***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: Background In spite of the large body of evidence available in the literature , definition and treatment of  Post-Herpetic Neuralgia ( PHN )  are still lacking a consistent and universally recognized st and ardization . Furthermore , many issues concerning diagnosis , prediction and prevention of PHN need to be clarified in view of recent contributions . Objectives To assess whether PHN may be better defined , predicted , treated and prevented in light of recent data , and whether available alternative or adjunctive therapies may improve pain relief in treatment recalcitrant PHN . Methods Systematic review s , meta-analyses , r and omized controlled trials , cohort studies and protocol s were search ed ; the search sources included PubMed , Cochrane Library , NICE , and DARE . More than 130 papers were selected and evaluated . Results Diagnosis of PHN is essentially clinical , but it can be improved by resorting to the many tools available , including some practical and accessible question naires . Prediction of PHN can be now much more accurate , taking into consideration a few well vali date d clinical and anamnestic variables . Treatment of PHN is presently based on a well characterized array of drugs and drug associations , including , among others , tricyclic antidepressants , gabapentinoids , opioids and many topical formulations . It is still unsatisfactory , however , in a substantial proportion of patients , especially those with many comorbidities and intense pain at herpes zoster ( HZ ) presentation , so that this frequent complication of HZ still strongly impacts on the quality of life of affected patients . Conclusion Further efforts are needed to improve the management of PHN . Potentially relevant interventions may include early antiviral therapy of acute HZ , prevention of HZ by adult vaccination , as well as new therapeutic approaches for patients experiencing PHN Herpes zoster results from the reactivation of latent varicella-zoster virus located in the dorsal root ganglia . The condition is common in elderly and immunocompromised patients . Although herpes zoster is not a reportable disease , an estimated 300 000 to 500 000 cases occur annually in the United States [ 1 ] . In immunocompetent persons , the most notable manifestations are acute neuritis and persistent pain , traditionally called postherpetic neuralgia . Recent clinical trials of acyclovir [ 2 - 5 ] , valaciclovir [ 6 ] , and famciclovir [ 7 , 8 ] showed that antiviral therapy helps heal cutaneous lesions and relieve pain in patients with herpes zoster . When our clinical trial was initiated , several studies had already reported that corticosteroid therapy could potentially decrease the incidence or duration of postherpetic neuralgia [ 9 - 14 ] . Despite their small sample sizes and use of inadequate controls , these clinical trials result ed in the widespread adoption of prednisone as the st and ard therapy for herpes zoster . It was hoped that this agent would prevent persistent or chronic pain . More recent studies [ 15 - 18 ] did not confirm the validity of this approach . A large study that used acyclovir with or without prednisolone for as long as 21 days showed no beneficial effect of steroids on persistent pain [ 19 ] . Nevertheless , many physicians continue to use therapy with both antiviral drugs and corticosteroids to manage herpes zoster . We and other members of the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group did a clinical trial to determine the effect of adding corticosteroids to acyclovir for the treatment of herpes zoster . Our key study end points were measurements of pain and quality of life . Methods Patients Eligible participants were immunocompetent adults older than 50 years of age who presented with a localized dermatomal vesicular rash that was clinical ly consistent with herpes zoster and had been present for less than 72 hours . Patients were referred to participating investigators by community physicians or from university-affiliated clinics . The diagnosis was confirmed by the isolation of varicellazoster virus in tissue culture and by serologic testing . We excluded patients who required immunosuppressive therapy ; patients with cancer ; women capable of conceiving and bearing a child ; patients who had a history of hypertension ( diastolic pressure > 100 mm Hg ) or were receiving antihypertensive treatment ; patients with osteoporosis or insulin-dependent diabetes mellitus ; patients who had received other antiviral drugs or immune globulin products within the 4 weeks before the study began ; and patients with a history of glycosuria or hyperglycemia . Other concurrent medications or illnesses did not warrant exclusion . All patients gave informed consent before r and omization . The informed consent document was approved by all local institutional review boards in compliance with regulations of the U.S. Food and Drug Administration . Interventions We used a 2 2 factorial study design to r and omly allocate the 208 eligible and consenting patients . Patients received one of the following regimens : 1 ) acyclovir plus prednisone , 2 ) acyclovir plus prednisone placebo , 3 ) prednisone plus acyclovir placebo , or 4 ) placebos for both prednisone and acyclovir . Acyclovir was administered orally , 800 mg five times daily , for 21 days . Prednisone was administered orally at 60 mg/d for days 1 to 7 , 30 mg/d for days 8 to 14 , and 15 mg/d for days 15 to 21 . All research personnel remained blinded to drug assignments until the study was completed and the data base was locked . All matched medications ( acyclovir plus prednisone placebo and prednisone plus acyclovir placebo ) were identical in taste and appearance . With a 2 2 factorial design , two treatments are evaluated simultaneously in one study . This design allows the assessment of an individual intervention and of the combined effects of multiple interventions ( in our study , acyclovir and prednisone ) . The main or individual effect of acyclovir represents the difference between the effect of acyclovir therapy and the effect of no acyclovir therapy . We compared the patients who received acyclovir  ( the acyclovir plus prednisone group and the acyclovir plus prednisone placebo group ) with the patients who did not receive acyclovir  ( the prednisone plus acyclovir placebo group and the placebo group ) . Similarly , the main effect of prednisone represents the difference between the effect of prednisone therapy and the effect of no prednisone therapy . We compared the two groups that received prednisone with the two groups that did not . This study design also allowed us to compare the combined effect of acyclovir and prednisone therapy with the effect of either therapy alone or with the effect of placebo . Outcome Measures and Surveillance Our primary end points were the persistence of pain and assessment s of quality of life ( return to 100 % usual activity , return to uninterrupted sleep , and cessation of use of analgesic agents ) during a 6-month period . Secondary end points were cutaneous healing and clinical or laboratory evidence of toxicity . After enrollment , patients were evaluated daily until the skin was completely healed . The number of new vesicles formed , extent of healing ( measured by the presence of vesiculation , pustulation , scabbing , and total healing ) , severity of pain , and analgesic requirements were recorded at each visit . Acute neuritis was assessed during the first month after enrollment . Each patient was asked to rate his or her pain as none , mild , moderate , or severe or incapacitating . The effect of herpes zoster on usual activity ( measured as a percentage reduction in activity ) , continued analgesic requirements , and the ability to sleep without interruption was also recorded at each visit . After lesions had completely healed , patients were followed monthly for the 6 months after therapy began and were assessed for persistence of pain , analgesic requirements , and quality -of-life measures . We used two analyses to measure chronic pain . First , postherpetic neuralgia was defined as pain that was present 30 days after disease onset and that continued until complete resolution or 6 months . Because we sought to maintain the principles of the intention-to-treat analysis and include patients with no pain at 30 days after disease onset , we assigned such patients a value of zero for the time to resolution of postherpetic neuralgia . Second , pain associated with zoster was defined as the continuum of pain extending from study enrollment until final resolution . This second analysis included all patients from the time of enrollment . For all pain analyses , resolution of pain was defined as the last occurrence of any pain attributed to herpes zoster . Time to return to uninterrupted sleep was assessed by the patient as the time when he or she was no longer awakened by pain or altered sensations attributable to herpes zoster . Similarly , times to cessation of the use of analgesic agents and return to 100 % usual activity were defined as the first recorded time to that event with no subsequent documented relapse . Blood and urine sample s were tested for evidence of treatment toxicity every week for the first 4 weeks . Assessment s included a complete blood count with differential and platelet determinations ; urinalysis ; and quantitation of serum and urine levels of urea , creatinine , bilirubin , glucose , and aspartate glutamyltransferase . Adverse clinical events , regardless of their probability of being associated with drug administration , were reported immediately by telephone or facsimile to the central unit at the University of Alabama at Birmingham . R and omization The Biostatistical Unit of the National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group at the University of Alabama at Birmingham used a computer-generated r and omization code to r and omly assign patients to one of the four treatment groups . R and omization was done in blocks of four . Estimation of Sample Size The sample size was calculated according to assumptions of the main effect of acyclovir that were based on data available when the trial was design ed . The null hypothesis was that patients receiving acyclovir and those not receiving acyclovir would have equal rates of persistent pain at 6 months . On the basis of a one-sided test procedure that had a significance level of 0.025 and of a projected 20 % detected difference between treatment groups , we calculated that a sample size of 256 patients was needed to achieve a power of 90 % . Because of slow accrual during the latter stages of the trial ( which was probably caused by the widespread acceptance and availability of oral acyclovir ) , the study was terminated with a total enrollment of 208 patients . Two hundred one of the 208 patients were included in the final analysis , yielding a power of 82 % . Interim Analysis A Data Safety and Monitoring Board was established by the National Institute of Allergy and Infectious Diseases through the Division of Microbiology and Infectious Diseases to monitor the progress of the trial and any adverse events . However , no interim analyses of efficacy end points were done . Statistical Analysis The clinical response measurements for time-to-event variables were estimated using the Kaplan-Meier method and were compared using the log-rank test . We used a Cox regression model to analyze the main effects of acyclovir and prednisone and their interaction , with adjustments for other covariates . The main effects of acyclovir and prednisone were each represented in the Cox model as a dummy variable coded as 0 or 1 . The interaction of these drugs was represented as the product of the two dummy variables . We also used a Cox model to compare each treatment group with the placebo group , with adjustment for all specified covariates ( sex , race , age , duration of lesions before enrollment , number of lesions at entry , Healthy patients with early painful herpes zoster were treated with corticosteroid orally or lactose tablets in a double-blind fashion . The duration of postherpetic neuralgia was shortened by treatment with the corticosteroid . Corticosteroid therapy did not affect pain during the first two weeks or the rate of skin healing . The duration of postherpetic neuralgia could not be predicted by the healing rate of the skin .  Control patients less than 60 years old had rapid resolution of their neuralgia while those more than 60 years old had slower resolution of the pain .  Corticosteroid therapy did not cause generalization of the eruption The effects of prednisone , oral acyclovir , and radiotherapy were compared with placebo in the prevention of  post-herpetic neuralgia .  No treatment used was able to prevent , with statistical significance , post-herpetic neuralgia , although prednisone and acyclovir showed some pain reduction in the acute phase . Radiotherapy was of no value in either the acute or post-herpetic phase Over an 18-month period , all incident cases of neurological disorders were ascertained prospect ively in an unselected urban population based in 13 general practice s in the London area by a General Practice Linkage Scheme with the National Hospital for Neurology and Neurosurgery . In three of these practice s , the lifetime prevalence of neurological disorders was also assessed . A population of 100 230 patients registered with participating general practice s was followed prospect ively for the onset of neurological disorders . Multiple methods of case finding were used to maintain accuracy . The age- and sex-adjusted incidence rates of neurological disorders were calculated . The lifetime prevalence of neurological disorders was surveyed in 27 658 of the patients . The age- and sex-adjusted incidence rates were calculated for major neurological conditions . [ These are expressed as rates per 100 000 persons per annum , with 95 % confidence intervals ( CI ) in parentheses ] . The commonest of these were first cerebrovascular events , 205 ( CI : 183 , 230 ) ; shingles , 140 ( CI : 104 , 184 ) ; diabetic polyneuropathy , 54 ( CI : 33 , 83 ) ; compressive neuropathies , 49 ( CI : 39 , 61 ) ; epilepsy , 46 ( CI : 36 , 60 ) ; Parkinson 's disease , 19 ( CI : 12 , 27 ) 
    Output:
    
There were no significant differences in serious or non-serious adverse events between the corticosteroid and placebo groups .
There is moderate quality evidence that corticosteroids given acutely during zoster infection are ineffective in preventing postherpetic neuralgia .
In people with acute herpes zoster the risks of administration of corticosteroids do not appear to be greater than with placebo , based on moderate quality evidence .
Corticosteroids have been recommended to relieve the zoster-associated pain in the acute phase of disease .