Therapeutic approach to FSGS in children Therapy of primary focal segmental glomerulosclerosis -LRB- FSGS -RRB- in children incorporates conservative management and immunosuppression regimens to control proteinuria and preserve kidney function . In long-term cohort studies in adults and children with primary FSGS , renal survival has been directly associated with degree of proteinuria control . This educational article reviews the current therapeutic approach toward children with primary FSGS . Introduction Focal segmental glomerulosclerosis -LRB- FSGS -RRB- is a histologic finding that may result from a variety of insults to the kidney . FSGS typically presents with proteinuria and has a high risk of progressive loss of renal function -LSB- 1 -RSB- . Treatment of secondary forms of FSGS targets control of the underlying condition . Therapy of primary FSGS incorporates conservative management and immunosuppression regimens to control proteinuria and preserve kidney function . In long-term cohort studies in adults and children with primary FSGS , renal survival has been directly associated with degree of proteinuria control -LRB- Fig. 1 -RRB- -LSB- 2 , 3 -RSB- . Patients who are resistant to therapies have a significant likelihood of progressing to end-stage renal disease -LRB- ESRD -RRB- and are a group in need of novel therapies to delay or prevent this outcome -LSB- 4 -RSB- . Fig. 1a Kaplan -- Meyer analysis of the risk of end-stage renal disease -LRB- ESRD -RRB- by proteinuria remission status in children with primary focal segmental glomerulosclerosis -LRB- FSGS -RRB- . b Kidney survival by proteinuria remission status in adults with primary FSGS . CR complete remission , PR partial remission , NR no remission Genetic considerations An undefined proportion of patients with classically defined primary FSGS harbor genetic mutations in podocyte-specific genes such as nephrin , podocin , α-actinin-4 , and CD2AP -LSB- 5 , 6 -RSB- . There are conflicting reports about the effectiveness of immune-based therapy in the setting of these mutations , but the likelihood of a positive response may be low -LSB- 7 -RSB- . Although mutation-linked cases of FSGS may have a lower response rate to conventional immunomodulatory treatment , these patients still manifest the progressive fibrosis that is observed in nongenetic FSGS . Nonimmunosuppressive therapy Diuretic therapy Control of edema in nephrotic syndrome allows not only cosmetic improvement but is expected to decrease pulmonary effusions , decrease ascites , and lower the risk of peritonitis and skin-related problems from edema . Overaggressive diuresis in patients with intravascular depletion may be a risk factor , however , in developing thrombotic complications and acute renal insufficiency . Loop diuretics are often required for control of edema in patients with proteinuria in the nephrotic range . Delivery of the diuretic to the site of action -LRB- lumen of the tubule -RRB- is often impaired in nephrotic syndrome due to decreased glomerular filtration rate -LRB- GFR -RRB- , increased binding of the diuretic to intraluminal albumin , and/or decreased delivery of sodium to sites of diuretic activity . An increase of sodium reabsorption in the distal tubule in response to loop diuretic activity may add to resistance to loop diuretics . This distal compensatory mechanism may be diminished by the use of a combination of loop and distal diuretics -LRB- thiazides -RRB- -LSB- 8 -RSB- . Though the addition of aldosterone inhibitors -LRB- spironolactone -RRB- is theoretically attractive under the theory that edema is in part driven by aldosterone , it is unclear whether spironolactone or other similar medications are clinically helpful to control edema -LSB- 9 -- 11 -RSB- An additional advantage to the use of aldosterone inhibitors such as spironolactone is suggested by the antifibrotic properties of these agents , which will be discussed below -LSB- 12 -RSB- . Combined albumin and furosemide therapy for anasarca has been studied , as well . Na et al. showed evidence for a mild increase in water diuresis but little evidence that the concomitant use of albumin adds to the natruretic effect of furosemide -LSB- 13 , 14 -RSB- . Fliser et al. -LSB- 15 -RSB- showed a moderate -LRB- 20 % -RRB- increase in water and salt excretion when comparing albumin and furosemide to furosemide alone . Haws et al. -LSB- 16 -RSB- also showed a mild but transient benefit of albumin and furosemide therapy but commented on the potential serious complications of hypertension , respiratory distress , congestive heart failure , and electrolyte disturbances . Thus , the combination of albumin and furosemide infusions , whether in combination or sequential , may provide a small transient benefit in the therapy of children with severe edema -LSB- 17 -RSB- . Treatment of hyperlipidemia For patients who become nephrotic from the progression of FSGS , hyperlipidemia is an almost universal finding . Whether the hyperlipidemia associated with nephrotic syndrome should be specifically targeted for treatment in children separately from nephrotic syndrome treatment itself has been a question for more than 20 years . The childhood origin of atherosclerotic disease and increased risk for cardiovascular disease secondary to chronic kidney disease supports an interventional approach . The report of the expert panel on blood cholesterol levels in children and adolescents -LSB- 18 -RSB- from the National Cholesterol Education Program -LRB- NCEP -RRB- defined categories of hypercholesterolemia in children for total cholesterol and low-density lipoprotein -LRB- LDL -RRB- cholesterol levels . High levels for total cholesterol were defined as ≥ 200 mg/dl and for LDL cholesterol as ≥ 130 mg/dl . Dietary treatment of hyperlipidemia is the first-line intervention . In adults with nephrotic syndrome , soy-based vegetarian diets and supplemented low protein diets have been shown to have potential benefits , decreasing both proteinuria and cholesterol , but have not been shown to slow the decline in GFR -LSB- 19 , 20 -RSB- . Dietary therapy for dyslipidemia has been effective in reducing lipid levels in children with primary lipid disorders -LSB- 21 -RSB- . Based on the report from the NCEP , pharmacologic therapy for children ages 10 years and older should be considered after an adequate trial of diet therapy if LDL cholesterol remains ≥ 160 mg/dl in children with significant risk for cardiovascular disease , as is seen in children with FSGS . Recommendations for pharmacologic therapy for hyperlipidemia in children from the report suggested that bile acid sequestrants cholestyramine and colestipol should be the first-line agents for treating children with lipid disorders -LSB- 18 -RSB- . This was due mainly to concerns about the safety of 3-hydroxy-3-methylglutaryl coenzyme A -LRB- HMG CoA -RRB- reductase inhibitors -LRB- statins -RRB- in children . While they are effective in lowering cholesterol and are relatively safe , bile acid sequestrants pose particular problems in children . They are not very palatable , and they may affect absorption of other medications being used , including thiazide diuretics , propranolol , corticosteroids , thyroid hormones , and loop diuretics . A new medication in this category , colesevelam , apparently does not have these problems but is not approved for use in children . Since the NCEP report in 1992 , several studies have been published suggesting that statins are safe in children as young as 4 years of age with familial hypercholesterolemia and do not adversely affect growth , hormone levels , or sexual development -LSB- 21 -- 23 -RSB- . Statins are effective in treating the hypercholesterolemia of nephrotic syndrome , with decreases in total cholesterol levels up to 45 % -LSB- 24 -RSB- . The long-term benefit of statins on renal function may be positive . Down stream from glomerular injury , high levels of urinary protein pass to the renal tubule and are reabsorbed . Protein reabsorption may injure the renal tubule . Statins may inhibit this tubular protein reabsorption and thereby protect from additional renal injury . Whether statins provide renoprotective effects in children has not been well studied , but there are several studies in adults with nondiabetic proteinuria that indicate that statins may slow GFR decline -LSB- 25 -RSB- . In these studies , the greatest benefit seemed to accrue in patients with the greatest amount of proteinuria and renal insufficiency . The side effects of statins have mainly been limited to myopathy and hepatotoxicity -LSB- 26 , 27 -RSB- . Drugs in the fibrate class have also been used alone and in combination to treat hypercholesterolemia in children with nephrotic syndrome -LSB- 28 -RSB- . The use of gemfibrozil with a statin may increase the incidence of myopathy . Fenofibrate , approved for adult use in January 2006 , may have less interaction due different hepatic metabolism -LSB- 29 -RSB- . The long-term safety of fibrates in children has not been well established . Alteration of the renin-angiotensin-aldosterone axis Blood pressure control for children with FSGS targets values less than or equal to the 90th percentile for age , gender , and height and is consistent with recommendations for all children with kidney disease . Evidence from many trials using angiotensin-converting enzyme inhibitor -LRB- ACE-I -RRB- and/or angiotensin receptor blocker -LRB- ARB -RRB- therapy in patients with proteinuria indicate that , beyond their antihypertensive effect , both are effective in reducing proteinuria in a wide variety of renal diseases . Few studies have had significant numbers of patients with FSGS specifically , and fewer still have included children with FSGS . In 1988 , Trachtman and Gauthier reported a 50 -- 70 % reduction in proteinuria in children with steroid-resistant nephrotic syndrome -LRB- SRNS -RRB- using ACE-I therapy -LSB- 30 -RSB- . Bagga et al. -LSB- 31 -RSB- , in a randomized , crossover trial of low-dose -LRB- 0.2 mg/kg -RRB- vs. high-dose -LRB- 0.6 mg/kg -RRB- enalapril in 25 patients with SRNS showed dose related responses , with average urine albumin/creatinine ratio reductions of 33 % and 52 % , respectively . Blood pressure control was similar between the two groups . Several other studies of enalapril and ramipril in children with a variety of proteinuric renal diseases have confirmed the efficacy of these drugs in reducing proteinuria in many , but not all , treated children -LSB- 32 -- 35 -RSB- . In the Ramipril Efficacy in Nephropathy -LRB- REIN -RRB- study , a double-blind study in adults with nondiabetic nephropathy , treatment with ramipril seemed to reduce both proteinuria and the rate of GFR decline more than could be attributed to blood pressure control alone -LSB- 36 -RSB- . Wühl et al. , in a similar trial in almost 400 children with hypoplasia/dysplasia -LRB- 70 % -RRB- and glomerulopathies -LRB- 13 % -RRB- , had similar findings -LSB- 37 -RSB- . There have been many studies in adults with renal disease comparing combined ACE-I/angiotensin receptor blocker -LRB- ARB -RRB- therapy with monotherapy alone -LSB- 38 , 39 -RSB- . Though differing in design and findings , overall , the studies seem to indicate greater reduction in proteinuria without a greater frequency of side effects -LSB- 39 -- 41 -RSB- . Yang et al. -LSB- 41 -RSB- reported greater reduction in proteinuria with combined therapy in a small group of five children with immunoglobulin -LRB- Ig -RRB- A nephropathy and heavy proteinuria , with no significant side effects noted . The most concerning side effect of ACE-I and ARB therapy is in females of childbearing years , with significant risk of fetal abnormalities reported with in utero exposure -LSB- 42 -RSB- . Other side effects of ACE-I therapy were noted in 2.4 % of children in one large series with ramipril in children with chronic renal failure -LSB- 37 -RSB- . These side effects included decreases in GFR and hemoglobin and increases in serum potassium levels . Acute renal failure , often associated with hypovolemia , has been noted and seems to respond to discontinuation of the medicine until the acute illness resolves . Angioedema and nonproductive cough have been encountered with the use of ACE-I therapy in adults and are less frequently reported in children . ARBs seem to have a lower incidence of angioedema and cough -LSB- 43 , 44 -RSB- . The incidence of recurrent angioedema in those who experience ACE-I-associated angioedema and are switched to ARB therapy appears to be low -LSB- 45 -RSB- . Aldosterone inhibitors have shown potential for alteration of the fibrotic mechanisms in animal models of kidney fibrosis , in the reduction of proteinuria in diabetic nephropathy , and in proteinuric chronic kidney diseases -LSB- 12 , 46 , 47 -RSB- . In the later study of 40 patients with a variety of proteinuric kidney diseases , the combination of ACE-I and aldosterone inhibitor therapy led to a decrease in mean urinary protein excretion in the ten patients assigned to this study arm -LSB- 48 -RSB- . Studies in humans with FSGS have not been published . Antioxidants The potential for antioxidant therapy in FSGS stems from experimental data that supports a role for excessive free radicals in multiple disease states , including chronic kidney disease . Based on antioxidant properties , vitamin E has been evaluated as a potential therapy for FSGS in one small study by Tahzib et al. . In this open-label study , 11 children with FSGS were treated with vitamin E for approximately 3 months . A reduction in protein excretion was noted -LSB- 49 -RSB- . The antioxidant properties of vitamin E and the relatively low risk for adverse effects of this agent make this an interesting , if unproven , therapeutic option . The combined conservative management approach may control morbidity but leave the majority of patients with uncontrolled urinary protein excretion and risk for progression of disease . The typical approach to FSGS therapy in children is to add immunosuppression at the onset of therapy . Immunosuppression Corticosteroids Corticosteroids have long been the mainstay of treatment for childhood nephrotic syndrome , regardless of its etiology . The huge role that these agents play is evident in the way this disease is classified : steroid responsive , steroid dependent , and steroid resistant . The International Study of Kidney Disease in Children -LRB- ISKDC -RRB- standard dosing has been , and generally continues to be , applied . That is , an 8-week course of oral prednisone at 60 mg/m2/day for 4 weeks , followed by 40 mg/m2 on alternate days for 4 weeks -LSB- 50 -RSB- . Initial ISKDC data showed a corticosteroid response rate of approximately 30 % of the 37 children with FSGS studied , and subsequent studies have been consistent in showing a response to oral corticosteroids in a minority of FSGS patients -LSB- 51 -RSB- . However , a response to corticosteroids is generally consistent with a more favorable prognosis , even when an initial response is followed by resistance after a subsequent relapse . There are also reported population differences in the response to steroid treatment , such as decreased response in African Americans and Hispanics -LSB- 52 -RSB- . Some literature is emerging that shows a lower response rate for patients with the nephrosis 2 homolog , podocin -LRB- human -RRB- -LRB- NPHS2 -RRB- mutation -LSB- 53 -RSB- . The more recent debate has been about what steroid , how much steroid , and for how long , before a patient can be definitely declared unresponsive . Certainly , data in adult patients advocate prolonged oral corticosteroid administration , in some cases > 6 months -LSB- 54 -RSB- . There have been no pediatric trials of prolonged oral corticosteroid use in patients with FSGS . The regimens used vary tremendously , with the most dramatic differences occurring between pediatric nephrologists and internist nephrologists . Due to the generally poor response to the standard oral dosing , some pediatric protocols have advocated high doses of intravenous methylprednisolone , with varying degrees of success -LSB- 54 , 55 -RSB- . Corticosteroids remain a key component of many therapeutic regimens for FSGS , usually in combination with the various other drugs used to treat this disease , such as alkylating agents or calcineurin inhibitors . Of course , corticosteroid therapy is not without side effects . These include hypertension , growth impairment with prolonged therapy , susceptibility to infection , diabetes mellitus , and osteoporosis -LSB- 55 -RSB- . These side effects have led to the tendency toward lower corticosteroid doses and shorter , rather than prolonged , courses . Calcineurin inhibitors Cyclosporine A The rationale behind the initial use of cyclosporine A -LRB- CsA -RRB- in FSGS and other forms of nephrotic syndrome is the evidence in animal models that the disease may be mediated by lymphokines that mediate glomerular basement membrane damage although it is unclear that this is actually the case . CsA acts on T-helper cells to inhibit interleukin-2 -LRB- IL-2 -RRB- production , cytotoxic T-cell proliferation , and activation of B-cell responses by helper T-cells . However , CsA likely induces remission in proteinuria by two other mechanisms : induction of vasoconstriction of the glomerular afferent arteriole and interference with glomerular basement membrane permselectivity to proteins -LSB- 56 -RSB- . It has been two decades since CsA was first reported to show some benefit for patients with idiopathic nephrotic syndrome , especially for patients with steroid-responsive disease who had frequent relapses . One randomized trial of 49 steroid-resistant patients assigned to either CsA or placebo for 6 months showed a benefit in the CsA arm , with a response rate of 70 % -LRB- complete or partial remission -RRB- . This is the only medication with documented efficacy for steroid-resistant FSGS in controlled clinical trials in both adults and children -LSB- 57 , 58 -RSB- . A major concern of long-term CsA treatment is the well-documented potential for nephrotoxicity . Another is the high relapse rate after drug withdrawal . In the Cattran study -LSB- 57 -RSB- , 60 % of the patients who responded to treatment had relapsed by week 78 . There is also now concern being raised about secondary resistance developing in patients treated with CsA : an initial induction of remission , relapse when the drug is withdrawn , and resistance on reinstitution of the drug -LSB- 59 -RSB- . In this study of 32 children , the diagnosis of FSGS and the presence of C4 or C1q during immunofluorescence staining of kidney tissue appear to correlate with an increased risk of secondary resistance . There are still no guidelines for standardized dosing or duration of treatment of children with steroid-resistant nephrotic syndrome , which probably accounts for the variability in reported response to treatment in the literature . Side effects of CsA treatment include hypertension , hirsutism , and gingival hyperplasia . As a result of these and the risk for nephrotoxicity , treatment with cyclosporine has not been without controversy in terms of perceived optimal daily dosing , blood level to be maintained , and duration of treatment . A recent Egyptian study in 117 children with nephrotic syndrome , which included 79 patients with FSGS , used low-dose , long-term CsA -LRB- more than 2 years of treatment -RRB- -LSB- 60 -RSB- . The starting dose of 4 -- 5 mg/kg per day was adjusted to maintain a whole-blood trough level of 100 -- 150 ng/ml during the first 2 months and 50 -- 100 ng/ml thereafter . In these subjects with steroid-resistant FSGS , the investigators were able to achieve an almost 70 % complete remission rate during the 6 months of therapy . Unfortunately , the relapse rate was substantial upon withdrawal of CsA . Overall , it appears that , as with corticosteroids , a positive response to CsA , even if followed by a relapse , is a good prognostic indicator with regard to the risk for progression to ESRD -LSB- 57 -RSB- . Tacrolimus This newer and more potent calcineurin inhibitor has not undergone a controlled clinical trial for the treatment of FSGS , but there are anecdotal reports of responses in patients with nephrotic syndrome , some of whom had FSGS -LSB- 61 -RSB- . One retrospective study of 16 children with treatment-resistant nephrotic syndrome , including 13 with FSGS , documented reduction in urinary protein excretion in 13 while on therapy and subsequent relapse in three of the 13 -LSB- 62 -RSB- . There are also two small prospective studies in adults that showed a positive response -LSB- 63 , 64 -RSB- . In these small studies , tacrolimus appeared to present a problem similar to that of CsA , with a majority of patients relapsing on drug withdrawal -LSB- 63 -RSB- . Alkylating agents DNA alkylating agents such as cyclophosphamide and chlorambucil have been in use since the 1980s for several glomerular diseases , including FSGS . The use of these agents has been limited due to potential side effects , including bone marrow suppression , infertility , hemorrhagic cystitis , and possible future malignancy risk . A retrospective cohort of 29 patients suggested that cyclophosphamide may have some survival benefit in those with at least a partial response measured by impact on proteinuria and progression of chronic kidney disease -LSB- 65 -RSB- . A randomized trial in 1996 from the ISKDC evaluated 60 children with FSGS and their response to daily oral cyclophosphamide and alternate day prednisone vs. alternate day prednisone alone . There was no difference in renal survival or proteinuria between the two groups -LSB- 66 -RSB- . Due to unfavorable toxic side effects and variable reported efficacy in the literature , alkylating agents are falling out of favor for primary therapy in FSGS . Mycophenolate mofetil Mycophenolate mofetil -LRB- MMF -RRB- was introduced in the mid-1990s as an immunosuppressive agent for organ transplantation . Due to its steroid-sparing effect , efforts have been made to expand its clinical application to several glomerular diseases , including FSGS . MMF blocks de novo synthesis of T - and B-cell lymphocytes through noncompetitive , reversible inhibition of inosine monophosphate dehydrogenase . Data on the use of MMF in FSGS has been limited to a few uncontrolled trials with small numbers of patients , but it shows early promise . Choi et al. reported 46 patients with primary glomerulopathies , including 18 patients with FSGS . They found a statistically significant decrease in proteinuria in patients receiving MMF as adjunctive therapy -LSB- 67 -RSB- . Cattran et al. reported an open-label , 6-month trial of MMF in 18 patients with steroid-resistant FSGS , 12 of whom were also resistant to alkylating agents and/or calcineurin inhibitors . Although patients did not achieve complete remission , four of 18 had a reduction in proteinuria during therapy -LSB- 68 -RSB- . A similar decrease in proteinuria was documented in a series of nine children and young adults with steroid-resistant FSGS who were treated with pulse steroids and MMF -LSB- 69 -RSB- . Overall , MMF is showing early promise as a steroid-sparing therapy in FSGS , but questions remain about length of therapy , escalation of dosing , and long-term malignancy risks . Sirolimus The utility of sirolimus in the treatment of FSGS has been entertained in patients with intolerance or resistance to corticosteroid therapy . One prospective nonrandomized study documented a reduction of proteinuria in 12 of 21 patients treated with 6 months of sirolimus -LSB- 70 -RSB- . Conversely , a study of six FSGS patients treated with sirolimus documented a decline in kidney function in five patients . None had a complete remission -LSB- 71 -RSB- . In transplant recipients , the use of sirolimus in conjunction with calcineurin inhibitors has also been associated with acute renal failure -LSB- 72 -RSB- . Consequently , sirolimus is not recommended for the treatment of FSGS due to the associated renal toxicity . Plasmapheresis In multiple-drug-resistant primary FSGS , the use of plasmapheresis has been considered a rescue option . The generally accepted rationale is for the removal of a circulating factor from the plasma that alters glomerular barrier function -LSB- 73 -RSB- . In primary FSGS in the native kidneys , two small studies encompassing 19 patients reported a response rate between 12 % and 55 % -LSB- 74 , 75 -RSB- . The best response was seen using a protocol of plasmapheresis , corticosteroids , and cyclophosphamide , making it difficult to attribute the full response to plasmapheresis alone -LSB- 75 -RSB- . A single case report of a child with resistant disease demonstrated improved proteinuria and serum creatinine -LSB- 76 -RSB- . At present , plasmapheresis is considered a rescue therapy and is an invasive procedure with significant risks of infection , hypocalcemia , and bleeding . Plasmapheresis is considered an option for prevention or treatment of recurrent FSGS in the transplant recipient based on uncontrolled studies -LSB- 77 , 78 -RSB- . Antifibrotic therapy There are a large number of patients with multiple-drug-resistant FSGS who are at substantial risk of progression to ESRD and for whom there are no proven therapeutic options . The past decade has witnessed striking advances in understanding the cellular and molecular basis of renal fibrosis and its contribution to progressive kidney failure . Several therapeutic targets have been identified in animal models of fibrosis in the kidney , including molecules involved in the recruitment and activation of mononuclear cells -LRB- e.g. , chemokines , lymphokines , adhesion molecules -RRB- , recruitment and activation of interstitial myofibroblasts , fibrogenic molecules -LSB- e.g. , transforming growth factor -LRB- TGF -RRB- - β , endothelin-1 , angiotensin II , tumor necrosis factor -LRB- TNF -RRB- - α , and platelet-derived growth factor -LRB- PDGF -RRB- - β -RSB- , angiogenic factors -LSB- e.g. , vascular endothelial growth factor -LRB- VEGF -RRB- -RSB- , antiapoptotic molecules , inhibitors of matrix synthesis , and molecules that enhance matrix degradation -LRB- matrix-degrading proteases , blockers of protease inhibitors -RRB- -LSB- 79 -- 83 -RSB- . Crossing many of these mechanisms , peroxisome proliferator activator receptor-γ -LRB- PPARγ -RRB- agonists alter regulation of renal cell differentiation and proliferation -LSB- 84 -- 87 -RSB- , extracellular matrix production , macrophage accumulation , tissue inflammation , and apoptosis -LSB- 88 -RSB- . The most effective treatment to prevent progression of fibrosis and kidney failure in FSGS is likely to entail a combination of drugs that modulate mediators of fibrosis . The progression of kidney fibrosis is interrupted in part by the use of ACE-I and ARB agents in FSGS therapy . Future therapeutic options are likely to emanate from this area of research . Conclusions Current strategies for control of FSGS use a stepwise approach with a goal of normalization of urinary protein excretion and the prevention of kidney failure . Progress in this field remains a priority in order to prevent the trajectory toward renal failure for patients proven to be resistant to treatment and to identify therapeutic regimens with minimal toxicity . CME questions -LRB- Answers appear following the reference list -RRB- A 14-year-old boy presents with nephrotic syndrome , normal serum creatinine , and normal blood pressure . He is diagnosed with FSGS by kidney biopsy and treated with corticosteroids . What is the most likely response to corticosteroids in this setting ? Complete remission with corticosteroid therapyDependence on corticosteroidsFailure to respond to corticosteroids but improves with cyclosporineFailure to control proteinuria and progression to kidney failureFactors that seem to confer an unfavorable prognosis in children with nephrotic syndrome are : Primary resistance to corticosteroidsResistance to cyclosporinePresence of NPHS2 podocin mutationAfrican American or Hispanic ethnicityAll of the aboveIn the management of FSGS , progressive kidney fibrosis may be slowed by : FurosemideAngiotensin receptor blockadeCholestyraminePrednisoneBoth b and dFSGS patients with NPHS2 podocin mutation are more likely to respond to corticosteroids than patients without a podocin mutation -LRB- T/F -RRB- . Cyclophosphamide is considered a mainstay in therapy for FSGS to prevent progression to end-stage renal failure -LRB- T/F -RRB- .

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O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O B O B O O O O O O O O B O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B O B O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O B O O O O O O O B O B O O O O O O O O O O O O O O O B O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O B O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O B O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O B O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O B O O O O O O O O O B O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O B O B O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O B O O O O O O O B O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O


A multidisciplinary , multifactorial intervention program reduces postoperative falls and injuries after femoral neck fracture Introduction This study evaluates whether a postoperative multidisciplinary , intervention program , including systematic assessment and treatment of fall risk factors , active prevention , detection , and treatment of postoperative complications , could reduce inpatient falls and fall-related injuries after a femoral neck fracture . Introduction Nearly all hip fractures occur as a result of a fall -LSB- 1 -RSB- and many fall again soon after sustaining the fracture -LSB- 2 -RSB- . Osteoporosis with low bone mineral density -LRB- BMD -RRB- puts older people who fall at high risk of sustaining fractures -LSB- 3 , 4 -RSB- . A first hip fracture is associated with a 2.5-fold increased risk of a subsequent fracture -LSB- 5 -RSB- . A population-based study among people aged 85 years or older showed that 21 % of those with a hip fracture had suffered at least two hip fractures -LSB- 6 -RSB- . Previous research has identified several fall risk factors such as comorbidity , functional disability , previous falls , and use of drugs -LSB- 7 -- 11 -RSB- but also aging -LSB- 12 , 13 -RSB- and among the oldest old , male sex -LSB- 14 -RSB- . Delirium , which is very common after hip fracture surgery , especially among those with a cognitive decline -LSB- 15 , 16 -RSB- , has been found to be one of the most important risk factors for falls among older people -LSB- 10 -RSB- . Multi factorial intervention strategies among community-living older people can prevent falls -LSB- 17 -- 20 -RSB- and are the recommendations in fall prevention interventions nowadays -LSB- 21 -RSB- . The recommendations in fall prevention programs is that they should include gait training , advice on use of assistive devices , medication reviews , exercise programs including balance training , treatment of hypotension , environmental modification , and treatment of cardiovascular disorders . In long-term care the program recommends also to include staff education -LSB- 21 -RSB- . Most fall prevention studies are performed in the community , but multidisciplinary and multifactorial interventions have also been shown to be beneficial in residential care facilities -LSB- 22 -RSB- . Few fall prevention studies have been carried out in hospitals ; there have been a few studies with single interventions among older patients in rehabilitation units , without any significant effects -LSB- 23 -- 25 -RSB- . Recently two studies , one using multiple interventions -LSB- 26 -RSB- and one using a multidisciplinary fall prevention approach -LSB- 27 -RSB- , have demonstrated a reduction in falls . None of these fall prevention studies have focused on hip fracture patients or tried to reduce postoperative complications as a fall prevention measure . Considering the lack of fall prevention studies in hospitals , especially after recent hip fracture surgery , this is an area of interest for study . The aim of this study was thus to evaluate if a postoperative multidisciplinary , multifactorial intervention program could reduce inpatient falls and fall-related injuries in patients with femoral neck fractures . Methods Recruitment and randomization This study included patients with femoral neck fracture aged ≥ 70 years , consecutively admitted to the orthopedic department at the Umeå University Hospital , Sweden , between May 2000 and December 2002 , and the study was designed according to the CONSORT guidelines -LSB- 28 -RSB- . In Sweden different surgery methods are used depending on the displacement of the femoral neck fracture . In the present study patients with undisplaced fracture were operated on using internal fixation -LRB- IF -RRB- and patients with displaced fracture were operated on using hemiarthroplasty -LRB- HAP -RRB- . If patients had severe rheumatoid arthritis , severe hip osteoarthritis , or pathological fracture they were excluded , by the surgeon on duty , because of the need for a different surgery method , such as total hip arthroplasty -LRB- THA -RRB- . Patients with severe renal failure were excluded , by the anesthesiologist , because of their morbidity . Patients being bedridden before the fracture occurred were also excluded . In the emergency room the patients were asked both in writing and orally if they were willing to participate in the study . The next of kin was always asked prior to the inclusion in patients with cognitive impairment . The patients or their next of kin could at any time decline participation . A total of 258 patients met the inclusion criteria ; 11 patients declined to participate and 48 patients were not invited to participate because they had sustained the fracture in the hospital or the inclusion routines failed -LRB- Fig. 1 -RRB- . These 59 patients were more likely to be men -LRB- p = 0.033 -RRB- and living in their own house/apartment -LRB- p = 0.009 -RRB- , but there was no difference in age -LRB- p = 0.354 -RRB- compared to the participating patients . The remaining 199 patients -LRB- Table 1 -RRB- consented to participate . All patients received the same preoperative treatment . Patients were randomized , to postoperative care in a geriatric ward with a special intervention program or to conventional care in an orthopedic ward , in opaque sealed envelopes . The lots in the envelopes were sequentially numbered . All participants received this envelope while in the emergency room but the envelope was not opened until immediately before surgery to ensure that all patients received similar preoperative treatment . Persons not involved in the study performed these procedures . The randomization was stratified according to the operation methods used in the study . Depending on the degree of dislocation , the patients were treated with IF using two hook-pins -LRB- Swemac Ortopedica , Linköping , Sweden -RRB- -LRB- n = 38 intervention vs n = 31 control -RRB- or with bipolar hemiarthroplasty -LRB- Link , Hamburg , Germany -RRB- -LRB- n = 57 vs 54 -RRB- . Basocervical fractures -LRB- n = 7 vs 10 -RRB- were operated on using a dynamic hip screw -LRB- DHS , Stratec Medical , Oberdorf , Switzerland -RRB- and one had a resection of the femoral head due to a deterioration in medical status and one died before surgery -LRB- both were in the control group -RRB- . Fig. 1Flow chart for the randomized trialTable 1Basic characteristics and assessments during hospitalization among participants in the intervention and control groups . SD standard deviation , ADL activity of daily living Intervention -LRB- n = 102 -RRB- Control -LRB- n = 97 -RRB- p valueSociodemographic Age , mean ± SD82 .3 ± 6.682.0 ± 5.90.724 Females74740 .546 Independent living before the fracture66600 .677 Health and medical problems Stroke -LRB- n = 102/93 -RRB- 29200.265 Dementia28360 .145 Previous hip fracture -LRB- n = 102/96 -RRB- a16140 .829 Depression -LRB- n = 102/95 -RRB- 33450.031 Diabetes -LRB- n = 102/95 -RRB- 23170.417 Cardiovascular disease -LRB- n = 101/93 -RRB- 57530.938 Medications on admission Number of drugs , mean ± SD5 .8 ± 3.85.9 ± 3.60.867 Antidepressants 29450.009 Sensory impairments Impaired hearing -LRB- n = 94/82 -RRB- 42340.667 Impaired vision -LRB- n = 91/74 -RRB- 37270.584 Functional performance before fracture Use of roller walker -LRB- n = 101/93 -RRB- 56520.948 Use of wheelchair -LRB- n = 101/93 -RRB- 23160.334 Previous falls , last month -LRB- n = 99/90 -RRB- b24250 .580 Walking independently , at least indoors -LRB- n = 101/94 -RRB- 85850.191 Staircase of ADL , median -LRB- Q1 , Q3 -RRB- -LRB- n = 92/88 -RRB- 5 -LRB- 1 -- 7.75 -RRB- 5 -LRB- 0.25 -- 7 -RRB- 0.859 Assessments during hospitalization Mini Mental State Examination , mean ± SD -LRB- n = 93/90 -RRB- 17.4 ± 8.215.7 ± 9.10.191 Organic Brain Syndrome Scale , mean ± SD -LRB- n = 94/90 -RRB- 10.1 ± 10.812.5 ± 11.40.148 Geriatric Depression Scale , mean ± SD -LRB- n = 81/68 -RRB- 5.2 ± 3.64.5 ± 3.50.271 aExcept for the present hip fracturebExcept for the fall that caused the hip fracture Intervention The intervention ward was a geriatric unit specializing in geriatric orthopedic patients . The staff worked in teams to apply comprehensive geriatric assessments , management , and rehabilitation -LSB- 29 , 30 -RSB- . Active prevention , detection , and treatment of postoperative complications such as falls , delirium , pain , and decubitus ulcers was systematically implemented daily during the hospitalization -LRB- Table 2 -RRB- . The staffing at the intervention ward were 1.07 nurses/aides per bed . Table 2Main content of the postoperative program and differences between the two groups Intervention groupControl groupWard layoutSingle and double roomsSingle , double , and four-bed rooms24-bed ward , extra beds when needed27-bed ward , extra beds when neededThe geriatric control ward was similar to the intervention wardStaffing1 .07 nurses/aides per bed1 .01 nurses per bedTwo full-time physiotherapistsTwo full-time physiotherapistsTwo full-time occupational therapists0 .5 occupational therapist0 .2 dieticianNo dieticianThe geriatric control ward had staffing similar to the intervention wardStaff educationA 4-day course in caring , rehabilitation , teamwork , and medical knowledge including sessions about how to prevent , detect , and treat various postoperative complications such as postoperative delirium and fallsNo specific education before or during the projectTeamworkTeam included registered nurses -LRB- RN -RRB- , licensed practical nurses -LRB- LPN -RRB- , physiotherapists -LRB- PT -RRB- , occupational therapists -LRB- OT -RRB- , dietician , and geriatriciansNo corresponding teamwork at the orthopedic unitClose cooperation between orthopedic surgeons and geriatricians in the medical care of the patientsThe geriatric ward , where some of the control group patients were cared for , used teamwork similar to that in the intervention wardIndividual care planningAll team members assessed each patient as soon as possible , usually within 24 h , to be able to start the individual care planningIndividual care planning was used in the orthopedic unit but not routinely as in the intervention wardTeam planning of the patients ' individual rehabilitation process and goals twice a weekAt the geriatric rehabilitation unit there was weekly individual care planningPrevention and treatment of complicationsInvestigation as far as possible regarding how and why they sustained the hip fracture , through analyzing external and internal fall risk factorsNo routine analysis of why the patients had fractured their hipsAn action to prevent new falls and fractures was implemented including global ratings of the patients ' fall risk every week during team meetingsNo attempt was made to systematically prevent further fallsCalcium and vitamin D and other pharmacological treatments for osteoporosis were used when indicatedNo routine prescription of calcium and vitamin DActive prevention , detection , and treatment of postoperative complications such as delirium , pain , and decubitus ulcers was systematicAssessments for postoperative complications were made with check-ups for , i.e. , saturation , hemoglobin , nutrition , bladder and bowel function , home situation etc. , but these check-ups were not carried out systematically as in the intervention groupOxygen-enriched air during the 1st postoperative day and longer if necessary until the measured oxygen saturation was stableUrinary tract infections and other infections were screened for and treatedIf a urinary catheter was used it should be discontinued within 24 h postoperativelyRegular screening for urinary retention , and prevention and treatment of constipationBlood transfusion was prescribed if B-hemoglobin < 100 g/l and < 110 for those at risk of delirium or those already deliriousIf the patient slept badly , the reason was investigated and the aim was then to treat the causeNutritionFood and liquid registration was systematically performed and protein-enriched meals were served to all patients during the first 4 postoperative days and longer if necessaryA dietician was not available at the orthopedic unitNutritional and protein drinks were served every dayNo routine nutrition registration or protein-enriched meals were available for the patientsRehabilitationMobilization within the first 24 h after surgeryMobilization usually within the first 24 hThe training included both specific exercise and other rehabilitation procedures delivered by a PT and OT , as well as basic daily ADL performance training , by caring staff . The patients should always do as much as they could by themselves before they were helpedThe PT on the ward mobilized the patients together with the caring staff . The PT aimed to meet the lucid patients every day . Functional retraining in ADL situations was not always given . The OT at the orthopedic unit only met the patients for consultationThe rehabilitation was based on functional retraining with special focus on fall risk factorsThe geriatric control ward had both specific exercise and other rehabilitation procedures delivered by a PT and OT , similar to the intervention ward but did not systematically focus on fall risk factorsHome visit by an OT and/or a PTNo home visits were made by staff from the orthopedic unit The control ward was a specialist orthopedic unit following the conventional postoperative routines . A geriatric unit , specializing in general geriatric patients , was used for those who needed longer rehabilitation -LRB- n = 40 -RRB- . The staffing at the orthopedic unit was 1.01 nurses/aides per bed and 1.07 for the geriatric control ward . The main content of both the intervention program and the conventional care is described in Table 2 . The staffs on the intervention and control wards were not aware of the nature of the present study . Data collection Two registered nurses were employed and performed the assessments during hospitalization . Medical , social , and functional data were collected from the patients , relatives , staff , and medical records on admission . Complications during hospitalization , including falls , length of stay , morbidity , and mortality , were systematically registered in the medical and nursing records . Nurses are obliged by law to document any falls in the records -LSB- 31 -RSB- . A fall was defined as an incident when the patient unintentionally came to rest on the floor and included syncopal falls . Numbers of falls and time lapse to first fall after admission were calculated . The Abbreviated Injury Scale -LRB- AIS -RRB- -LSB- 32 -RSB- was used to classify the injuries resulting from a fall . The maximum injury -LRB- MAIS -RRB- connected with each incident was recorded . A few days after surgery , patients were assessed and interviewed regarding their cognitive status using the Mini Mental State Examination -LRB- MMSE -RRB- -LSB- 33 -RSB- . The modified Organic Brain Syndrome Scale -LRB- OBS Scale -RRB- -LSB- 34 -RSB- was used to assess cognitive , perceptual , emotional , and personality characteristics as well as fluctuations in clinical states . Mental state changes were also documented from medical records . Depression during hospitalization was diagnosed due to current treatment with antidepressants and depression screened using the Geriatric Depression Scale -LRB- GDS-15 -RRB- -LSB- 35 -RSB- in combination with depressive symptoms observed and registered by the OBS Scale . The patients ' vision and hearing were assessed by their ability to read 3-mm block letters with or without glasses , and their ability to hear a normal speaking voice from a distance of 1 m. Activities of daily living -LRB- ADL -RRB- prior to the fracture were measured retrospectively using the Staircase of ADL -LSB- 36 -RSB- . A geriatrician , unaware of study group allocation , analyzed all assessments and documentation , after the study was finished , for completion of the final diagnoses according to the same criteria for all patients . The Ethics Committee of the Faculty of Medicine at Umeå University approved the study -LRB- § 00-137 -RRB- . Statistical analysis The sample size was calculated to detect a 50 % reduction of number of fallers between the intervention and control groups at a significance level of 0.050 , based on our previous multifactorial fall intervention study in institutional care -LSB- 22 -RSB- . Student 's t-test , Pearson 's χ2 test , and the Mann-Whitney U test were performed to analyze group differences regarding basic characteristics and postoperative complications . We analyzed outcomes on an intention to treat basis . The incidence of falls between intervention and control groups was compared in three ways . First , an unadjusted comparison using Pearson 's χ2 and Fisher 's exact test regarding number of patients who fell and injuries . Second , the fall incidence rate was compared between intervention and control groups by calculating the fall incidence rate ratio -LRB- IRR -RRB- using a negative binomial regression , with adjustment for observation time and for overdispersion . Negative binomial regression -LRB- Nbreg -RRB- is a generalization of the Poisson regression model and is recommended for evaluating the efficacy of fall prevention programs -LSB- 37 -RSB- . Third , a Cox regression was used to compare the time lapse to first fall between groups -LRB- hazard rate ratio , HRR -RRB- . The difference in fall risk between groups was further illustrated by a Kaplan-Meier graph . Basic characteristics that differed between the intervention and the control groups , corresponding to a p value < 0.150 -LRB- depression , antidepressants , and dementia , Table 1 -RRB- , were considered as covariates in the Poisson -LRB- Nbreg -RRB- and the Cox regression models . However , the inclusion of these variables had only marginal effects on the log-likelihood values of the models as well as on the IRR and HRR values and standard errors for the group allocation variable -LRB- intervention or control -RRB- . In addition , none of the variables showed significant effects on the dependent variable and are therefore not included in the Poisson -LRB- Nbreg -RRB- and Cox regression analyses . Pearson 's χ2 test and Fisher 's exact test were also used to analyze the associations between falls and days with delirium between the groups . All calculations were carried out using SPSS v 11.0 and STATA 9 statistical software for Macintosh . A p value < 0.050 was considered statistically significant . Results During hospitalization 12 patients in the intervention group sustained 18 falls -LRB- range : 1 -- 3 -RRB- and in the control group 26 patients sustained 60 falls -LRB- 30 falls in the orthopedic unit and 30 in the geriatric control unit -RRB- -LRB- range : 1 -- 11 -RRB- . Among patients with dementia 1 patient sustained a single fall in the intervention group and 11 patients sustained 34 falls in the control group -LRB- Table 3 -RRB- . Table 3Falls during hospitalization . CI confidence interval , IRR incidence rate ratio Intervention -LRB- n = 102 -RRB- Control -LRB- n = 97 -RRB- p valueNumber of falls1860Postoperative in-hospital days2 ,8603,685 Crude fall incidence rate -LRB- number of falls/1 ,000 days -RRB- 6.2916.28 IRR -LRB- 95 % CI -RRB- 0.38 -LRB- 0.20 -- 0.76 -RRB- a1 .00 -LRB- Ref . -RRB- 0.006 Number of fallers12260 .007 Number of fallers with injuries due to falls3150 .002 Number of fallers with fractures due to falls040 .055 Number of falls among people with dementia134IRR -LRB- 95 % CI -RRB- among people with dementia0 .07 -LRB- 0.01 -- 0.57 -RRB- a1 .00 -LRB- Ref . -RRB- 0.013 Number of fallers among people with dementia -LRB- n = 28/36 -RRB- 1110.006 aNegative binomial regression analyses adjusted for overdispersion and controlled for dementia , depression , and use of antidepressants The crude postoperative fall incidence rate was 6.29 / 1,000 days in the intervention group vs 16.28 / 1,000 days in the control group . Using a negative binomial regression , the fall incidence was significantly lower in the intervention group , IRR 0.38 -LRB- 95 % CI : 0.20 -- 0.76 , p = 0.006 -RRB- , and among patients with dementia , IRR 0.07 -LRB- 95 % CI : 0.01 -- 0.57 , p = 0.013 -RRB- -LRB- Table 3 -RRB- . In Fig. 2 , a Kaplan-Meier survival analysis of time lapse to first fall illustrates the difference between the two groups with a significantly reduced fall rate in the intervention group -LRB- log rank p value 0.008 -RRB- . Fig. 2Kaplan-Meir survival graph The difference in fall risk , expressed as time lapse to first fall , was compared between intervention and control groups in a Cox regression -LRB- HRR -RRB- . Including all patients in the calculation , the fall risk was significantly lower in the intervention group , HRR 0.41 -LRB- 95 % CI : 0.20 -- 0.82 , p = 0.012 -RRB- . There were in total 3 minor or moderate injuries -LRB- MAIS 1-2 -RRB- in the intervention group compared to 15 in the control group according to the AIS . The serious injuries -LRB- MAIS 3 -RRB- were new fractures of which four , two hip fractures , one rib fracture with pneumothorax , and one with multiple skull fractures , occurred in the control group and none in the intervention group -LRB- Fisher 's exact test : p = 0.055 -RRB- . Three of the patients who fell in the intervention group -LRB- 25 % -RRB- and 12 in the control group -LRB- 46 % -RRB- fell during a day when they were delirious -LRB- p = 0.294 -RRB- . Analyzing the number of falls revealed that 4 of 18 -LRB- 22 % -RRB- falls in the intervention group and 27 of 60 -LRB- 45 % -RRB- in the control group occurred on a day when the patient was delirious , p = 0.083 . Apart from the falls there were fewer other postoperative complications in the intervention group , such as fewer patients with postoperative delirium -LRB- p = 0.003 -RRB- and fewer delirious days -LRB- p ≤ 0.001 -RRB- , urinary tract infections -LRB- p = 0.005 -RRB- , sleeping disturbances -LRB- p = 0.009 -RRB- , nutritional problems -LRB- p = 0.038 -RRB- , and decubitus ulcers -LRB- p = 0.010 -RRB- . The postoperative in-hospital stay was shorter in the intervention group , 28.0 ± 17.9 days vs 38.0 ± 40.6 days , p = 0.028 . Among those ten with the longest postoperative in-hospital stays in the control group there were eight patients with any fall and two had had new fractures . Discussion The present study shows that the number of falls and time lapse to first fall can be reduced during in-hospital rehabilitation after a femoral neck fracture . A multidisciplinary , multifactorial geriatric care program with systematic assessment and treatment of fall risk factors as well as active prevention , detection , and treatment of other postoperative complications resulted in fewer patients who fell , a lower total number of falls , and fewer injuries . To our knowledge this is the first fall intervention study in this group of patients , despite the fact that this is a group of patients with a high fall risk . In general there are few fall prevention studies in hospital settings . Two -LSB- 26 , 27 -RSB- with positive outcomes in other patient groups and on subacute wards have recently been published . The first one -LSB- 26 -RSB- reduced falls at three subacute rehabilitation wards , but the differences were most obvious after 45 days of observation . Thus the results were not comparable with those from the present study , which included both the acute and rehabilitation hospital stay . The other study -LSB- 27 -RSB- resulted in fewer fallers , falls , and injuries on a geriatric ward but the differences disappeared when the results were adjusted for observation time . Those studies used a multidisciplinary approach in their fall intervention similar to that used in the present study , but in the present study we have , in addition , focused on inpatient complications associated with falls such as delirium and urinary tract infections . One of those studies -LSB- 27 -RSB- tried to manage the delirious patients using bedrails , alarms , and changing the furniture arrangements for the patients , but no mention was made of any prevention and treatment of the underlying causes of delirium . The use of physical restraints was not included in the intervention program in the present study . The studies above used fall risk assessment tools to recognize those with a high fall risk . In the present study , we used a rehabilitation and care program including assessment of risk factors for falls and global ratings for each patient during team meetings . A critique of fall risk assessment tools is that few have been tested for validity and reliability testing in a new independent sample . When using fall prediction tools in different clinical settings the specificity decreases -LSB- 38 -RSB- . A limitation in the present study is that some falls could have been missed , but we presume that there were very few . For one thing the nurses are obliged to document falls in the records . Also hip fracture surgery patients can hardly get up by themselves after a fall so soon after the surgery and are , therefore , bound to be noticed ; but if there were any missing falls there would probably be no difference between the groups . Another limitation is that the fall registration could not be blinded regarding group allocation , but the staffs on each ward were not aware of the comparison with another ward regarding falls and injuries . The study sample is also quite small , but the sample size is calculated according to the results from a previous study -LSB- 22 -RSB- . The method of concealment could have been improved , but one strength was that none from the research team performed this procedure and the envelopes were not opened until the intervention was to begin . Other strengths were the intention to treat analyses , the few patients who refused to participate , and that there were no crossover effects due to staff changing wards during the study period . One may speculate that the successful reduction in number of falls in the present study could be a result of the active prevention , detection , and treatment of postoperative complications after surgery . During the period of hospitalization there were differences between the groups regarding some complications associated with falls among older people in residential care facilities and in hospitals , such as delirium and urinary tract infections . The reduction of postoperative delirium can probably explain much of the difference between the groups regarding the numbers of falls and the number of patients who fell . There are studies that have found that delirium is an important risk factor for falls -LSB- 10 -RSB- . Demented patients especially are at high risk of developing delirium when they are treated for femoral neck fractures -LSB- 15 , 16 -RSB- and these patients seemed to have benefited most in this study from the intervention program regarding prevention of postoperative falls . Our findings support an earlier non-randomized study that fewer injurious falls occur when the incidence and duration of delirium was reduced -LSB- 39 -RSB- . The investigation into why the patients had fractured their hip and why they fell may also have influenced the result , as well as the investigation and rehabilitation concerning external fall risk factors such as the use of walking aids , safe transfers , balance , and mobility . It seems that teamwork and individual care planning alone do not have the same effect on falls , as half the falls in the control group occurred in the geriatric control ward , a ward specializing in geriatric patients where teamwork , as well as individual care planning , is applied . In the community and residential care facilities , interdisciplinary and multifactorial fall prevention studies have shown positive effects on the reduction in the number of falls and injuries -LSB- 19 , 22 -RSB- . Among those with cognitive decline or dementia there is no evidence that such strategies prevent falls -LSB- 40 , 41 -RSB- , but the present study allowed the conclusion that at least during the in-hospital stay , this group of patients could benefit from such strategies . The reduced number of falls and injuries also probably contributed to the shorter hospitalization seen in the intervention group . The program seems easy applicable both in the acute postoperative care as well in the post-acute rehabilitation settings and except for the staff education there were no increased costs . Conclusion A team applying comprehensive geriatric assessment and rehabilitation , including prevention , detection , and treatment of fall risk factors , can successfully prevent inpatient falls and injuries , even in patients with dementia .

O O O O B O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O 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O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I B O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B I O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O B O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O O