***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Abstract Background : A recent 2-year r and omized controlled trial indicated that the transthyretin ( TTR ) tetramer stabilizer , diflunisal , inhibits polyneuropathy progression and preserves quality of life in hereditary ATTR amyloidosis . However , its long-term outcomes are unknown . Here , we report tolerance and efficacy of long-term diflunisal administration in hereditary ATTR amyloidosis . Methods : Diflunisal was administered orally at 500 mg/day to 40 Japanese hereditary ATTR amyloidosis patents who were not c and i date s for liver transplantation . The observation period ranged from 2 to 116 months ( mean ± SD : 38.0 ± 31.2 months ) . Results : Diflunisal-related adverse events included deterioration of renal function and thrombocytopenia result ing in discontinuation of the drug in three patients . Orally administered diflunisal significantly increased serum TTR concentration ( p = 0.001 ) and stabilized TTR tetramer structure in each patient . Longitudinal analyses of data collected at baseline , 24 months , and after 24 months confirmed sustaining effects of diflunisal on both neurological and cardiac functions . Notably , ulnar compound muscle action potential amplitude , cardiac wall thickness , and ejection fraction were not deteriorated after 24 months of treatment . Conclusions : Diflunisal was tolerated well by most hereditary ATTR amyloidosis patients , although renal function and blood cell counts must be carefully monitored . Clinical effects of diflunisal were sustained after 2 years of treatment Background —Transthyretin ( TTR ) amyloidosis is a progressive systemic disorder caused by misfolded TTR monomers that cumulatively deposit in the heart and systemically as amyloid . Methods and Results —This phase 2 open-label trial evaluated the stabilization of TTR tetramers using 20 mg of tafamidis daily at week 6 ( primary end point ) , month 6 , and month 12 , as well as safety of tafamidis treatment and efficacy with respect to progression of TTR amyloid cardiomyopathy . Thirty-one wild-type patients ( median age , 76.7 years ; 93.5 % men ) with a median disease duration of 55.6 months and mild to moderate heart failure ( 96.8 % ; New York Heart Association , classes I – II ) were enrolled . Thirty of 31 patients ( 96.8 % ) achieved TTR stabilization after 6 weeks and 25 of 28 patients ( 89.3 % ) after 12 months . After 12 months of treatment , 3 patients discontinued prematurely , 2 patients died , 7 patients were hospitalized because of cardiovascular events , 20 of 28 patients demonstrated preserved New York Heart Association classification status , but 15 of 31 ( 48.4 % ) patients had clinical progression ( eg , admission for cardiac failure , atrial fibrillation , and syncope ) . N-terminal prohormone brain natriuretic peptide levels did not increase significantly over time , troponin I and troponin T increased moderately , and no consistent clinical ly relevant changes were seen in echocardiographic cardiac assessment s.  Tafamidis treatment was generally well tolerated although 7 of 31 patients had bouts of diarrhea . Conclusions —Tafamidis treatment effectively achieved and maintained TTR stabilization and was well tolerated . The absence of significant changes in most biochemical and echocardiographic parameters suggests that further evaluation of tafamidis in TTR amyloid cardiomyopathy is warranted . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT00694161 OBJECTIVE To evaluate the long-term efficacy and safety of diflunisal in late-onset familial amyloid polyneuropathy ( FAP ) in a Japanese endemic area . METHODS Consecutive six FAP patients ( mean age : 65.8 ± 7.3 years ) with a transthyretin ( TTR ) Val30Met mutation from an endemic area of late-onset FAP were prospect ively recruited to an open label study with oral diflunisal ( 250 mg twice a day ) . We evaluated clinical symptoms , Kumamoto FAP score , modified body mass index ( m BMI ) , Medical Research Council sum score , nerve conduction studies ( NCS ) , electrocardiogram ( ECG ) , ECG Holter monitor test , echocardiography , and (123)iodine-metaiodobenzylguanidine ( (123)I-MIBG ) myocardial scintigraphy . RESULTS One patient ceased to take diflunisal because of hematuria which was reversible . The other five patients were treated with diflunisal for 3 - 5 ( 4.4 ± 0.9 years ) years . Autonomic symptoms ( orthostatic hypotension and gastrointestinal symptoms ) disappeared after treatment in two of the four patients with the symptoms . Delayed heart to mediastinum ratio on (123)I-MIBG imaging , a marker of cardiac postganglionic sympathetic nerve function , increased during the three-year treatment . m BMI was maintained through observation period . While , motor and sensory symptoms , Kumamoto FAP scores , and data on NCS gradually deteriorated . CONCLUSION Diflunisal might be effective especially for autonomic dysfunction in late-onset FAP with a TTR Val30Met mutation Abstract Background : Tafamidis , a non-NSAID highly specific transthyretin stabilizer , delayed neurologic disease progression as measured by Neuropathy Impairment Score – Lower Limbs ( NIS-LL ) in an 18-month , double-blind , placebo-controlled r and omized trial in 128 patients with early-stage transthyretin V30 M familial amyloid polyneuropathy ( ATTRV30M-FAP ) . The current post hoc analyses aim ed to further evaluate the effects of tafamidis in delaying ATTRV30M-FAP progression in this trial . Methods : Pre-specified , repeated- measures analysis of change from baseline in NIS-LL in this trial ( Clinical Trials.gov NCT00409175 ) was repeated with addition of baseline as covariate and multiple imputation analysis for missing data by treatment group . Change in NIS-LL plus three small-fiber nerve tests ( NIS-LL + Σ3 ) and NIS-LL plus seven nerve tests ( NIS-LL + Σ7 ) were assessed without baseline as covariate . Treatment outcomes over the NIS-LL , Σ3 , Σ7 , modified body mass index and Norfolk Quality of Life – Diabetic Neuropathy Total Quality of Life Score were also examined using multivariate analysis techniques . Results : Neuropathy progression based on NIS-LL change from baseline to Month 18 remained significantly reduced for tafamidis versus placebo in the baseline-adjusted and multiple imputation analyses . NIS-LL + Σ3 and NIS-LL + Σ7 captured significant treatment group differences . Multivariate analyses provided strong statistical evidence for a superior tafamidis treatment effect . Conclusions : These supportive analyses confirm that tafamidis delays neurologic progression in early-stage ATTRV30M-FAP . Trial registration number : NCT00409175 Introduction Gastrointestinal symptoms are common among patients with transthyretin familial amyloid polyneuropathy ( TTR-FAP ) . This post hoc analysis evaluated the nutritional status of TTR-FAP patients treated with tafamidis while enrolled in clinical trials . Methods Nutritional status was measured by the modified body mass index ( m BMI = BMI × albumin level ) . Treatment-related changes in m BMI were reported for 71 Val30Met TTR-FAP patients who completed an 18-month , r and omized , double-blind , placebo-controlled trial and who continued into its open-label , 12-month extension . Results At month 18 , m BMI worsened in the placebo group ( n = 33 ) ( −33 ± 16 kg/m2 g/l , P = 0.04 versus baseline ) but improved in the tafamidis group ( n = 38 ) ( + 37 ± 14 kg/m2 g/l , P = 0.01 versus baseline ) such that the effect size between the groups was statistically significant ( P = 0.001 ) . By month 30 ( completion of the open-label extension ) , placebo patients with 12 months of tafamidis treatment and tafamidis-treated patients with 30 months of treatment both tended to increase their m BMI ( 28 ± 19 kg/m2 g/l and 16 ± 18 kg/m2 g/l , respectively ) . Increase in BMI was most pronounced in patients with low BMI at entry into the studies . Conclusions m BMI is well suited to monitor disease progression in TTR-FAP patients . The delay in neurological deterioration brought about by tafamidis treatment in clinical trials is associated with improvements in , or maintenance of , m BMI . Funding This study was sponsored by Pfizer Inc. , New York , USA Tafamidis , a transthyretin ( TTR ) kinetic stabilizer , delayed neuropathic progression in patients with Val30Met TTR familial amyloid polyneuropathy ( TTR-FAP ) in an 18-month r and omized controlled trial ( study Fx-005 ) . This 12-month , open-label extension study evaluated the long-term safety , tolerability , and efficacy of tafamidis 20 mg once daily in 86 patients who earlier received blinded treatment with tafamidis or placebo .  Efficacy measures included the Neuropathy Impairment Score in the Lower Limbs ( NIS-LL ) , Norfolk Quality of Life-Diabetic Neuropathy total quality of life ( TQOL ) score , and changes in neurologic function and nutritional status . We quantified the monthly rates of change in efficacy measures , and TTR stabilization , and monitored adverse events ( AEs ) . Patients who continued on tafamidis had stable rates of change in NIS-LL ( from 0.08 to 0.11/month ; p = 0.60 ) and TQOL ( from −0.03 to 0.25 ; p = 0.16 ) . In patients switched from placebo , the monthly rate of change in NIS-LL declined ( from 0.34 to 0.16/month ; p = 0.01 ) , as did TQOL score ( from 0.61 to −0.16 ; p < 0.001 ) . Patients treated with tafamidis for 30 months had 55.9 % greater preservation of neurologic function as measured by the NIS-LL than patients in whom tafamidis was initiated later . Plasma TTR was stabilized in 94.1 % of patients treated with tafamidis for 30 months . AEs were similar between groups ; no patients discontinued because of an AE . Long-term tafamidis was well tolerated , with the reduced rate of neurologic deterioration sustained over 30 months . Tafamidis also slowed neurologic impairment in patients previously given placebo , but treatment benefits were greater when tafamidis was begun earlier Abstract Background : The objective of the present study was to evaluate the long-term safety and efficacy of tafamidis in treating hereditary transthyretin amyloid polyneuropathy .  Methods : A prospect ively planned interim analysis was conducted on an on-going , phase III , open-label extension study following an 18-month , r and omized , controlled study and 12-month , open-label extension study in ATTRV30 M patients and a single-arm , open-label study in non-ATTRV30 M patients . Thirty-seven ATTRV30 M patients received placebo for 18 months , then switched to tafamidis and 38 ATTRV30 M patients and 18 non-ATTRV30 M patients continuously received tafamidis from day 1 , up to 6 years . Results : Long-term tafamidis was associated with a favourable safety/tolerability profile , without any unexpected adverse events . Patients initiating tafamidis at the start of the r and omized study had less polyneuropathy progression versus those switching to tafamidis following 18 months of placebo and were less likely to progress to the next ambulatory stage after up to 6 years follow-up . In the patients who switched from placebo to tafamidis , polyneuropathy progression and deterioration in quality of life slowed significantly during long-term tafamidis treatment as compared with the previous placebo treatment . In non-ATTRV30 M patients , some polyneuropathy progression was observed across all efficacy measures . Conclusions : These data provide evidence for the long-term ( up to 6 years ) safety and efficacy of tafamidis . Clinical Trials.gov : IMPORTANCE Familial amyloid polyneuropathy , a lethal genetic disease caused by aggregation of variant transthyretin , induces progressive peripheral nerve deficits and disability . Diflunisal , a nonsteroidal anti-inflammatory agent , stabilizes transthyretin tetramers and prevents amyloid fibril formation in vitro . OBJECTIVE To determine the effect of diflunisal on polyneuropathy progression in patients with familial amyloid polyneuropathy 
    Output:
    
This systematic review and meta- analysis has demonstrated that tafamidis delays neurologic progression and preserves a better nutritional status and the quality of life .
The rates of adverse events did not differ between the patients in the tafamidis and placebo groups .
Tafamidis might be a safer noninvasive option for patients with TTR-FAP