Mean Annual Rate Of Decline Research Articles

Transcorneal Electrical Stimulation Dose-Dependently Slows the Visual Field Loss in Retinitis Pigmentosa.

To assess whether transcorneal electrical stimulation (TcES) current-dependently slows progressive loss of visual field area (VFA) in retinitis pigmentosa (RP). Data from 51 patients with RP who received monocular TcES treatment once weekly over 1 year in an interventional, randomized study have been analyzed a posteriori. Current amplitudes were 0.1 to 1.0 mA in the TcES-treated group (n = 31) and 0.0 mA in the sham group (n = 20). VFA was assessed in both eyes (semiautomatic kinetic perimetry, Goldmann targets V4e, III4e). Annual decline rate (ADR) of exponential loss and model-independent percentage reduction of VFA at treatment cessation were correlated to current amplitude. For V4e, mean ADR was -4.1% in TcES-treated eyes, -6.4% in untreated fellow eyes, and -7.2% in placebo-treated eyes; mean VFA reduction in TcES-treated eyes was 64% less than in untreated fellow eyes (P=0.013) and 72% less than in placebo-treated eyes (P=0.103). Individual VFA reductions correlated with current amplitude (P=0.043) and tended toward zero in patients who received 0.8 to 1.0 mA. For III4e, there was a marginally significant current-dependency of interocular difference in reduction (P=0.11). ADR and VFA reduction did not significantly correlate with baseline VFA. Loss of VFA (V4e) in patients with RP was significantly reduced in treated eyes compared to untreated eyes by regular use of TcES in a dose-dependent manner. No dependence of effects on the initial extent of VFA loss was found. TcES provides potential for preservation of visual field in patients with RP.

Relation of middle cerebral artery flow velocity and risk of cognitive decline: A prospective community-based study

ObjectivesHemodynamic parameters measured by the Transcranial Doppler Ultrasound (TCD) are related to cognitive impairment in many cross-sectional studies, but the longitudinal evidence is scarce. In this study, we aim to verify the association between flow velocity of Middle Cerebral Artery (MCA) and the longitudinal cognitive decline in community dwelling older adults. Materials and methodsParticipants were administered TCD examination at the baseline. The Peak Systolic Velocity (PSV), Mean Flow Velocity (MFV), and Pulsatility Index (PI) of MCA segments on left middle (LmMCA), left proximal (LpMCA), right middle (RmMCA), and right proximal (RpMCA) were obtained. Mini-mental state examination (MMSE) were conducted at both baseline and follow-up. ResultsOne hundred and thirteen participants without dementia were followed up for 6.3 years in average. The mean annual rate of decline in the MMSE score was 0.15 (min to max: −1.0 to 1.2). LpMCA PSV (β = −0.0034, r = −0.231, P = 0.022) and LpMCA MFV (β = −0.0049, r = −0.217, P = 0.031) were inversely associated with annual rate of decline in the MMSE score after adjusting for age, gender, education year, APOE ε4, obesity, hypertension, diabetes mellitus, stroke, and coronary heart disease. ConclusionsBlood flow velocity of left proximal MCA was inversely related to global cognitive decline. Cerebral blood flow velocity may impact the cognitive function.

Incidence of end-stage renal disease and risk factors for progression of renal dysfunction in Japanese patients with type 2 diabetes: the Fukuoka Diabetes Registry.

Epidemiological data regarding diabetic kidney disease are accumulated insufficiently in Japan. We prospectively investigated the incidence of end-stage renal disease (ESRD) and risk factors for progression of renal dysfunction in Japanese patients with type 2 diabetes. 4904 participants with type 2 diabetes (mean age 65years, mean estimated glomerular filtration rate (eGFR) 75mL/min/1.73m2, proportion of eGFR < 60mL/min/1.73m2 21%) were investigated for the progression to ESRD requiring dialysis in multicenter outpatients registry for 5years. Risk factors for progression of renal dysfunction (≥ 30% decline in eGFR from the baseline and annual eGFR decline rates) were evaluated. The incidence rates of ESRD and all-cause mortality were 4.1/1000 person-years and 12.3/1000 person-years, respectively, and increased according to stages of chronic kidney disease (eGFR < 30mL/min/1.73m2, incidence of ESRD 176.6/1000 person-years, all-cause mortality 57.4/1000 person-years). Incidence of ≥ 30% decline in eGFR from the baseline was 16.4% at 5years, and the mean annual decline rate was -1.84mL/min/1.73m2/year. The progression of renal dysfunction was significantly associated with older age, poor glycemic control, blood pressure, albuminuria, eGFR, previous cardiovascular disease, lifestyle factors (body mass index, reduced intake of dietary fiber, increased intake of sodium, no regular exercise), and depressive symptoms. This prospective study has emphasized the importance of multifactorial interventions on risk factors to suppress the high incidence of ESRD in Japanese patients with type 2 diabetes.

Efficacy and safety of nintedanib in patients with systemic sclerosis-associated interstitial lung disease treated with mycophenolate: a subgroup analysis of the SENSCIS trial

In the Safety and Efficacy of Nintedanib in Systemic Sclerosis (SENSCIS) trial, nintedanib reduced the rate of decline in forced vital capacity (FVC) in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). Patients on stable treatment with mycophenolate for at least 6 months before randomisation could participate. The aim of this subgroup analysis was to examine the efficacy and safety of nintedanib by mycophenolate use at baseline. The SENSCIS trial was a randomised, double-blind, placebo-controlled trial, in which patients with SSc-ILD were randomly assigned (1:1) to receive 150 mg of oral nintedanib twice daily or placebo for at least 52 weeks. In a prespecified subgroup analysis, we analysed the primary endpoint of rate of decline in FVC over 52 weeks by mycophenolate use at baseline. In a post-hoc analysis, we analysed the proportion of patients with an absolute decrease in FVC of at least 3·3% predicted at week 52 (proposed minimal clinically important difference estimate for worsening of FVC in patients with SSc-ILD) in subgroups by mycophenolate use at baseline. Adverse events were reported in subgroups by mycophenolate use at baseline. Analyses were done in all participants who received at least one dose of study drug. We analysed the annual rate of decline in FVC using a random coefficient regression model (with random slopes and intercepts) including anti-topoisomerase I antibody status, age, height, sex, and baseline FVC as covariates and terms for baseline-by-time, treatment-by-subgroup, and treatment-by-subgroup-by-time interactions. SENSCIS is registered with ClinicalTrials.gov, NCT02597933, and is now complete. Between Nov 30, 2015, and Oct 31, 2017, 819 participants were screened and 576 were enrolled, randomly assigned to, and treated with nintedanib (n=288) or placebo (n=288). 139 (48%) of 288 in the nintedanib group and 140 (49%) of 288 in the placebo group were taking mycophenolate at baseline. In patients taking mycophenolate at baseline, the adjusted mean annual rate of decline in FVC was -40·2 mL per year (SE 19·8) with nintedanib and -66·5 mL per year (19·3) with placebo (difference: 26·3 mL per year [95% CI -27·9 to 80·6]). In patients not taking mycophenolate at baseline, the adjusted mean annual rate of decline in FVC was -63·9 mL per year (SE 19·3) with nintedanib and -119·3 mL per year (19·0) with placebo (difference: 55·4 mL per year [95% CI 2·3 to 108·5]). We found no heterogeneity in the effect of nintedanib versus placebo on the annual rate of decline in FVC between the subgroups by mycophenolate use (p value for interaction=0·45). In a post-hoc analysis, the proportion of patients with an absolute decrease in FVC of at least 3·3% predicted was lower with nintedanib than with placebo in both patients taking mycophenolate (40 [29%] of 138 vs 56 [40%] of 140; odds ratio 0·61 [0·37 to 1·01]) and those not taking mycophenolate (59 [40%] of 149 vs 70 [47%] of 148; 0·73 [0·46 to 1·16]) at baseline. The adverse event profile of nintedanib was similar between the subgroups. Diarrhoea, the most common adverse event, was reported in 106 (76%) of 139 patients in the nintedanib group and 48 (34%) of 140 in the placebo group among those taking mycophenolate at baseline, and in 112 (75%) of 149 in the nintedanib group and 43 (29%) of 148 in the placebo group among those not taking mycophenolate at baseline. Over the entire trial period, 19 patients died (ten in the nintedanib group and nine in the placebo group). One death in the nintedanib group was considered to be related to study drug. Nintedanib reduced the progression of interstitial lung disease both in patients with SSc-ILD who were and were not using mycophenolate at baseline, with no heterogeneity in its treatment effect detected between the subgroups. The adverse event profile of nintedanib was similar in the subgroups by mycophenolate use. Our findings suggest that the combination of mycophenolate and nintedanib offers a safe treatment option for patients with SSc-ILD. More data are needed on the benefits of initial combination therapy versus a sequential approach to treatment of SSc-ILD. Boehringer Ingelheim.

The natural history of progressive fibrosing interstitial lung diseases.

We used data from the INBUILD and INPULSIS trials to investigate the natural history of progressive fibrosing interstitial lung diseases (ILDs).Subjects in the two INPULSIS trials had a clinical diagnosis of idiopathic pulmonary fibrosis (IPF) while subjects in the INBUILD trial had a progressive fibrosing ILD other than IPF and met protocol-defined criteria for ILD progression despite management. Using data from the placebo groups, we compared the rate of decline in forced vital capacity (FVC) (mL·year−1) and mortality over 52 weeks in the INBUILD trial with pooled data from the INPULSIS trials.The adjusted mean annual rate of decline in FVC in the INBUILD trial (n=331) was similar to that observed in the INPULSIS trials (n=423) (−192.9 mL·year−1 and −221.0 mL·year−1, respectively; nominal p-value=0.19). The proportion of subjects who had a relative decline in FVC >10% predicted at Week 52 was 48.9% in the INBUILD trial and 48.7% in the INPULSIS trials, and the proportion who died over 52 weeks was 5.1% in the INBUILD trial and 7.8% in the INPULSIS trials. A relative decline in FVC >10% predicted was associated with an increased risk of death in the INBUILD trial (hazard ratio 3.64) and the INPULSIS trials (hazard ratio 3.95).These findings indicate that patients with fibrosing ILDs other than IPF, who are progressing despite management, have a subsequent clinical course similar to patients with untreated IPF, with a high risk of further ILD progression and early mortality.

Gastrointestinal adverse effects of nintedanib and the associated risk factors in patients with idiopathic pulmonary fibrosis

Nausea and diarrhea are the most common adverse effects of nintedanib in patients with idiopathic pulmonary fibrosis (IPF). However, the clinical risk factors for these side effects remain unknown. In the present study, we investigated the characteristics of patients who developed gastrointestinal side effects during nintedanib treatment for IPF and determined the risk factors for these side effects. We enrolled 77 patients with IPF who received nintedanib between October 2015 and March 2018. Performance status (PS) as a patient’s general condition, body mass index (BMI), modified Medical Research Council Dyspnea Scale score, severity of IPF at nintedanib initiation, and gastrointestinal toxicity of nintedanib were evaluated. In total, 25 and 27 patients exhibited nausea and diarrhea, respectively, during the follow-up period. A poor PS, low BMI, and full dosage of nintedanib at treatment initiation were risk factors for nausea. A low BMI was a significant risk factor for diarrhea, which could be prevented by combination treatment with nintedanib and prednisolone. In addition, the mean annual rate of decline in forced vital capacity was significantly greater in patients with nausea than in patients without nausea. In conclusion, our findings suggest that patients with a low BMI and/or poor PS and those who receive the full nintedanib dosage at treatment initiation are more susceptible to gastrointestinal adverse effects during nintedanib treatment. Addition of prednisolone to the treatment regimen may prevent the development of diarrhea during treatment.

P.53 - Effects of long-term treatment with eteplirsen on cardiac function

Duchenne muscular dystrophy (DMD) is an X-linked, recessive genetic disease characterized by dystrophin deficiency or absence. Eteplirsen, a phosphorodiamidate morpholino oligomer, targets DMD pre-mRNA to trigger skipping of exon 51 in order to restore the reading frame, thereby enabling production of internally truncated dystrophin protein. Herein we report effects of long-term treatment with eteplirsen on cardiac function in patients with DMD in comparison to reports from disease natural history and a clinical study of perindopril. Eteplirsen patients were treated in two consecutive studies. Study 201 was a randomized, double-blind, 28-week trial. Patients aged 7–13 years with DMD amenable to exon 51 skipping were randomized to receive 1 of 2 once-weekly intravenous (IV) eteplirsen infusions (30 mg/kg, n = 4; 50 mg/kg, n = 4) or placebo (n = 4). At week 25, all patients received open-label eteplirsen through week 28. Study 202 was an open-label extension of study 201; all patients received once-weekly eteplirsen at the same dose (30 mg/kg or 50 mg/kg) for up to 240 weeks. Both trials included longitudinal evaluation of cardiac function using echocardiographic left ventricular ejection fraction (LVEF). We found that the mean annual rate of decline in ejection fraction for eteplirsen-treated patients over the 240-week trial was 0.18%. A study of perindopril (N = 57; mean age at baseline, 10.6 years) reported a 1.28% annual decline in perindopril-treated patients (n = 28) and a 1.88% annual decline in placebo-to-perindopril patients (n = 29; placebo treatment, 3 years; perindopril treatment, 2 years) over the 5-year study period, as measured by radionuclide ventriculography. A disease natural history study of 98 DMD patients aged 7–29 years reported a 0.58% annual decline in LVEF, as measured by magnetic resonance. In conclusion, safety monitoring showed gross LVEF stability in eteplirsen-treated patients over the 240-week study period.

Voluntary recording scheme reveals ongoing decline in the United Kingdom hazel dormouse Muscardinus avellanarius population

Abstract In order to conserve threatened species, knowledge of the status, trends and trajectories of populations is required. Co‐ordinating collection of these data is challenging, especially for inconspicuous species such as the hazel dormouse Muscardinus avellanarius. The UK National Dormouse Monitoring Programme (NDMP) is comprised of nest box recording schemes organised by volunteers. The number, size, and coverage of these schemes has varied over time. Such changes risk conflation of genuine population trends with covarying artefacts, including survey effort and expansion into sites of variable quality. We provide a robust analysis of count data from 400 NDMP sites from 1993 to 2014 and demonstrate that changes in counts are not an artefact of survey characteristics. In relation to the International Union for Conservation of Nature (IUCN) Red List criteria, we conclude that dormouse counts in nest boxes are an index of abundance appropriate to the taxon and allow the inference of population reduction of 72% (95% confidence intervals 62–79%) over the 22 years from 1993 to 2014, equivalent to a mean annual rate of decline of 5.8% (4.5–7.1%). This decline is ongoing. We highlight difficulties in assigning an IUCN Red List conservation category to a population, given variation in apparent trends over consecutive time‐periods. In eight out of 13 sliding window intervals of 10 years from 1993 to 2014, the 95% confidence intervals overlap a decline of 50%. While average population decline over 10‐year periods suggests that the hazel dormouse should be classified as Vulnerable, a precautionary approach would not rule out the category of Endangered in the United Kingdom, given the lower bounds of population change estimates, the mean annual rate of decline and ongoing decline. Ongoing decline in the hazel dormouse population is despite a high level of species protection and widespread conservation measures. The hazel dormouse is a UK Biodiversity Action Plan Priority Species and a European Protected Species, and the causes of population reduction are not well understood and may not have ceased. An urgent appraisal of dormouse conservation is required to ensure the species’ favourable conservation status.

Abstract P185: Fish Intake is Associated with Slower Cognitive Decline in Chinese Older Adults: a Longitudinal Study from the China Health and Nutrition Survey

Introduction: With global population aging, identifying public health strategies to prevent or reduce cognitive decline is of increasing importance. This study explores the potential role of a modifiable dietary behavior, fish consumption, to reduce the rate of cognitive decline in a cohort of Chinese older adults. Methods: This study comprised adults aged ≥55 who completed a brief cognitive screening test at two or more waves of the China Health and Nutrition Survey (CHNS) from 1997 to 2004. The cognitive screening test had a maximum of 31 points and assessed immediate and delayed memory, attention, calculation, and orientation. Diet was measured by 3-day 24-hour recalls. Multivariable-adjusted linear mixed-effects models were used to evaluate the relation of fish intake at baseline with changes in cognitive scores, adjusting for age, gender, region, urbanization index, education, household income, energy intake, physical activity, current alcohol use, current smoking, and consumption of fresh vegetables, fruits, fresh legumes, and high-fat meat, as well as time, and time interactions with each covariate. Based on the distribution of fish intake, we compared consumption ≥1 vs. &lt;1 serving/week. Sensitivity analysis included 1) removing shellfish and/or preserved fish; 2) exploring potential confounding by or interactions with hypertension or body mass index; 3) excluding those with the lowest 10% baseline cognitive scores; 4) adjusting for dietary patterns to determine if associations were independent of overall eating patterns; 5) using propensity score analysis to ensure comparability of the fish intake groups. Results: The average follow-up among 1566 older adults was 5.3 years, with a mean annual rate of decline 0.40 points. Since age significantly modified the fish-cognitive change association (p=0.003), we stratified analysis by adults &lt;65 (n=968) at first measure, and ≥65 (n=598). No significant associations were found among adults &lt;65. Among adults ≥65, compared with persons who consumed fish &lt;1 serving/week, the average rate of global cognitive decline was reduced by 0.35 points per year or 55% (p = 0.001) among those consuming fish ≥1 serving/week. Results remained consistent in sensitivity analysis. When the cognitive test items were analyzed based on the domain assessed, fish intake was associated with a significantly slower rate of decline in memory scores among adults ≥65. The average rate of memory decline was reduced by 60% among persons who consumed fish ≥1 serving/week. Conclusions: Fish intake of at least 1 serving per week predicted a slower rate of cognitive decline among Chinese adults ≥65 years old, particularly for immediate and delayed memory. The cognitive benefits of fish intake were not apparent among Chinese adults aged 55 to 64. This is the first study in Chinese older adults to evaluate the role of fish consumption on cognitive decline.

Rescaling of aerial survey data with information from small numbers of telemetry tags to estimate the size of a declining harbour seal population

ABSTRACT Estimates of both absolute abundance and trends in abundance are among the most basic pieces of information required for planning the conservation and management of wildlife populations. They are important for understanding both the current situation of species and potential risks to them. This study presents estimates of the size of the harbour seal (Phoca vitulina) population associated with the Orkney Islands, a part of northern Scotland that used to contain one of the largest concentrations of this species in Europe. The numbers of animals counted during aerial surveys of this area have decreased substantially over the period 2001–2010. ARGOS transmitters attached to flipper tags were used to rescale the counts into estimates of abundance and to confirm the rate of decline of this population. Females hauled out for more of the survey window (0.84; bootstrap 95% CI: 0.63–0.99) than males (0.61; bootstrap 95% CI: 0.34–0.86). The animals hauled out less during weekends (0.57; bootstrap 95% CI: 0.40–0.74) than during the week (0.76; bootstrap 95% CI: 0.58–0.91). The sex‐ratios of this population is unknown. Assuming it was close to 1:1, then there were around 3586 (bootstrap 95% CI: 2970–4542) harbour seals in Orkney in 2010. A female‐skewed sex‐ratio would reduce the population estimate, and a changing sex‐ratio might mean the counts understate the real decline. The mean annual rate of decline in the Orkney population of harbour seals, over the period 2001–2010, is estimated at 13% (95% CI: 10.8–14.8). Similar data for Arisaig, on the west coast of Scotland, shows an increase of around 2% (95% CI: 1.5–2.4) and, assuming an equal sex‐ratio, 923 animals (95% CI: 765–1169) in 2007. Copyright © 2012 John Wiley &amp; Sons, Ltd.

Trends in Coronary Revascularization in the United States From 2001 to 2009

There is speculation that the volume of percutaneous coronary interventions (PCIs) has been decreasing over the past several years. Published studies of PCI volume have evaluated regional or hospital trends, but few have captured national data. This study describes the use of coronary angiography and revascularization methods in Medicare patients from 2001 to 2009. This retrospective study used data from the Centers for Medicare & Medicaid Services from 2001 to 2009. The annual number of coronary angiograms, PCI, intravascular ultrasound, fractional flow reserve, and coronary artery bypass graft (CABG) surgery procedures were determined from billing data and adjusted for the number of Medicare recipients. From 2001 to 2009, the average year-to-year increase for PCI was 1.3% per 1000 beneficiaries, whereas the mean annual decrease for CABG surgery was 5%. However, the increase in PCI volume occurred primarily from 2001 to 2004, as there was a mean annual rate of decline of 2.5% from 2004 to 2009; similar trends were seen with diagnostic angiography. The use of intravascular ultrasound and fractional flow reserve steadily increased over time. This study confirms recent speculation that PCI volume has begun to decrease. Although rates of CABG have waned for several decades, all forms of coronary revascularization have been declining since 2004.

News &amp; Notes

AbstractLoop diuretics may increase bone loss in menContinuous use of a loop diuretic could double the rate of bone loss in elderly men, according to a new analysis of the Osteoporotic Fractures in Men study (Arch Intern Med 2008; 168: 735–40).This analysis of a subgroup of 3269 of the original 5995 men over 65 for whom a DEXA scan was available at baseline and after a mean follow‐up of 4.6 years identified 84 who had continuously used a loop diuretic, 181 with intermittent use and 3004 never‐users.After adjustment for risk factors, the mean annual rate of decline in bone mineral density (BMD) at the hip was 0.78 per cent among continuous users, 0.58 per cent with intermittent use and 0.33 per cent among never‐users; there were similar trends at the femoral neck and trochanter.Cochrane reviews finasterideTreatment with finasteride reduces the risk of prostate cancer in men at increased risk by about one‐quarter, a new Cochrane review reveals (Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD007091. DOI: 10.1002/ 14651858.CD007091).The risk reduction with finasteride did not vary with age, ethnicity or family history but was not evident in men with prostate‐specific antigen &gt;4ng/ml. The analysis was dominated by the Prostate Cancer Prevention Trial, which reported an increase in men with high‐grade tumours during finasteride therapy.Only one report of dutasteride was included, suggesting a 51 per cent risk reduction in cancers detected.New GnRH antagonistsGermany is the first country in Europe to have the new GnRH receptor antagonist abarelix (Plenaxis) for the treatment of hormone‐dependent prostate cancer. Manufacturer Speciality European Pharma says that abarelix, by contrast with agonist therapies, reduces testosterone levels rapidly and is not associated with hormonal surge or flare. Registration is now underway across Europe.Phase III data presented at the 23rd Annual European Association of Urology Congress in Milan revealed the rapid onset of effect with Ferring's GnRH antagonist degarelix. After 14 days, serum testosterone was &lt;5ng/ml in all patients treated with degarelix and in 18 per cent of those assigned to monthly leuprorelin. The median reduction in prostate‐specific antigen was 64 per cent with degarelix and 18 per cent with the LHRH analogue.Transdermal testosterone little benefit for womenWomen who report decreased sexual satisfaction derive little benefit from transdermal testosterone, an Australian trial has shown (Ann Intern Med 2008; 148: 569–77).261 women aged 35–46 who reported decreased sexual satisfaction compared with historical experience were randomised to receive placebo or testosterone spray at doses of 56, 90 or 180µl for 16 weeks. Baseline morning serum free testosterone level was less than 3.8pmol/l.The primary endpoint was the number of satisfactory sexual events (SSEs) in the 28 days up to week 16.The rate ratios of SSEs compared with placebo for 56, 90 and 180µl doses were 1.34, 1.48 and 1.38, respectively; of these, only the response to the 90µl dose was statistically significant but the absolute difference was small – equivalent to an increase of 0.8 SSE per month. The commonest adverse effect was dose–related hypertrichosis at the site. Copyright © 2008 Wiley Interface Ltd

The impact of HIV on chronic kidney disease outcomes

Chronic kidney disease (CKD) is a known complication of the human immunodeficiency virus (HIV) but outcomes among HIV-infected patients with kidney disease are unknown. We studied a national sample of 202,927 patients with CKD (stage 3 or higher) for death, end-stage renal disease (ESRD) and the mean annual rate of decline in estimated glomerular filtration rate (eGFR) over a median period of 3.8 years. Within this sample, 0.3% of the patients were diagnosed with HIV, 43.5% were diabetic, whereas the remainder had neither disease. In this national CKD cohort, HIV-infected black patients were at higher risk of death, a similar risk for ESRD and loss of eGFR than black patients with diabetes. HIV-infected white patients experienced higher rates of death but a lower risk of ESRD than their counterparts with diabetes. Our results highlight a need to study mortality and mechanisms of ESRD in the HIV infected population.

Determinants of Skeletal Loss and Recovery in Anorexia Nervosa

Anorexia nervosa (AN) is complicated by severe bone loss. The effects of persistent undernutrition and consequent neuroendocrine dysfunction on bone mass and the factors influencing skeletal recovery have not been well characterized. The objective of the study was to determine the rate of bone loss at the spine and hip in women with AN and whether resumption of menstrual function and/or improvement in weight are determinants of skeletal recovery in AN. The study had a longitudinal design. The study was conducted at a clinical research center. Participants included 75 ambulatory women with AN. Bone mineral density (BMD) and body composition were measured with dual x-ray absorptiometry. In women not receiving oral contraceptives, those who did not improve weight or resume menses had a mean annual rate of decline of 2.6% at the spine and 2.4% at the hip. Those who resumed menses and improved weight had a mean annual increase of 3.1% at the posteroanterior spine and 1.8% at the hip. Women who recovered menses demonstrated a mean increase of posteroanterior spine but not hip BMD, independent of weight gain. Women who improved weight, regardless of whether they recovered menstrual function, demonstrated a mean increase of hip, but not spine, BMD. Increase in fat-free mass was a more significant determinant of increased BMD than weight or fat mass gain. In women receiving oral contraceptives, there was no increase in BMD at any site despite a mean 11.7% weight increase. These data suggest that rapid bone loss, at an average annual rate of about 2.5%, occurs in young women with active AN. Resumption of menstrual function is important for spine BMD recovery, whereas weight gain is critical for hip BMD recovery. We did not observe an increase in BMD with weight gain in women receiving oral contraceptives. Therefore, improvements in reproduction function and weight, with increases in lean body mass a critical component, are both necessary for skeletal recovery in women with AN.

A Need to Study the Immune Status of Frail Older Adults

A Need to Study the Immune Status of Frail Older Adults

Physical training for cystic fibrosis.

Physical training may form an important part of the care package for patients with cystic fibrosis. To determine whether a prescribed regime of physical training produces improvement or prevents deterioration in physiological and clinical outcomes in cystic fibrosis compared to no training. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group specialist trials register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings. Date of the most recent search: August 2001. All randomised controlled clinical trials in which a prescribed regime of physical training is compared to no physical training in patients with cystic fibrosis. Two reviewers independently selected trials for inclusion, assessed methodological quality and extracted data. Of the sixteen trials identified six trials, which included 184 patients, met the inclusion criteria. Exercise tolerance in the short term, during an acute admission was improved in patients who received physical training. In a three year study there was no improvement in exercise tolerance at the end of the study period. Over three years there was a significantly greater mean annual rate of decline in FVC in the control group compared to the exercise group WMD 2.17 (95%CI 0.47, 3.87). Changes in other lung function parameters showed a similar trend, but these were not statistically significant. Conclusions about the efficacy of physical training in cystic fibrosis are limited by the small size, short duration and incomplete reporting of most of the trials included in this review. Physical training is already part of the care package offered to most patients with cystic fibrosis and there is no evidence to actively discourage this. Further research is needed to assess comprehensively the net benefit of the addition of physical training to the care of cystic fibrosis patients.

Second extinction of capercaillie ( Tetrao urogallus) in Scotland?

The capercaillie ( Tetrao urogallus L.), a large forest gamebird reintroduced into Scotland in the 1830s, has been declining since the 1970s. This has been attributed to a reduced reproductive rate associated with climate change, and deaths of full-grown birds flying into forest fences. Here, three independent estimates are combined to show that in the 1990s the mean annual rate of decline for adult hens was 18% (S.E. 5%). Without fence deaths, it is calculated that the hen population could have increased at an annual rate of 6% (S.E. 10%). If recent trends persist, the bird will soon be extinct again in Scotland, but without forest fences it would probably survive.

Long-term comparative trial of positive expiratory pressure versus oscillating positive expiratory pressure (flutter) physiotherapy in the treatment of cystic fibrosis

Objective: The objective was to evaluate the long-term effects of physiotherapy with an oscillating positive pressure device (“flutter”) compared with physiotherapy with the use of a positive expiratory pressure (PEP) mask in patients with cystic fibrosis (CF). Study design: Forty children with CF were randomly assigned to performing physiotherapy with the PEP mask or the flutter device for 1 year. Clinical status, pulmonary function, and compliance were measured at regular intervals throughout the study. Results: The flutter group demonstrated a greater mean annual rate of decline in forced vital capacity compared with the PEP group (–8.62 ± 15.5 vs 0.06 ± 7.9; P =.05) with a similar trend in forced expiratory volume in 1 second (–10.95 ± 19.96 vs –1.24 ± 9.9; P =.08). There was a significant decline in Huang scores (P =.05), increased hospitalizations (18 vs 5; P =.03), and antibiotic use in the flutter group. Conclusion: Flutter was not as effective in maintaining pulmonary function in this group of patients with CF compared with PEP and was more costly because of the increased number of hospitalizations and antibiotic use.(J Pediatr 2001;138:845-50)

Role of conventional physiotherapy in cystic fibrosis

Because of the time and the emotional cost involved in performing daily conventional chest physiotherapy in patients with cystic fibrosis, a 3-year prospective study was undertaken to compare the long-term effects of postural drainage accompanied by percussion and the forced expiratory technique with the effects of the forced expiratory technique alone. Patients who performed the forced expiratory technique alone had mean annual rates of decline that were significantly different from zero for forced expiratory volume in 1 second (p less than 0.001), forced expiratory flow between 25% and 75% of vital capacity (p less than 0.001), and Shwachman clinical score (p less than 0.004). In the group performing conventional physiotherapy with percussion and postural drainage, only the mean annual rate of decline for forced expiratory flow between 25% and 75% of vital capacity was significantly different from zero (p less than 0.03), and it was significantly different from the mean rate of decline associated with the forces expiratory technique alone (p less than 0.04). We conclude that conventional chest physiotherapy should remain a standard component of therapy in cystic fibrosis.