Best Practices for Chiropractic Management of Adult Patients With Mechanical Low Back Pain: A Clinical Practice Guideline for Chiropractors in the United States.

OBJECTIVE: The purpose of this paper was to update the previously published 2016 best-practice recommendations for chiropractic management of adults with mechanical low back pain (LBP) in the United States. METHODS: Two experienced health librarians conducted the literature searches for clinical practice guidelines and other relevant literature, and the investigators performed quality assessment of included studies. PubMed was searched from March 2015 to September 2021. A steering committee of 10 experts in chiropractic research, education, and practice used the most current relevant guidelines and publications to update care recommendations. A panel of 69 experts used a modified Delphi process to rate the recommendations. RESULTS: The literature search yielded 14 clinical practice guidelines, 10 systematic reviews, and 5 randomized controlled trials (all high quality). Sixty-nine members of the panel rated 38 recommendations. All but 1 statement achieved consensus in the first round, and the final statement reached consensus in the second round. Recommendations covered the clinical encounter from history, physical examination, and diagnostic considerations through informed consent, co-management, and treatment considerations for patients with mechanical LBP. CONCLUSION: This paper updates a previously published best-practice document for chiropractic management of adults with mechanical LBP.

Production and Clinical Evaluation of Norwalk GI.1 Virus Lot 001-09NV in Norovirus Vaccine Development.

BACKGROUND: Human noroviruses (HuNoV) are the leading cause of gastroenteritis. No vaccine is currently available to prevent norovirus illness or infection. Safe, infectious challenge strains are needed to assess vaccine efficacy in the controlled human infection model (CHIM). METHODS: A stock of HuNoV strain Norwalk virus ([NV] GI.1) was prepared. Healthy, genetically susceptible adults were inoculated with NV Lot 001-09NV and monitored for infection, gastroenteritis symptoms, and immune responses. RESULTS: Lot 001-09NV induced gastroenteritis in 9 (56%) and infection in 11 (69%) of 16 genetically susceptible subjects. All infected subjects developed strong immune responses to GI.1 with a 30-fold (geometric mean titer) increase in blocking titers (BT50) and a 161-fold increase in GI.1-specific immunoglobulin (Ig)G titers when compared with baseline. GI.1-specific cellular responses in peripheral blood were observed 9 days postchallenge with an average of 3253 IgA and 1227 IgG antibody-secreting cells per million peripheral blood mononuclear cells. CONCLUSIONS: GI.1 Lot 001-09NV appears to be similar in virulence to previous passages of NV strain 8fIIa. The safety profile, attack rate, and duration of illness make GI.1 Lot 001-09NV a useful challenge strain for future vaccine studies aimed at establishing immune correlates.

The Neurophysiological Lesion: A Scoping Review.

Objective: The purpose of this study was to examine the extent of the literature on the neurophysiological lesion as referenced in functional neurology. Methods: A literature search was performed within the period from 2010 to March 2021. Search terms included central sensitization, central sensitivity syndrome, nociplastic pain, cold hyperalgesia, heat hyperalgesia, mechanical hyperalgesia, dynamic mechanical allodynia, temporal summation, spatial summation, and descending inhibition. A qualitative synthesis summarized the research findings, including clinical conditions and effect of spinal manipulation. Results: There were 30 studies, which included 7 high-level studies (meta-analysis or systematic reviews), 22 randomized controlled studies, and 1 scoping review. The findings suggest the existence of the changes in the central integrated state of a population of neurons with various disorders, experimentally induced stimulation, and treatment. The current literature suggests plasticity of the central integrative state (CIS) with the onset of pathologies and the changes in the CIS with different conservative nonpharmacologic treatments. Conclusions: This review suggests changes in the resting state of the CIS of a population of neurons that exist in the physiologic lesion may change in response to various therapies, including manipulative therapy. The findings from this review provide support of the hypothesis that nonpharmacologic conservative care may affect the neurophysiological lesion. However, studies were heterogeneous and evidence was lacking in the translation of targeting the therapies to distinct neuronal areas for clinical outcomes to treat specific disease states.

An investigation into chiropractic intern adherence to radiographic guidelines in clinical decisions with a descriptive comparison to clinical practitioners.

OBJECTIVE: The purpose of this study was to assess chiropractic interns' knowledge and adherence to radiographic clinical practice guidelines (CPGs) and compare their clinical decisions to previous surveys of established practitioners in Canada and Australia. METHODS: A clinical decision-making survey was administered to 88 interns. The survey contained clinical scenarios and vignettes with inquiries regarding indications for radiographic referral, the likelihood of referral, and the application of CPGs. RESULTS: Forty-four percent (43.75%) of the interns were aware of CPGs, 38.75% were unsure, and 17.5% were not aware. When asked specific questions about the appropriateness of diagnostic imaging, the interns' responses were similar to those of practitioners in Canada and Australia. When interns evaluated a clinical vignette, there was lower compliance with CPGs. CONCLUSION: The interns' clinical decisions regarding the use of diagnostic radiography did not significantly differ from those of practitioners who were surveyed in other related studies. Interns were inconsistent in applying their decision making in clinical cases. Notwithstanding the similarities with practitioners, some deviation from the guidelines indicates the need for further intern education to improve the implementation of CPGs for optimal cost-effective and clinically appropriate care.

The Rise and Fall of SARS-CoV-2 Variants and Ongoing Diversification of Omicron.

In late December of 2019, high-throughput sequencing technologies enabled rapid identification of SARS-CoV-2 as the etiological agent of COVID-19, and global sequencing efforts are now a critical tool for monitoring the ongoing spread and evolution of this virus. Here, we provide a short retrospective analysis of SARS-CoV-2 variants by analyzing a subset (n = 97,437) of all publicly available SARS-CoV-2 genomes (n = ~11.9 million) that were randomly selected but equally distributed over the course of the pandemic. We plot the appearance of new variants of concern (VOCs) over time and show that the mutation rates in Omicron (BA.1) and Omicron sub-lineages (BA.2-BA.5) are significantly elevated compared to previously identified SARS-CoV-2 variants. Mutations in Omicron are primarily restricted to the spike and nucleocapsid proteins, while 24 other viral proteins-including those involved in SARS-CoV-2 replication-are generally conserved. Collectively, this suggests that the genetic distinction of Omicron primarily arose from selective pressures on the spike, and that the fidelity of replication of this variant has not been altered.

The Role of Chiropractic Care in Providing Health Promotion and Clinical Preventive Services for Adult Patients with Musculoskeletal Pain: A Clinical Practice Guideline.

Objective: To develop evidence-based recommendations on best practices for delivery of clinical preventive services by chiropractors and to offer practical resources to empower provider applications in practice. Design: Clinical practice guideline based on evidence-based recommendations of a panel of practitioners and experts on clinical preventive services. Methods: Synthesizing the results of a literature search for relevant clinical practice guidelines and systematic reviews, a multidisciplinary steering committee with training and experience in health promotion, clinical prevention, and/or evidence-based chiropractic practice drafted a set of recommendations. A Delphi panel of experienced practitioners and faculty, primarily but not exclusively chiropractors, rated the recommendations by using the formal consensus methodology established by the RAND Corporation/University of California. Results: The Delphi consensus process was conducted during January-February 2021. The 65-member Delphi panel reached a high level of consensus on appropriate application of clinical preventive services for screening and health promotion counseling within the chiropractic scope of practice. Interprofessional collaboration for the successful delivery of clinical preventive services was emphasized. Recommendations were made on primary, secondary, tertiary, and quaternary prevention of musculoskeletal pain. Conclusions: Application of this guideline in chiropractic practice may facilitate consistent and appropriate use of screening and preventive services and foster interprofessional collaboration to promote clinical preventive services and contribute to improved public health.

Noroviruses as a cause of diarrhea in travelers to Guatemala, India, and Mexico.

Noroviruses (NoVs) are increasingly being recognized as an important enteric pathogen of gastroenteritis worldwide. The prevalence of NoVs as a cause of diarrhea acquired by travelers in developing countries is not well known. We examined the prevalence and importance of NoV infection in three international traveler cohorts with diarrhea acquired in three developing regions of the world, Mexico, Guatemala, and India. We also characterized the demographics and symptoms associated with NoV diarrhea in these travelers. Stool samples from 571 international travelers with diarrhea were evaluated for traditional enteropathogens. NoVs were identified using reverse transcription-PCR and probe hybridization. NoVs were identified in 10.2% of cases of travelers' diarrhea and, overall, was the second most common pathogen, following diarrheagenic Escherichia coli. The detection of NoV diarrhea significantly varied over the three study time periods in Guadalajara, Mexico, ranging from 3 of 98 (3.0%) diarrheal stools to 12 of 100 (12.0%) fecal specimens (P=0.03). The frequency of NoV diarrhea was also dependent upon the geographic region, with 17 of 100 (17.0%) travelers to Guatemala, 23 of 194 (11.9%) travelers to India, and 3 of 79 (3.8%) travelers to Mexico testing positive for NoVs from 2002 to 2003 (P=0.02). NoVs are important pathogens of travelers' diarrhea in multiple regions of the world. Significant variation in the prevalence of NoV diarrhea and in the predominant genogroup infecting travelers was demonstrated, dependent upon the specific geographic location and over time.

Low-Level Laser Light Therapy Dosage Variables vs Treatment Efficacy of Neuromusculoskeletal Conditions: A Scoping Review.

OBJECTIVE: The purpose of this scoping review was to identify and synthesize literature on dosage variables on the efficacy of low-level laser therapy (LLLT) for neuromusculoskeletal conditions. METHODS: A scoping literature review was conducted by searching the following databases: the Cochrane Library, the Cumulative Index to Nursing and Allied Health Literature, Medline, the Physiotherapy Evidence Database, the Index to Chiropractic Literature, manufacturer websites, and online guidelines. The search was modeled after STARLITE criteria. The reporting used Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews (PRISMA-ScR). Articles were included if LLLT was used in any treatment group for a neuromusculoskeletal complaint with dosage and effectiveness reported. This was tabulated by source, dosage variables, conditions, outcome measures, and conclusions. Data were charted in Excel format. Frequency counts were performed on ordinal data. Descriptive statistics were computed for the continuous data. RESULTS: A total of 86 articles were included in the review. They revealed a broad range of musculoskeletal conditions and diverse dosage parameters. Seven individual parameters were found that would alter the dosage. Although duration of application is an independent clinical factor, the negative-outcome studies were inconsistent in duration. There was lack of statistical difference between the studies with improved vs unimproved outcomes. No statistical differences were noted between the dosage parameters and efficacy. CONCLUSION: Although many articles were found on LLLT for neuromusculoskeletal conditions, the studies had amorphous parameters. A heterogeneity of reported doses precluded the synthesis of sufficient evidence to correlate dosage variables with improved or unimproved outcomes. Therefore, based on the current literature, dosage variables for the efficacy of LLLT for neuromusculoskeletal conditions are uncertain at this time.

Best Practices for Chiropractic Management of Patients with Chronic Musculoskeletal Pain: A Clinical Practice Guideline.

Objective: To develop an evidence-based clinical practice guideline (CPG) through a broad-based consensus process on best practices for chiropractic management of patients with chronic musculoskeletal (MSK) pain. Design: CPG based on evidence-based recommendations of a panel of experts in chronic MSK pain management. Methods: Using systematic reviews identified in an initial literature search, a steering committee of experts in research and management of patients with chronic MSK pain drafted a set of recommendations. Additional supportive literature was identified to supplement gaps in the evidence base. A multidisciplinary panel of experienced practitioners and educators rated the recommendations through a formal Delphi consensus process using the RAND Corporation/University of California, Los Angeles, methodology. Results: The Delphi process was conducted January-February 2020. The 62-member Delphi panel reached consensus on chiropractic management of five common chronic MSK pain conditions: low-back pain (LBP), neck pain, tension headache, osteoarthritis (knee and hip), and fibromyalgia. Recommendations were made for nonpharmacological treatments, including acupuncture, spinal manipulation/mobilization, and other manual therapy; modalities such as low-level laser and interferential current; exercise, including yoga; mind-body interventions, including mindfulness meditation and cognitive behavior therapy; and lifestyle modifications such as diet and tobacco cessation. Recommendations covered many aspects of the clinical encounter, from informed consent through diagnosis, assessment, treatment planning and implementation, and concurrent management and referral. Appropriate referral and comanagement were emphasized. Conclusions: These evidence-based recommendations for a variety of conservative treatment approaches to the management of common chronic MSK pain conditions may advance consistency of care, foster collaboration between provider groups, and thereby improve patient outcomes.

Survey of chiropractic clinicians on self-reported knowledge and recognition of concussion injuries.

Background: There has been little study of the recognition of mild traumatic brain injury (MTBI) by the chiropractic practitioner, or of the inquiry by the clinician to assess those patients who may be suffering from the condition, but fail to report the symptoms. Although severe cases of TBI are more often recognized and treated by attendance to hospital or emergency room, MTBI is less recognizable and would present a long-term risk to the patient. Given the clinical risk associated with failure to recognize such injuries, training of the clinician in the subtle signs of MTBI is imperative. What we currently know about training in the recognition of MTBI is from limited recent knowledge based studies. This study is intended to assess the self-reported mild traumatic brain injury (MTBI) knowledge, recognition and treatment by chiropractic practitioners. Methods: A previously published standardized set of survey items was distributed to a captive audience of chiropractic practitioners at the July 2016 Texas Chiropractic College annual symposium. The sample population was a convenience sample of chiropractic clinicians who were assessed for MTBI knowledge and common practices. Results: There was a response rate of 43% of the 125 attendees. The survey demonstrated confidence in MTBI diagnosis. Average MTBI knowledge and recognition score was only 27% ± 22%. Frequency of MTBI patients presenting to the chiropractic clinician office was an average of less than one per month. Sixty nine percent (69%) of the clinicians relied upon their history and clinical exam for diagnosis. There was no knowledge of the Balance Error Scoring system and only 20% utilized the Standardized Concussion Assessment Tool (SCAT). The primary action of the chiropractic clinician who suspected MTBI was to refer to a neurological specialist (76%). A small minority of practitioners would provide treatment. Conclusions: There is an overconfidence of the chiropractic practitioner in recognition of MTBI which is incongruent with the low knowledge scores. Further education of the chiropractic clinician is warranted. Trial registration: University Hospital Medical Information Network Clinical Trials Registry. Retrospectively registered (UMIN-CTR), trial number: UMIN#000029744 (Receipt# R000033980) data: October 27, 2017.​Date of enrollment 7/14/2016.

Clinical endpoints in the controlled human challenge model for Shigella: A call for standardization and the development of a disease severity score.

BACKGROUND: Since 1946 the controlled human infection model (CHIM) for Shigella has been used to improve understanding of disease pathogenesis, describe clinical and immunologic responses to infection and as a tool for vaccine development. As the frequency and intent for use in vaccine comparisons increases, standardization of the primary endpoint definition is necessary. METHODS: Subject-level data were obtained from previously conducted experimental Shigella CHIM studies. Signs and symptoms severity were categorized consistently across all studies. Sign and symptom correlations were estimated and univariate models were utilized to describe the association between stool output and other Shigella-attributable signs and symptoms. Multiple correspondence and hierarchical clustering analyses were performed to describe the co-occurrence of signs and symptoms. A disease score is proposed based on the co-occurrence of these events. RESULTS: Data were obtained on 54 subjects receiving 800 to 2000 colony forming units (cfu) of S. flexneri. The median maximum 24 hour stool output was 514 ml (IQR: 300, 998 ml) with a median frequency of 6 (IQR: 4, 9). Subjects reported abdominal pain or cramps (81.5%), headache (66.7%) and anorexia (64.8%), 50.0% had a fever and 27.8% had gross blood in multiple loose stools. Multiple correspondence analyses highlighted co-occurrence of symptoms based on severity. A 3-parameter disease severity score predicted shigellosis endpoints and better differentiated disease spectrum. CONCLUSION: Dichotomous endpoints for Shigella CHIM fail to fully account for disease variability. An ordinal disease score characterizing the breadth of disease severity may enable a better characterization of shigellosis and can decrease sample size requirements. Furthermore, the disease severity score may be a useful tool for portfolio management by enabling prioritization across vaccine candidates with comparable efficacy estimates using dichotomous endpoints.

Treatment of travelers' diarrhea: randomized trial comparing rifaximin, rifaximin plus loperamide, and loperamide alone.

BACKGROUND & AIMS: Antimotility agents provide rapid temporary relief of acute diarrhea, whereas antibiotics slowly cure the illness. Thus, the combination of an antimotility agent and an antibiotic may provide greater therapeutic benefit than either drug alone. This study evaluated the efficacy and safety of rifaximin-loperamide in the treatment of travelers' diarrhea. METHODS: Consenting adults with acute diarrhea (> or =3 unformed stools in 24 hours with > or =1 symptom of enteric infection) were randomized to receive rifaximin 200 mg 3 times daily for 3 days; loperamide 4 mg initially followed by 2 mg after each unformed stool; or a combination of both drugs using the same dosing regimen. The primary end point was the median time from beginning therapy until passing the last unformed stool. RESULTS: A total of 310 patients completed treatment with rifaximin (n = 102), loperamide (n = 104), or rifaximin-loperamide combination therapy (n = 104). The groups showed demographic similarity. Rifaximin and rifaximin-loperamide significantly reduced the median time until passage of the last unformed stool (32.5 +/- 4.14 h and 27.3 +/- 4.13 h, respectively) vs loperamide (69 +/- 4.11 h; P = .0019). The mean number of unformed stools passed during illness was lower with rifaximin-loperamide (3.99 +/- 4.28) compared with rifaximin (6.23 +/- 6.90; P = .004) or loperamide alone (6.72 +/- 6.93; P = .002). All treatments were well tolerated with a low incidence of adverse events. CONCLUSIONS: Rifaximin-loperamide therapy provided rapid symptomatic improvement and greater overall wellness compared with either agent alone.

Rifaximin treatment of pathogen-negative travelers' diarrhea.

BACKGROUND: Antibacterial drugs appear to be effective in shortening the illness of a majority of cases of travelers' diarrhea. METHODS: This was a subanalysis from two randomized, double-blind, placebo-controlled trials in adult travelers with acute diarrhea treated with rifaximin 200 mg three times a day or placebo for 3 days. Efficacy was assessed by the interval beginning with the first dose of medication and ending with the last unformed stool passed after becoming well [time to last unformed stool (TLUS)]; number of unformed stools passed; percent with clinical improvement; and incidence of wellness achieved. RESULTS: Stool pathogens were not identified in pretreatment samples in 122 of 322 (38%) patients and 106 of 230 (46%) randomized to rifaximin and placebo, respectively. Among pathogen-negative patients, rifaximin was more effective than placebo for median TLUS (33 vs 68 h, p < 0.005), mean number of unformed stools passed (6.5 vs 8.6, p < 0.0001), and clinical wellness (77% vs 61%, p = 0.01). The adverse-event profiles between rifaximin and placebo were similar. CONCLUSIONS: More than one third of patients with travelers' diarrhea had pathogen-negative illness. Rifaximin was effective in treating the illness without associated side effects. These results are consistent with the hypothesis that undetected bacterial pathogens are the most likely cause of travelers' diarrhea without definable cause.

Spinal synovial cysts and intersegmental instability: a chiropractic case.

OBJECTIVE: This article presents a case in which synovial cysts appeared to cause compromise of the neural foramina and thecal sac with presenting neurological signs. CLINICAL FEATURES: A 67-year-old female patient with a history of lumbar synovial cysts and synovectomy presented with recurrence of bilateral low back, leg pain, and apparent neurological compromise along with a recurrence of lumbar synovial cyst as evidenced on magnetic resonance images. INTERVENTIONS AND OUTCOME: Flexion distraction therapy, performance of Williams low back exercises and interferential therapy resulted in 50% relief. Frequency of care was progressively diminished as she improved. The patient experienced recurrence of severe episodes; multifidi strengthening exercises were provided to address a concomitant spondylolisthesis and instability, resulting in a cessation of these episodes and improvement in functional activities. CONCLUSION: Distraction therapy seemed to alleviate the constant pain without surgical intervention. In this case, the synovial cyst may have been an incidental finding versus a primary cause of the low back and leg pain. For similar patients, in the absence of correlative progressive neurological signs, surgical intervention may not be necessary.

A Literature Review of Electronic Health Records in Chiropractic Practice: Common Challenges and Solutions.

OBJECTIVE: The purpose of this study was to review the literature on current challenges and propose solutions for the optimal utilization of the electronic health records (EHRs) in chiropractic practice. METHODS: A search was performed in the PubMed, Index of Chiropractic Literature, and Current Index to Nursing and Allied Health Literature databases from November 2005 to February 2015. A combination of the following key words was used: electronic health records, electronic medical records, implementation, documentation, benefits, and challenges. Articles were categorized into common problems and solutions. These were filtered by application to chiropractic or educational institutions. RESULTS: The search resulted in 45 papers, which included case reports of EHR implementation, governmental insurance reports, commentaries, controlled studies, narrative reviews of past experiences with conversion from paper systems, and the implementation of EHRs in small offices and chiropractic offices. Minimal literature was found that directly related to chiropractic EHRs. Improper utilization, incorrect use of the software, faulty implementation, workflow burdens, financial considerations, and insufficient training were found to negatively affect the quality of the record. CONCLUSIONS: Documentation errors are often innate in the EHR software. Improper utilization, insufficient training, or difficulty in integration of the EHR into the clinical office setting results in poor implementation of the electronic version of the clinical record. Solutions that may decrease documentation errors include EHR training, continued financial incentives, and appropriate implementation process and utilization of available software features.

Survey of Primary Contact Medical and Chiropractic Clinicians on Self-Reported Knowledge and Recognition of Mild Traumatic Brain Injuries: A Pilot Study.

OBJECTIVE: The purpose of this study was to assess the self-reported knowledge of concussion recognition and treatment with first-contact family medical and chiropractic practitioners by means of a pilot study of the need, construct validity, and feasibility for further investigation of mild traumatic brain injury (MTBI) knowledge base. METHODS: Two hundred forty-eight practicing chiropractic and 120 medical physicians in the south and northeastern sections of the United States were contacted by e-mail, telephone, and postal mail to answer an 18-item survey on knowledge, diagnosis, and common practice with respect to traumatic brain injury patients. Descriptive analysis was used to assess common trends. RESULTS: Twenty-three chiropractic and 11 medical primary care practitioners returned completed surveys, making this a low-power pilot study. The majority claimed confidence in diagnosis of MTBI, but a lack of knowledge of many of the assessment tools and the international guidelines. Chiropractic and medical clinicians revealed similar competencies and differing deficiencies. Both groups admitted infrequent diagnosis of MTBI in practice. There was recognition of major TBI signs, but lack of recognition or inquiry for subtle MTBI signs. CONCLUSIONS: There is a need and feasibility for further study of the knowledge transfer to the chiropractic physician with a larger population. These findings correlate with similar medical practitioner studies, and may also support previous findings of underreporting of the prevalence of MTBI. The survey instrument appears to provide valid data on knowledge of MTBIs, with some modifications.

Medications for the prevention and treatment of travellers' diarrhea.

BACKGROUND: . Travellers' diarrhea (TD) remains one of the most common illnesses encountered by travellers to less developed areas of the world. Because bacterial pathogens such as enterotoxigenic Escherichia coli (ETEC), enteroaggregative E. coli , Campylobacter spp. and Shigella spp. are the most frequent causes, antibiotics have been useful in both prevention and treatment of TD. METHODS.: Results of trials that assessed the use of medications for the prevention and treatment of TD were identified through PubMed and MEDLINE searches using search terms 'travellers' diarrhea', 'prevention' and 'treatment'. References of articles were also screened for additional relevant studies. RESULTS.: Prevention of TD with antibiotics has been recommended only under special circumstances. Doxycycline, trimethoprim-sulfamethoxazole, fluoroquinolones and rifaximin have been used for prevention, but at present the first three antibiotics may have limited use secondary to increasing resistance, leaving rifaximin as the only current option. Bismuth subsalicylate (BSS) (Pepto-Bismol tablets) is also an option for prophylaxis. Treatment with antibiotics has been recommended for moderate to severe TD. Azithromycin is the drug of choice, especially in Asia where Campylobacter is common. Fluoroquinolone antibiotics continue to be effectively used in Latin America and Africa where ETEC is predominant. BSS and loperamide (LOP) also are effective as standalone treatments. LOP may be used alone for treatment of mild TD or in conjunction with antibiotics for treatment of TD. CONCLUSIONS: . Historically, antibiotic prophylaxis has not been routinely recommended and has been reserved for special circumstances such as when a traveller with an underlying illness cannot tolerate TD. Antibiotics with or without LOP have been useful in shortening the duration and severity of TD. Emerging antibiotic resistance, limited new antibiotic alternatives and faecal carriage of antibiotic-resistant bacteria by travellers may prompt a re-evaluation of classic recommendations for treatment and prevention of TD with antibiotics.

Rifaximin, a nonabsorbed oral antibiotic, prevents shigellosis after experimental challenge.

BACKGROUND: This double-blind, placebo-controlled study was conducted to assess the efficacy of the nonabsorbed oral antibiotic rifaximin to prevent shigellosis in volunteers challenged with Shigella flexneri. METHODS: Volunteers were randomized to receive either prophylactic rifaximin (200 mg 3 times daily for 3 days; n = 15) or placebo (n = 10) on days 0, 1, and 2. On day 1, volunteers were challenged with approximately 1500 colony-forming units of S. flexneri 2a strain 2457T given orally in sodium bicarbonate buffer. RESULTS: The incidence of diarrhea was 0 with rifaximin, compared with 60% with placebo (P = .001). The median time to onset of diarrhea was 78.5 h with placebo (P < .001). The incidence of dysentery was 0 for rifaximin and 10% for placebo (P = .4). The incidence of colonization with Shigella was 0 with rifaximin, compared with 50% with placebo (P < .005). A significant serum or mucosal immune response after challenge by at least 1 indicator (immunoglobulin A titer, immunoglobulin G titer, and immunoglobulin A antibody-secreting cell count) was 0 with rifaximin and 80% with placebo (P < .001). CONCLUSIONS: Rifaximin was effective and well tolerated, compared with placebo, in preventing shigellosis in this double-blind study of volunteers challenged with S. flexneri 2a.

A randomized, double-blind, multicenter study of rifaximin compared with placebo and with ciprofloxacin in the treatment of travelers' diarrhea.

Rifaximin was compared with placebo and ciprofloxacin for treatment of travelers' diarrhea in a randomized, double-blind clinical trial. Adult travelers (N = 399) consulting travel clinics in Mexico, Guatemala, and India were randomized to receive rifaximin 200 mg three times a day, ciprofloxacin (500 mg two times a day and placebo once a day), or placebo three times a day for 3 days. Patients recorded in daily diaries the time and consistency of each stool and documented symptoms for 5 days after treatment. Stool samples were collected for microbiologic evaluations before and after treatment. The median time to last unformed stool (TLUS) in the rifaximin group (32.0 hours) was less than one half that in the placebo group (65.5 hours; P = 0.001; risk ratio 1.6; 95% confidence interval 1.2, 2.2; primary efficacy endpoint). The median TLUS in the ciprofloxacin group was 28.8 hours (P = 0.0003 versus placebo; P = 0.35 versus rifaximin). Rifaximin was less effective than ciprofloxacin for invasive intestinal bacterial pathogens. Oral rifaximin is a safe and effective treatment of travelers' diarrhea caused by noninvasive pathogens.

Helicobacter pylori-associated chronic atrophic gastritis involving the gastric body and severe disease by Vibrio cholerae.

Evidence has associated chronic infection by Helicobacter pylori with chronic gastritis, low gastric acid production and an increased risk of life-threatening cholera. However, the relationship of specific patterns of histological damage in the gastric mucosa associated with H. pylori infection and the occurrence of cholera has not been described. The purpose of this study was to compare the gastric pH and histopathological findings in gastric biopsies taken from patients with severe diarrhoeal disease due to Vibrio cholerae with those taken from a control (cholera-negative) population. Thirty-five H. pylori-positive patients who had severe dehydration from culture-confirmed cholera (cases) and 40 patients with H. pylori but with no history of cholera (controls) were recruited. Gastric pH was measured and multiple biopsies were taken from the gastric antrum and body for histopathological examination. The results revealed that patients with severe cholera had a significantly higher prevalence of hypochlorhydria at endoscopy compared with controls. Furthermore, cases had significantly more chronic atrophic gastritis (45.7% vs. 12.5%; P=0.002) and intestinal metaplasia (37.1% vs. 2.5%; P<0.01) in the gastric body than controls. Our findings suggest that the nature and location of these gastric lesions may predispose a subset of H. pylori-infected individuals to severe disease by V. cholerae.