ATW1H%ASUACAD.BITNET@oac.ucla.edu (Dr David Dodell) (06/21/89)
--- begin part 3 of 7 cut here ---
though the populations in 1985 and 1986 were not fully independent, the
injury/illness rate of 13.7 cases per 100 workers for 1986 represents a
statistically significant decrease of 67% from the company's 1985 rate of 41.8
(chi-square test, p less than 0.05) (Table 1).
After intervention, sprains/strains decreased 80% to 2.2 injuries per 100
workers, contusions decreased 63% to 3.7, scratches/abrasions decreased 85% to
0.6, and other injuries (e.g., multiple injuries, inflamed joints, burns)
decreased 58% to 3.4 (Table 1). Injuries to the finger, back, hand, and other
body parts (e.g., shoulders, arms, toes) also showed statistically significant
declines (chi-square test, p less than 0.005) (Table 1). These analyses take
into account the effect of multiple comparisons on the significance level.
The turnover rate for the company's workforce between 1985 and 1986 was
4%, and the composition of the workforce remained stable. Hourly workers
accounted for 295 (85%) of the company's 349 full-time employees in 1985 and
for 268 (83%) of 321 full-time workers in 1986. Age and sex distributions for
the hourly workforce were comparable between 1985 and 1986. Machine operators
and assemblers were the most frequently injured workers in both years,
Health InfoCom Network News Page 20
Volume 2, Number 25 June 20, 1989
accounting for 42% and 25%, respectively, of the injuries in 1985, and for 57%
and 16%, respectively, of the injuries in 1986.
Direct costs associated with the implementation of changes in the
company's procedures for handling materials totaled $190,000; however, on its
1986 workers' compensation insurance premium, the company received a $100,000
rebate, which was attributed to an improvement in its safety record.
Reported by: R Brewer, MD, D Oleske, PhD, J Hahn, MD, P Doan, M Leibold, Rush-
Presbyterian-St. Luke's Medical Center, Chicago, Illinois. Div of Safety
Research, National Institute for Occupational Safety and Health; Div of Injury
Epidemiology and Control, Center for Environmental Health and Injury Control,
CDC.
Editorial Note: Workplace injury rates can be reduced by changing the
procedures governing the handling of materials. This report describes the
approach taken by an automotive parts manufacturing company in characterizing
injuries related to materials handling, targeting interventions, and
evaluating the impact of intervention measures.
Musculoskeletal injuries (sprains/strains; inflammation and irritation of
joints; fractures and dislocations) and dermatologic injuries (contusions;
cuts/lacerations; scratches/abrasions) are common, sometimes disabling, work-
related health problems. According to data provided by the BLS,
musculoskeletal injuries accounted for 57% and dermatologic injuries for 23%
of the total occupational injuries and illnesses reported nationwide in 1985
(2). Sprains/strains accounted for 43%, and contusions accounted for 10% of
the total (2).
Poorly designed procedures for handling materials are associated with an
increased risk of both musculoskeletal and dermatologic injuries (3). The
weight of the material being handled has been identified as the factor most
associated with an increased risk of injury (4).
Given the relatively stable workforce of the Chicago automotive parts
company, the decline in injury rates from 1985 to 1986, particularly for
sprains/strains and for contusions, suggests that the changes in procedures
for handling materials were effective. These changes are generally consistent
with findings of previous epidemiologic and ergonomic studies that identified
associations between injury rates and materials handling procedures (5,6).
However, the declines may also reflect the effect of the workers' additional
on-the-job experience.
The experience of this company illustrates the impact that changes in
procedures for handling materials may have on the occurrence of work-related
injuries. Ergonomic interventions, taking into account worker capabilities and
limitations, were applied to specific tasks associated with the most frequent
injuries. The company's rebate on its 1986 workers' compensation insurance
premium helped to offset the initial expense associated with the
implementation of changes in procedures for handling materials. Thus, the
potential for substantial cost savings exists when effective injury-control
programs are implemented in the workplace.
Ergonomic interventions can also be applied to the control of injuries in
other worksites. To measure the effectiveness of ergonomic interventions, the
age, sex, job training, and job experience of the workforce should be
identified both before and after intervention. Also, the extent and severity
of the injuries should be measured before and after intervention measures.
Ergonomic interventions should be applied separately from health education
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Volume 2, Number 25 June 20, 1989
programs (e.g., safety films and lectures) if their individual effect on
injury rates is to be evaluated. Broader application of both epidemiologic
and ergonomic models to the planning and evaluation of injury-control programs
should be encouraged to reduce the incidence and cost of work-related
injuries.
References
1. Bureau of Labor Statistics. Occupational injuries and illnesses in the
United States by industry, 1986. Washington, DC: US Department of Labor,
Bureau of Labor Statistics, 1988. (Bulletin no. 2308).
2. Bureau of Labor Statistics. Supplementary Data System (machine-readable
data files). Washington, DC: US Department of Labor, Bureau of Labor
Statistics, 1985.
3. NIOSH. Work practices guide for manual lifting. Cincinnati: US Department
of Health and Human Services, Public Health Service, 1981:130; DHHS
publication no. (NIOSH)81-122.
4. NIOSH. Work practices guide for manual lifting. Cincinnati: US Department
of Health and Human Services, Public Health Service, 1981:14; DHHS publication
no. (NIOSH)81-122.
5. Snook SH, Campanelli, RA, Hart JW. A study of three preventive approaches
to low back injury. J Occup Med 1978;20:478-81.
6. Klein BP, Jensen RC, Sanderson LM. Assessment of workers' compensation
claims for back strains/sprains. J Occup Med 1984;26:443-8.
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Volume 2, Number 25 June 20, 1989
Guidelines for Prophylaxis Against Pneumocystis carinii Pneumonia for Persons
Infected with Human Immunodeficiency Virus
U.S. Department of Health and Human Services
Public Health Service
Centers for Disease Control
Center for Infectious Diseases
AIDS Program
Atlanta, Georgia 30333
Serial publications to the MMWR are published by the Epidemiology Program
Office, Centers for Disease Control, Public Health Service, U.S. Department
of Health and Human Services, Atlanta, Georgia 30333. SUGGESTED CITATION
Centers for Disease Control. Guidelines for prophylaxis against Pneumocystis
carinii pneumonia for persons infected with human immunodeficiency virus. MMWR
1989;38(no. S-5: (inclusive page numbers)).
Centers for Disease Control Walter R. Dowdle, Ph.D
Acting Director
Gary R. Noble, M.D., M.P.H.
Deputy Director (HIV)
The material in this report was prepared for publication by:
Center for Infectious Diseases Frederick A. Murphy,
D.V.M., Ph.D.
Director
AIDS Program James W. Curran, MD., M.P.H.
Director
The production of this report as an MMWR serial publication was
coordinated in:
Epidemiology Program Office Michael B. Gregg, M.D.
Acting Director
Richard A. Goodman, M.D., M.P.H.
Editor, MMWR Series
Editorial Services Elliott Churchill, M.A.
Chief
Ruth C. Greenberg
Editorial Assistant
Copies of this document are available from the National AIDS Information
Clearinghouse, P.O. Box 6003, Rockville, MD 20850; telephone 800-458-5231.
Guidelines for Prophylaxis Against Pneumocystis carinii Pneumonia for Persons
Infected with Human Immunodeficiency Virus
Pneumocystis carinii pneumonia (PCP), the most common presenting
manifestation of the acquired immunodeficiency syndrome (AIDS), is a major
and recurring cause of morbidity and mortality for persons infected with
the human immunodeficiency virus (HIV). In recent years, important
advances have been made in understanding which patient subpopulations are
at highest risk for developing PCP and in the design of chemotherapeutic
Health InfoCom Network News Page 23
Volume 2, Number 25 June 20, 1989
regimens that can reduce the frequency of this illness. Recently, a number
of experts* convened by the National Institutes of Health independently
reviewed data on prophylaxis against PCP among persons infected with HIV,
and then provided recommendations to the U.S. Public Health Service
concerning which persons should receive prophylaxis and what specific
prophylactic regimens should be used. The resulting guidelines are
detailed below.
BACKGROUND
Since the early 1980's, management of PCP has become increasingly
successful, and several effective chemotherapeutic regimens are available (1).
However, such conventional therapy as trimethoprim-sulfamethoxazole or
parenteral pentamidine is often complicated by adverse reactions that may
require termination of the therapy (2), and the mortality for first episodes
of PCP is still 5%-20%. Thus, prevention of PCP is a preferred alternative to
treating patients for successive episodes of this disease.
Prophylaxis against PCP is categorized as primary if the goal is to
prevent an initial episode for a person who has never had PCP. Prophylaxis is
categorized as secondary if the goal is to prevent subsequent episodes for a
person who has already had at least one episode of PCP. Risk of an Initial
Episode of PCP
Immunologic and clinical parameters can be helpful in determining which
HIV-infected persons are at particular risk for having PCP and, therefore,
which are most likely to benefit from prophylaxis against PCP. In the
Multicenter AIDS Cohort Study (MACS), an ongoing prospective epidemiologic
investigation of the transmission and natural history of HIV infection among
homosexual men (3), there was a strong association (p less than 0.001) between
the baseline numbers of T-helper lymphocytes (CD4+ cells) and the incidence of
PCP (Table 1). Additionally, a Kaplan-Meier estimate for 323 participants
whose counts of CD4+ cells were less than 200/mm3 during the study showed that
the proportions who had PCP by 6, 12, and 36 months were 13%, 24%, and 39%,
respectively.
Similar results were seen when MACS data were analyzed by fraction of CD4+
cells expressed as a percentage of total lymphocytes rather than by absolute
number of such cells. In a multivariate analysis of the prospective MACS data,
thrush and persistent fever (temperature of greater than 100 degrees F) were
additional independent predictors of the development of PCP among patients
with CD4+ counts of less than 200/mm3at their most recent evaluation (Panel of
experts,* Phair and Munoz).
A retrospective study to investigate the levels of CD4+ at which adult
patients develop PCP confirms the MACS data (4). For the 49 episodes of PCP
studied, the CD4+ counts were 1-365/mm3 (median 26/mm3), and the percentage of
circulating lymphocytes that were CD4+ positive was 0-25% (median 4%) within
60 days before the episode (Figure 1). Risk of Recurrent PCP
For HIV-infected persons who have had one episode of PCP, there is a high
probability that a second episode will occur if no prophylactic measures are
taken. Although zidovudine will reduce the frequency of second episodes (5),
some persons who receive zidovudine have been reported to have subsequent
episodes. In an ongoing study of HIV-infected patients who have had a recently
documented episode of PCP (AIDS Clinical Trial Group Study 002), zidovudine
therapy was started using two different dosing regimens (6). The study has not
yet been unblinded so that investigators can determine which patients received
which zidovudine regimen. A preliminary analysis was done on the risk of
Health InfoCom Network News Page 24
Volume 2, Number 25 June 20, 1989
recurrent PCP for 318 patients followed for up to 6 months and for 122
patients followed up to 12 months on zidovudine (Figure 2) (Panel of experts,*
Fischl). These results indicate a need for PCP prophylaxis in addition to
antiretroviral therapy.
REGIMENS FOR PROPHYLAXIS
The two compounds studied most extensively for prophylaxis against PCP
have been trimethoprim-sulfamethoxazole, given orally, and pentamidine, given
as an aerosol. Trimethoprim-Sulfamethoxazole
The efficacy of trimethoprim-sulfamethoxazole for prophylaxis against PCP
has been clearly demonstrated among pediatric cancer patients (7-8). The only
reported randomized controlled trial of this drug combination for HIV-infected
persons was a primary-prophylaxis study of 60 adult AIDS patients with Kaposi
sarcoma, and compared the effect of no treatment with that of a regimen of 160
mg trimethoprim plus 800 mg sulfamethoxazole twice daily plus 5 mg leucovorin
calcium once daily (9). Compared with untreated patients, those who received
prophylaxis had fewer episodes of PCP and lived longer. Adverse reactions were
common (50%) and included nausea, vomiting, pruritus, and rash, although these
reactions also occurred commonly among patients who were not receiving
trimethoprim-sulfamethoxazole. Only five patients (17%) had to discontinue
prophylaxis. There are no results from controlled trials currently available
for analysis to indicate whether trimethoprim-sulfamethoxazole would be
effective or tolerated in other populations of HIV-infected patients. Aerosol
Pentamidine
Clinical studies of aerosol pentamidine for prophylaxis against PCP have
been completed by two pharmaceutical sponsors. These studies have used
different nebulizing devices and different dosing regimens.
In July 1987, a randomized, nonblinded dose-comparison study of aerosol
pentamidine was begun in 14 community treatment centers (10). The trial was
open to adult patients who had already had PCP (secondary prophylaxis) as well
as patients with Kaposi sarcoma and other symptomatic HIV-associated
conditions who had never had PCP (primary prophylaxis). Patients were randomly
assigned to three dose schedules: 30 mg every 2 weeks, 150 mg every 2 weeks,
or 300 mg every 4 weeks of pentamidine delivered by the Respirgard II jet
nebulizer (Marquest, Englewood, CO).
An interim analysis 1 year after the start of randomization (mean follow-
up of 10 months) showed that 76 PCP episodes (13 first episodes and 63
recurrent episodes) had occurred: 33/135 (24%) in the 30-mg group, 25/134
(19%) in the 150-mg group, and 18/139 (13%) in the 300-mg group. For patients
receiving secondary prophylaxis, the regimen of 300 mg every 4 weeks was
associated with substantially fewer episodes of PCP than the regimen of 30 mg
every 2 weeks. There are insufficient data currently available from patients
receiving primary prophylaxis to demonstrate statistically significant
treatment effects among the regimens.
The most common adverse effects during treatment were cough and, less
frequently, wheezing--particularly among smokers and patients with a history
of asthma. These effects could be reduced or prevented by pretreatment with
inhaled bronchodilators. No systemic toxicity of the type associated with
parenteral pentamidine (e.g., renal insufficiency, hypoglycemia, or
neutropenia) was detected, although other reports suggest that systemic
adverse effects can occur. Patients tolerated the therapy well with
supervision, and only two had withdrawn because of side effects at the time
the interim analysis was done.
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Volume 2, Number 25 June 20, 1989
On the basis of these interim results and existing epidemiologic data from
natural-history studies, the Food and Drug Administration approved a treatment
IND for aerosol pentamidine as both primary and secondary prophylaxis,
recommending the 300-mg dose every 4 weeks and recommending delivery via the
Respirgard II jet nebulizer. The indication for primary prophylaxis in the
treatment IND is a CD4+ count of less than 200/mm3. Secondary prophylaxis is
indicated for anyone who completes therapy for an episode of PCP.
Other nebulizers have been used in trials of aerosol pentamidine
prophylaxis. A double-blinded, placebo-controlled randomized multicenter trial
has recently been conducted in Canada which assessed the safety and efficacy
of aerosol pentamidine administered by a Fisons ultrasonic nebulizer (five 60-
mg loading doses followed by biweekly doses of 60 mg). These findings have
been submitted to the FDA. A study using the Fisons nebulizer and three
different doses of aerosol pentamidine has also been completed in the United
States and is currently being evaluated.
RECOMMENDATIONS
On the basis of the data summarized above and the opinions of individual
members of the panel of experts, the Public Health Service recommends that--
unless contraindications exist--physicians should initiate prophylaxis against
PCP for any HIV-infected adult patient who has already had an episode of PCP,
even if the patient has been receiving zidovudine. Unless contraindicated,
prophylaxis should also be initiated for HIV-infected patients who have never
had an episode of PCP if their CD4+ cell count is less than 200/mm3 or if
their CD4+ cells are less than 20% of total lymphocytes. Patients with CD4+
cell counts of less than 100/mm3 or CD4+ cells less than 10% and patients with
oral thrush or persistent fever (temperature of greater than 100 degrees F)
are at particularly high risk for PCP. Patient Evaluation
For HIV-infected persons, CD4+ lymphocyte percentages or counts should be
monitored at least every 6 months. Some experts prefer to obtain a second
count within a few months of the first count to assess the rate of decline.
Subsequent CD4+ enumerations may be desirable at intervals of less than 6
months in certain situations such as: a) the presence of fever or thrush, b) a
recent rapid decline in CD4+ cell count, c) a CD4+ percentage in the 20-30
range, or d) a CD4+ absolute number in the 200-300/mm3 range. If a decision to
start prophylaxis is to be made on the basis of a low CD4+ cell count or
percentage, the CD4+ enumeration should probably be repeated, unless previous
determinations indicate the low count or percentage is consistent with an
established trend.
Some patients may have discordant CD4+ percentages and absolute counts,
i.e., the percentage may be greater than 20% while the CD4+ count may be less
than 200/mm3, or vice versa. In such cases, it is probably prudent--after
reconfirming the CD4+ enumerations--to assume that the patient is at high risk
for PCP if either of these two parameters is in the high-risk range.
Clinicians should be aware that in certain unusual circumstances, either
the absolute CD4+ count or the CD4+ percentage may not be an accurate
reflection of susceptibility to PCP. For example, after splenectomy, HIV-
infected patients may be susceptible despite normal CD4+ counts. Conversely,
some laboratory reagents may not detect CD4+ markers on the T-helper cells of
all persons (11), so that such persons may speciously appear to be in the
susceptible range. In situations in which this phenomenon is suspected (e.g.,
when the sum of the number of CD4+ cells and CD8+ cells does not approximately
equal the number of CD3+ cells), the lymphocyte sample should be retested with
Health InfoCom Network News Page 26
Volume 2, Number 25 June 20, 1989
other CD4+ reagents.
Before prophylaxis against PCP is administered, patients must be evaluated
to exclude certain active pulmonary diseases. If symptoms, signs, or
radiologic abnormalities suggest that active disease is present, a thorough
evaluation for community-acquired pathogens (e.g., Pneumococcus),
opportunistic pathogens (e.g., Pneumocystis, cytomegalovirus), communicable
pathogens (e.g., Mycobacterium tuberculosis), tumors, or other processes is
indicated. As with other HIV-infected persons, these patients should be given
a Mantoux skin test with 5-TU tuberculin, PPD (12).
Choice of Prophylactic Agent
Scientific studies available to date suggest the following two approaches
are effective and safe, although neither has been approved as labelling
indications by the Food and Drug Administration. 1) Although it has been
studied less extensively among HIV-infected persons than aerosol pentamindine,
oral trimethoprim-sulfamethoxazole (160 mg trimethoprim and 800 mg of
sulfamethoxazole) can be given twice daily with 5 mg leucovorin once daily.
This form of prophylaxis should not be given to patients with a history of
type-I hypersensitivity (angioedema or anaphylaxis) or prior episodes of
Stevens-Johnson syndrome associated with sulfonamides or trimethoprim. The
efficacy of leucovorin in prevention of toxicity is unknown. 2) Aerosol
pentamidine can be given as 300 mg every 4 weeks via the Respirgard II jet
nebulizer. The dose should be diluted in 6 ml of sterile water and delivered
at 6 liters/minute from a 50-PSI compressed air source until the reservoir is
dry. (Further information can be obtained by telephoning the Treatment IND
number: 1-800-727-7003.) Because other doses and aerosol delivery systems have
not yet been adequately studied and analyzed, no recommendations regarding
such systems can be made. For patients who develop cough or wheezing while
receiving aerosol pentamidine, pretreatment with a bronchodilator can be tried
before the aerosol therapy is given again. Patients with asthma or an
extensive history of smoking may not tolerate this form of therapy, and it may
not be prudent treatment for a patient with a prior life-threatening reaction
to parenteral pentamidine.Since neither aerosol pentamidine nor oral
trimethoprim-sulfamethoxazole prophylaxis is known to be safe in association
with pregnancy, it is inadvisable to give either agent to HIV-infected
pregnant women. Rather, such women should be monitored carefully for symptoms,
signs, or laboratory abnormalities suggestive of PCP. Prophylaxis can then be
considered for use in the postpartum period. Careful monitoring is also
indicated for patients intolerant of aerosol pentamidine and trimethoprim-
sulfamethoxazole, or for those unwilling to receive prophylaxis.Alternative
regimens that are of unproven efficacy and safety for humans, but that might
be considered for prophylaxis, include dapsone (daily or weekly), dapsone plus
trimethoprim (daily or weekly), or dapsone plus pyrimethamine (daily or
weekly) and pyrimethamine-sulfadoxine (weekly).
Follow-Up of Patients Receiving Prophylaxis
Since none of the regimens has been shown to be completely protective
against PCP for HIV-infected persons, patients who receive prophylaxis should
be monitored closely for evidence of PCP, as well as other pulmonary
infections. If prophylaxis is discontinued, the patient will again be at
increased risk for developing PCP.
Prophylaxis failures have been reported in which persons given aerosol
pentamidine, especially at low doses, later had PCP in the upper lobes of the
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Volume 2, Number 25 June 20, 1989
lung (13). In addition, prophylaxis using aerosol pentamidine does not offer
protection against extrapulmonary pneumocystosis (14).
Prophylaxis for Infants and Children
Pneumocystis carinii pneumonia is a common manifestation of pediatric
AIDS. Most experts agree that some form of prophylaxis is warranted for HIV-
infected pediatric patients who are at high risk for PCP on the basis of
criteria that are analagous to those described above for adults. However,
there are insufficient data about the efficacy or toxicity of prophylactic
regimens for pediatric patients, so that no scientifically validated
guidelines can be provided as yet. There are no data concerning the
appropriate dose or delivery system of aerosol pentamidine for infants or
children. The appropriate dose of trimethoprim-sulfamethoxazole prophylaxis
might be estimated from trials involving pediatric cancer patients (e.g.,
trimethoprim 75 mg/M2 plus sulfamethoxazole 375 mg/M2 given orally every 12
hours) (7,8).
Further Information
Several studies are under way to gain additional information about
prophylaxis against PCP. Information about these studies can be obtained from
the National Institute of Allergy and Infectious Diseases Information Office
(1-800-TRIALS-A) or the American Foundation for AIDS Research (212-333-3118).
EDITORIAL COMMENTARY
These guidelines for prophylaxis against PCP indicate a medical benefit
from the careful clinical and immunologic monitoring of persons infected with
HIV and have several important implications. First, the guidelines are likely
to increase the demand for HIV antibody testing by persons who believe they
may be at risk for infection. The Public Health Service has estimated that
between 945,000 and 1.4 million persons in the United States are infected with
HIV (15). Of these persons, CDC estimates that approximately 120,000 have been
informed of their infection status as a result of voluntary antibody testing
carried out in public (primarily Federally funded) HIV counseling and testing
centers. The number of persons found through other sources of testing to be
infected is unknown, but it is likely that many persons who are infected are
not aware of their infection. Persons at risk who have not had HIV antibody
testing should now consider such testing because they may be candidates for
prophylaxis against PCP if they are found to be infected.
Second, the guidelines are likely to increase the demand for medical
services by asymptomatic HIV-infected persons. Such persons will need medical
evaluation to determine whether they are candidates for prophylaxis against
PCP, and--if prophylaxis is given--these persons will need medical follow-up.
All persons found to be infected at HIV counseling and testing centers should
be referred for further medical evaluation, including a measurement of their
CD4+ cells. Facilities offering HIV counseling and testing should develop
referral networks of medical-care providers sufficient to evaluate and care
for the infected persons they identify. These networks should include services
related to family planning and treatment for intravenous drug addiction,
sexually transmitted disease, and tuberculosis.
Third, the guidelines are likely to increase the demand for flow-cytometr y
services to quantify CD4+ cells from HIV-infected persons. Laboratories to
Health InfoCom Network News Page 28
Volume 2, Number 25 June 20, 1989
which samples are referred for flow cytometry should have prior experience,
since methodology can greatly influence the quality of test results. Although
there are no true reference standards for evaluating blood cells, quality can
be assured by adhering to criteria that address sample collection,
preparation, instrument calibration and standardization, flow cytometric
analysis, and adequate training of operators (16). Either absolute CD4+ counts
or percentage CD4+ cells can be used in monitoring HIV-infected persons. There
appears to be less day-to-day fluctuation in percentage of CD4+ cells compared
with absolute number, suggesting that the former measure may be more reliable
(4,17). This finding is not unexpected since the percentage of CD4+ cells is
directly measured by flow cytometry, whereas the absolute number is calculated
from the absolute and differential white-blood-cell count and the percentage
of CD4+ cells.
Fourth, health-care providers who administer aerosol pentamidine as
prophylaxis against PCP should be aware of several occupational safety issues.
In particular, they should note the recommendation to exclude active pulmonary
disease before starting prophylaxis. A recent investigation of M. tuberculosis
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