A multicentre integration of a computer-led follow-up of prostate cancer is valid and safe.

OBJECTIVE: To test a computer-led follow-up service for prostate cancer in two UK hospitals; the testing aimed to validate the computer expert system in making clinical decisions according to the individual patient's clinical need with a valid model accurately identify patients with disease recurrence or treatment failure based on their blood test and clinical picture. PATIENTS AND METHODS: A clinical-decision support system (CDSS) was developed from European (European Association of Urology) and national (National Institute for Health and Care Excellence) guidelines along with knowledge acquired from Urologists. This model was then applied in two UK hospitals to review patients after prostate cancer treatment. These patients' data (n = 200) were then reviewed by two independent urology consultants (blinded from the CDSS and the other consultant's rating) and the agreement was calculated by kappa statistics for validation. The second endpoint was to verify the system by estimating the system reliability. RESULTS: The two individual urology consultants identified 12% and 15% of the patients to have potential disease progression and recommended their referral to urology care. The kappa coefficient for the agreement between the CDSS and the two consultants was 0.81 (P < 0.001) and 0.84 (P < 0.001). The agreement amongst both specialist was also high with k = 0.83 (P < 0.001). The system reliability was estimated on all cases and this demonstrated 100% repeatability of the decisions. CONCLUSION: A CDSS follow-up is a valid model for providing safe follow-up for prostate cancer.

Evaluation of a retrospective diary for peri-conceptual and mid-pregnancy drinking in Scotland: a cross-sectional study.

INTRODUCTION: Heavy episodic ("binge") drinking among women in Scotland is commonplace; prepregnancy drinking is associated with continued antenatal drinking. Evidence for effectiveness of standardized antenatal alcohol assessment is lacking. Alcohol-exposed pregnancies may be missed. We assessed peri-conceptual and mid-pregnancy consumption using a week-long retrospective diary and standard alcohol questionnaires, and evaluated the agreement between these instruments. MATERIAL AND METHODS: Cross-sectional study in two Scottish health board areas involving 510 women attending mid-pregnancy ultrasound scan clinics. Face-to-face administration of alcohol retrospective diary and AUDIT or AUDIT-C assessed weekly and daily alcohol consumption levels and patterns. Depression-Anxiety-Stress Scale (DASS-21) assessed maternal wellbeing. A sub-sample (n = 30) provided hair for alcohol metabolite analysis. Pearson's correlation coefficient investigated associations between questionnaires and alcohol metabolite data. RESULTS: The response rate was 73.8%. The retrospective diary correlated moderately with AUDIT-C and AUDIT but elicited reports of significantly higher peri-conceptual consumption, (median unit consumption on "drinking days" 6.8; range 0.4-63.8). Additional "special occasions" consumption ranged from 1 to 125 units per week. Correlations between DASS-21 and retrospective diary were weak. Biomarker analysis identified three instances of hazardous peri-conceptual drinking. CONCLUSIONS: Women reported higher consumption levels when completing the retrospective diary, especially regarding peri-conceptual "binge" drinking. Routine clinical practice methods may not capture potentially harmful or irregular drinking patterns. Given the association between prepregnancy and antenatal drinking, and alcohol's known teratogenic effects, particularly in the first trimester, the retrospective diary may be a useful low-tech tool to gather information on alcohol intake patterns and levels.

Psychoactive prescribing for older people--what difference does 15 years make?

OBJECTIVE: The objective of the study was to review prescribing of psychoactive medications for older residents of the Tayside region of Scotland. METHODS: The analysis used community prescribing data in 1995 and 2010 for all older residents in Tayside. For each psychoactive drug class, the name of the most recently prescribed drug and the date prescribed were extracted. The relative risk (RR) and 95% confidence intervals (CI) for patients receiving psychoactive medication in 2010 were compared with those for patients in 1995. Psychoactive prescribing was analyzed by year, age, gender, and deprivation classification. The chi-squared test was used to calculate statistical significance. RESULTS: Total psychoactive prescribing in people over the age of 65 years has increased comparing 1995 with 2010. Antidepressant [RR = 2.5 (95% CI 2.41-2.59) p < 0.001] and opioid analgesia [RR = 1.21 (1.19-1.24) p < 0.001] prescriptions increased between 1995 and 2010. Hypnotics/anxiolytic [RR = 0.69 (0.66-0.71) p < 0.001] and antipsychotic [RR = 0.83 (0.77-0.88) p < 0.001] prescriptions decreased between 1995 and 2010. An increase in psychoactive prescribing is particularly marked in lower socioeconomic groups. Patients in the least affluent fifth of the population had RR = 1.25 (1.20-1.29) [p < 0.001] of being prescribed one to two psychoactive medications and RR = 1.81 (1.56-2.10) [p < 0.001] of being prescribed three or more psychoactive medications in 2010 compared with those in 1995. The RRs for the most affluent fifth were RR = 1.14 (1.1-1.19) [p < 0.001] and RR = 1.2 (1.01-1.42) [p < 0.001] for one to two, and three or more medications, respectively. CONCLUSION: Psychoactive medication prescribing has increased comparing 1995 with 2010, with increases disproportionately affecting patients in lower socioeconomic groups. The availability of new psychoactive drugs, safety concerns, and economic factors may explain these increases.

Peri-Conceptual and Mid-Pregnancy Alcohol Consumption: A Comparison between Areas of High and Low Deprivation in Scotland.

BACKGROUND: Alcohol-related mortality and morbidity among women has increased over recent decades, especially in areas of higher deprivation. Pre-pregnancy alcohol use is associated with continued consumption in pregnancy. We assessed whether general population alcohol consumption patterns were reflected among pregnant women in two Scottish areas with different deprivation levels. METHODS: Cross-sectional study in two health boards (HB1, lower deprivation levels, n = 274; HB2, higher deprivation levels, n = 236), using face-to-face 7-day Retrospective Diary estimation of peri-conceptual and mid-pregnancy alcohol consumption. RESULTS: A greater proportion of women in HB2 (higher deprivation area) sometimes drank peri-conceptually, but women in HB1 (lower deprivation area) were more likely to drink every week (49.6 vs 29.7%; p < 0.001) and to exceed daily limits (6 units) at least once each week (32.1 vs 14.8%; p < 0.001). After pregnancy recognition, consumption levels fell sharply, but women in HB2 were more likely to drink above recommended daily limits (2 units) each week (2.5 vs 0.0%; p < 0.05). However, women in HB1 were more likely to drink frequently. Women with the highest deprivation scores in each area drank on average less than women with the lowest deprivation scores. CONCLUSIONS: Heavy episodic and frequent consumption was more common in the lower deprivation area, in contrast with general population data. Eliciting a detailed alcohol history at the antenatal booking visit, and not simply establishing whether the woman is currently drinking, is essential. Inconsistent messages about the effects of alcohol in pregnancy may have contributed to the mixed picture we found concerning peri-conceptual and mid-pregnancy alcohol consumption.

The aneurysmal arteriovenous fistula - morphological study and assessment of clinical implications. A pilot study.

Aneurysmal dilation of arteriovenous fistulae used for haemodialysis is a recognised complication but its clinical significance is a contentious issue. Our aims were to describe aneurysmal fistulae morphologically and clinically.Sixty patients underwent duplex scanning to measure the maximum diameter and skin thickness of their fistula. Haemodialysis function and bleeding risk were assessed clinically.The 75th percentile of maximum diameter was 2.05 cm. In addition to conventional diameter measurement, we describe a novel volume measurement technique which may be of value. No relationship was found between maximum diameter or volume and function, skin thickness or bleeding.Some studies define aneurysm at 2 cm (75th percentile); however, this definition and other arbitrary definitions lack clinical significance. This work suggests that fistula dilation should be considered together with clinical issues when determining the clinical significance of an aneurysm. Our finding that haemodialysis function, skin thickness and bleeding were not associated with diameter needs further study.

The use and efficacy of intra-operative stress tests in supination-external rotation IV ankle fracture fixation.

This study examines stress radiograph use in SER IV ankle fracture fixation; the efficacy of external rotation (ERST) and lateral hook (LHST) stress tests with incidence of subsequent fixation failure secondary to syndesmotic diastasis. 154 skeletally mature patients were admitted to our unit with ankle fractures in 12 months. 42 non-SER fractures and 32 SER fractures treated without ORIF were excluded, as were 14 which featured a syndesmotic screw in the primary ORIF. The remaining 66 SER IV fixations were included in the final sample (17 men, 49 women; median age 49 years). No stress test was performed in 51.5% of cases without a single subsequent failure in these fixations. ERST was the more commonly performed test (incidence 30.3%); negative predictive value (NPV) 0.95. Incidence of LHST was 18.2%; NPV 0.83. Both tests were performed in 6.1% of cases; NPV 0.75. The incidence of failure secondary to syndesmotic diastasis was 6.1% (4/66). Notably, there were no failures in the cases where no stress test was performed. Use of either or both external rotation and lateral hook stress tests resulted in failures to detect syndesmotic diastasis with consequent failure of fixation. This study suggests that syndesmotic injuries are not missed due to an absence of a stress test but that stress tests are not sufficiently sensitive or correctly interpreted. Clinical judgement in cases where syndesmotic injury is not present appears accurate. If syndesmotic injury is clinically suspected, apply caution and insert a syndesmotic screw rather than relying on stress test results.

Total knee arthroplasty in the elderly: does age affect pain, function or complications?

BACKGROUND: TKA is one of the most commonly performed procedures in the elderly, yet whether age influences postoperative pain, function, and complication rates is not fully understood for this group. This is because the current literature has limited followup, small sample sizes, and no comparator group. QUESTIONS/PURPOSES: We therefore asked if increasing age adversely affects postoperative pain, Knee Society Scores(©), and complication rates. METHODS: We retrospectively reviewed all 438 patients 80 years or older who underwent primary TKA between 1995 and 2005. We established a comparator group of 2754 patients younger than 80 years. We assessed pain, the Knee Society Score(©) (KSS), and the Knee Society Function Score(©) (KSFS). The number and type of complications were recorded and those graded 2 or more using the classification of Dindo et al. were analyzed. Minimum followup was 5 years (mean, 6 years; range, 5-15.5 years). RESULTS: We found no difference in pain scores at 3, 5, and 10 years between the two groups. The KSS was comparable between groups at Year 5, but the KSFS was lower in the octogenarians. Major complications rates were higher in the octogenarian group (19% versus 15%). CONCLUSIONS: When compared with younger patients, octogenarians can expect comparable pain relief and KSS but lower function and more complications.

Outcomes of total hip arthroplasty in the octogenarian population.

BACKGROUND: The outcomes of total hip arthroplasty (THA) in the elderly population are uncertain. With the rapid expansion of this population group, this study aims to determine whether increasing age affects the outcomes of THA by utilising the largest patient cohort and follow-up period within the literature. PATIENTS AND METHODS: All patients of 80 years and over who underwent primary THA between 1994 and 2004 at the authors' institution were compared to a cohort aged under 80 with the same diagnoses and during the same time period. Mean follow-up time was 5.9 years with a select group being reviewed at year 10. RESULTS: Pain scores were comparable at year five, whilst mean Harris hip scores were significantly lower in the octogenarians. Median hospital stay was three days longer in the elderly group. Complication rates were also higher (38.1% cf 28.7%) however fewer cases of revision were noted (1.4% cf 3.8%). Patient satisfaction was comparable between groups. CONCLUSION: This study suggests pain improvement, low revision rates and high satisfaction are sufficient to justify THA in the elderly population.

Impact of student choice on academic performance: cross-sectional and longitudinal observations of a student cohort.

BACKGROUND: Student choice plays a prominent role in the undergraduate curriculum in many contemporary medical schools. A key unanswered question relates to its impact on academic performance. METHODS: We studied 301 students who were in years 2 and 3 of their medical studies in 2005/06. We investigated the relationship between SSC grade and allocated preference. Separately, we examined the impact of 'self-proposing' (students designing and completing their own SSC) on academic performance in other, standard-set, summative assessments throughout the curriculum. The chi-squared test was used to compare academic performance in SSC according to allocated preference. Generalised estimating equations were used to investigate the effect of self-proposing on performance in standard-set examinations. RESULTS: (1) Performance in staff-designed SSC was not related to allocated preference. (2) Performance in year 1 main examination was one of the key predictors of performance in written and OSCE examinations in years 2, 3 and 4 (p<0.001). (3) The higher the score in the year 1 examination, the more likely a student was to self-propose in subsequent years (OR [CI] 1.07 [1.03-1.11], p<0.001). (4) Academic performance of students who self-proposed at least once in years 2 and/or 3 varied according to gender and year of course. CONCLUSION: In this study, no association was observed between allocated preference and SSC grade. The effect of self-proposing on academic performance in standard-set examinations was small. Our findings suggest instead that academically brighter students are more likely to design their own modules. Although student choice may have educational benefits, this report does not provide convincing evidence that it improves academic performance.

Primary total knee arthroplasty in patients with Parkinson's disease: analysis of outcomes.

The prevalence of Parkinson's disease is expected to rise. We evaluated the short-term clinical outcomes following primary Total Knee Arthroplasty (TKA) in a group of patients with Parkinson's disease in a case controlled study. Within the review period 32 TKAs were implanted in patients with Parkinson's disease and 33 TKAs were implanted in an age-matched control group (mean age: 73 years). Pre-operatively there were no between-group differences in Knee Society Score, Pain score, Knee Society Function Score or range of movement. Knee Society Score (KSS) improved in both groups post-operatively with no significant between-group differences (p = 0.707). Pain score also improved in both groups. There was no functional improvement following TKA in the Parkinson group. Total Knee Arthroplasty provided excellent pain relief in patients with Parkinson's disease with an acceptable complication profile, although functional ability did not improve.

Thermal fusion: effects and interactions of temperature, compression, and duration variables.

BACKGROUND: The constraints imposed by minimal access surgery have driven the need for enabling technologies for thermal vessel occlusion or "tissue welding." The objective of this study was to determine the values of, and interaction between, tissue temperature, apposition force, and clamp time for optimum tissue welding. METHODS: A dedicated experimental device with heated occluding jaws was used for ex vivo experiments on harvested sheep carotid vessels. The device allowed individual variation of temperature (60, 70, 80, and 90 °C), compression force (20, 40, 60, and 80 N) and clamp time (5, 10, 15 s). Weld strength was measured by burst pressure. RESULTS: The best seal quality was obtained at a temperature of 90 °C (p = 0.03), a compression force between 60 and 80 N (p = 0.03), and clamp time of 10 s (p = 0.058). The individual effects of temperature, compression force, and clamp time were all significant at p < 0.001. Although all three were considered to have large effects, clamp time had a reduced effect, relative to temperature and compression force. CONCLUSIONS: Temperature, compression force, and clamp time influence the quality of thermal welding, but the interaction between temperature and apposition force appears to be more dominant.

Dose-intensified treatment of Burkitt lymphoma and B-cell lymphoma unclassifiable, (with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma) in young adults (<50 years): a comparison of two adapted BFM protocols.

The chemotherapy dose-intensity in two adapted German BFM paediatric protocols (BFM 90 and NHL 86) was compared in contemporaneously treated adults <50 years with Burkitt lymphoma and B-cell lymphoma unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (collectively referred to as BL). In BFM 90, primary prophylaxis with Granulocyte-colony-stimulating factor was used, postinduction treatment was started at granulocytes > or =0.5 x 10(9)/L (> or =1.0 x 10(9)/L in NHL 86) with a higher mean methotrexate dose (2.9 g/m(2)/cycle, n = 23; 1.6 g/m(2)/cycle in NHL 86, n = 22, P < 0.001). Intervals between consecutive treatment-cycles were shorter in BFM 90 (P < 0.001) with no additional toxicity. However, the two-year failure-free survival with BFM 90 (82%) was similar to that achieved with NHL 86 (72%, P = 0.33). We conclude that BFM 90 enables safe intensification of therapy in young adults with BL compared to NHL 86, but registry-based studies are required to further evaluate the antineoplastic effects and cost-effectiveness of the two therapeutic approaches.

Is familial adenomatous polyposis associated with sensorineural hearing loss?

Abstract The mutation causing familial adenomatous polyposis (FAP) affects the adenomatous polyposis coli (Apc) gene, which has a role in the cytoskeleton and has been shown to be important in the structure of supporting cells in the cochlea. One previous study suggested that FAP sufferers may have sensorineural hearing loss. In order to demonstrate whether this is the case we invited patients known to suffer from familial adenomatous polyposis to take part in our study. Audiograms were performed and compared to normal values for that patient's age and gender calculated using ISO standard data. Thirteen patients were included in the study analysis. No conductive hearing losses were identified. A statistically significant greater hearing loss was identified at 500 Hz (2.8 dBHL, P = 0.03) and 1000 Hz (2.5 dBHL, P = 0.05). No audiometric difference could be identified between the patients with FAP and attenuated FAP. A power calculation demonstrated that the study was of adequate size. This study did not demonstrate a clinically significant difference in hearing loss between the FAP group and the calculated normal values.

Association between bisphosphonate therapy and outcomes from rehabilitation in older people.

BACKGROUND: Bisphosphonate therapy may have actions beyond bone, including effects on cardiovascular, immune and muscle function. We tested whether bisphosphonate treatment is associated with improved outcomes in older people undergoing inpatient rehabilitation. METHODS: Analysis of prospectively collected, linked routine clinical datasets. Participants were divided into never users of bisphosphonates, use prior to rehabilitation only, use after rehabilitation only, and current users (use before and after rehabilitation). We calculated change in 20-point Barthel scores during rehabilitation, adjusting for comorbid disease and laboratory data using multivariable regression analysis. Cox regression analyses were performed to analyse the association between bisphosphonate use and time to death or hospitalisation. RESULTS: 2797 patients were included in the analysis. Current bisphosphonate users showed greater improvement in Barthel score during rehabilitation than non-users (5.0 points [95%CI 4.3-5.7] vs 3.8 [95%CI 3.6-3.9]), but no difference compared to those receiving bisphosphonates only after discharge (5.1 [95%CI 4.6-5.5]). Previous bisphosphonate use was significantly associated with time to death (adjusted hazard ratio 1.41 [95%CI 1.15-1.73]) but less strongly with time to combined endpoint of hospitalisation or death (adjusted hazard ratio 1.18 [95%CI 0.98-1.48]). Use after discharge from rehabilitation was associated with reduced risk of death (adjusted hazard ratio 0.64 [95%CI 0.55-0.73]; hazard ratio per year of bisphosphonate prescription 0.98 [95%CI 0.97-0.99]). CONCLUSION: Bisphosphonate use is unlikely to be causally associated with improved physical function in older people, but continuing use may be associated with lower risk of death.

Identifying risk factors for progression to critical care admission and death among individuals with acute pancreatitis: a record linkage analysis of Scottish healthcare databases.

OBJECTIVES: Acute pancreatitis (AP) can initiate systemic complications that require support in critical care (CC). Our objective was to use the unified national health record to define the epidemiology of AP in Scotland, with a specific focus on deterministic and prognostic factors for CC admission in AP. SETTING: Health boards in Scotland (n=4). PARTICIPANTS: We included all individuals in a retrospective observational cohort with at least one episode of AP (ICD10 code K85) occurring in Scotland from 1 April 2009 to 31 March 2012. 3340 individuals were coded as AP. METHODS: Data from 16 sources, spanning general practice, community prescribing, Accident and Emergency attendances, hospital in-patient, CC and mortality registries, were linked by a unique patient identifier in a national safe haven. Logistic regression and gamma models were used to define independent predictive factors for severe AP (sAP) requiring CC admission or leading to death. RESULTS: 2053 individuals (61.5% (95% CI 59.8% to 63.2%)) met the definition for true AP (tAP). 368 patients (17.9% of tAP (95% CI 16.2% to 19.6%)) were admitted to CC. Predictors of sAP were pre-existing angina or hypertension, hypocalcaemia and age 30-39 years, if type 2 diabetes mellitus was present. The risk of sAP was lower in patients with multiple previous episodes of AP. In-hospital mortality in tAP was 5.0% (95% CI 4.1% to 5.9%) overall and 21.7% (95% CI 19.9% to 23.5%) in those with tAP necessitating CC admission. CONCLUSIONS: National record-linkage analysis of routinely collected data constitutes a powerful resource to model CC admission and prognosticate death during AP. Mortality in patients with AP who require CC admission remains high.

Manipulation in the Treatment of Plantar Digital Neuralgia: A Retrospective Study of 38 Cases.

OBJECTIVE: The purpose of this retrospective case series is to describe treatment outcomes for patients with plantar digital neuralgia (PDN) (Morton's neuroma) who were treated using foot manipulation. METHODS: Charts were reviewed retrospectively for patients with a diagnosis of PDN and who received a minimum of 6 treatments consisting of manipulation alone. Visual analogue pain scales (VAS) and pressure threshold meter readings (PTM) were extracted as outcome measures. RESULTS: Thirty-eight cases met inclusion criteria. Mean pretreatment duration of pain was 28 months. Mean pretreatment VAS was 69.5/100 mm. Mean pretreatment PTM was 2.54 Kp. By the sixth treatment, 30 (79%) of the 38 patients scored a VAS of 0 mm and a further 4 (10%) were below 10 mm. Contralateral limb PTM showed a mean pre-treatment score of 5.5 Kp, which rose slightly to 5.85 Kp. This compared to a pre-treatment score of 2.54 Kp rising to 5.86 Kp in the affected limb. This represents a 126% increase in the affected side compared to 6.5% in the unaffected limb. Statistical analysis demonstrated a significant linear trend between decreasing VAS and manipulation (P < .001). CONCLUSION: The patients with PDN who were included in this case series improved with conservative care that included only foot manipulation.

Exploration of preterm birth rates associated with different models of antenatal midwifery care in Scotland: Unmatched retrospective cohort analysis.

OBJECTIVES: preterm birth represents a significant personal, clinical, organisational and financial burden. Strategies to reduce the preterm birth rate have had limited success. Limited evidence indicates that certain antenatal care models may offer some protection, although the causal mechanism is not understood. We sought to compare preterm birth rates for mixed-risk pregnant women accessing antenatal care organised at a freestanding midwifery unit (FMU) and mixed-risk pregnant women attending an obstetric unit (OU) with related community-based antenatal care. METHODS: unmatched retrospective 4-year Scottish cohort analysis (2008-2011) of mixed-risk pregnant women accessing (i) FMU antenatal care (n=1107); (ii) combined community-based and OU antenatal care (n=7567). Data were accessed via the Information and Statistics Division of the NHS in Scotland. Aggregates analysis and binary logistic regression were used to compare the cohorts׳ rates of preterm birth; and of spontaneous labour onset, use of pharmacological analgesia, unassisted vertex birth, and low birth weight. Odds ratios were adjusted for age, parity, deprivation score and smoking status in pregnancy. FINDINGS: after adjustment the 'mixed risk' FMU cohort had a statistically significantly reduced risk of preterm birth (5.1% [n=57] versus 7.7% [n=583]; AOR 0.73 [95% CI 0.55-0.98]; p=0.034). Differences in these secondary outcome measures were also statistically significant: spontaneous labour onset (FMU 83.9% versus OU 74.6%; AOR 1.74 [95% CI 1.46-2.08]; p<0.001); minimal intrapartum analgesia (FMU 53.7% versus OU 34.4%; AOR 2.17 [95% CI 1.90-2.49]; p<0.001); spontaneous vertex delivery (FMU 71.9% versus OU 63.5%; AOR 1.46 [95% CI 1.32-1.78]; p<0.001). Incidence of low birth weight was not statistically significant after adjustment for other variables. There was no significant difference in the rate of perinatal or neonatal death. CONCLUSIONS: given this study׳s methodological limitations, we can only claim associations between the care model and or chosen outcomes. Although both cohorts were mixed risk, differences in risk levels could have contributed to these findings. Nevertheless, the significant difference in preterm birth rates in this study resonates with other research, including the recent Cochrane review of midwife-led continuity models. Because of the multiplicity of risk factors for preterm birth we need to explore the salient features of the FMU model which may be contributing to this apparent protective effect. Because a randomised controlled trial would necessarily restrict choice to pregnant women, we feel that this option is problematic in exploring this further. We therefore plan to conduct a prospective matched cohort analysis together with a survey of unit practices and experiences.

Long-term effect of lithium maintenance therapy on estimated glomerular filtration rate in patients with affective disorders: a population-based cohort study.

BACKGROUND: For more than 40 years, the long-term effect of lithium maintenance therapy on renal function has been debated. We aimed to assess the effect of lithium maintenance therapy on estimated glomerular filtration rate (eFGR) in patients with affective disorders, and explore predictors for a decrease in eGFR. METHODS: This population-based cohort study included adult patients (18-65 years of age at baseline) in Tayside (Scotland, UK) who had recently started on lithium maintenance treatment between Jan 1, 2000, and Dec 31, 2011 (retrospectively assigned to the lithium group) or those with exposure to other first-line drugs used in the treatment of affective disorders (quetiapine, olanzapine, and semisodium valproate) during the same period (retrospectively assigned to the comparator group). Patients had to have at least 6 months of (incidence) exposure to lithium or any of the comparator drugs, at least two eGFR values available in the observation period (one at baseline and at least one after ≥6 months post baseline). We excluded patients with previous exposure to lithium or one of the comparator drugs, those with a previous diagnosis of schizophrenia or other psychotic disorder, those with glomerular disease, tubulo-interstitial disease, or chronic kidney disease stages 4-5 at baseline, and those who had undergone renal transplant before exposure. Maximum follow-up was 12 years. Data were provided by the University of Dundee Health Informatics Centre, who have access to health-related population-based datasets containing data for every patient registered with a regional family doctor. Each patient has a unique ten-digit identifier, the Community Health Index, enabling us to link laboratory tests, dispensed community prescriptions, Scottish Morbidity Records, and mortality records to the patient. All data were anonymised according to Health Informatics Centre standard operating procedures. The primary outcome was the change per year in the eGFR, adjusted for age, sex, and baseline eGFR, and analysed by random coefficient models. FINDINGS: 1120 patients (305 exposed to lithium and 815 to comparator drugs) qualified for inclusion, providing 13 963 eGFR values over 12 years. The mean duration of exposure to lithium was 55 months (SD 42; range 6-144). Mean annual decline in eGFR (adjusted for age, sex, and baseline eGFR) was 1·3 mL/min per 1·73 m(2) (SE 0·2) in the lithium group, which did not differ significantly to that in the comparator group (0·9 mL/min/1·73 m(2) [SE 0·15]). After adjustment for additional confounders, the monthly decline in eGFR attributable to lithium exposure amounted to 0·02 mL/min per 1·73 m(2) (SE 0·02, p=0·30). As a post-hoc secondary outcome, we estimated the annual decline in eGFR for the lithium group to be 1·0 mL/min per 1·73 m(2) (SE 0·2), which again did not differ significantly to that in the comparator group (0·4 mL/min/1·73 m(2) [SE 0·2]. Modelling identified significant predictors for eGFR decline as age, baseline eGFR, comorbidities, co-prescriptions of nephrotoxic drugs, and episodes of lithium toxicity; however, duration of exposure to lithium and mean serum lithium level were not significant predictors for eGFR decline. INTERPRETATION: Our analysis suggests no effect of stable lithium maintenance therapy (lithium levels in therapeutic range) on the rate of change in eGFR over time. Our results therefore contradict the idea that long-term lithium therapy is associated with nephrotoxicity in the absence of episodes of acute intoxication and that duration of therapy and cumulative dose are the major determinants of toxicity. FUNDING: None.

Analysis of hyponatraemia associated post-operative mortality in 3897 hip fracture patients.

Hyponatraemia is common in hospitalised patients. In recent years the relationship between hyponatraemia and bone metabolism, falls and fractures has become more established. This study evaluates the prevalence of hyponatraemia (plasma sodium<135mmol/l) in 3897 patients undergoing operative treatment for hip fracture and the relationship between hyponatraemia and mortality in these patients. Hyponatraemia was an independent risk factor for increased post-operative mortality on multivariate analysis. Median age at admission was 83 years. Hyponatraemia was present in 19.1% of patients with hip fracture on admission, 29.5% of patients in the first 24h post-operatively and 20% of patients at discharge. There was a significant association between hyponatraemia and time from admission to surgery indicating that patients admitted with hyponatraemia waited longer. The median follow-up time was 863 (range 0-4352) days. There were 2460 deaths (63.1% of the original 3897 patients) prior to the censor date. A total of 1144 patients (29.4% of the original 3897 patients) died within 12 months of discharge. Median time to death for patients with and without hyponatraemia on admission was 34 months (SE 1.7 months) and 41 months (SE 2.5 months) respectively (p=0.003). Median time to death for patients with and without hyponatraemia within 24h post-operatively was 35 months (SE 2.5 months) and 42 months (SE 1.7 months) respectively (p=0.004). Following elimination of other independent variables associated with increased mortality, hyponatraemia on admission was associated with an increased risk of death (adjusted HR 1.15, p=0.005). Post-operative hyponatraemia was also associated with an increased risk of death (adjusted HR 1.15, p=0.006). Trends suggested that hyponatraemia within 48h of discharge was associated with an increased risk of death (adjusted HR 1.15, p=0.636). Hyponatraemia is common in elderly patients with hip fractures both at initial presentation and during admission. In this vulnerable patient group, hyponatraemia may delay time to definitive surgery and is a potentially reversible cause of increased post-operative mortality. Every effort should be made to identify and correct hyponatraemia in hip fracture patients.

Characterizing patients with chronic heart failure in community care after hospitalization: a potential role for ivabradine.

AIMS: To identify the prevalence and characteristics of recently hospitalized chronic heart failure (CHF) patients in community care who meet the indication for ivabradine. METHODS: A retrospective clinical audit of CHF patients recently hospitalized with acute decompensated heart failure (ADHF) and subsequently referred to the Tayside Heart Failure Nurse Liaison Service (THFNLS), a Scottish nurse-led community heart failure liaison service. Inclusion criteria were previous hospitalization with ADHF, subsequent referral to the THFNLS, data for ≥ 2 nurse visits, and a recorded pulse. The main outcome measure was the proportion of patients who meet the indicated criteria for ivabradine. RESULTS: In the UK, ivabradine is indicated for CHF with systolic dysfunction in patients in sinus rhythm, with a heart rate ≥ 75 bpm, and NYHA class II-class IV. After up-titration of a beta-blocker, 19.0% of patients in the full dataset (158 of 830) met the indication for ivabradine at the last visit. Of these "ivabradine-suitable" patients, 101 of 158 (63.9%) received bisoprolol "at any time" during the study period; 20 of 158 (12.7%) achieved the target dose (10 mg daily); 52 of 158 (32.9%) received 5 mg or 7.5 mg daily; and 93 of 158 (58.9%) received <5 mg daily. CONCLUSIONS: In this group of Scottish patients previously hospitalized with ADHF and under the care of a protocol-driven clinic, 19% met the indication for ivabradine and may benefit from the increased control of CHF that ivabradine can provide. Among these "ivabradine-suitable" patients, <15% achieved the target dose of beta-blockers, illustrating the substantial clinical need for a well-tolerated and effective therapy such as ivabradine.