The Nottingham Spinal Health (NoSH) Study: a cohort study of patients hospitalised with vertebral fragility fractures

© 2019, The Author(s). Summary: Patients hospitalised with vertebral fragility fractures were elderly, multimorbid and frail and lead to poor outcomes. Their hospital treatment needs to consider this alongside their acute fracture. A systematic organised model of care, such as an adaptation of orthogeriatric hip fracture care, will offer a more holistic approach potentially improving their outcomes. Purpose: Patients admitted to hospital with vertebral fragility fractures are elderly and have complex care needs who may benefit from specialist multidisciplinary input. To date, their characteristics and outcomes have not been reported sufficiently. This study aims to justify such a service. Methods: Patients admitted with an acute vertebral fragility fracture over 12 months were prospectively recruited from a university hospital in England. Data were collected soon after their admission, at discharge from hospital and 6 months after their hospital discharge on their characteristics, pain, physical functioning, and clinical outcomes. Results: Data from 90 participants were analysed. They were mainly elderly (mean age 79.7 years), multimorbid (69% had ≥ 3 comorbid condition), frail (56% had a Clinical Frailty Scale score ≥ 5), cognitively impaired (54% had a MoCA score of < 23) and at high risk of falls (65% had fallen ≥ 2 in the previous year). Eighteen percent died at 6 months. At 6 months post-hospital discharge, 12% required a new care home admission, 37% still reported their pain to be severe and physical functioning was worse compared with their preadmission state. Conclusion: Patients hospitalised with vertebral fragility fractures were elderly, multimorbid, frail and are susceptible to persistent pain and disability. Their treatment in hospital needs to consider this alongside their acute fracture. A systematic organised model of care, such as an adaptation of orthogeriatric hip fracture care, will offer a more holistic approach potentially improving their outcomes

Community falls prevention for people who call an emergency ambulance after a fall: randomised controlled trial

Objective To evaluate whether a service to prevent falls in the community would help reduce the rate of falls in older people who call an emergency ambulance when they fall but are not taken to hospital

Trialling technologies to reduce hospital in‐patient falls: an agential realist analysis

This paper analyses the 'failure' of a patient safety intervention. Our study was part of an RCT of bed and bedside chair pressure sensors linked to radio pagers to prevent bedside falls in older people admitted to hospital. We use agential realism within science and technology studies to examine the fall and its prevention as a situated phenomenon of knowledge that is made and unmade through intra-actions between environment, culture, humans and technologies. We show that neither the intervention (the pressure sensor system), nor the outcome (fall prevention) could be disentangled from the broader sociomaterial context of the ward, the patients, the nurses and (especially) their work through the RCT. We argue that the RCT design, by virtue of its unacknowledged assumptions, played a part in creating the negative findings. The study also raises wider questions about the kind of subjectivities, agencies and power relations these entanglements might effect and (re)produce in the hospital ward

Assessing the effectiveness of bisphosphonates for the prevention of fragility fractures: an updated systematic review and network meta-analyses

Bisphosphonates have been found to be effective in preventing fragility fractures. However, their comparative effectiveness in populations at risk has yet to be defined. In light of recent clinical trials, we aimed to compare four bisphosphonates (alendronate, ibandronate, risedronate, and zoledronate) and to identify which are the most effective for the prevention of fragility fractures. This is an update of a systematic review previously published as part of a NICE HTA report. We conducted a systematic review and network meta-analysis, updating the estimates regarding the comparative effectiveness of the aforementioned bisphosphonates. Studies identified from published and unpublished sources between 2014 and 2021 were added to the studies identified in the previous review. Screening, data extraction and risk of bias assessment were independently undertaken by two reviewers. Outcomes were fractures, femoral neck bone mineral density (BMD), mortality, and adverse events. We identified 25 additional trials, resulting in a total population of 47,007 participants. All treatments had beneficial effects on fractures versus placebo with zoledronate being the most effective treatment in preventing vertebral fractures HR = 0.38 (95%CrI: 0.28, 0.49). Zoledronate HR = 0.71 (95%CrI: 0.61, 0.81) and risedronate HR = 0.70 (95%CrI: 0.53, 0.84) were found to be the most effective treatments in preventing non-vertebral fractures. All treatments were associated with increases in femoral neck BMD versus placebo with zoledronate being the most effective treatment MD = 4.02 (95%CrI: 3.2, 4.84). There was a paucity of data regarding hip and wrist fractures. Depending on its cost-effectiveness, zoledronate could be considered a first-line option for people at increased risk of fragility fractures

Comparing medication adherence in patients receiving bisphosphonates for preventing fragility fractures: a comprehensive systematic review and network meta-analysis

Background: Bisphosphonates are effective in preventing fragility fractures; however, high rates of adherence are needed to preserve clinical benefits. Objective: To investigate persistence and compliance to oral and intravenous bisphosphonates (alendronate, ibandronate, risedronate, and zoledronate). Methods: Searches of 12 databases, unpublished sources, and trial registries were conducted, covering the period from 2000 to April 2021. Screening, data extraction, and risk of bias assessment (Cochrane Collaboration risk-of-bias tool 1.0 & ROBINS-I) were independently undertaken by two study authors. Randomised controlled trials (RCTs) and observational studies that used prescription claim databases or hospital medical records to examine patients’ adherence were included. Network meta-analyses (NMA) embedded within a Bayesian framework were conducted, investigating users’ likelihood in discontinuing bisphosphonate treatment. Where meta-analysis was not possible, data were synthesised using the vote-counting synthesis method. Results: Fifty-nine RCTs and 43 observational studies were identified, resulting in a total population of 2,656,659 participants. Data from 59 RCTs and 24 observational studies were used to populate NMAs. Zoledronate users were the least likely to discontinue their treatment HR = 0.73 (95%CrI: 0.61, 0.88). Higher rates of compliance were observed in those receiving intravenous treatments. The paucity of data and the heterogeneity in the reported medication possession ratio thresholds precluded a NMA of compliance data. Conclusions: Users of intravenously administered bisphosphonates were found to be the most adherent to treatment among bisphosphonates’ users. Patterns of adherence will permit the more precise estimation of clinical and cost-effectiveness of bisphosphonates. Trial registration: PROSPERO 2020 CRD42020177166

Acceptability of bisphosphonates among patients, clinicians and managers: a systematic review and framework synthesis

Objective: To explore the acceptability of different bisphosphonate regimens for the treatment of osteoporosis among patients, clinicians and managers, payers and academics. Design: A systematic review of primary qualitative studies. Seven databases were searched from inception to July 2019. Screening, data extraction and quality assessment of full-articles selected for inclusion were performed independently by two authors. A framework synthesis was applied to extracted data based on the theoretical framework of acceptability (TFA). The TFA includes seven domains relating to sense-making, emotions, opportunity costs, burden, perceived effectiveness, ethicality and self-efficacy. Confidence in synthesis findings was assessed. Setting: Any developed country healthcare setting. Participants: Patients, healthcare professionals, managers, payers and academics. Intervention: Experiences and views of oral and intravenous bisphosphonates. Results: Twenty-five studies were included, mostly describing perceptions of oral bisphosphonates. We identified, with high confidence, how patients and healthcare professionals make sense (coherence) of bisphosphonates by balancing perceptions of need against concerns, how uncertainty prevails about bisphosphonate perceived effectiveness and a number of individual and service factors that have potential to increase self-efficacy in recommending and adhering to bisphosphonates. We identified, with moderate confidence, that bisphosphonate taking induces concern, but has the potential to engender reassurance, and that both side effects and special instructions for taking oral bisphosphonates can result in treatment burden. Finally, we identified with low confidence that multimorbidity plays a role in people’s perception of bisphosphonate acceptability. Conclusion: By using the lens of acceptability, our findings demonstrate with high confidence that a theoretically informed, whole-system approach is necessary to both understand and improve adherence. Clinicians and patients need supporting to understand the need for bisphosphonates, and clinicians need to clarify to patients what constitutes bisphosphonate treatment success. Further research is needed to explore perspectives of male patients and those with multimorbidity receiving bisphosphonates, and patients receiving intravenous treatment

Venous cerebral blood flow quantification and cognition in patients with sickle cell anemia

Prior studies have described high venous signal qualitatively using arterial spin labelling (ASL) in patients with sickle cell anemia (SCA), consistent with arteriovenous shunting. We aimed to quantify the effect and explored cross-sectional associations with arterial oxygen content (CaO2), disease-modifying treatments, silent cerebral infarction (SCI), and cognitive performance. 94 patients with SCA and 42 controls underwent cognitive assessment and MRI with single- and multi- inflow time (TI) ASL sequences. Cerebral blood flow (CBF) and bolus arrival time (BAT) were examined across gray and white matter and high-signal regions of the sagittal sinus. Across gray and white matter, increases in CBF and reductions in BAT were observed in association with reduced CaO2 in patients, irrespective of sequence. Across high-signal sagittal sinus regions, CBF was also increased in association with reduced CaO2 using both sequences. However, BAT was increased rather than reduced in patients across these regions, with no association with CaO2. Using the multiTI sequence in patients, increases in CBF across white matter and high-signal sagittal sinus regions were associated with poorer cognitive performance. These novel findings highlight the utility of multiTI ASL in illuminating, and identifying objectively quantifiable and functionally significant markers of, regional hemodynamic stress in patients with SCA

White Matter Integrity and Processing Speed in Sickle Cell Anemia

Objective The purpose of this retrospective cross-sectional study was to investigate whether changes in white matter integrity are related to slower processing speed in sickle cell anemia. Methods Thirty-seven patients with silent cerebral infarction, 46 patients with normal MRI, and 32 sibling controls (age range 8–37 years) underwent cognitive assessment using the Wechsler scales and 3-tesla MRI. Tract-based spatial statistics analyses of diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) parameters were performed. Results Processing speed index (PSI) was lower in patients than controls by 9.34 points (95% confi- dence interval: 4.635–14.855, p = 0.0003). Full Scale IQ was lower by 4.14 scaled points (95% confidence interval: −1.066 to 9.551, p = 0.1), but this difference was abolished when PSI was included as a covariate (p = 0.18). There were no differences in cognition between patients with and without silent cerebral infarction, and both groups had lower PSI than controls (both p < 0.001). In patients, arterial oxygen content, socioeconomic status, age, and male sex were identified as predictors of PSI, and correlations were found between PSI and DTI scalars (fractional anisotropy r = 0.614, p < 0.00001; r = −0.457, p < 0.00001; mean diffusivity r = −0.341, p = 0.0016; radial diffusivity r = −0.457, p < 0.00001) and NODDI parameters (intracellular volume fraction r = 0.364, p = 0.0007) in widespread regions. Conclusion Our results extend previous reports of impairment that is independent of presence of infarction and may worsen with age. We identify processing speed as a vulnerable domain, with deficits potentially mediating difficulties across other domains, and provide evidence that reduced processing speed is related to the integrity of normal-appearing white matter using microstructure parameters from DTI and NODDI

Study of montelukast in children with sickle cell disease (SMILES): a study protocol for a randomised controlled trial

BACKGROUND: Young children with sickle cell anaemia (SCA) often have slowed processing speed associated with reduced brain white matter integrity, low oxygen saturation, and sleep-disordered breathing (SDB), related in part to enlarged adenoids and tonsils. Common treatments for SDB include adenotonsillectomy and nocturnal continuous positive airway pressure (CPAP), but adenotonsillectomy is an invasive surgical procedure, and CPAP is rarely well-tolerated. Further, there is no current consensus on the ability of these treatments to improve cognitive function. Several double-blind, randomised controlled trials (RCTs) have demonstrated the efficacy of montelukast, a safe, well-tolerated anti-inflammatory agent, as a treatment for airway obstruction and reducing adenoid size for children who do not have SCA. However, we do not yet know whether montelukast reduces adenoid size and improves cognition function in young children with SCA. METHODS: The Study of Montelukast In Children with Sickle Cell Disease (SMILES) is a 12-week multicentre, double-blind, RCT. SMILES aims to recruit 200 paediatric patients with SCA and SDB aged 3-7.99 years to assess the extent to which montelukast can improve cognitive function (i.e. processing speed) and sleep and reduce adenoidal size and white matter damage compared to placebo. Patients will be randomised to either montelukast or placebo for 12 weeks. The primary objective of the SMILES trial is to assess the effect of montelukast on processing speed in young children with SCA. At baseline and post-treatment, we will administer a cognitive evaluation; caregivers will complete questionnaires (e.g. sleep, pain) and measures of demographics. Laboratory values will be obtained from medical records collected as part of standard care. If a family agrees, patients will undergo brain MRIs for adenoid size and other structural and haemodynamic quantitative measures at baseline and post-treatment, and we will obtain overnight oximetry. DISCUSSION: Findings from this study will increase our understanding of whether montelukast is an effective treatment for young children with SCA. Using cognitive testing and MRI, the SMILES trial hopes to gain critical knowledge to help develop targeted interventions to improve the outcomes of young children with SCA. TRIAL REGISTRATION: ClinicalTrials.gov NCT04351698 . Registered on April 17, 2020. European Clinical Trials Database (EudraCT No. 2017-004539-36). Registered on May 19, 2020