Person:

Komaroff, Anthony

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, commonly accompanied by cognitive dysfunction, sleeping disturbances, orthostatic intolerance, fever, lymphadenopathy, and irritable bowel syndrome (IBS). The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. We pursued rigorous clinical characterization, fecal bacterial metagenomics, and plasma immune molecule analyses in 50 ME/CFS patients and 50 healthy controls frequency-matched for age, sex, race/ethnicity, geographic site, and season of sampling. Results: Topological analysis revealed associations between IBS co-morbidity, body mass index, fecal bacterial composition, and bacterial metabolic pathways but not plasma immune molecules. IBS co-morbidity was the strongest driving factor in the separation of topological networks based on bacterial profiles and metabolic pathways. Predictive selection models based on bacterial profiles supported findings from topological analyses indicating that ME/CFS subgroups, defined by IBS status, could be distinguished from control subjects with high predictive accuracy. Bacterial taxa predictive of ME/CFS patients with IBS were distinct from taxa associated with ME/CFS patients without IBS. Increased abundance of unclassified Alistipes and decreased Faecalibacterium emerged as the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroides abundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS. Despite findings of differences in bacterial taxa and metabolic pathways defining ME/CFS subgroups, decreased metabolic pathways associated with unsaturated fatty acid biosynthesis and increased atrazine degradation pathways were independent of IBS co-morbidity. Increased vitamin B6 biosynthesis/salvage and pyrimidine ribonucleoside degradation were the top metabolic pathways in ME/CFS without IBS as well as in the total ME/CFS cohort. In ME/CFS subgroups, symptom severity measures including pain, fatigue, and reduced motivation were correlated with the abundance of distinct bacterial taxa and metabolic pathways. Conclusions: Independent of IBS, ME/CFS is associated with dysbiosis and distinct bacterial metabolic disturbances that may influence disease severity. However, our findings indicate that dysbiotic features that are uniquely ME/CFS-associated may be masked by disturbances arising from the high prevalence of IBS co-morbidity in ME/CFS. These insights may enable more accurate diagnosis and lead to insights that inform the development of specific therapeutic strategies in ME/CFS subgroups. Electronic supplementary material The online version of this article (doi:10.1186/s40168-017-0261-y) contains supplementary material, which is available to authorized users.

We conducted a prospective study in a prepaid primary-care practice (health-maintenance organization) of a system in which nurses and physician assistants used protocols, and compared the efficiency and costs of this "new-health-practitioner" protocol system to a physician-only nonprotocol system. In five months, we studied 472 patients with any of four common acute complaints — respiratory infections, urinary and vaginal infections, headache, and abdominal pain; a subset of 203 patients was randomly allocated between the two systems. In the new-health-practitioner system physician time per patient was reduced by 92 per cent, from 11.8 to 0.9 minutes, and average visit costs — including practitioner time and charges for laboratory tests and medications — were 20 per cent less (P = 0.01). We conclude that this protocol system saves physician time and reduces costs. (N Engl J Med 298:305–309, 1978)

Background: The computerized display of charges for ancillary tests in outpatients has been found to affect physician-ordering behavior, but this issue has not been studied in inpatients.

Objective: To assess whether the computerized display of charges for clinical laboratory or radiological tests affected physician-ordering behavior.

Patients and methods: Two prospective controlled trials, randomized by patient, were performed. Each trial included all medical and surgical inpatients at 1 large teaching hospital during 4 and 7 months: 3536 intervention and 3554 control inpatients in the group with clinical laboratory tests, and 8728 intervention and 8653 control inpatients in the group with radiological tests. The intervention consisted of the computerized display of charges for tests at the time of ordering.

Main outcome measures: The number of clinical laboratory and radiological tests ordered per admission and the charges for these tests.

Results: For the clinical laboratory tests, during a 4-month study period, patients in the intervention group had 4.5% fewer tests ordered, and the total charges for these tests were 4.2% lower, although neither difference was statistically significant. Compared with historical controls from the same 4-month period a year before, the charges for the tests per admission had decreased 13.3%, but the decrease was temporally correlated with a restriction of future ordering of tests, and not with the introduction of the display of charges. For the radiological tests, during a 7-month period, the intervention group had almost identical numbers of tests ordered and charges for these tests.

Conclusions: The computerized display of charges had no statistically significant effect on the number of clinical laboratory tests or radiological procedures ordered or performed, although small trends were present for clinical laboratory tests. More intensive interventions may be needed to affect physician test utilization.

For patients visiting a primary care office practice for acute low back pain, we compared the benefits, risks, and costs of obtaining a roentgenogram of the lumbar spine routinely at the initial visit with performing a roentgenogram only if the patient's pain does not improve during and eight-week follow-up period. The cost-effectiveness analysis indicated that, to avert one day of physical suffering in a population of patients, the population would have to be subjected to the additional risk of 3,188 mrad of radiation and an additional cost of $2,072. While, in the individual case, circumstances might lead to a different conclusion, in general, the risks and costs of obtaining lumbar roentgenograms at the initial visit in patients with acute low back pain do not seem to justify the relatively small associated benefit.

The association of cigarette smoking with the occurrence and severity of an acute respiratory tract illness (ARTI) was studied. Clinical data were obtained prospectively on 867 men and women with an ARTI and on a control group of 289 women. Three hundred seven (57%) of the 534 women in the ARTI group were smokers, compared with 97 (34%) of the 289 women in the control group, a highly significant difference. Of the 867 men and women with ARTIs, 506 were smokers. Smokers had a statistically significant greater likelihood of having a lower respiratory tract illness (57% v 45%), a longer duration of cough (8.9 v 6.8 days), and a greater frequency of abnormal auscultatory findings (31% v 20%) than did the 361 nonsmokers. Cigarette smoking may thus contribute to the substantial morbidity and lost productivity resulting from ARTI.

To the Editor.— The recent warning in The Medical Letter1 regarding the mutagenicity and possible carcinogenicity of metronidazole (Flagyl) raises the question of whether there is an alternative treatment of equal efficacy that is not equally suspect.The pharmacologic treatment options seem to include orally administered nitroimidazole drugs other than metronidazole, or topical agents available in vaginal-tablet or suppository form, such as furazolidone and nifuroxime (components of Tricofuron). None of the other nitroimidazoles are currently available in the United States, although tinidazole (Fasigyn) will apparently soon be released. Tinidazole2 and nimorazole are reported to have a better than 90% cure rate. However, the mutagenicity of nimorazole was demonstrated in the same study that implicated metronidazole,3 and subsequent research by the same group has apparently also demonstrated the mutagenic potential of tinidazole (C. E. Voogd, unpublished data).The efficacy of topically applied furazolidone, alone or in combination with

Physician assistants used problem-oriented protocols in management of patients with diabetes and hypertension. The protocols directed the physician assistant in determining what data to collect, and whether the patients required a physician's care at that visit. Physicians verified the ability of the physician assistants to collect history and physical-examination data accurately, noting false-positive findings on 11 per cent of 381 visits, and false-negative findings on 1 per cent of visits. Subsequently, physicians selected certain patients as "suitable" to be managed by the physician assistants. "Suitable" patients were then randomly assigned to be seen by the physician assistants (experimental visits) or physicians (control visits) on return visits. On 37 percent of experimental visits over an 11-month period, the patients went home without seeing a physician. Physicians accepted the protocol disposition decision in 94 per cent of the cases. Patients accepted the system, as reflected by their attendance rate at the clinic.

Lead-screening programs may reduce childhood disabilities, but at what cost? Through a review of the literature, we performed a cost-effectiveness analysis in which the costs, savings, and health benefits of two lead-screening strategies — employing either a free erythrocyte protoporphyrin assay or blood lead measurement — were compared with each other and with a strategy of no screening in a population of three-year-old children.

When the prevalence of lead poisoning among the children screened is 7 per cent or more, we estimate that free erythrocyte protoporphyrin screening averts morbidity and results In net savings: It is both better and cheaper than no screening.

At prevalences below 7 per cent, the net positive costs from screening and early treatment must be weighed against the noneconomic benefits of improved quality of life and considered in relation to other investments that could be made to benefit society. At all prevalence rates, free erythrocyte protoporphyrin screening is more cost effective than blood lead screening.

Created five years ago, the Regional Medical Programs now have established organizations that cover the entire country. Private medicine is involved to a degree unparalleled in any other federal health program. In many cases the Programs have served to bring together elements of the health-care delivery system that have previously been isolated from one another. In other cases they have promoted the extension of recent medical advances out from the medical centers, improving the care given by private practitioners and community hospitals. Yet confusion exists over the mission of the Regional Medical Programs, and the means by which to achieve that mission. Particularly at issue is their role in changing, rather than simply upgrading, the existing health-care delivery system. It remains to be seen whether they are faced with a golden opportunity or an insoluble dilemma.