Capturing what matters: updating NICE methods guidance on measuring and valuing health.

In July 2019, the National Institute for Health and Care Excellence (NICE) initiated a major review of its health technology evaluation methods to update its methods guide. This update has recently concluded with the publication of its health technology evaluation manual in January 2022. This paper reports the methods and findings of the review in relation to the recommended approach to use for the measurement and valuation of health-related quality of life (HRQoL) in submissions to NICE. Issues related to (i) the methods to use when NICE's preferred measure (EQ-5D) is not appropriate or not available; (ii) adjusting health state utility values over time to account for age; (iii) measuring and valuing HRQoL in children and young people; and (iv) including carers' QoL in economic evaluations were included in this review. This commentary summarises the methods used to undertake the review, its findings, and the changes to NICE methods that were proposed based on these findings. It also outlines topics where further research is needed before definitive methods guidance can be issued. The broad proposals described here were subject to a public consultation in 2020 and a further consultation on the updated methods guidance was completed in October 2021 before the publication of the manual in January 2022.

Comprehensive Medical Support in Complex Emergencies (CMSCE): pilot course review.

Global threats to health and health security are growing. Fragile and failed states, armed groups, ungoverned spaces, outbreaks and potential unknown "Disease X" threats, antimicrobial resistance (AMR), hybrid and gray zone conflict all exacerbate complex medical emergencies. These growing threats increase preventable morbidity and mortality of the most vulnerable populations. In an effort to promote best practices, standardize responses, and prevent excess death and disability in these contexts, The Kofi Annan International Peacekeeping Training Centre (KAIPTC), with support from multiple international partners and a volunteer facilitator faculty, administered the pilot course for military and civilian health officers involved in U.N. peacekeeping missions entitled, "Comprehensive Medical Support in Complex Emergencies (CMSCE 19)." This brief review paper provides a description of the process in designing and delivering an interdisciplinary course for providers and decision makers responding to complex emergencies. We conclude with best practices and next steps for course evolution.

Comorbid disease burden among MS patients 1968-2012: A Swedish register-based cohort study.

BACKGROUND: People with multiple sclerosis (pwMS) have increased comorbid disease (CMD) risk. Most previous studies have not considered overall CMD burden. OBJECTIVE: To describe lifetime CMD burden among pwMS. METHODS: PwMS identified using Swedish registers between 1968 and 2012 (n = 25,476) were matched by sex, age, and county of residence with general-population comparators (n = 251,170). Prevalence, prevalence ratios (PRs), survival functions, and hazard ratios by MS status, age, and time period compared seven CMD: autoimmune, cardiovascular, depression, diabetes, respiratory, renal, and seizures. RESULTS: The magnitude of the PRs for each CMD and age group decreased across time, with higher PRs in earlier time periods. Before 1990, younger age groups had higher PRs, and after 1990, older age groups had higher PRs. Male pwMS had higher burden compared with females. Overall, renal, respiratory, and seizures had the highest PRs. Before 2001, 50% of pwMS received a first/additional CMD diagnosis 20 years prior to people without MS, which reduced to 4 years after 2001. PwMS had four times higher rates of first/additional diagnoses in earlier time periods, which reduced to less than two times higher in recent time periods compared to people without MS. CONCLUSION: Swedish pwMS have increased CMD burden compared with the general population, but this has reduced over time.

Health Utilities and Costs for Motor Neurone Disease.

BACKGROUND: Motor neurone disease (MND) places a significant burden on patients, their carers, and healthcare systems. OBJECTIVES: To estimate health utilities and costs of MND within the UK setting. METHODS: Patients with MND, recruited via 22 regional clinics, completed a postal questionnaire of a cost and quality-of-life survey. Health outcome assessment included the EuroQoL (EQ)-5D-5L, EQ-5D-visual analogue scale, Amyotrophic Lateral Sclerosis Utility Index, and the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised. Clinical staging was based on the Kings and Milano-Torino (MiToS) systems. The questionnaire asked about patients' use of primary, secondary, and community care services in the previous 3 months. Variability in total costs was examined using regression models. RESULTS: 595 patients were included in the health utility analysis, of whom 584 patients also completed a resource use questionnaire. Mean health utility decreased and costs increased between consecutive Kings stages, from 0.76 (95% CI 0.71-0.80) and £1096 (£757-£1240) in Kings stage 1, to 0.50 (0.45-0.54) and £3311 (£2666-£4151) in stage 4, respectively. The changes by MiToS stages were from 0.71 (0.69-0.73) and £1115 (£937-£1130) in MiToS stage 0, to 0.25 (0.07-0.42) and £2899 (£2190-£3840) in stage 2. Kings stages 3 and 4 and MiToS stages 1 and 2, respectively, were significant in explaining variability in total costs. CONCLUSIONS: The impact of MND on health utilities and costs differs by disease severity. The data provided here can be used in cost-effectiveness analyses and to inform decision-making regarding healthcare provision for people with MND.

Mapping ALSFRS-R and ALSUI to EQ-5D in Patients with Motor Neuron Disease.

BACKGROUND: The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) is the preferred measure of health outcome in clinical trials in motor neuron disease (MND). It, however, does not provide a preference-based health utility score required for estimating quality-adjusted life-years in economic evaluations for health technology assessments. OBJECTIVES: To develop algorithms for mapping from measures used in MND clinical studies to allow for future prediction of the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) utility in populations of patients with MND when utility data have not been collected. METHODS: Direct mapping models were developed using ordinary least squares and Tobit regression analyses to estimate EQ-5D-5L utilities (based on English tariffs), with ALSFRS-R total, domain, and item scores used as explanatory variables, using patient-level data from a UK cohort study. Indirect mapping models were also used to map EQ-5D-5L domains, using the same variables, along with the Neuropathic Pain Scale and the Hospital and Anxiety Depression Scale for MND using multinomial logistic regression analysis. Goodness of fit was assessed along with predicted values for each mapping model. RESULTS: The best-performing model predicting EQ-5D-5L utilities used five items of the ALSFRS-R items as explanatory variables in a stepwise ordinary least squares regression. The mean squared error was 0.0228, and the mean absolute error was 0.1173. Prediction was good, with 55.4% of estimated values within 0.1 and 91.4% within 0.25 of the observed EQ-5D-5L utility value. Indirect mapping using the Neuropathic Pain Scale and the Hospital and Anxiety Depression Scale for MND provided less predictive power than direct mapping models. CONCLUSIONS: This is the first study to present mapping algorithms to crosswalk between ALSFRS-R and EQ-5D-5L. This analysis demonstrates that the ALSFRS-R can be used to estimate EQ-5D-5L utilities when they have not been collected directly within a trial.

Reply to Hurlburt.

Hurlburt (2018) states that Brouwers et al. (2018) find a much lower frequency of reported inner speech while reading than we find in Moore and Schwitzgebel (2018), and he attributes the difference to methodological shortcomings in Moore and Schwitzgebel's method. However, the method in Brouwers et al. has complementary shortcomings, and an apples-to-apples comparison of the data between the two studies shows a considerably smaller difference in results than the top-line percentages that Hurlburt emphasizes.

The experience of reading.

What do people consciously experience when they read? There has been almost no rigorous research on this question, and opinions diverge radically among both philosophers and psychologists. We describe three studies of the phenomenology of reading and its relationship to memory of textual detail and general cognitive abilities. We find three main results. First, there is substantial variability in reports about reading experience, both within and between participants. Second, reported reading experience varies with passage type: passages with dialogue prompted increased reports of inner speech, while passages with vivid visual detail prompted increased reports of visual imagery. Third, reports of visual imagery experiences, inner speech experiences, and experiences of conscious visual perception of the words on the page were at best weakly related to general cognitive abilities and memory of visual and auditory details.

Efficacy and safety of SBR759, a novel calcium-free, iron (III)-based phosphate binder, versus placebo in chronic kidney disease stage V Japanese patients on maintenance renal replacement therapy.

BACKGROUND: SBR759, an iron (III)-based oral phosphate binder, was developed for the treatment of hyperphosphataemia in chronic kidney disease stage V patients receiving maintenance renal replacement therapy (RRT). Serum phosphate-lowering efficacy and dose response of SBR759 (3-, 6-, 9- and 12-g/day doses) were compared with placebo. METHODS: Japanese patients with hyperphosphataemia (P ≥ 5.5 mg/dL [≥ 1.78 mmol/L]) receiving maintenance RRT (N = 63) were randomised to receive either SBR759 (3-, 6-, 9-, 12-g/day dose) or placebo (12-g/day dose) for 4 weeks. The primary endpoint was change from baseline in 72-h post-dialysis serum phosphate levels at week 4 for different doses of SBR759 versus placebo. Secondary endpoints were change from baseline in serum phosphate levels and dose-dependent efficacy of SBR759 during the 4-week treatment period. RESULTS: SBR759 showed significant reduction in serum phosphate levels compared with placebo at week 4, demonstrating a significant linear dose response (P < 0.001). Incidence of adverse events was comparable between the SBR759 treatment groups (7/13 and 5/12 in the 3- and 12-g/day groups, respectively, and 8/13 in the 6- and 9-g/day groups) and was 6/12 in the placebo group. Discoloured faeces and diarrhoea were the most frequently reported adverse events. Two serious adverse events were reported--one in the SBR759 3-g/day group (1/13, skin ulcer) and one in the SBR759 12-g/day group (1/12, arthralgia). CONCLUSIONS: SBR759 showed significant phosphate-lowering efficacy and dose-dependent response compared with placebo in patients with chronic kidney disease receiving RRT.

Understanding the unconscious mind: Jungian psychology and mental health nursing.

How might the unconscious part of the mind affect mental health patients' emotions or behaviour? How might the unconscious motivations of mental health nurses affect their patients? The discovery of "the unconscious" two centuries ago has allowed philosophers and scientists, such as C. G. Jung, to explore the field. Contemporary mental health care subscribes to a dominance of neurobiological approaches, neglecting the unconscious or relegating it to that of a merely biological process. Approaching this subject from the perspective of Jung, we make a case for the inclusion of theoretical concepts about the unconscious in the discourse of mental health nursing. Such awareness may help mental health nurses to better understand the mental disease, disorder, and distress found in patients. It also may help them understand their own conflicts and motivations that, in turn, can have an affect on their patients.

Improving Data Collection in Pregnancy Safety Studies: Towards Standardisation of Data Elements in Pregnancy Reports from Public and Private Partners, A Contribution from the ConcePTION Project.

INTRODUCTION AND OBJECTIVE: The ConcePTION project aims to improve the way medication use during pregnancy is studied. This includes exploring the possibility of developing a distributed data processing and analysis infrastructure using a common data model that could form a foundational platform for future surveillance and research. A prerequisite would be that data from various data access providers (DAPs) can be harmonised according to an agreed set of standard rules concerning the structure and content of the data. To do so, a reference framework of core data elements (CDEs) recommended for primary data studies on drug safety during pregnancy was previously developed. The aim of this study was to assess the ability of several public and private DAPs using different primary data sources focusing on multiple sclerosis, as a pilot, to map their respective data variables and definitions with the CDE recommendations framework. METHODS: Four pregnancy registries (Gilenya, Novartis; Aubagio, Sanofi; the Organization of Teratology Information Specialists [OTIS]; Aubagio, Sanofi; the Dutch Pregnancy Drug Register, Lareb), two enhanced pharmacovigilance programmes (Gilenya PRIM, Novartis; MAPLE-MS, Merck Healthcare KGaA) and four Teratology Information Services (UK TIS, Jerusalem TIS, Zerifin TIS, Swiss TIS) participated in the study. The ConcePTION primary data source CDE includes 51 items covering administrative functions, the description of pregnancy, maternal medical history, maternal illnesses arising in pregnancy, delivery details, and pregnancy and infant outcomes. For each variable in the CDE, the DAPs identified whether their variables were: identical to the one mentioned in the CDE; derived; similar but with a divergent definition; or not available. RESULTS: The majority of the DAP data variables were either directly taken (85%, n = 305/357, range 73-94% between DAPs) or derived by combining different variables (12%, n = 42/357, range 0-24% between DAPs) to conform to the CDE variables and definitions. For very few of the DAP variables, alignment with the CDE items was not possible, either because of divergent definitions (1%, n = 3/357, range 0-2% between DAPs) or because the variables were not available (2%, n = 7/357, range 0-4% between DAPs). CONCLUSIONS: Data access providers participating in this study presented a very high proportion of variables matching the CDE items, indicating that alignment of definitions and harmonisation of data analysis by different stakeholders to accelerate and strengthen pregnancy pharmacovigilance safety data analyses could be feasible.

The packaging of different cargo into enveloped viral nanoparticles.

Viral nanoparticles used for biomedical applications must be able to discriminate between tumor or virus-infected host cells and healthy host cells. In addition, viral nanoparticles must have the flexibility to incorporate a wide range of cargo, from inorganic metals to mRNAs to small molecules. Alphaviruses are a family of enveloped viruses for which some species are intrinsically capable of systemic tumor targeting. Alphavirus virus-like particles, or viral nanoparticles, can be generated from in vitro self-assembled core-like particles using nonviral nucleic acid. In this work, we expand on the types of cargo that can be incorporated into alphavirus core-like particles and the molecular requirements for packaging this cargo. We demonstrate that different core-like particle templates can be further enveloped to form viral nanoparticles that are capable of cell entry. We propose that alphaviruses can be selectively modified to create viral nanoparticles for biomedical applications and basic research.

Core Data Elements for Pregnancy Pharmacovigilance Studies Using Primary Source Data Collection Methods: Recommendations from the IMI ConcePTION Project.

INTRODUCTION AND OBJECTIVE: The risks and benefits of medication use in pregnancy are typically established through post-marketing observational studies. As there is currently no standardised or systematic approach to the post-marketing assessment of medication safety in pregnancy, data generated through pregnancy pharmacovigilance (PregPV) research can be heterogenous and difficult to interpret. The aim of this article is to describe the development of a reference framework of core data elements (CDEs) for collection in primary source PregPV studies that can be used to standardise data collection procedures and, thereby, improve data harmonisation and evidence synthesis capabilities. METHODS: This CDE reference framework was developed within the Innovative Medicines Initiative (IMI) ConcePTION project by experts in pharmacovigilance, pharmacoepidemiology, medical statistics, risk-benefit communication, clinical teratology, reproductive toxicology, genetics, obstetrics, paediatrics, and child psychology. The framework was produced through a scoping review of data collection systems used by established PregPV datasets, followed by extensive discussion and debate around the value, definition, and derivation of each data item identified from these systems. RESULTS: The finalised listing of CDEs comprises 98 individual data elements, arranged into 14 tables of related fields. These data elements are openly available on the European Network of Teratology Information Services (ENTIS) website ( http://www.entis-org.eu/cde ). DISCUSSION: With this set of recommendations, we aim to standardise PregPV primary source data collection processes to improve the speed at which high-quality evidence-based statements can be provided about the safety of medication use in pregnancy.

Artificial gravity training reduces bed rest-induced cardiovascular deconditioning.

We studied 15 men (8 treatment, 7 control) before and after 21 days of 6º head-down tilt to determine whether daily, 1-h exposures to 1.0 G(z) (at the heart) artificial gravity (AG) would prevent bed rest-induced cardiovascular deconditioning. Testing included echocardiographic analysis of cardiac function, plasma volume (PV), aerobic power (VO(2)pk) and cardiovascular and neuroendocrine responses to 80º head-up tilt (HUT). Data collected during HUT were ECG, stroke volume (SV), blood pressure (BP) and blood for catecholamines and vasoactive hormones. Heart rate (HR), cardiac output (CO), total peripheral resistance, and spectral power of BP and HR were calculated. Bed rest decreased PV, supine and HUT SV, and indices of cardiac function in both groups. Although PV was decreased in control and AG after bed rest, AG attenuated the decrease in orthostatic tolerance [pre- to post-bed rest change; control: -11.8 ± 2.0, AG: -6.0 ± 2.8 min (p = 0.012)] and VO(2)pk [pre- to post-bed rest change; control: -0.39 ± 0.11, AG: -0.17 ± 0.06 L/min (p = 0.041)]. AG prevented increases in pre-tilt levels of plasma renin activity [pre- to post-bed rest change; control: 1.53 ± 0.23, AG: -0.07 ± 0.34 ng/mL/h (p = 0.001)] and angiotensin II [pre- to post-bed rest change; control: 3.00 ± 1.04, AG: -0.63 ± 0.81 pg/mL (p = 0.009)] and increased HUT aldosterone [post-bed rest; control: 107 ± 30 pg/mL, AG: 229 ± 68 pg/mL (p = 0.045)] and norepinephrine [post-bed rest; control: 453 ± 107, AG: 732 ± 131 pg/mL (p = 0.003)]. We conclude that AG can mitigate some aspects of bed rest-induced cardiovascular deconditioning, including orthostatic intolerance and aerobic power. Mechanisms of improvement were not cardiac-mediated, but likely through improved sympathetic responsiveness to orthostatic stress.

Implementing clinical supervision for ICU Outreach Nurses: a case study of their journey.

INTRODUCTION: Many health services with Intensive Care Units have developed ward liaison programs, managed by Outreach Nurses, to facilitate the transition for patients between the intensive care and general wards. This paper reports a case study of clinical supervision for two Outreach Nurses as they adapted to their new, largely autonomous role in an Australian tertiary hospital. METHOD: Individual clinical supervision was provided fortnightly to two Outreach Nurses over 12 months by an experienced facilitator, and evaluated using a case study methodology. The Outreach Nurses completed a journal that captured their personal and professional growth and the supervisor also provided a reflective account. An interview was conducted with both Outreach Nurses to evaluate their experiences of clinical supervision. FINDINGS: Key themes emerging from all the data sources included: respect for clinical supervision and the supervisor; role clarification; understanding and dealing with interpersonal issues; dedicated time for reflection; facing up to issues and letting them go. CONCLUSION: The Outreach Nurses described the personal and professional benefits of clinical supervision and highlighted how it was successfully implemented for them in a busy clinical environment with limited available resources.

Is It Time to Call 'Code Blue' on Nursing Infrastructure? A Nurse's Perspective from the COVID-19 Front-line.

The COVID-19 pandemic has highlighted the significance of every role within the interdisciplinary team and has exacerbated the challenges posed to every member. From the nursing perspective, many of these challenges were present before the pandemic but have become significantly larger problems that continue to demand global attention. This has provided an opportunity to critically evaluate and learn from the challenges the pandemic has both highlighted and created. We conclude that the nursing infrastructure requires a revolution in order to support, grow and retain nurses, who are vital to the delivery of high-quality healthcare.

Cryptococcal Meningitis Reported With Fingolimod Treatment: Case Series.

BACKGROUND AND OBJECTIVES: To describe the characteristics of patients with MS reporting cryptococcal meningitis (CM) while treated with fingolimod. METHODS: The Novartis safety database was searched for cases with CM between January 26, 2006, and February 28, 2020. The reporting rate of CM was estimated based on the case reports received and exposure to fingolimod in the postmarketing setting during the relevant period. RESULTS: A total of 60 case reports of CM were identified, mostly from the United States. The median age was 48 years, and 51.8% were women. Most of the patients had recovered or were recovering at the time of final report. A fatal outcome occurred in 13 cases. During the study period, the rate of CM in patients with MS receiving fingolimod was estimated to be 8 per 100,000 patient-years (95% CI: 6.0; 10.0). The incidence of CM seemed to increase with duration of treatment; however, this relationship remains uncertain due to wide CIs and missing data. DISCUSSION: The causal relationship between fingolimod treatment and CM is not yet fully understood. The CM mortality rate in fingolimod-treated patients is similar to that reported in HIV-negative patients. Vigilance for signs and symptoms of CM in patients receiving fingolimod, particularly the new onset of headaches and altered mental status, is essential. Early diagnosis and treatment are critical to reducing CM-associated mortality.

Induction of tier-2 neutralizing antibodies in mice with a DNA-encoded HIV envelope native like trimer.

HIV Envelope (Env) is the main vaccine target for induction of neutralizing antibodies. Stabilizing Env into native-like trimer (NLT) conformations is required for recombinant protein immunogens to induce autologous neutralizing antibodies(nAbs) against difficult to neutralize HIV strains (tier-2) in rabbits and non-human primates. Immunizations of mice with NLTs have generally failed to induce tier-2 nAbs. Here, we show that DNA-encoded NLTs fold properly in vivo and induce autologous tier-2 nAbs in mice. DNA-encoded NLTs also uniquely induce both CD4 + and CD8 + T-cell responses as compared to corresponding protein immunizations. Murine neutralizing antibodies are identified with an advanced sequencing technology. The structure of an Env-Ab (C05) complex, as determined by cryo-EM, identifies a previously undescribed neutralizing Env C3/V5 epitope. Beyond potential functional immunity gains, DNA vaccines permit in vivo folding of structured antigens and provide significant cost and speed advantages for enabling rapid evaluation of new HIV vaccines.

Nucleic acid delivery of immune-focused SARS-CoV-2 nanoparticles drives rapid and potent immunogenicity capable of single-dose protection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines may target epitopes that reduce durability or increase the potential for escape from vaccine-induced immunity. Using synthetic vaccinology, we have developed rationally immune-focused SARS-CoV-2 Spike-based vaccines. Glycans can be employed to alter antibody responses to infection and vaccines. Utilizing computational modeling and in vitro screening, we have incorporated glycans into the receptor-binding domain (RBD) and assessed antigenic profiles. We demonstrate that glycan-coated RBD immunogens elicit stronger neutralizing antibodies and have engineered seven multivalent configurations. Advanced DNA delivery of engineered nanoparticle vaccines rapidly elicits potent neutralizing antibodies in guinea pigs, hamsters, and multiple mouse models, including human ACE2 and human antibody repertoire transgenics. RBD nanoparticles induce high levels of cross-neutralizing antibodies against variants of concern with durable titers beyond 6 months. Single, low-dose immunization protects against a lethal SARS-CoV-2 challenge. Single-dose coronavirus vaccines via DNA-launched nanoparticles provide a platform for rapid clinical translation of potent and durable coronavirus vaccines.

Improved late survival and disability after stroke with therapeutic anticoagulation for atrial fibrillation: a population study.

BACKGROUND AND PURPOSE: Although therapeutic anticoagulation improves early (within 1 month) outcomes after ischemic stroke in hospital-admitted patients with atrial fibrillation, no information exists on late outcomes in unselected population-based studies, including patients with all stroke (ischemic and hemorrhagic). METHODS: We identified patients with atrial fibrillation and stroke in a prospective, population-based study in North Dublin. Clinical characteristics, stroke subtype, stroke severity (National Institutes of Health Stroke Scale), prestroke antithrombotic medication, and International Normalized Ratio (INR) at onset were documented. Modified Rankin Scale (mRS) score was measured before stroke and at 7, 28, and 90 days; 1 year; and 2 years after stroke. RESULTS: One hundred seventy-five patients had atrial fibrillation-associated stroke and medication data at stroke onset (159 ischemic, 16 hemorrhagic); 17% of those with ischemic stroke were anticoagulated before stroke (27 of 159.) On multivariable analysis, therapeutic INR was associated with improved late survival after ischemic stroke (adjusted 2-year odds ratio for death=0.08; 95% CI, 0.01 to 0.78; P=0.03). This survival benefit persisted when patients with hemorrhagic stroke were included (2-year survival; 70.5% therapeutic INR, 14.3% nontherapeutic INR; log-rank P<0.001; odds ratio for death=0.27; 95% CI, 0.09 to 0.88; P=0.03). Admission INR was inversely correlated with early and late modified Rankin Scale score (2-year Spearman ρ=-0.65; P<0.0003). An INR of 2 to 3 at ischemic stroke onset was associated with greater early (72 hours to 28 days) modified Rankin Scale score improvement (P=0.04) and good functional outcome (modified Rankin Scale score=0 to 2) at 1 year (adjusted odds ratio=4.8; 95% CI, 1.45 to 23.8; P=0.04). CONCLUSIONS: In addition to improving short-term outcome in selected hospital-treated patient groups, therapeutic anticoagulation may provide important benefits for long-term stroke outcomes in unselected populations.

Current and future treatment options in osteoporosis.

PURPOSE: The incidence of osteoporosis-related fractures will increase substantially over the coming decades as the population ages globally. This has important economic and public health implications, contributing substantially to morbidity and excess mortality in this population. METHODS: When prescribing for older patients the effectiveness profile of drugs needs to be balanced against their tolerability in individual patients. RESULTS: Currently we have good anti-fracture data to support the use of many available anti-resorptive and anabolic drugs including bisphosphonates, strontium ranelate and recombinant human parathyroid hormone. We also have evidence to demonstrate the importance of calcium and vitamin D repletion in these patients. However, in recent years our understanding of normal bone physiology and the mechanisms underlying the development of osteoporosis has significantly advanced and this has led to the development of new therapies. Novel agents, particularly denosumab, but also inhibitors of cathepsin K and anabolic agents that act on Wnt signalling, will increase the therapeutic options for clinicians in the coming years. CONCLUSION: This review discusses the evidence supporting the use of currently available treatment options for osteoporosis and potential future advances in drug therapy. Particular consideration should be given when prescribing for certain older patients who have issues with compliance or tolerance and also in those with co-morbidities or levels of frailty that may restrict the choice of therapy. Understanding the evidence for the benefit and possible harm of osteoporosis treatments is critical to appropriate management of this patient population.