Management of Low Back Pain: A Case Series Illustrating the Pragmatic Combination of Treatment- and Mechanism-Based Classification Systems

This case series describes the pragmatic use of a treatment-based classification system for the management of four patients with a chief complaint of low back pain. Patients were initially classified into stabilization, manipulation, or specific exercise subgroups based on history and clinical examination. Each patient was reassessed during the course of clinical care to determine whether to continue treating according to the initially assigned subgroup or to alter management and incorporate a mechanism-based classification addressing identified impairments. Patient #1 was initially classified in the manipulation category. Within three visits, he reported being “a great deal better” on the Global Rating of Change (GROC) and had a 6-point improvement in his Oswestry Disability Index (ODI). Patient #2, classified in the specific exercise/extension category, reported being “moderately better” using the GROC and had a 22-point improvement in her ODI within six visits. Patient #3, classified in the stabilization category, reported being “a very great deal better” on the GROC and had a 30-point improvement in his ODI Index within four visits. Patient #4 was categorized initially in the manipulation category and subsequently in the specific exercise category; after five visits, he noted being “quite a bit better” using the GROC and he reported a 58-point improvement on his ODI. All four patients in this study were managed using a dynamic pragmatic treatment-based classification approach that allowed for the change of subgroup classification and treatment of impairments and all achieved a clinically meaningful improvement in pain and disabilityKey Words: Low Back Pain, Manipulation, Stabilization, Specific Exercise, Treatment-Based Classification, Mechanism-Based ClassificationThe prevalence of low back pain (LBP) in the US, as well as the disability and financial burden associated with it, continues to increase¹. Treatment costs are consistently rising by at least 7% per year in the United States, and they have a total impact in excess of $170 billion annually. The direct costs of LBP are reportedly between $33 to $55 billion per year². Additionally, individuals with LBP experience health expenditures that are 60% greater than those without LBP, 37% of which are a direct result of physical therapy (PT) and allied specialist services³.Multiple diagnostic classification systems have been developed in an attempt to guide clinicians in the management of LBP⁴. Generally, these diagnostic systems can be classified into unidimensional systems, which include pathoanatomical, signs and symptoms, prognosis, and mechanism-based classification systems, and a single multidimensional classification system. The pathoanatomical classification system attempts to identify the nociceptive source of the patient''s symptoms based on diagnostic imaging or diagnostic injections⁵. The signs and symptoms classification system utilizes a treatment-based approach, wherein a cluster of signs and symptoms from the patient history and physical examination are used to classify patients with LBP into subgroups with specific implications for management^{6, 7}. The prognosis classification system is based on the potential future outcome of the patient⁸. The mechanism-based classification system is based on the premise that impairments identified during examination are the cause of musculoskeletal pain and dysfunction⁹. Finally, the multi-dimensional classification system classifies patients by a combination of the following: the stage of disorder, pathoanatomical diagnosis, signs and symptoms, and psychosocial factors⁸.Delitto et al⁶ have proposed a treatment-based classification system to categorize patients with acute LBP; this system has subsequently been supported in the literature^{10, 11}. Specific findings based on patient history, symptom behavior, and clinical signs serve to facilitate classification of the patient into a subgroup that then receives treatment from which they are most likely to benefit. Although Delitto et al⁶ originally based this system on the limited available evidence and expert opinion at the time, recent randomized trials^{10, 11} have supported the use of this classification-based treatment approach in the management of patients with LBP. Classification-based treatment has been shown to be more effective in improving patient outcomes than management strategies that are based on practice guidelines and treatment not matched to a specific subgroup^{10, 11}. Fritz et al¹² have refined the classification system proposed by Delitto et al⁶ and have constructed a decision-making algorithm that divides subjects into a manipulation, specific exercise, or stabilization subgroup (Figure ​(Figure11).Open in a separate windowFig. 1Decision-making algorithm used by clinicians in this study to identify appropriate subgrouping of patientsSLR- straight leg raise; ROM- range of motion; LBP- low back pain; FABQ- Fear Avoidance Beliefs Questionnaire; FABQPA-Fear Avoidance Beliefs Questionnaire Physical Activity SubscaleThe importance of matching patient treatment to a specific subgroup has continued to receive widespread attention^{13, 14}. Flynn et al¹⁵ established a clinical prediction rule (CPR) to accurately identify subgroups of patients likely to benefit from thrust spinal manipulation. An increase in likelihood of success with manipulation, from 45% to 95%, occurred when patients satisfied four of the five criteria comprising the CPR. The five variables included duration of symptoms < 16 days; Fear Avoidance Beliefs Questionnaire (FABQ) work subscale score < 19; at least one hip with > 35° internal rotation; hypomobility in the lumbar spine, and no symptoms distal to the knee¹⁵. More recently, this CPR was validated through a multi-center randomized clinical trial¹⁶.Long et al¹⁷ investigated a subgroup of patients expected to respond to a specific exercise preference. Patients found to have a directional preference through examination were randomized into matched direction, opposite direction, and general exercises. Those treated in the matched direction group reported significant improvements with regard to back pain intensity, leg pain intensity, Roland-Morris Disability score, medication use, and interference with activity when compared to both other groups.Hicks et al¹⁸ developed a preliminary CPR to identify patients likely to respond favorably to specific stabilization exercises. The four variables indicative of success included age < 40 years old; average straight leg raise > 91°; the presence of aberrant movements; and a positive prone instability test. The presence of three or more of these four variables indicated the best prognosis for success with specific stabilization exercise. Brennan et al¹¹ also demonstrated that patients with LBP achieved greater and more rapid functional improvement if they received intervention strategies matched to their specific subgroup.Each of the aforementioned studies investigated the treatment of non-specific LBP within subgroups using a treatment-based classification system. With the exception of the study by Brennan et al¹¹, each of these studies used a matched versus unmatched treatment approach. In contrast, Brennan et al¹¹ used a more pragmatic approach to more closely mimic clinical practice. In their study, a randomized treatment group decision determined the initial intervention, and if the patient progressed into a second, sub-acute stage, a more general approach was used. In this sub-actue stage progression of treatment was permitted to more accurately reflect clinical practice in which treatment is typically altered and advanced as improvements are made. Clinicians were able to use the mechanism-based classification approach to address impairments in muscle length as they saw fit.In clinical practice, therapists often combine treatment- and mechanism-based classification systems. This case series describes a dynamic pragmatic management approach combining a treatment-based and mechanism-based classification system in four patients referred to physical therapy with a chief complaint of LBP.     

Repeating cytological preparations on liquid‐based cytology samples: A methodological advantage?

This study investigates the rule that repeating cytological preparations on liquid-based cytology improves sample adequacy, diagnosis, microbiological, and hormonal evaluations. We reviewed 156 cases of pap-stained preparations of exfoliated cervical cells in two slides processed by DNA-Cytoliq System. After sample repeat/dilution, limiting factors affecting sample adequacy were removed in nine cases and three unsatisfactory cases were reclassified as satisfactory. Diagnosis was altered in 24 cases. Of these, the original diagnosis in 15 was atypical squamous cells of undetermined significance; after the second slide examination, diagnosis in 5 of the 15 cases changed to low-grade squamous intraepithelial lesion, 3 to high-grade squamous intraepithelial lesion, and 7 to absence of lesion. Microbiological evaluation was altered, with Candida sp. detected in two repeated slides. Repeat slide preparation or dilution of residual samples enhances cytological diagnosis and decreases effects of limiting factors in manually processed DIGENE DCS LBC.     

Protection against cutaneous leishmaniasis by intranasal vaccination with lipophosphoglycan

We previously showed the opposing effect of systemic and mucosal vaccination with whole Leishmania amazonensis antigen (LaAg). Here, the role played by lipophosphoglycan (LPG) as the key disease-promoting component of intramuscular (i.m.) LaAg and its usefulness as a defined intranasal vaccine was investigated in murine cutaneous leishmaniasis. BALB/c mice were twice vaccinated by the i.m. route with 25mug of intact LaAg or with LaAg that was pretreated with anti-LPG 3A1-La monoclonal antibody, prior to infection with L. amazonensis. LPG neutralization rendered the otherwise disease-promoting LaAg antigen protective, as observed by the smaller lesion sizes and reduced parasite burden. The increased resistance was accompanied by a markedly lower antigen-driven TGF-beta and IL-10 responses in the lesion-draining lymph nodes, concomitant with significantly higher IFN-gamma production. To test for intranasal efficacy, 10 microg of affinity-purified LPG and its parental LaAg were twice instilled in the nostrils prior to L. amazonensis infection. In both cases, similarly slower lesion growth and lower parasite burden were found that was associated with increased IFN-gamma and IL-10 responses in the lesion-draining lymph nodes. These results support a role for LPG in the dual route-related effect of LaAg and shows its strong potential as a defined needle-free and adjuvant-free vaccine for cutaneous leishmaniasis.     

Tactile Feedback can be Used to Redistribute Flexion Motion Across Spine Motion Segments

This experiment investigates the efficacy of tactile feedback in affecting changes to dynamic spine movements. A sample of (n = 24) young, healthy males were assessed while completing targeted spine flexion movements with instruction to minimize stretching of the skin beneath an applied tactile stimulus (liquid bandage). Localized tactile stimuli were placed bilaterally at either lumbar (L4), lower thoracic (T10) or upper thoracic (T4) levels. Results demonstrate that localized tactile feedback elicited a re-distribution of spine flexion movement across spine sub-sections (e.g. lumbar vs. thoracic) and intervertebral segments (e.g. C7/T1 through L5/S1). Further, tactile feedback successfully limited the magnitude of end-range flexion, but did not limit functional mid-range spine flexion. Finally, tactile feedback located in the lower thoracic region (T10) increased thoracic flexion variability; however, tactile feedback located at the T4 and L4 regions had no significant effect on movement variability. These findings provide evidence that spine neuromuscular control patterns can be altered using simple tactile stimuli. In terms of low back injury prevention and/or rehabilitation, the tactile feedback investigated here has apparent utility in limiting recognized mechanical risk factors for low back injury; specifically, the local incidence of flexion at specific spine levels, and the incidence of end-range flexion.     

Nasal nitric oxide concentration is decreased in heart failure patients receiving nitrates

Summary— Nitric oxide (NO) is a free radical gas and a short-lived messenger which has many paracrine functions. Direct assessment of NO production is very difficult in vivo. However, the paranasal cavities generate a high amount of NO which diffuses in the nasal cavity where it can be easily measured. Several studies have suggested alterations of the NO production in heart failure. Thus, we assessed nasal NO concentration in normal subjects and in heart failure patients. The nasal NO concentration averaged 227 ± 10 ppb in the control group (n = 20), and 210 ± 10, 198 ± 20 and 159 ± 54 ppb in New York Heart Association (NYHA) class II (n = 30), III (n = 28) and IV (n = 7) patients, respectively (mean ± standard error [SE], not significant using analysis of variance [ANOVA]). Nasal NO level was not influenced by age, sex or etiology of the heart failure or by treatment with frusemide, angiotensin-converting enzyme inhibitor or digoxin. However, treatment with NO-releasing drugs (nitrates or molsidomine) significantly decreased the nasal NO level in heart failure patients. A two-way ANOVA revealed that treatment with a NO-releasing drug influenced nasal NO concentration (P = 0.0005), whereas NYHA class did not (P = 0.23), with a trend towards an interaction between the two parameters (P = 0.09): the inhibitory effect of NO-releasing drug on nasal NO concentration was more pronounced in severe heart failure. In an additional group of 12 patients (NYHA class II or III), the nasal NO concentration was 174 ± 19 ppb during NO-releasing drug treatment and increased to 231 ± 27 ppb 3 days after withdrawal of the nitrates (P = 0.0007 using paired t-test). Conversely, the nasal NO concentration in another group of seven patients (NYHA class II or III) was 219 ± 32 ppb without nitrate treatment and decreased to 188 ± 28 ppb 7 days after nitrate addition (P = 0.02 using paired (test). In contrast, the nasal NO concentration in another group of ten ischemic patients without heart failure was 203 ± 25 ppb without nitrate treatment and was similar (207 ± 28 ppb) 7 days after nitrate addition (not significant using paired t-test). In conclusion, nasal NO production is normal in heart failure, except in patients receiving NO-releasing drugs. Nasal NO concentration could be useful for investigating the mechanism(s) by which exogenous NO donors decrease endogenous NO production.     

Participation of the Prostaglandins in the Control of Renal Blood Flow during Acute Reduction of Cardiac Output in the Dog

To determine whether renal prostaglandins participate in the regulation of renal blood flow during acute reduction of cardiac output, cardiac venous return was decreased in 17 anesthetized dogs by inflating a balloon placed in the thoracic inferior vena cava. This maneuver decreased cardiac output from 3.69±0.09 liters/min (mean±SEM) to 2.15±0.19 liters/min (P < 0.01) and the mean arterial blood pressure from 132±4 to 111±5 mm Hg (P < 0.01) and increased total peripheral vascular resistance from 37.6±2.5 to 57.9±4.8 arbitrary resistance units (RU) (P < 0.01). In marked contrast, only slight and insignificant decreases in the renal blood flow from 224±16 to 203±19 ml/min and renal vascular resistance from 0.66±0.06 to 0.61±0.05 arbitrary resistance units (ru) were observed during inflation of the balloon. Concomitant with these hemodynamic changes, plasma renin activity and plasma norepinephrine concentration increased significantly in both the arterial and renal venous bloods. Plasma concentration of prostaglandin E₂ in renal venous blood increased from 34±6 to 129±24 pg/ml (P < 0.01). The subsequent administration of indomethacin or meclofenamate had no significant effect on mean arterial pressure, cardiac output, and total peripheral vascular resistance, but reduced renal blood flow from 203±19 to 156±21 ml/min (P < 0.01) and increased renal vascular resistance from 0.61±0.05 to 1.05±0.21 ru (P < 0.01). Simultaneously, the plasma concentration of prostaglandin E₂ in renal venous blood fell from 129±24 to 19±3 pg/ml (P < 0.01). Administration of indomethacin to five dogs without prior obstruction of the inferior vena cava had no effect upon renal blood flow or renal vascular resistance. The results indicate that acute reduction of cardiac output enhances renal renin secretion and the activity of the renal adrenergic nerves as well as renal prostaglandin synthesis without significantly changing renal blood flow or renal vascular resistance. Inhibition of prostaglandin synthesis during acute reduction of cardiac output results in an increased renal vascular resistance and reduced renal blood flow. Accordingly, that data provide evidence that renal prostaglandins counteract in the kidney the vasoconstrictor mechanisms activated during acute reduction of cardiac output.     

Nonpeptide factor Xa inhibitors III: effects of DPC423, an orally-active pyrazole antithrombotic agent,on arterial thrombosis in rabbits

DPC423 [1-[3-(aminomethyl)phenyl]-N-[3-fluoro-2'-(methylsulfonyl)[1,1'-biphenyl]-4-yl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide] is a synthetic, competitive, and selective inhibitor of coagulation factor Xa (fXa) (K(i): 0.15 nM in humans, 0.3 nM in rabbit). The objective of this study was to compare effects of DPC423, enoxaparin (low-molecular-weight heparin), and argatroban (thrombin inhibitor) on arterial thrombosis and hemostasis in rabbit models of electrically induced carotid artery thrombosis and cuticle bleeding, respectively. Compounds were infused i.v. continuously from 60 min before artery injury or cuticle transection to the end of experiment. Carotid blood flow was used as a marker of antithrombotic effect. Antithrombotic ED(50) values were 0.4 mg/kg/h for enoxaparin (n = 6), 0.13 mg/kg/h for argatroban (n = 6), and 0.6 mg/kg/h for DPC423 (n = 12). DPC423 at the maximum antithrombotic dose increased activated partial thromboplastin time and prothrombin time (n = 6) by 1.8 +/- 0.07- and 1.8 +/- 0.13-fold, respectively, without changes in thrombin time and ex vivo thrombin activity. The antithrombotic effect of DPC423 was significantly correlated with its ex vivo anti-fXa activity (r = 0.86). DPC423 at 1, 3, and 10 mg/kg p.o. increased carotid blood flow (percent control) at 45 min to 10 +/- 4, 24 +/- 6, and 74 +/- 7, respectively (n = 6/group). Cuticle bleeding times (percent change over control) determined at the maximum antithrombotic dose were 88 +/- 12 for argatroban, 69 +/- 13 for heparin, 4 +/- 3 for enoxaparin, 5 +/- 4 for DPC423, and -3 +/- 2 for the vehicle (n = 5-6/group), suggesting dissociation of antithrombotic and bleeding time effects for DPC423 and enoxaparin. The combination of aspirin and DPC423 at ineffective antithrombotic doses produced significant antithrombotic effect. Therefore, these results suggest that DPC423 is a clinically useful oral anticoagulant for the prevention of arterial thrombosis.     

Characterization of the human neutrophil C1q receptor and functional effects of free ligand on activated neutrophils

The partial characterization and expression of the C1q receptor (C1q-R) in relation to other complement receptors present on the surface of neutrophils has been examined, as well as the effects of free C1q on cell function. A polyclonal anti-C1q-R antibody recognizes a 68-kD neutrophil surface protein. C1q-R expression was not upregulated upon warming, priming, or exposure to FMLP, but decreased after exposure to phorbol myristate acetate (PMA), because of shedding of the receptor into the extracellular medium, as detected by enzyme-linked immunosorbent assay. CR3 and CR1 expression was upregulated from intracellular pools after cell stimulation by PMA. No evidence of intracellular pools of C1q-R was found, as assessed by immunoblotting of subcellular fractions. But C1q-R appeared to be expressed early in cell differentiation, was detected on undifferentiated HL-60 cells, and like CR3 expression, increased upon 5 days differentiation towards a neutrophil lineage. However, C1q-R expression decreased upon additional culture, whereas CR3 expression continued to increase. A large variation in the percentage of peripheral cells expressing C1q receptors in donors was observed, ranging from 13% to 100%, contrasting with CR3 receptors that exhibited less variability. Interactions between free monomeric C1q and neutrophils were also studied. Incubation of stimulated neutrophils with 10 to 100 micrograms/mL C1q resulted in a further increase in CR3 expression and adherence to albumin-coated surfaces. Staphylococci opsonized with low quantities of C1q (0.1 to 1 microgram/mL) mediated a moderate and sustained respiratory burst in neutrophils, whereas a burst of similar magnitude was generated only with free C1q at concentrations 10- to 100-fold higher. Stimulation was only partially inhibited if cells were first treated with anti-C1q-R antibody, suggesting other C1q binding proteins may be present on the cell surface. In summary, neutrophil C1q receptor is approximately 68-kD, exhibits varying expression on different subjects, and is not upregulated from intracellular stores on exposure to soluble stimuli. Stimulated, but not resting, neutrophils selectively respond to raised levels of free C1q, resulting in altered cell function and enhanced CR3 receptor expression. These studies thus suggest complex roles for C1q in neutrophil function.