrals came from a range of departments across the Trust, with the majority from A&E. Pre-pandemic, the population supported by the service included higher proportions of males and people aged 40 and over than at other IDVA services; this continued during the pandemic. The qualitative findings indicated a flexible response during the pandemic, enabled by strong working relationships and by using workarounds. CONCLUSIONS: The hospital-based IDVAs provided an efficient, flexible serviceduring the COVID-19 pandemic. Referrals increased during the first lockdown and subsequent relaxing of restrictions. Locating the IDVAs within a team working across the organisation, and building good working relationships facilitated an effective disclosure and referral route, which endured through social restrictions. The IDVAs supported high-risk victims who may otherwise not have been identified in traditional community-based DVA settings during the pandemic. Hospital-based IDVA services can broaden access by supporting vulnerable, at risk populations whose needs may not be identified at other services.

Diffusing wave microrheology of highly scattering concentrated monodisperse emulsions.

Motivated by improvements in diffusing wave spectroscopy (DWS) for nonergodic, highly optically scattering soft matter and by cursory treatment of collective scattering effects in prior DWS microrheology experiments, we investigate the low-frequency plateau elastic shear moduli [Formula: see text] of concentrated, monodisperse, disordered oil-in-water emulsions as droplets jam. In such experiments, the droplets play dual roles both as optical probes and as the jammed objects that impart shear elasticity. Here, we demonstrate that collective scattering significantly affects DWS mean-square displacements (MSDs) in dense colloidal emulsions. By measuring and analyzing the scattering mean free path as a function of droplet volume fraction φ, we obtain a φ-dependent average structure factor. We use this to correct DWS MSDs by up to a factor of 4 and then calculate [Formula: see text] predicted by the generalized Stokes-Einstein relation. We show that DWS-microrheological [Formula: see text] agrees well with mechanically measured [Formula: see text] over about three orders of magnitude when droplets are jammed but only weakly deformed. Moreover, both of these measurements are consistent with predictions of an entropic-electrostatic-interfacial (EEI) model, based on quasi-equilibrium free-energy minimization of disordered, screened-charge-stabilized, deformable droplets, which accurately describes prior mechanical measurements of [Formula: see text] made on similar disordered monodisperse emulsions over a wide range of droplet radii and φ. This very good quantitative agreement between DWS microrheology, mechanical rheometry, and the EEI model provides a comprehensive and self-consistent view of weakly jammed emulsions. Extensions of this approach may improve DWS microrheology on other systems of dense, jammed colloids that are highly scattering.

Long-wavelength fluctuations and anomalous dynamics in 2-dimensional liquids.

In 2-dimensional systems at finite temperature, long-wavelength Mermin-Wagner fluctuations prevent the existence of translational long-range order. Their dynamical signature, which is the divergence of the vibrational amplitude with the system size, also affects disordered solids, and it washes out the transient solid-like response generally exhibited by liquids cooled below their melting temperatures. Through a combined numerical and experimental investigation, here we show that long-wavelength fluctuations are also relevant at high temperature, where the liquid dynamics do not reveal a transient solid-like response. In this regime, these fluctuations induce an unusual but ubiquitous decoupling between long-time diffusion coefficient D and structural relaxation time τ, where [Formula: see text], with [Formula: see text] Long-wavelength fluctuations have a negligible influence on the relaxation dynamics only at extremely high temperatures in molecular liquids or at extremely low densities in colloidal systems.

Identifying patients at risk of post-discharge complications related to COVID-19 infection.

SARS-CoV-2 infection is a multisystem disease with post-discharge sequelae. We report early follow-up data from one UK hospital of the initial 200 hospital inpatients with slow recovery from the condition. At 4 weeks post-discharge, 321/957 survivors (34%) had persistent symptoms. A structured outpatient clinical assessment protocol was designed, and outcomes from the first 200 patients seen 4-6 weeks post-discharge are presented here. In 80/200 (40%), we identified at follow-up a cardiorespiratory cause of breathlessness, including persistent parenchymal abnormality (64 patients), pulmonary embolism (four patients) and cardiac complications (eight patients). These findings occurred both in patients who had intensive care unit (ICU) admissions and those who had been managed on the ward, although patients requiring ICU admissions were more likely to have a significant cardiorespiratory cause found for their breathlessness, risk ratio 2.8 (95% CI 1.5 to 5.1).

Prediction of lattice energy of benzene crystals: A robust theoretical approach.

We present an inexpensive and robust theoretical approach based on the fragment molecular orbital methodology and the spin-ratio scaled second-order Møller-Plesset perturbation theory to predict the lattice energy of benzene crystals within 2 kJ⋅mol-1 . Inspired by the Harrison method to estimate the Madelung constant, the proposed approach calculates the lattice energy as a sum of two- and three-body interaction energies between a reference molecule and the surrounding molecules arranged in a sphere. The lattice energy converges rapidly at a radius of 13 Å. Adding the corrections to account for a higher correlated level of theory and basis set superposition for the Hartree Fock (HF) level produced a lattice energy of -57.5 kJ⋅mol-1 for the benzene crystal structure at 138 K. This estimate is within 1.6 kJ⋅mol-1 off the best theoretical prediction of -55.9 kJ⋅mol-1 . We applied this approach to calculate lattice energies of the crystal structures of phase I and phase II-polymorphs of benzene-observed at a higher temperature of 295 K. The stability of these polymorphs was correctly predicted, with phase II being energetically preferred by 3.7 kJ⋅mol-1 over phase I. The proposed approach gives a tremendous potential to predict stability of other molecular crystal polymorphs.

Effects of BNT162b2 mRNA vaccine on COVID-19 infection and hospitalisation amongst older people: matched case control study for England.

BACKGROUND: The BNT162b2 mRNA vaccine has been shown to be effective at preventing serious COVID-19 events in clinical trials. There is less evidence on effectiveness in real-world settings, especially for older people. Here, we aimed to estimate vaccine effectiveness in the context of the rapid NHS mass-vaccination programme in England, exploiting age-based vaccination eligibility thresholds to minimise and correct for selection bias. METHODS: We studied 170,226 individuals between the ages of 80 and 83 years from community settings outside care homes who received one dose of BNT162b2 mRNA between the 15 and 20 December 2020 and were scheduled a second dose 21 days later. We matched these vaccine recipients to slightly younger (aged 76-79 years) persons not yet eligible to receive the vaccine on gender, area of residence, area deprivation, health status, living arrangements, acute illness, and history of seasonal flu vaccination. We compared their rates of COVID-19 positivity and hospitalisation in the subsequent 45 days. We adjusted for the increasing concentration of COVID-19 positivity in the control population caused by the requirement to have no COVID-19 symptoms prior to vaccination. RESULTS: Emergency hospital admissions were 51.0% (95% confidence interval 19.9 to 69.5%) lower and positive COVID-19 tests were 55.2% (40.8 to 66.8%) lower for vaccinated individuals compared to matched controls 21 to 27 days after first vaccination. Emergency admissions were 75.6% (52.8 to 87.6%) lower, and positive COVID-19 tests were 70.1% (55.1 to 80.1%) lower 35 to 41 days after first vaccination when 79% of participants had received a second dose within 26 days of their first dose. CONCLUSIONS: Receipt of the BNT162b2 mRNA vaccine is effective at reducing COVID-19 hospitalisations and infections. The nationwide vaccination of older adults in England with the BNT162b2 mRNA vaccine reduced the burden of COVID-19.

Do different means of recording sexual orientation affect its relationship with health and wellbeing?

Analyses of an individual's sexual orientation over time are desirable for policy evaluations and in estimating causal effects. We explore whether accounting for those who change sexual orientation over two time points, to create a measure of fluidity, produces substantially different results compared to sexual orientation measured at one time point and extrapolated to subsequent survey waves. We use seven waves of the UK Household Longitudinal Study which asked sexual orientation identity questions at two time points: waves three (2011-2013) and nine (2017-2019). Using the relationship with sexual orientation and various health outcomes as an empirical example, via a correlated random effects estimation approach, we find that the infrequent reporting of sexual orientation could over-estimate the negative impact for lesbian, gay and "other" individuals and under-estimate the negative impact for bisexuals. We further test the feasibility of the fluidity measure by examining attrition by sexual orientation identity and find small but statistically significant probabilities of attrition. Correction for attrition bias through inverse probability weighting makes little difference to the results. These results highlight the importance of accounting for changes in sexual orientation in empirical analysis and that doing so is feasible.

Depletion torques between anisotropic colloidal particles.

We explore how the entropic notion of depletion forces between spheres, introduced by Asakura and Oosawa, can be extended to depletion torques that affect the orientations of colloidal particles having complex shapes. In prior experimental work, systems of microscale plate-like particles in the presence of a nanoscale depletion agent have been shown to form polymer-like columnar chains; restoring depletion torques act to align lithographically-structured platelets within a chain orientationally about the chain's axis. We consider depletion torques corresponding to parallel, face-to-face, near-contact pair interactions for complex-shaped, plate-like, prismatic lithographic particles in colloidal dispersions containing a spherical nanoscale depletion agent. We calculate depletion torques for a wide variety of such particles, including rotationally symmetric, asymmetric, achiral, chiral, and elongated particles. Moreover, we determine depletion torques between two non-parallel proximate square platelets connected by a lossless hinge along a common edge. Our investigations show that depletion torques can be tailored through lithographic or synthetic design of specific geometrical features in the shapes of particles.

Investigating the relationship between formal and informal care: An application using panel data for people living together.

There is limited evidence on the relationship between formal and informal care using panel data in a U.K. setting and focused specifically on people living together (co-residents). Using all 18 waves of the British Household Panel Survey (1991-2009), we analyse the effect of informal care given by co-residents on the use of formal home care and health care services more generally. To account for endogeneity, we estimate models using random effects instrumental variable regression using the number of daughters as a source of exogenous variation. We find that a 10% increase in the monthly provision of informal care hours decreases the probability of using home help (formal home care) by 1.02 percentage points (p < .05), equivalent to a 15.62% relative reduction. This effect was larger for home help provided by the state (ß = -.117) compared with non-state home help (ß = -.044). These results provide evidence that significant increases in the supply of informal care would reduce the demand for home-help provision.

The Kinetics, Thermodynamics and Mechanisms of Short Aromatic Peptide Self-Assembly.

The self-assembly of short aromatic peptides and peptide derivatives into a variety of different nano- and microstructures (fibrillar gels, crystals, spheres, plates) is a promising route toward the creation of bio-compatible materials with often unexpected and useful properties. Furthermore, such simple self-assembling systems have been proposed as model systems for the self-assembly of longer peptides, a process that can be linked to biological function and malfunction. Much effort has been made in the last 15 years to explore the space of peptide sequences, chemical modifications and solvent conditions in order to maximise the diversity of assembly morphologies and properties. However, quantitative studies of the corresponding mechanisms of, and driving forces for, peptide self-assembly have remained relatively scarce until recently. In this chapter we review the current state of understanding of the thermodynamic driving forces and self-assembly mechanisms of short aromatic peptides into supramolecular structures. We will focus on experimental studies of the assembly process and our perspective will be centered around diphenylalanine (FF), a key motif of the amyloid ß sequence and a paradigmatic self-assembly building block. Our main focus is the basic physical chemistry and key structural aspects of such systems, and we will also compare the mechanism of dipeptide aggregation with that of longer peptide sequences into amyloid fibrils, with discussion on how these mechanisms may be revealed through detailed analysis of growth kinetics, thermodynamics and other fundamental properties of the aggregation process.

Assembly of colloidal particles in solution.

Advances in both top-down and bottom-up syntheses of a wide variety of complex colloidal building blocks and also in methods of controlling their assembly in solution have led to new and interesting forms of highly controlled soft matter. In particular, top-down lithographic methods of producing monodisperse colloids now provide precise human-designed control over their sub-particle features, opening up a wide range of new possibilities for assembly structures that had been previously limited by the range of shapes available through bottom-up methods. Moreover, an increasing level of control over anisotropic interactions between these colloidal building blocks, which can be tailored through local geometries of sub-particle features as well as site-specific surface modifications, is giving rise to new demonstrations of massively parallel off-chip self-assembly of specific target structures with low defect rates. In particular, new experimental realizations of hierarchical self-assembly and control over the chiral purity of resulting assembly structures have been achieved. Increasingly, shape-dependent, shape-complementary, and roughness-controlled depletion attractions between non-spherical colloids are being used in novel ways to create assemblies that go far beyond early examples, such as fractal clusters formed by diffusion-limited and reaction-limited aggregation of spheres. As self-assembly methods have progressed, a wide variety of advanced directed assembly methods have also been developed; approaches based on microfluidic control and applying structured electromagnetic fields are particularly promising.

Influence of ionic constituents and electrical conductivity on the propagation of charged nanoscale objects in passivated gel electrophoresis.

When determining the electric field E acting on charged objects in gel electrophoresis, the electrical conductivity of the buffer solution is often overlooked; E is typically calculated by dividing the applied voltage by a separation distance between electrodes. However, as a consequence of electrolytic reactions, which occur at the electrodes, gradients in the ionic content of the buffer solution and its conductivity can potentially develop over time, thereby impacting E and affecting propagation velocities of charged objects, v, directly. Here, we explore how the types and concentrations of ionic constituents of the buffer solution, which largely control its conductivity, when used in passivated gel electrophoresis (P-gelEP), can influence E, thereby altering v of charged nanospheres propagating through large-pore gels. We measure the conductivity of the buffer solution in the center of the gel region near propagating bands of nanospheres, and we show that predictions of E based on conductivity closely correlate with v. We also explore P-gelEP involving two different types of passivation agents: nonionic polyethylene glycol (PEG) and anionic sodium dodecyl sulfate (SDS). Our observations indicate that using a conductivity model to determine E from the local current density and the conductivity where spheres are propagating can lead to a better estimate than the standard approach of a voltage divided by a separation. Moreover, this conductivity model also provides a starting point for interpreting the complex behavior created by amphiphilic ionic passivation agents, such as SDS, on propagating nanospheres used in some P-gelEP experiments.

Vibrational Modes and Dynamic Heterogeneity in a Near-Equilibrium 2D Glass of Colloidal Kites.

Using video microscopy and particle-tracking techniques developed for dense Brownian systems of polygons, we study the structure-dynamics relationship in a near-equilibrium 2D glass consisting of anisotropic Penrose kite-shaped colloids. Detailed vibrational properties of kite glasses, both translational and rotational, are obtained using covariance matrix techniques. Different from other colloidal glasses of spheres and ellipsoids, the vibrational modes of kite glasses at low frequencies show a strong translational character with spatially localized rotational modes and extended translational modes. Low-frequency quasilocalized soft modes commonly found in sphere glasses are absent in the translational phonon modes of kite glasses. Soft modes are observed predominantly in the rotational vibrations and correlate well with the spatial distribution of Debye-Waller factors. The local structural entropy field shows a strong correlation with the observed dynamic heterogeneity.

Surfactant Partitioning in Nanoemulsions.

Using a fractionated silicone oil-in-water nanoemulsion (NEM), which has a high ratio of surface area-to-volume, we investigate surfactant partitioning between the bulk continuous phase and the adsorbed interfacial phase. By adjusting the droplet volume fraction of this fractionated NEM and by using gravimetric and electrical conductivity methods, we measure the bulk and the surface concentrations of an ionic surfactant (sodium dodecyl sulfate, SDS), thereby obtaining a raw adsorption isotherm of SDS on the interfaces of the nanodroplets. To overcome significant uncertainties in the total surface area of this nanoemulsion, we have also measured the macroscopic interfacial tension (IFT) of silicone oil in contact with aqueous SDS solutions using the du Noüy ring method. We then scale the surface concentration of this raw isotherm using an appropriate Gibbs derivative based on the IFT measurement, yielding an adjusted isotherm. We show that this adjusted isotherm can be described using a simple Langmuir equation. In addition, we show that a significant and non-negligible percentage of surfactant typically partitions to nanodroplet interfaces after high-flow-rate emulsification (HFRE) has transformed a microscale premix emulsion into a NEM. We develop a model for predicting the final bulk surfactant concentration after HFRE given the initial bulk surfactant concentration before HFRE. We show that this model can be used to predict trends for surfactant partitioning in polydisperse nanoemulsions after HFRE.

Development of a resource allocation formula for substance misuse treatment services.

Background: Funding for substance misuse services comprises one-third of Public Health spend in England. The current allocation formula contains adjustments for actual activity, performance and need, proxied by the Standardized Mortality Ratio for under-75s (SMR < 75). Additional measures, such as deprivation, may better identify differential service need. Methods: We developed an age-standardized and an age-stratified model (over-18s, under-18s), with the outcome of expected/actual cost at postal sector/Local Authority level. A third, person-based model incorporated predictors of costs at the individual level. Each model incorporated both needs and supply variables, with the relative effects of their inclusion assessed. Results: Mean estimated annual cost (2013/14) per English Local Authority area was £5 032 802 (sd: 3 951 158). Costs for drug misuse treatment represented the majority (83%) of costs. Models achieved adjusted R-squared values of 0.522 (age-standardized), 0.533 (age-stratified over-18s), 0.232 (age-stratified under-18s) and 0.470 (person-based). Conclusion: Improvements can be made to the existing resource allocation formulae to better reflect population need. The person-based model permits inclusion of a range of needs variables, in addition to strong predictors of cost based on the receipt of treatment in the previous year. Adoption of this revised person-based formula for substance misuse would shift resources towards more deprived areas.