and $670,000 is to be spent by other agencies. b. Short-Term Benefits From an estimated base of 6,800 deaths in the population screened 171 which would occur without this program component,- a 1% reduction in immediate mortality is anticipated due to the successful treatment of acute pyelonephritis (if it is detected at an early stage before severe 181 tissue damage has occurred).- Therefore, a reduction in mortality of 70 deaths per year is estimated. In addition, there is a reduction in the prevalence of significant bacteriuria in 3,231,260 patients (50% of 6,462,520). This 50% reduc- tion is based on the supposition that the majority of cases detected will be of simple bacteriuria, in the absence of tissue infection, which responds well to treatment. It is understood that the first course of therapy for patients with bacteriuria in acute infections would be highly successful, but is is not anticipated that a permanent cure will be achieved in individuals with chronic urinary tract infections. With therapy, the number of morbid days could be reduced by 65% from the base of 24,557,580 to 15,962,427.191 C. Long-Term Benefits A significant benefit from this early detection program will be an ultimate reduction in mortality due to end-stage renal disease resulting 19Aj from earlier urinary tract infections.- After a diagnosis of infec- tion is made, further study of the patient would lead to the detection of factors predisposing to or associated with that infection. It should be pointed out that new methods of anti-infectious therapy could 201 possibly increase the cure rate for the population-at-risk to 75%.- (1) Annual Long-Term Benefits At present, it is estimated that 20% (1,750) of an esti- mated total cases (8,500) of end-stage kidney disease per year 211 can be averted by current medical therapy.- (2) Cumulative Long-Term Benefits It is estimated that in time 5% (323,126) of the 6,462,520 individuals having significant bacteriuria may have developed a significant urinary tract infection. Of this 5X, approximately 40% (129,250) may eventually die in renal failure. Implementation of the above program would be expected to reduce this mortality by 221 20% (25,850) based on current methods of therapy.- 3. Research Because of problems peculiar to urinary tract infection, [i.e., the poor response to therapy (20% cure rate) and the difficulty in isolating bacteria from end-stage kidneys resulting from infection], a great deal of research, both laboratory and clinical, must be undertaken before a more effective program can be administered in the prevention of urinary tract infections. a. Laboratory Research Laboratory research should be concentrated in these areas: 1) A relationship of viral agents to renal disease; 2) The identification and treatment of host-factors which predispose the host to urinary tract infections; 3) The role of immunologic phenomena in bacterial and/or viral infections of the kidney; 4) The role of vascular and metabolic diseases in urinary tract infections; 5) The role of various chemical agents (e.g., phenacetin) in renal tissue infection; 6) The nature of the exudative response to renal infection; 7) The nature of connective tissue proliferation in renal tissue; 8) A classification of the organisms causing renal infections and the identification of toxins, enzymes, etc., produced by these organisms; and 9) The pharmacology of specific antibiotics including drug inhibitors affecting the viability of microorganisms in renal tissue. No sound estimate can be made for the cost of each of these basic research programs, but approximately $1,500,000 should be 231 made available in the form of research grants from HEW.- b. Clinical Research Clinical research must include studies to evaluate therapeutic programs and long-term follow-up of patients with kidney infections, and attempts to identify crucial points in the natural history of the disease at which therapy is most effective. Other studies would be attempted with susceptible patients (pregnant females, persons with obstructive uropathy, diabetics, etc.) to discover pertinent facts in the pathogenesis of renal infection. It is estimated that each large scale clinical study will cost approximately $500,000 per 241 year.- This amount is based on existing cooperative studies and does not include the cost of hospitalization or laboratory tests which must be borne by other sources. Four cooperative studies will be developed, each costing $500,000: one study will address itself to a study of the natural history of renal infection; two, to therapeutic trials; and a fourth to the pathogenesis of the disease in susceptible sub-groups of patients. An additional $500,000 will be used for detailed studies on a small group of patients with renal infection. This study would encompass the definition of changes in renal function, the effects of specific antibacterial agents on the infection, the trial of new treatments such as chronic water loading, etc. Total clinical research expenditures will amount to $2,500,000 supported by HEW. Total costs for research will be $5,330,000 of which HEW would contribute $4,000,000; $1,330,000 would come from other sources. 4. Training Training includes the financial support of research fellows engaged in clinical laboratory studies, and the cost of relevant facilities. Support and laboratory facilities for approximately 12 fellows for one year would cost HEW approximately $400,000 plus $130,000 from other 251 sources, yielding a total of $530,000.- 5. Facilities This program utilizes only existing facilities; however, laboratory and hospital space is limited at present and in order to develop an efficient program as outlined, expanded facilities would undoubtedly be required for research and for the screening of patients for urinary tract infection. Consequently, it is anticipated that about $l,OOO,OOO would be expended by HEW and an additional $330,000 by other sources, yielding a total of $1,330,000. A benefit-cost summary associated with this program is presented in Table I. Table I INFECTIOUS DISEASES OF THE URINARY TRACT, HYPOTHETICAL PROGRAM AT CURRENT HEW EXPENDITURE LEVEL, BASED ON THE CURRENT STATE OF THE ART I 1 Short-Term Benefits Long-Term Benefits Reduction Reduction In Expenditures Per Year In 1 End-Stage Uremia 1 Total 1 Program (sI:FL) ($1,000) Mortality Prevalence Morbid Days 1 Per Year Cumulative 1 3 I.A. Screening, diagnosis and treatment of individuals in short and long-term hospitals and nursing homes as well as non-hospitalized pregnant females and diabetics. 1. Screening 1,803 9,017 2. Confirming test 84,457 3. Treatment 54,931 Sub-Total 1,803 148,405 B. Supportive education and administra- tion 2,000 2,670 Sub-Total 3,803 151,075 I II. Research 4,000 i 5,330 III; Training 400 530 IV. Facilities ,i 1,000 1,330 TOTAL 9,203 158,265 70 3,231,260 15,962,420 1,750 25,850 106 C. Infectious Diseases of the Urinary Tract, Hypothetical Program at Intermediate HEW Expenditure Level, Based on Current State of the Art 1. Introduction This program has four components: 1) Screening, diagnosis, treatment, and supportive education and administration; 2) Research; 3) Training; and 4) Facilities. As illustrated in Figure 2, the total cost for this program is estimated to be $174,252,000, of which HEW funds would account for $20,179,000. A discussion of the various program components follows. 2. Screening, Diagnosis, Treatment, and Supportive Education and Administration This program is concerned with the screening, diagnosis and treat- ment of infections of the urinary tract similar to those described in Section B.2. above. It has, however, been expanded to include all females 6 to 9 years of age who can realistically be reached in a screening program. It is felt that this group can best be reached through screening tests applied in elementary schools. a. Relevant Population and Program Component Costs Because of the difficulties anticipated in attempting to reach the entire female population 6 to 9 years of age, it is assumed that a successful program covering a two-year span will be able 261 271 to reach about 62% of these individuals.- Of 8,134,000- females in this age group, 5,040,OOO will be reached every two years, and 50% (2,520,OOO) of these individuals will be screened each year. costs ($1,000,000> 174.3 150 100 50 20.2 lm~Training (. 75) 1 Facilities(8.0)1 Diagnosis and Treatment (155.3) Research (7.3) Facilities (10. `HEW TOTAL -Training (1.0) Fig. 2. Infectious Diseases of the Urinary Tract, Hypothetical Program Costs at Intermediate HEW Expenditure Level,-Based on the Current State of the Art. 106a Cost of screening per individual in this additional population is estimated at $0.25 (as part of a general screening program). If 2,520,OOO are screened annually, the total cost will be $630,000 ($126,000 from HEW) yearly. Total cost for screening all the population-at-risk, reached by a general screening program, will be $9,647,000 ($1,929,000 from HEW). It is believed that 1% of these young females (25,200) will 291 have significant bacteriuria.- It is still assumed that only 85% (21,420) of these individuals can be screened, and that the test \- has associated with it a 5% false positive value so that 22,491 will have positive results. Confirmatory tests will be necessary both before and after therapy; therefore, at $7.50 per test, the total cost for confirmatory tests will be $330,000. For the entire surveyed population, the cost for these confirmatory tests will amount to $84,787,000, none of which will come from HEW. The treatment costs for each of the females 6 to 9 years of age is estimated at $10.00 for drugs and $15,00 for physicians' services, or a total cost for all of these individuals of $557,000. Total treatment costs for all groups surveyed having renal infections are $55,488,000. The costs outlined above are minimal and are based on conserva- tive estimates. They do not include, for example., intravenous pyelo- grams and other diagnostic studies necessary for complete diagnosis. Also note that the overlap in the female population 6 to'9 years of age and the other high-risk groups (that is, the individuals in short and long-term hospitals, nursing homes and the non- hospitalized pregnant females and diabetics) has not been taken into account and some double-counting may be present. The supportive education and administration portions of this program component are estimated at a level of $4,000,000 from 30/ HEW and $1,330,000 from other sources.- The educational program involves the extensive education of medical personnel throughout the country in the proper uses of catheters and antibiotics, the importance of follow-up studies on individuals with urinary tract infections, the natural history of pyelonephritis, the proper use of diagnostic techniques, etc. The focal centers of the educational program will be community hospitals from which information will be disseminated among appropriate personnel. Total costs for this program component are estimated at $155,252,000 ($5,929,000 from HEW). b. Short-Term Benefits In addition to the short-term benefits described in Section B.2. above, the following benefits are expected to result from the screen- ing of these young females: 1) Due to the current low mortality rate from urinary infec- tions in females 6 to 9 years of age, no estimate on the reduction of immediate mortality is made; 2) A 50% reduction in the prevalence rate from a base of 25,200 to 12,600;z'and 3) A 65% reduction of 311,220 in morbid days from a base of 32/ 478,000.- Total short-term benefits for all groups surveyed are 70 prevented deaths, a reduction in prevalence by 3,243,860, and a reduction in morbid days by 16,273,640. C. Long-Term Benefits - (1) Annual Long-Term Benefits Early diagnosis and treatment of urinary tract infections in this group of females 6 to 9 years of age will decrease the number of cases of renal failure by 20 per year. (A 33% reduction from a base line of 60 which would eventually have 33/ acquired end-stage uremia without this program).- There will be a reduction by 1,770 cases of end-stage uremia in all relevant groups from a base line of 8,560.%' (2) Cumulative Long-Term Benefits 351 Approximately 5% (2,520) of the 50,400- females with bacteriuria could eventually develop significant urinary tract 361 infections. Approximately 40% (l,OlO)- of these individuals would have developed end-stage uremia. Since the females in this age group can be reached at a very early stage of the 371 disease, a reduction in end-stage uremia by 33% (340)- is anticipated. About 26,190 cases of eventual renal failure in all groups surveyed will be avoided. 3. Research Again, clinical and laboratory research are the two major areas of effort. Given increased resources, it is realistic to project that two additional clinical research programs at $500,000 each could be added to the four existing ones at a total cost of $3,000,000. Laboratory research project expenditures could feasibly be increased to $2,000,000 (i.e., an increase of $500,000). Again, a $500,000 project designed to study susceptible sub-groups of patients is also anticipated. The total HEW support for research is $5,500,000, and it is anticipated that about $1,830,000 will be-generated from other sources. 4. Training Training expenditures are estimated to be $750,000 from HEW with an additional $250,000 from other sources. 5. Facilities In the intermediate health program, it is estimated that HEW will provide $8,000,000 in addition to an expected $2,670,000 from other sources. A benefit-cost summary associated with this program is presented in Table II. Table II INFECTIOUS DISEASES OF THE URINARY TRACT, HYPOTHETICAL PROGRAM AT INTERMEDIATE HEW EXPENDITURE LEVEL, BASED ON THE CURRENT STATE OF THE ART 7 Short-Term Benefits Long-Term Benefits - Reduction Reduction In Expenditures Per Year In End-Stage Uremia ? HEW Total Program ($1,000) ($1,000) Mortality Prevalence Morbid Days Per Year Cumulative I.A. Screening, diagnosis and treatment of individuals in short and long-term hospitals and nursing homes as well as non-hospitalized pregnant females, diabetics and females 6 to 9 years of age. 1. Screening 2. Confirming 3. Treatment Sub-Total B. Supportive education and administra- tion Sub-Total II. Research III. Training IV. Facilities D. Infectious Diseases of the Urinary Tract, Hypothetical Program at Accelerated HEW Expenditure Level, Based on Current State of the Art 1. Introduction This program has four components: 1) Screening, diagnosis, treatment, and supportive education and administration; 2) Research; 3) Training; and 4) Facilities. As illustrated in Figure 3, the total cost for this program is estimated at $189,013,000, of which HEW will contribute $27,394,000. A detailed discussion of the various program components follows. 2. Screening, Diagnosis, Treatment, and Supportive Education ,and Administration In addition to the high risk groups surveyed in Section B..2., this program component has been expanded to include all females 21 years of age and under. It is again postulated that the expected rewards from controlling infectious diseases of the urinary tract in these ,Eemales would be sizeable enough to merit its consideration. It is desirable to reach the majority of females in this age group through schools, colleges, and various youth programs such as Operation Headstart. a. Relevant Population and Program Component Costs A successful program will probably reach approximately 60% of the relevant female population. This program will again cover a two-year span so that one-half of this population will be screened every year. Therefore, of the 41,065,OOO females 21 years of age 381 and under in the U. S.,- 12,319,500 will be screened each year [i.e., 24,639,OOO (approximately 60%) of the total will be reached in costs ($1,000,000) 189 - 150 - 50 2 7.4 1 Diagnosis and Treatment (165.7) - Diagnosis and Treatment (9.9) Research (6.5) :CTraining (.98) Facilities (10) HEW - PROGRAM Research (8. `> & Training (1. Facilities (13.3) TOTAL Fig. 3. Infectious Diseases of the Urinary Tract, Hypothetical Program Costs at Accelerated HEW Expenditure Level, Based on the Current State of the Art. llla two years, and 50% of these, or 12,319,500, will be reached every year]. It is estimated that about 1% of the females 21 years of age and under, 246,390, will have significant bacteriuria; therefore, 123,195 will be detected each year. It is to be emphasized that this figure is quite conservative since it is known that females 391 12 to 16 years of age have a high incidence of bacteriuria,- and while no information was available regarding the incidence of bacteriuria in college-age females, it may be even higher than that of other school-age females. Screening costs in this female population are estimated at $0.25 per person (as part of a general screening program). If 12,319,500 are screened annually, the total cost will be $3,080,000 ($616,000 from HEW). Total screening costs for all the surveyed populations (includ- ing those described in Section B.2.) will be $12,097,000 ($2,419,000 from HEW. The number of confirmatory tests required for females 21 years of age and under will be 109,952 pre-therapy and 104,716 post-therapy 401 tests, and the cost for these tests will be $1,610,000 assuming a rate of $7.50 per test. For all the surveyed populations (including those described in Section B.2.) the total cost for confirmatory tests will be $86,067,000, none of which is assumed to come from HEW. The treatment costs for each female 21 years of age and under with a confirmed diagnosis of renal infection is estimated at $10.00 for drugs and $15.00 for physicians' services. This means that the 513 total cost for these affected females is $2,618,000, all of which comes from sources other than HEW. Total treatment costs for all population groups surveyed having renal infections are $57,549,000. The costs outlined are minimal and do not include such items as intravenous pyelograms and other diagnostic studies which are necessary for a complete diagnosis. Again, the overlap of the female population, 21 years of age and under, and the other high-risk groups has not been taken into account and some repetitious counting may be present. The supportive education and administrative portion of this program component is estimated to be $7,500,000 from HEW and $2,500,000 from other sources. It is anticipated that the educa- tional program will be intensified and similar to the one described in Section C.2.a. The total cost for this program component is estimated at $165,713,000 ($9,919,000 from HEW). b. Short-Term Benefits In addition to the short-term benefits described in Section B.2.b. above, the following results can be anticipated from a screening program in females 21 years of age and under: 1) No estimates were made on the reduction of immediate mortality due to the very low mortality rates from urinary tract infection in this population; 2) A 50% reduction (61,600) in prevalence rate from a base of 411 123,195;- and 3) A 65% reduction of 1,521,460 in morbid days from a base 42/ of 2,340,710.- Total short-term benefits in all groups surveyed with renal infections are 70 prevented deaths, a reduction in prevalance of cases by 3,292,860, and a reduction in the number of morbid days by 17,483,880. C. Long-Term Benefits (1) Annual Long-Term Benefits As a result of the early diagnosis and administration of treatment of urinary tract infections, a 33% reduction in the number of annual cases of renal failure is anticipated. This would amount to a decrease of 120 cases from a base line of 360 cases per year. There will be a reduction by 1,870 cases of renal failure in all relevant groups from a base line value of 8,860 cases 431 which would have occurred without this program.- (2) Cumulative Long-Term Benefits Of the 246,390 females with significant bacteriuria who can be reached by this program, approximately 5% (12,320) would 441 eventually develop significant urinary tract infection.- Of this group approximately 40%, 4,930, would eventually die in 45/ - renal failure. Implementation of the above program would be 461 expected to reduce this mortality figure by 33X, or 1,630.- A total of 27,480 cases of renal failure in all groups surveyed would be avoided. 3. Research Given the increased resources of this accelerated program, the number of clinical research projects could be doubled from the current level of 4 to 8 projects at $500,000 each for a total of $4,000,000. Laboratory research expenditures could feasibly be set at $2,000,000, with an additional $500,000 available for projects designed to study susceptible sub-groups of patients. Thus, the total HEW support for research would be $6,500,000. It is anticipated that an additional $2,170,000 would be contributed by other sources. 4. Training Training costs are estimated to be 15% of the research expenditures i.e., $1,300,500, of which $975,000 comes from HEW, and an additional $325,500 from other sources. 5. Facilities With an accelerated health program, it is estimated that HEW will expend about $10,000,000 for facilities in addition to $3,330,000 contributed by other sources. A benefit-cost summary associated with this program is presented in Table III. Table III INFECTIOUS DISEASES OF THE URINARY TRACT, HYPOTHETICAL PROGRAM AT ACCELERATED HEW EXPENDITURE LEVEL, BASED ON THE CURRENT STATE OF THE ART Short-Term Benefits Long-Term Benefits Reduction Reduction In Expenditures Per Year In End-Stage Uremia 1 HEW Total Program ($1,000) ($1,000) Mortality Prevalence Morbid Days Per Year Cumulative I.A. Screening, diagnosis and treatment of individuals in short and long-term hospitals and nursing homes as well as non-hospitalized pregnant females, diabetics, and females 21 years of age and under. 1. Screening 2,419 12,097 2. Confirming 86,067 3. Treatment 57,549 Sub-Total 2,419 155,713 B. Supportive education and administra- tion 7,500 10,000 Sub-Total 9,919 165,713 I. Research 6,500 8,670 III. Training 975 1,300 IV. Facilities 10,000 13,330 TOTAL 27,394 189,013 70 3,292,860 17,483,880 l.,870 27,480 E. Infectious Diseases of the Urinary Tract, Hypothetical Program for Fiscal Year 1975, at Accelerated HEW Expenditure Level, Based on Expected State of the Art in 1975 1. Introduction This program has four components: 1) Screening, diagnosis, treatment, and supportive education and administration; 2) Research; 3) Training; and 4) Facilities. The total estimated cost for this program is $215,471,000 of which HEW will contribute $31,228,000 (see Figure 4). Under an advanced state of the art it is assumed that the research efforts undertaken have made possible 1) more effective antimicrobial therapy, and 2) a better understanding of the pathophysiology of urinary tract infection, with new treatment methods for predisposing factors which sometimes lead to bacteriuria. A detailed discussion of the various program components follows. 2. but Screening, Diagnosis, Treatment and Supportive Education and Administration In 1975 the total U. S. population will have increased by 14$' there are no anticipated changes in the nature of the relevant population. a. Relevant Populations and Program Component Costs It is estimated that of a projected 33,227,580 hospitalized and nursing home residents, 6,645,520 will have significant bacter- 481 iuria (a 20% prevalence rate).- The non-hospitalized pregnant female population is estimated to be 5,126,580;*' assuming a 215.5 50 31.2 t Diagnosis & Treatment (11.3) Research (7.4) *-Training (1.1) Facilities (11.4) HEW Diagnosis & Treatment (188.9) Research (9.9) Facilities (15.2) TOTAL /Training (1.5) Fig. 4. Infectious Diseases of the Urinary Tract, Hypothetical Program Costs for Fiscal Year 1975, at Accelerated HEW Expenditure Level, Based on Expected Advanced State of the Art in 1975. llha prevalence rate of 6% for bacteriuria, 307,590 persons will have positive screening tests. The non-hospitalized diabetic population 501 will be 2,761,080- and approximately 414,160 will have bacteriuria (assuming a 15% prevalence rate in the diabetic population). While it is possible that significant improvements in the treatment and diagnosis of diabetic.s will have occurred, this assumption was not made. It is anticipated that 14,044,230 females under 21 years of age will be scresened yearly; 140,440 of these women will have significant bacte,riuria, assuming a 1% 511 prevalence rate.- (Note it is still assumed that only 60% of the females 21 years of age and under can 'be reached, and that the screening program will cover a two-year sp,an.) Cost of screening will be $13,790,000 ($2,758,000 to be borne by HEW). It is still assumed that the cost per test under a general screening program will be $0.25, and this (cost is applied to the 521 55,159,440- individuals to be screened each year. The cost of confirmatory tests remains at $7.50 per person. Total cost is approximately $98,150,000, excluding a second repeat test for false-positive patients. Treatment costs also remain the same, i.e., $10.00 for drugs for those individuals who are already under a physician's care. It is estimated that there are.6,262,180 of these individuals yielding a cost of $62,622,000. For those individuals who would not have been under a physician's care (the female population 21 years of age and under), $15.00 per individual for physicians' services is added. The cost of treatment for this group is $2,984,000 (119,374 x $25). 531 - Total cost of treatment is thus estimated to be $65,606,000. HEW is not responsible for the cost of confirmatory tests or treatment. Total cost for this initial portion of the program component is $177,511,000, of which $2,758,000 is to be borne by HEW. Support for education and administration is estimated to cost $8,550,000 for HEW, to include a more extensive educational program to reach the increased population. An additional $2,850,000 will come from outside sources. Therefore, the total cost for this program component is $188,911,000, of which $11,308,000 comes from HEW. b. Short-Term Benefits The estimated short-term benefits are as follows: 1) From a base line of 7,750 deaths in the group surveyed which would have occurred in the absence of any program, 541 a reduction of 80 deaths is estimated;- 2) It is estimated that there will be an 85% reduction (5,630,780) in prevalence from 7,507,710 cases [35 of the 85% (1,876,930) can be attributed to advances in the state of 551 the art];- and 3) It is estimated that the number of morbid days will be reduced by 85% (26,064,430) from a base line figure of 30,664,040 (20 of the 85% reduction, i.e., 6,132,810 is 561 attributed to advances in the state of the art).- C. Lens-Term Benefits (1) Annual Long-Term Benefits It is estimated that approximately 7,500 of the group surveyed per year will have developed end-stage renal failure without the program. Ideally this program would reduce this number by 55%, or 4,125 per year [of which 2,250 (approximately 30 of the 55% reduction) are due to advances in the state of 571 the art].- (2) Cumulative Long-Term Benefits About 5% of the individuals with bacteriuria would have developed significant urinary tract infections in the absence of any program. Approximately 40% of these persons would eventually die from uremia. Within the relevant population, 581 there would be 7,658,160 individuals having bacteriuria.- It can then be said that some 382,400 will probably develop significant urinary tract infections and 40%, or 153,000, of these would eventually die from uremia. It is estimated that the number of deaths resulting from end-stage kidney failure can be reduced by 55% or 84,150 (approximately 30 of the 55%, or 45,900, of the reduced number of deaths is due to advances 591 in the state of the art).- 3. Research Research expenditures will be increased in amount to $7,410,000 which will come from HEW, and an additional $2,470,000 to come from other sources. It is anticipated that a cure :Eor urinary tract infections may be found through the development of new antibiotics and new treatment methods for predisposing factors which sometimes lead TO bacteriuria. 4. Training Money expended for training purposes will total $1,480,000, about 15% of that spent for research. Of this amount, $l,llO,OOO will come from HEW and an additional $370,000 from other sources. 5. Facilities In an accelerated Health Program it is estimated that HEW will con- tribute $11,400,000 for facilities, Additional sources wilt1 contribute $3,800,000. A benefit-cost summary associated with this program is presented in Table IV. gJ F. Benefits Denendent on New Research Developments An annual reduction by 1,876,930 in the prevalence rate of renal infection and by 6,132,810 in the number of morbid days will be the short-term effects of new research developments. These statistics take into account a postulated 14% increase in the population of the U. S. from 1966 to 1975. Benefits based on 1966 population figures reveal a reduction in prevalence by 1,646,430 and in the number of morbid days by 5,379,660. In assessing the annual long-term benefits dependent on new developments, it is estimated that there will be a reduction of 2,250 cases of end-stage kidney disease per year, (1,970 cases based on 1966 U. S. population). Cumulative long-term benefits reveal that 50,650 (44,430 based on 1966 U. S. population) cases of renal failure will be avoided with the advent of new developments and techniques concerned with chronic kidney infections. Table IV INFECTIOUS DISEASES OF THE URINARY TRACT, HYPOTHETICAL PROGRAM FOR FISCAL YEAR 1975 AT ACCELERATED HEW EXPENDITURE LEVEL, BASED ON EXPECTED ADVANCED STATE OF THE ART IN 1975 1 . Short-Term Beneifts Long-Term Benefits Reduction Reduction In Expenditures Per Year In End-Stage Uremia Program ($1,000) ($1,000) Mortality Prevalence Morbid Days Per Year Cumulative I.A. Screening, diagnosis and treatment of individuals in short and long-term hospitals and nursing homes as well as non-hospitalized pregnant females, diabetics, and females 21 years of age and under. 1. Screening 2,758 13,790 2. Confirming 98,115 3. Treatment 65,606 Sub-Total 2,758 177,511 B. Supportive education and administra- tion 8,550 11,400 Sub-Total 11,308 188,911 II. Research 7,410 9,880 III. Training 1,110 1,480 IV. Facilities 11,400 15,200 TOTAL 31,228 215,471 80 5,630,780 26,064,430 4,125 84,150 III. HYPERSENSITIVITY DISEASES'OF THl3 KIDNEX x, Introduction This section describes program efforts projected to control renal disease resulting from hypersensitivity phenomena. 611 In 1966, an estimated U,719-- deaths resulted from kidney disease s,ssoci- sted with kWpersensitivity reactions; 106,000 individuals are estimated to have had hypersensitivity diseases of the kidney, requiring 4,074,OOO deys of restricted activity, 1,834,OOO days of bed disability, as well as 77'7,000 627 work-lOS8 days.- Four programs are considered in this analysis and discussed in det&l below (see Chapter 5, Research Methodology). B. Kidney Diseases Related to Hypersensitivity Phenomena, Hypothetical Program at Current HEW Expenditure Level, Based on the Current State of the Art 1. Introduction This program has four components: 1) Education and administration; 2) Research; 3) Training; and 4) Facilities. The total cost for this program is estimated to be $9,975,000 of which HEM's share is $7,480,000. Figure 5 illustrates costs for the various program components, and they are discussed below. 2. Education and Administration In order to bring an effective educational program to physicians, it is necesssry to supply the approximately 7,000 hospitals in the U. S. with appropriate materials and other educational support. Elstimating a cost of $140 per hospital, approximately $l,OOO,OOO will be needed for costs ($1,000,000) 150 100 50 10.3 7;s Education and Administration (I,53 Research (5.2) HEW Education and Administration Fig. 5. Kidney Diseases Related to Hypersensitivity Phenomena, Hypothetical Program Costs at Current HEW Expenditure Level, Based on Current State of the Art. 121a instruction in this area of kidney disease as part of a general educa- tional progrsm. In addition, about $500,000 will be required for the administration and implementation of this program. The total cost for HEN is then estimated at $1,500,000. An additional $500,000 is expected from other sources. Under the current state of the art postgraduate physician education seems to be the most effective approach for achieving immediate benefits. a. Short-Term Benefits It is estimated that this educational program would decrease the immediate annual mortality due to hypersensitivity diseases by 63/ approximately 5% (610) from a base line of X2,719- deaths per year. This figure is based on the assumption that improved understanding of diseases such as acute glomerulonephritis, and improved knowledge of fluid, electrolyte, and steroid therapy will have some impact on the immediate mortality from diseases associated with hypersensitivity phenomena. b. Long-Term Benefits Under the present state of the art, no long-term benefits are anticipated. 3. Research This most important program component is separated into clinical and laboratory research efforts. a. Clinical Research Following are some areas of disease which need clarification and study to determine their significance in hypersensitive renal' disease: J-23 1) Minimal persistent proteinuria; 2) Orthostatic proteinuria; 3) Childhood nephrotic syndrome; 4) Adult nephrotic syndrome; 5) Acute glomerulonephritis; 6) Systemic lupus erythematosus; 7) Miscellaneous collagen diseases; and 8) Any other related hypersensitivity diseases having renal involvement. The estimated cost for each study area is $500,000, yielding a total cost of $4,000,000 ($3,000,000 from HEW). Following are some comments on the present status in each of the above study areas: 1) Several universities have been approached on the possibility of conducting cooperative studies on the diseases listed above and have expressed interest in them. No further progress has been made due to a shortage of funds. 2) The Air Force is currently studying orthostatic proteinuria at Lackland Air Force Base, Texas. 3) There is an international cooperative study being conducted on the childhood nephrotic syndrome under the direction of Dr. Henry Barnett of the Albert Einstein Medical Center in New York City. 4) There is no coordinated activity eon the adult nephrotlc syndrome at the present time in the United States. However, in Great Britain, there is a stud;y sponsored by the British Medical Research Council on the controlled treatment of adult nephrotics with steroids. 5) There is a loose cooperative study on acute glomerulone:phritis under way in New York City. There is also a study being supported on the island of Trinidad which is designed to follow patients with acute glomerulonephritis. The re- surgence of the Red Lake epidemic of acute glomerulonephritis is also under study by Dr. Wanamaker's group at the University of Minnesota. 6) There is a loose cooperative study by several university centers emphasizing the pathology in nephritis resulting from systemic lupus erythematosus. 7) Other disease processes that might be grouped under the heading of hypersensitivity diseases are sub-acute glomerulo- nephritis, chronic glomerulonephritis, serum sickness nephritis, and nephrotoxic nephritis in animals. b. Laboratory Research There are at present approximately 30 immunology research units in existence. It is estimated that approximately 15 of these units are currently engaged in work which is applicable to hypersensitivity diseases of the kidney. The total contribution of funds for re:Levant studies to these laboratories would be approximately $1,500,000 ($lCO,OOO each) per year, of which HEN would contribute $l,l25,000. In addition, it is estimated that an additional $1,500,000 ($1,125,0OO from HEX) should be made available for grant support of individual 125 projects in other laboratories. At an average cost of $25,000 each this smount would support the work of 60 investigators. It is assumed that the total of $7,000,000 as described in the above categories will come from both federal and private funds, with the majority coming from HEW. 4. Training It is anticipated that each of the 15 involved immunology laboratories would provide training for two research fellows per year. The cost for this progrti would be approximately $5O,OOO per laboraWry per year,- 641 or a total of $75O,OOO for the whole program ($560,000 from HEW). 5* Facilities In order to continue expanding research capabilities and updating the necessary equipment, it is estimated that 15'$ of the yearly cost of laboratory research operations will be spent. The total cost of equip- ment updating for 15 laboratories amounts to $225,000 per year (15$ of which, $170,000, comes from HEW). 6. Summary The preceding discussion and estimates presume activity on a level considerably above the current status. There -Its a substantial initial cost in achieving the new elevated level of activity. Principal among these costs is the expense of constructing and providing adequate facilities. This amount should not be confused with the facilities estimate discussed above which is for the improvement of equipment intended to keep research workers supplied with the best equipment for their varied programs. A benefit-cost summary associated with this program is found in Table V. Table V KIDNEY DISEASES RFZATEDTO HYPERSENSITIVITY PHENOMENA, HYPO'IW3TICALPROGW AT CURRENTHEW MPEN-DITURELEVEL,EUSEDONTHE CURRENT STKI'% OF THE ART Program I. Education and administration II. Research III. Training IV. Facilities TOTAL Expenditures 1,500 2,000 5,250 7,000 560 750 170 225 7,480 Total ($1,000) i Short-Term Benefits Reduction Per Year In Mortality Prevalence 1 Morbid Days Per Year =I Cumulative + 9,975 610 - - - -