The role of depression in the association between mobilisation timing and live discharge after hip fracture surgery: Secondary analysis of the UK National Hip Fracture Database.

PURPOSE: The aim was to compare the probability of discharge after hip fracture surgery conditional on being alive and in hospital between patients mobilised within and beyond 36-hours of surgery across groups defined by depression. METHODS: Data were taken from the National Hip Fracture Database and included patients 60 years of age or older who underwent hip fracture surgery in England and Wales between 2014 and 2016. The conditional probability of postsurgical live discharge was estimated for patients mobilised early and for patients mobilised late across groups with and without depression. The association between mobilisation timing and the conditional probability of live discharge were also estimated separately through adjusted generalized linear models. RESULTS: Data were analysed for 116,274 patients. A diagnosis of depression was present in 8.31% patients. In those with depression, 7,412 (76.7%) patients mobilised early. In those without depression, 84,085 (78.9%) patients mobilised early. By day 30 after surgery, the adjusted odds ratio of discharge among those who mobilised early compared to late was 1.79 (95% CI: 1.56-2.05, p<0.001) and 1.92 (95% CI: 1.84-2.00, p<0.001) for those with and without depression, respectively. CONCLUSION: A similar proportion of patients with depression mobilised early after hip fracture surgery when compared to those without a diagnosis of depression. The association between mobilisation timing and time to live discharge was observed for patients with and without depression.

Barriers and facilitators of weight bearing after hip fracture surgery among older adults. A scoping review.

PURPOSE: This scoping review aimed to synthesise the available evidence on barriers and facilitators of weight bearing after hip fracture surgery in older adults. METHODS: Published (Cochrane Central, MEDLINE, EMBASE, CINAHL, and PEDro) and unpublished (Global Health, EThOS, WorldCat dissertation and thesis, ClinicalTrials.gov , OpenAIRE, DART-Europe) evidence was electronically searched from database inception to 29 March 2022. Barriers and facilitators of weight bearing were extracted and synthesised into patient, process (non-surgical), process (surgical), and structure-related barriers/facilitators using a narrative review approach. RESULTS: In total, 5594 were identified from the primary search strategy, 1314 duplicates were removed, 3769 were excluded on title and abstract screening, and 442 were excluded on full-text screening. In total, 69 studies (all from published literature sources) detailing 47 barriers and/or facilitators of weight bearing were included. Of barriers/facilitators identified, 27 were patient-, 8 non-surgical process-, 8 surgical process-, and 4 structure-related. Patient facilitators included anticoagulant, home discharge, and aid at discharge. Barriers included preoperative dementia and delirium, postoperative delirium, pressure sores, indoor falls, ventilator dependence, haematocrit < 36%, systemic sepsis, and acute renal failure. Non-surgical process facilitators included early surgery, early mobilisation, complete medical co-management, in-hospital rehabilitation, and patient-recorded nurses' notes. Barriers included increased operative time and standardised hip fracture care. Surgical process facilitators favoured intramedullary fixations and arthroplasty over extramedullary fixation. Structure facilitators favoured more recent years and different healthcare systems. Barriers included pre-holiday surgery and admissions in the first quarter of the year. CONCLUSION: Most patient/surgery-related barriers/facilitators may inform future risk stratification. Future research should examine additional process/structure barriers and facilitators amenable to intervention. Furthermore, patient barriers/facilitators need to be investigated by replicating the studies identified and augmenting them with more specific details on weight bearing outcomes.

Effect of inpatient rehabilitation treatment ingredients on functioning, quality of life, length of stay, discharge destination, and mortality among older adults with unplanned admission: an overview review.

BACKGROUND: To synthesise the evidence for the effectiveness of inpatient rehabilitation treatment ingredients (versus any comparison) on functioning, quality of life, length of stay, discharge destination, and mortality among older adults with an unplanned hospital admission. METHODS: A systematic search of Cochrane Library, MEDLINE, Embase, PsychInfo, PEDro, BASE, and OpenGrey for published and unpublished systematic reviews of inpatient rehabilitation interventions for older adults following an unplanned admission to hospital from database inception to December 2020. Duplicate screening for eligibility, quality assessment, and data extraction including extraction of treatment components and their respective ingredients employing the Treatment Theory framework. Random effects meta-analyses were completed overall and by treatment ingredient. Statistical heterogeneity was assessed with the inconsistency-value (I2). RESULTS: Systematic reviews (n = 12) of moderate to low quality, including 44 non-overlapping relevant RCTs were included. When incorporated in a rehabilitation intervention, there was a large effect of endurance exercise, early intervention and shaping knowledge on walking endurance after the inpatient stay versus comparison. Early intervention, repeated practice activities, goals and planning, increased medical care and/or discharge planning increased the likelihood of discharge home versus comparison. The evidence for activities of daily living (ADL) was conflicting. Rehabilitation interventions were not effective for functional mobility, strength, or quality of life, or reduce length of stay or mortality. Therefore, we did not explore the potential role of treatment ingredients for these outcomes. CONCLUSION: Benefits observed were often for subgroups of the older adult population e.g., endurance exercise was effective for endurance in older adults with chronic obstructive pulmonary disease, and early intervention was effective for endurance for those with hip fracture. Future research should determine whether the effectiveness of these treatment ingredients observed in subgroups, are generalisable to older adults more broadly. There is a need for more transparent reporting of intervention components and ingredients according to established frameworks to enable future synthesis and/or replication. TRIAL REGISTRATION: PROSPERO Registration CRD42018114323 .

The impact of the frequency, duration and type of physiotherapy on discharge after hip fracture surgery: a secondary analysis of UK national linked audit data.

Additional physiotherapy in the first postoperative week was associated with fewer days to discharge after hip fracture surgery. A 7-day physiotherapy service in the first postoperative week should be considered as a new key performance indicator in evaluating the quality of care for patients admitted with a hip fracture. INTRODUCTION: To examine the association between physiotherapy in the first week after hip fracture surgery and discharge from acute hospital. METHODS: We linked data from the UK Physiotherapy Hip Fracture Sprint Audit to hospital records for 5395 patients with hip fracture in May and June 2017. We estimated the association between the number of days patients received physiotherapy in the first postoperative week; its overall duration (< 2 h, ≥ 2 h; 30-min increment) and type (mobilisation alone, mobilisation and exercise) and the cumulative probability of discharge from acute hospital over 30 days, using proportional odds regression adjusted for confounders and the competing risk of death. RESULTS: The crude and adjusted odds ratios of discharge were 1.24 (95% CI 1.19-1.30) and 1.26 (95% CI 1.19-1.33) for an additional day of physiotherapy, 1.34 (95% CI 1.18-1.52) and 1.33 (95% CI 1.12-1.57) for ≥ 2 versus < 2 h physiotherapy, and 1.11 (95% CI 1.08-1.15) and 1.10 (95% CI 1.05-1.15) for an additional 30-min of physiotherapy. Physiotherapy type was not associated with discharge. CONCLUSION: We report an association between physiotherapy and discharge after hip fracture. An average UK hospital admitting 375 patients annually may save 456 bed-days if current provision increased so all patients with hip fracture received physiotherapy on 6-7 days in the first postoperative week. A 7-day physiotherapy service totalling at least 2 h in the first postoperative week may be considered a key performance indicator of acute care quality after hip fracture.

Prognostic factors of depression and depressive symptoms after hip fracture surgery: systematic review.

BACKGROUND: Patients with hip fracture and depression are less likely to recover functional ability. This review sought to identify prognostic factors of depression or depressive symptoms up to 1 year after hip fracture surgery in adults. This review also sought to describe proposed underlying mechanisms for their association with depression or depressive symptoms. METHODS: We searched for published (MEDLINE, Embase, PsychInfo, CINAHL and Web of Science Core Collection) and unpublished (OpenGrey, Greynet, BASE, conference proceedings) studies. We did not impose any date, geographical, or language limitations. Screening (Covidence), extraction (Checklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies, adapted for use with prognostic factors studies Checklist), and quality appraisal (Quality in Prognosis Studies tool) were completed in duplicate. Results were summarised narratively. RESULTS: In total, 37 prognostic factors were identified from 12 studies included in this review. The quality of the underlying evidence was poor, with all studies at high risk of bias in at least one domain. Most factors did not have a proposed mechanism for the association. Where factors were investigated by more than one study, the evidence was often conflicting. CONCLUSION: Due to conflicting and low quality of available evidence it is not possible to make clinical recommendations based on factors prognostic of depression or depressive symptoms after hip fracture. Further high-quality research investigating prognostic factors is warranted to inform future intervention and/or stratified approaches to care after hip fracture. TRIAL REGISTRATION: Prospero registration: CRD42019138690 .

The role of infiltrating lymphocytes in the neo-adjuvant treatment of women with HER2-positive breast cancer.

BACKGROUND: Pre-treatment tumour-associated lymphocytes (TILs) and stromal lymphocytes (SLs) are independent predictive markers of future pathological complete response (pCR) in HER2-positive breast cancer. Whilst studies have correlated baseline lymphocyte levels with subsequent pCR, few have studied the impact of neoadjuvant therapy on the immune environment. METHODS: We performed TIL analysis and T-cell analysis by IHC on the pretreatment and 'On-treatment' samples from patients recruited on the Phase-II TCHL (NCT01485926) clinical trial. Data were analysed using the Wilcoxon signed-rank test and the Spearman rank correlation. RESULTS: In our sample cohort (n = 66), patients who achieved a pCR at surgery, post-chemotherapy, had significantly higher counts of TILs (p = 0.05) but not SLs (p = 0.08) in their pre-treatment tumour samples. Patients who achieved a subsequent pCR after completing neo-adjuvant chemotherapy had significantly higher SLs (p = 9.09 × 10-3) but not TILs (p = 0.1) in their 'On-treatment' tumour biopsies. In a small cohort of samples (n = 16), infiltrating lymphocyte counts increased after 1 cycle of neo-adjuvant chemotherapy only in those tumours of patients who did not achieve a subsequent pCR. Finally, reduced CD3 + (p = 0.04, rho = 0.60) and CD4 + (p = 0.01, rho = 0.72) T-cell counts in 'On-treatment' biopsies were associated with decreased residual tumour content post-1 cycle of treatment; the latter being significantly associated with increased likelihood of subsequent pCR (p < 0.01). CONCLUSIONS: The immune system may be 'primed' prior to neoadjuvant treatment in those patients who subsequently achieve a pCR. In those patients who achieve a pCR, their immune response may return to baseline after only 1 cycle of treatment. However, in those who did not achieve a pCR, neo-adjuvant treatment may stimulate lymphocyte influx into the tumour.

Inequity in rehabilitation interventions after hip fracture: a systematic review.

OBJECTIVE: to determine the extent to which equity factors contributed to eligibility criteria of trials of rehabilitation interventions after hip fracture. We define equity factors as those that stratify healthcare opportunities and outcomes. DESIGN: systematic search of MEDLINE, Embase, CINHAL, PEDro, Open Grey, BASE and ClinicalTrials.gov for randomised controlled trials of rehabilitation interventions after hip fracture published between 1 January 2008 and 30 May 2018. Trials not published in English, secondary prevention or new models of service delivery (e.g. orthogeriatric care pathway) were excluded. Duplicate screening for eligibility, risk of bias (Cochrane Risk of Bias Tool) and data extraction (Cochrane's PROGRESS-Plus framework). RESULTS: twenty-three published, eight protocol, four registered ongoing randomised controlled trials (4,449 participants) were identified. A total of 69 equity factors contributed to eligibility criteria of the 35 trials. For more than 50% of trials, potential participants were excluded based on residency in a nursing home, cognitive impairment, mobility/functional impairment, minimum age and/or non-surgical candidacy. Where reported, this equated to the exclusion of 2,383 out of 8,736 (27.3%) potential participants based on equity factors. Residency in a nursing home and cognitive impairment were the main drivers of these exclusions. CONCLUSION: the generalisability of trial results to the underlying population of frail older adults is limited. Yet, this is the evidence base underpinning current service design. Future trials should include participants with cognitive impairment and those admitted from nursing homes. For those excluded, an evidence-informed reasoning for the exclusion should be explicitly stated. PROSPERO: CRD42018085930.

Prognostic factors of in-hospital complications after hip fracture surgery: a scoping review.

INTRODUCTION: To examine prognostic factors that influence complications after hip fracture surgery. To summarize proposed underlying mechanisms for their influence. METHODS: We reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Scoping Review extension. We searched MEDLINE, Embase, CINAHL, AgeLine, Cochrane Library, and reference lists of retrieved studies for studies of prognostic factor/s of postoperative in-hospital medical complication/s among patients 50 years and older treated surgically for non-pathological closed hip fracture, published in English on January 2008-January 2018. We excluded studies of surgery type or in-hospital medications. Screening was duplicated by two independent reviewers. One reviewer completed the extraction with accuracy checks by the second reviewer. We summarized the extent, nature, and proposed underlying mechanisms for the prognostic factors of complications narratively and in a dependency graph. RESULTS: We identified 44 prognostic factors of in-hospital complications after hip fracture surgery from 56 studies. Of these, we identified 7 patient factors-dehydration, anemia, hypotension, heart rate variability, pressure risk, nutrition, and indwelling catheter use; and 7 process factors-time to surgery, anesthetic type, transfusion strategy, orthopedic versus geriatric/co-managed care, multidisciplinary care pathway, and potentially modifiable during index hospitalization. We identified underlying mechanisms for 15 of 44 factors. The reported association between 12 prognostic factors and complications was inconsistent across studies. CONCLUSIONS: Most factors were reported by one study with no proposed underlying mechanism for their influence. Where reported by more than one study, there was inconsistency in reported associations and the conceptualization of complications differed, limiting comparison across studies. It is therefore not possible to be certain whether intervening on these factors would reduce the rate of complications after hip fracture surgery.

Discharge destination following hip fracture in Canada among previously community-dwelling older adults, 2004-2012: database study.

Little is known about post-acute care following hip fracture surgery. We investigated discharge destinations from surgical hospitals for nine Canadian provinces. We identified significant heterogeneity in discharge patterns across provinces suggesting different post-acute recovery pathways. Further work is required to determine the impact on patient outcomes and health system costs. INTRODUCTION: To examine discharge destinations by provinces in Canada, adjusting for patient, injury, and care characteristics. METHODS: We analyzed population-based hospital discharge abstracts from a national administrative database for community-dwelling patients who underwent hip fracture surgery between 2004 and 2012 in Canada. Discharge destination was categorized as rehabilitation, home, acute care, and continuing care. Multinomial logistic regression modeling compared proportions of discharge to rehabilitation, acute care, and continuing care versus home between each province and Ontario. Adjusted risk differences and risk ratios were estimated. RESULTS: Of 111,952 previously community-dwelling patients aged 65 years or older, 22.5% were discharged to rehabilitation, 31.6% to home, 27.0% to acute care, and 18.2% to continuing care, with significant variation across provinces (p < 0.001). The proportion of discharge to rehabilitation ranged from 2.4% in British Columbia to 41.0% in Ontario while the proportion discharged home ranged from 20.3% in Prince Edward Island to 52.2% in British Columbia. The proportion of discharge to acute care ranged from 15.2% in Ontario to 58.8% in Saskatchewan while the proportion discharged to continuing care ranged from 9.3% in Manitoba and Prince Edward Island to 22.9% in New Brunswick. Adjusting for hospital type changed the direction of the provincial effect on discharge to continuing care in two provinces, but statistical significance remained consistent with the primary analysis. CONCLUSIONS: Discharge destination from the surgical hospital after hip fracture is highly variable across nine Canadian provinces. Further work is required to determine the impact of this heterogeneity on patient outcomes and health system costs.

The uptake of the hip fracture core outcome set: analysis of 20 years of hip fracture trials.

BACKGROUND: clinical trials test the effectiveness or efficacy of treatments. It is important that researchers evaluate interventions with the most meaningful outcome measures. The 2014 hip fracture core outcome set recommended that mortality, mobility, pain, activities of daily living and health-related quality of life (HRQOL) should be assessed in all trials of patient with hip fracture. The purpose of this analysis was to determine the uptake of these recommendation. METHODS: all trials registered from 1997 to 2018 recruiting participants following hip fracture were identified from the ClinicalTrials.gov trials registry. The frequency of each core domain adopted annually were assessed. RESULTS: 311 trials were identified and analysed. On analysing trial registries for years which presented a minimum of 10 registrations, full core outcome set adoption ranged from 0% (2017; 2018) to 24% (2009). Mortality and mobility were the most consistently reported domains (mortality: 27% (2017) to 56% (2011); mobility: 36% (2015) to 60% (2004)). In contrast, pain and HRQOL were least reported (pain: 14% (2017) to 61% (2015); HRQOL: 10% (2010) to 11% (2008)). There was no clear change in core outcome domain set adoption following the publication of Hayward et al.'s (2014) core outcome set. CONCLUSIONS: there has been limited adoption of the hip fracture core outcome set from its publication in 2014. Further consideration to improve implementation is required to improved uptake.

Orientation and verbal fluency in the English Longitudinal Study of Ageing: modifiable risk factors for falls?

OBJECTIVES: To determine the relationship between falls and deficits in specific cognitive domains in older adults. DESIGN: An analysis of the English Longitudinal Study of Ageing (ELSA) cohort. SETTING: United Kingdom community-based. PARTICIPANTS: 5197 community-dwelling older adults recruited to a prospective longitudinal cohort study. MEASUREMENTS: Data on the occurrence of falls and number of falls, which occurred during a 12-month follow-up period, were assessed against the specific cognitive domains of memory, numeracy skills, and executive function. Binomial logistic regression was performed to evaluate the association between each cognitive domain and the dichotomous outcome of falls in the preceding 12 months using unadjusted and adjusted models. RESULTS: Of the 5197 participants included in the analysis, 1308 (25%) reported a fall in the preceding 12 months. There was no significant association between the occurrence of a fall and specific forms of cognitive dysfunction after adjusting for self-reported hearing, self-reported eyesight, and functional performance. After adjustment, only orientation (odds ratio [OR]: 0.80; 95% confidence intervals [CI]: 0.65-0.98, p = 0.03) and verbal fluency (adjusted OR: 0.98; 95% CI: 0.96-1.00; p = 0.05) remained significant for predicting recurrent falls. CONCLUSIONS: The cognitive phenotype rather than cognitive impairment per se may predict future falls in those presenting with more than one fall.

Prognostic factors of functional outcome after hip fracture surgery: a systematic review.

Objective: this systematic review aimed to identify immutable and modifiable prognostic factors of functional outcomes and their proposed mechanism after hip fracture surgery. Design: systematic search of MEDLINE, Embase, CINAHL, PEDRO, OpenGrey and ClinicalTrials.gov for observational studies of prognostic factors of functional outcome after hip fracture among surgically treated adults with mean age of 65 years and older. Study selection, quality assessment, and data extraction were completed independently by two reviewers. The Quality in Prognosis Studies Tool was used for quality assessment and assigning a level of evidence to factors. Proposed mechanisms for reported associations were extracted from discussion sections. Results: from 33 studies of 9,552 patients, we identified 25 prognostic factors of functional outcome after hip fracture surgery. We organised factors into groups: demographics, injury and comorbidities, body composition, complications, and acute care. We assigned two factors a weak evidence level-anaemia and cognition. We assigned Parkinson's disease an inconclusive evidence level. We could not assign an evidence level to the remaining 22 factors due to the high risk of bias across studies. Frailty was the proposed mechanism for the association between anaemia and functional outcome. Medication management, perceived potential, complications and time to mobility were proposed as mechanisms for the association between cognition and functional outcome. Conclusion: we identified one modifiable and one immutable prognostic factor for functional outcomes after hip fracture surgery. Future research may target patients with anaemia or cognitive impairment by intervening on the prognostic factor or the underlying mechanisms.

Time to surgery after hip fracture across Canada by timing of admission.

The extent of Canadian provincial variation in hip fracture surgical timing is unclear. Provinces performed a similar proportion of surgeries within three inpatient days after adjustment. Time to surgery varied by timing of admission across provinces. This may reflect different approaches to providing access to hip fracture surgery. INTRODUCTION: The aim of this study was to compare whether time to surgery after hip fracture varies across Canadian provinces for surgically fit patients and their subgroups defined by timing of admission. METHODS: We retrieved hospitalization records for 140,235 patients 65 years and older, treated surgically for hip fracture between 2004 and 2012 in Canada (excluding Quebec). We studied the proportion of surgeries on admission day and within 3 inpatient days, and times required for 33%, 66%, and 90% of surgeries across provinces and by subgroups defined by timing of admission. Differences were adjusted for patient, injury, and care characteristics. RESULTS: Overall, provinces performed similar proportions of surgeries within the recommended three inpatient days, with all provinces requiring one additional day to perform the recommended 90% of surgeries. Prince Edward Island performed 7.0% more surgeries on admission day than Ontario irrespective of timing of admission (difference = 7.0; 95% CI 4.0, 9.9). The proportion of surgeries on admission day was 6.3% lower in Manitoba (difference = - 6.3; 95% CI - 12.1, - 0.6), and 7.7% lower in Saskatchewan (difference = - 7.7; 95% CI - 12.7, - 2.8) compared to Ontario. These differences persisted for late weekday and weekend admissions. The time required for 33%, 66%, and 90% of surgeries ranged from 1 to 2, 2-3, and 3-4 days, respectively, across provinces by timing of admission. CONCLUSIONS: Provinces performed similarly with respect to recommended time for hip fracture surgery. The proportion of surgeries on admission day, and time required to complete 33% and 66% of surgeries, varied across provinces and by timing of admission. This may reflect different provincial approaches to providing access to hip fracture surgery.

No One Saw This Coming: Endoparasitic Mites Behind the Eyes of a Double-Crested Cormorant.

We found hundreds of mites behind the eyes of a Double-crested Cormorant, Phalacrocorax auritus (Suliformes: Phalacrocoracidae). The mites were Neottialges evansi (Acari: Hypoderatidae), representing the first report of this parasite in P. auritus from western North America. Deutonymphs of N. evansi are endoparasites, typically reported infecting fat deposits over the pectoral muscles, axillary areas, and vent of cormorants. Here mites infected only orbital tissues, a new infection site for hypoderatid mites. We suggest a lack of reports of this infection site could be explained by limited scrutiny of orbits, and deutonymphs mites infecting orbits may be more common than expected.

The influence of geographical location, host maturity and sex on intestinal helminth communities of the double-crested cormorant Phalacrocorax auritus from the eastern United States.

Here the intestinal helminth infracommunities of 218 double-crested cormorants (Phalacrocorax auritus) from 11 locations in Alabama, Minnesota, Mississippi and Vermont are documented. Trematode infections were present in 98% of hosts; 65% of cormorants carried cestode infections, 4% were infected with acanthocephalans and 66% had nematode intestinal parasites. Parasite infracommunities of hosts collected on wintering grounds had higher richness and diversity than did birds collected on breeding grounds. Differences in parasite richness and diversity between male and female P. auritus were also detected, but not between immature and mature bird hosts. Parasite intensity did not differ by sex, maturity, or between breeding and wintering season. The most common parasite was Drepanocephalus auritus (spathans), which is recognized as a disease agent that negatively impacts the catfish aquaculture industry in the US. Echinochasmus sp. in double-crested cormorants is documented for the first time in the United States. We suggest that the differences observed among parasite infracommunities could be associated with the foraging distances travelled by P. auritus during breeding and wintering seasons, which is limited by allocation of parental care during the breeding season.

Patient and system factors of mortality after hip fracture: a scoping review.

BACKGROUND: Several patient and health system factors were associated with the risk of death among patients with hip fracture. However, without knowledge of underlying mechanisms interventions to improve survival post hip fracture can only be designed on the basis of the found statistical associations. METHODS: We used the framework developed by Arksey and O'Malley and Levac et al. for synthesis of factors and mechanisms of mortality post low energy hip fracture in adults over the age of 50 years, published in English, between September 1, 2009 and October 1, 2014 and indexed in MEDLINE. Proposed mechanisms for reported associations were extracted from the discussion sections. RESULTS: We synthesized the evidence from 56 articles that reported on 35 patient and 9 system factors of mortality post hip fracture. For 21 factors we found proposed biological mechanisms for their association with mortality which included complications, comorbidity, cardiorespiratory function, immune function, bone remodeling and glycemic control. CONCLUSIONS: The majority of patient and system factors of mortality post hip fracture were reported by only one or two articles and with no proposed mechanisms for their effects on mortality. Where reported, underlying mechanisms are often based on a single article and should be confirmed with further study. Therefore, one cannot be certain whether intervening on such factors may produce expected results.

Pre-treatment protoporphyrin IX concentration in actinic keratosis lesions may be a predictive biomarker of response to aminolevulinic-acid based photodynamic therapy.

BACKGROUND: Although aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) photodynamic therapy (PDT) is an effective FDA-approved therapy for actinic keratosis (AK), a substantial fraction of patients (up to 25%) do not respond to treatment. This study examined the feasibility of using pre-treatment measurements of PpIX concentration in AK lesions to predict response of ALA-PpIX PDT. METHODS: A non-invasive fiber-optic fluorescence spectroscopy system was used to measure PpIX concentration in patients undergoing standard-of-care ALA-PDT for AK. All patients provided assessments of pain at the time of treatment (n=70), and a subset reported pain and erythema 48-76 h after treatment (n=13). RESULTS: PpIX concentration was significantly higher in lesions of patients reporting high levels of pain (VAS score ≥5) immediately after treatment vs. patients reporting pain scores below VAS=5 (p<0.022) (n=70). However, pain was not an exclusive indicator of PpIX concentration as many patients with low PpIX concentration reported high pain. In a subpopulation of patients surveyed in the days after treatment (n=13), PpIX concentration measured on the day of treatment was uncorrelated with pain-reported immediately after treatment (r=0.17, p<0.57), but positive correlations were found between PpIX concentration and patient-reported pain (r=0.55, p<0.051) and erythema (r=0.58, p<0.039) in the 48-72 h following treatment. CONCLUSIONS: These data suggest that in vivo optical measurements of PpIX concentration acquired before light delivery may be an objective predictor of response to ALA-PpIX PDT. Identification of non-responding patients on the day of treatment could facilitate the use of interventions that may improve outcomes.

Excess mortality associated with second hip fracture.

UNLABELLED: Hip fracture increases death risk. Ten percent of survivors have second hip fracture. It is not known if second hip fracture further increases death risk. Here, we report that second hip fracture increases death risk beyond that expected for an increase in age. Secondary prevention after hip fracture could save lives. INTRODUCTION: The purpose of this study is to determine if second hip fracture is associated with an increased death rate. METHODS: We retrieved 42,435 hospitalization records of patients aged 60 years or older, who were discharged after admission for hip fracture surgery between 1990 and 2005 in British Columbia, Canada. The outcome variable was the time to death. RESULTS: During follow-up, the average monthly death rate was 16.2 (95 % CI 16.0-16.4) per 1000 patient-months for those without second hip fracture and 21.1 (95 % CI 20.2-22.1) per 1000 patient-months for those with second hip fracture. The hazard of death was 55 % higher for patients with second hip fracture compared to those without second hip fracture (HR = 1.55, 95 % CI 1.47-1.63). The hazard of death was 58 % higher for men with second hip fracture than in men without second hip fracture (HR = 1.58, 95 % CI 1.42-1.75). The hazard of death was 54 % higher for women with second hip fracture compared to women without second hip fracture (HR = 1.54, 95 % CI 1.46-1.63). These sex-specific HRs were not statistically different (p = 0.70). CONCLUSION: Our results are the first to show that second hip fracture increases the risk of death above that anticipated for an increase in age for both men and women. Effective secondary prevention strategies could not only reduce morbidity after hip fracture but could also save lives.