Clinical Health Updates

Caffeine potentiates ibuprofen for tension headaches

Clinical Question:
Does the addition of caffeine to ibuprofen improve the analgesic effectiveness in the treatment of tension headache?

Bottom Line:
Sensitive methods have been introduced to assess differences in analgesia among over-the-counter analgesic agents in relieving tension-type headache pain. The addition of 200 mg caffeine to standard (400 mg) doses of ibuprofen enhanced the analgesic activity of the drug, reducing the duration and intensity of headache. This synergy has been exploited with other analgesics such as Excedrin or Fiorinal, but no products in the U.S. currently contain this combination.

Reference:
Diamond S, Balm TK, Freitag FG. Ibuprofen plus caffeine in the treatment of tension-type headache. Clin Pharmacol Ther 2000;68:312-9.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
Caffeine is added to several different analgesics purportedly to improve their effectiveness in the treatment of pain. This study compared ibuprofen or caffeine, alone or in combination, with placebo in the treatment of tension headaches previously determined to be responsive to nonprescription analgesics. 331 patients were given one of the four possible treatments with instructions to take it when they had their next headache and to record the time to improvement of their headache. These patients were a tightly-strung group, experiencing 3 to 15 tension-type headaches a month for at least a year. 80% of patients receiving ibuprofen and caffeine experienced a meaningful improvement in headache as compared with 67% or 61% receiving either ibuprofen or caffeine alone and 56% of patients receiving placebo. Overall rates of achieving complete relief were not different between the groups, probably because of the small study size. For patients benefiting from treatment, the onset of effectiveness was significantly faster (median 52 minutes) with the combination as compared with placebo or ibuprofen alone (P < 0.05). The subjects overall evaluations were higher for the combination than for either agent alone or for placebo (P= 0.007). Caffeine-related side effects were reported, as one might surmise, more frequently by the patients receiving caffeine, including nervousness, nausea, and dizziness.

Intranasal zolmitriptan effective for cluster headaches

Clinical Question:
Is intranasal zolmitriptan effective in treating cluster headaches?

Bottom Line:
Five-milligram and 10-mg doses of zolmitriptan intranasal spray are effective within 30 minutes and well tolerated in the treatment of acute cluster headache.

Reference:
Cittadini E, May A, Straube A, Evers S, Bussone G, Goadsby PJ. Effectiveness of intranasal zolmitriptan in acute cluster headache: a randomized, placebo-controlled, double-blind crossover study. Arch Neurol 2006;63:1537-1542.

Study Design:
Cross-over trial (randomized)

Synopsis:
Cluster headache is a form of primary headache in which attacks are rapid in onset with very severe pain. The mainstays of acute therapy are inhaled oxygen and sumatriptan succinate injection. The authors evaluate zolmitriptan nasal spray in the acute treatment of cluster headache. Ninety-two patients, aged 40 +/- 10 years (mean +/- SD) (80 men and 12 women), with International Headache Society-defined cluster headache were randomized into a placebo-controlled, double-blind crossover study. Patients treated 3 headache attacks using placebo for 1 attack, 5 mg of zolmitriptan nasal spray (ZNS5) for 1 attack, and 10 mg of zolmitriptan nasal spray for 1 attack. The primary end point was headache relief at 30 minutes, defined as reduction from moderate, severe, or very severe pain to no or mild pain. The study was approved by the appropriate ethics committees. Sixty-nine patients were available for an intention-to-treat analysis. The 30-minute headache relief rates were placebo, 21%; ZNS5, 40%; and ZNS10, 62%. Modeling the response as a binary outcome, the Wald test was significant for the overall regression (chi(2)(1) = 29.4; P<.001), with both ZNS5 and ZNS10 giving significant effects against placebo. Headache relief rates for patients with episodic cluster headache were 30% for placebo, 47% for ZNS5, and 80% for ZNS10, while corresponding rates for patients with chronic cluster headache were 14%, 28%, and 36%, respectively. Zolmitriptan was also well tolerated.

Duloxetine decreases pain of diabetic neuropathy

Clinical Question:
Does duloxetine reduce pain in patients with diabetic peripheral neuropathy?

Bottom Line:
This study confirms previous findings that duloxetine at 60 mg QD and 60 mg BID is effective and safe in the management of diabetic peripheral neuropathic pain.Higher doses of duloxetine didn’t provide much additional benefit. The biases in this study favor treatment, so it is likely that the real benefit is less than what these investigators observed. Finally, we don’t know if duloxetine is any more effective than other treatments used for painful diabetic neuropathy.

Reference:
Wernicke JF, Pritchett YL, D’Souza DN, et al. A randomized controlled trial of duloxetine in diabetic peripheral neuropathic pain. Neurology 2006;67:1411-1420.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
Serotonin (5-HT) and norepinephrine (NE) are involved in pain modulation via descending inhibitory pathways in the brain and spinal cord. The authors assess the efficacy of duloxetine, a dual reuptake inhibitor of 5-HT and NE, on the reduction of pain severity, as well as secondary outcome measures in patients with diabetic peripheral neuropathic pain (DPNP). In this double-blind study, patients with DPNP and without comorbid depression were randomly assigned to treatment with duloxetine 60 mg once daily (QD), duloxetine 60 mg twice daily (BID), or placebo for 12 weeks. The primary outcome measure was the weekly mean score of 24-hour average pain severity on the 11-point Likert scale. Secondary measures and health outcome measures were also assessed. Duloxetine 60 mg QD and 60 mg BID demonstrated improvement in the management of DPNP and showed rapid onset of action, with separation from placebo beginning at week 1 on the 24-hour average pain severity score. For all secondary measures for pain (except allodynia), mean changes showed an advantage of duloxetine over placebo, with no significant difference between 60 mg QD and 60 mg BID. Clinical Global Impression of Severity and Patient’s Global Impression of Improvement evaluation demonstrated greater improvement on duloxetine- vs placebo-treated patients. Duloxetine showed no notable interference on diabetic controls, and both doses were safely administered.

Clinical criteria predict serious head injury risk in kids (CHALICE)

Clinical Question:
Can clinical factors be used to identify children with low risk of serious intracranial pathology after head injury?

Bottom Line:
Clinical factors can accurately predict which children don’t have serious intracranial pathology after head injury. A highly sensitive clinical decision rule is derived for the identification of children who should undergo computed tomography scanning after head injury. This rule has the potential to improve and standardise the care of children presenting with head injuries. Validation of this rule in new cohorts of patients should now be undertaken.

Reference:
Dunning J, Daly JP, Lomas JP, et al, for the Children’s Head injury ALgorithm for the prediction of Important Clinical Events study group. Derivation of the children?s head injury algorithm for the prediction of important clinical events decision rule for head injury in children. Arch Dis Child 2006;91:885-891.

Study Design:
Cohort (prospective)

Synopsis:
This team of researchers identified more than 22,000 children younger than 16 years with any head injury. Specially trained physicians assessed each child with a standardized history and physical, including mechanism of injury and Glasgow Coma Scale. The authors then developed a set of clinical criteria to identify children with “clinically significant intracranial injury,” defined as death as a result of head injury, requirement for neurosurgical intervention, or marked abnormalities on the computed tomography (CT) scan. A total of 744 of the children provided CT scans, but all children completed a clinical follow-up with the authors. The clinical prediction rule (summarized below) was highly sensitive (98%; 95% CI, 96-100) and also had decent specificity (87%; 86-87). The positive likelihood ratio of 7.5 (6.9-7.7) and negative likelihood ratio of 0.02 (0-0.05) suggests this rule is best at ruling out serious intracranial injury. This prediction rule needs to be validated.

The clinical decision rule:
A CT scan is required if any of the following criteria are present:
History:
Witnessed loss of consciousness of greater than 5 minutes duration
History of amnesia (either antegrade or retrograde) of greater than 5 minutes duration
Abnormal drowsiness
More than 3 discrete episodes of vomiting after head injury
Suspicion of nonaccidental injury
Seizure after head injury in a patient who has no history of epilepsy
Examination:
Glasgow Coma Score (GCS) <14, or GCS <15 if younger than 1 year
Suspicion of penetrating or depressed skull injury or tense fontanelle
Signs of a basal skull fracture (blood or cerebrospinal fluid from ear or nose, panda eyes, Battle’s sign, hemotympanum, facial crepitus, or serious facial injury)
Focal neurologic deficit
Presence of bruise, swelling or laceration >5 cm if younger than 1 year
Mechanism:
High-speed road traffic accident either as pedestrian, cyclist, or occupant (defined as accident with speed above 40 miles per hour)
Fall of more than 3 m in height
High-speed injury from a projectile or an object
If none of the above variables are present, the patient is at low risk of intracranial pathology.

Atypical antipsychotics minimally effective, poorly tolerated in AD

Clinical Question:
Are the newer atypical antipsychotics effective in patients with Alzheimer’s disease?

Bottom Line:
Atypical antipsychotics are minimally, if at all, effective for patients with Alzheimer’s disease (AD), and they have significant adverse effects. They should not be routinely used for the treatment of psychosis, agitation, or aggression in these patients.

Reference:
Schneider LS, Tariot PN, Dagerman KS, et al, with the CATIE-AD Study Group. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s disease. N Engl J Med 2006;355:1525-1538.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
Although atypical antipsychotics are widely used in the treatment of psychosis, agitation, and aggression in patients with AD, clinical trials to date have been of limited duration and have not adequately addressed the tolerability of the drugs. In addition, there are new concerns regarding the safety of these drugs, with recent studies* finding an increased risk of death (relative risk = 1.6 – 1.7). In this study, the authors identified 421 outpatients with probable AD, a Mini-Mental State score between 5 and 26, and delusions, hallucinations, aggression, or agitation. They were randomized in a 2:2:2:3 ratio to olanzapine (Zyprexa, 2.5 mg or 5.0 mg), quetiapine (Seroquel, 25 mg or 50 mg), risperidone (Risperdal, 0.5 mg or 1.0 mg), or placebo. Whether to use the smaller or larger dose of each drug was determined by the study physicians, who were blinded to treatment assignment. They chose an unidentified small or large pill from an envelope, then adjusted the dose on the basis of patient response. Patients were followed up for up to 3 years; the primary outcomes were the time to discontinuation of the study drug and the degree of improvement on the Clinical Global Impression of Change (CGIC) scale at week 12. Groups were balanced at the start of the study and analysis was by intention to treat. The patients’ mean Mini-Mental State score was 15, their average age was 78 years, 56% were women, and 18% were African-American.

The average final doses of each drug were olanzapine 5.5 mg, quetiapine 56 mg, and risperidone 1.0 mg. The mean time to discontinuation was between 5.3 weeks and 8.1 weeks for the 4 groups, with no significant difference between groups. The atypical antipsychotics were more likely to be discontinued because of adverse effects (16% – 24% vs 5% for placebo), while placebo was more likely to be discontinued because of lack of efficacy (70% vs 39% – 53% vs 70% for active drugs). There was no significant difference between groups regarding the response as measured by the CGIC scale at 12 weeks (21% for placebo vs 26% – 32% for active drugs). Adverse effects occurring more frequently in patients receiving an active drug included parkinsonism or extrapyramidal signs (olanzapine and risperidone), sedation and weight increase (all 3 active drugs), and confusion (olanzapine and risperidone).

Treating isolated systolic HTN in elderly prevents strokes

Clinical Question:
Is treating systolic hypertension in the elderly beneficial?

Bottom Line:
Among elderly patients with isolated systolic hypertension, antihypertensive drug treatment starting with nitrendipine reduces the rate of cardiovascular complications. Treatment of 1000 patients for 5 years with this type of regimen may prevent 29 strokes or 53 major cardiovascular endpoints.

Reference:
Staessen JA, Fagard R, Thijs L, et al. Randomised double−blind comparison of placebo and active treatment for older
patients with isolated systolic hypertension. Lancet 1997;350:757−64.

Study Design:
Randomized controlled trial

Synopsis:
Isolated systolic hypertension occurs in about 15% of people aged 60 years or older. In 1989, the European Working Party on High Blood Pressure in the Elderly investigated whether active treatment could reduce cardiovascular complications of isolated systolic hypertension. Fatal and non-fatal stroke combined was the primary endpoint. All patients (> 60 years) were initially started on masked placebo. At three run-in visits 1 month apart, their average sitting systolic blood pressure was 160-219 mm Hg with a diastolic blood pressure lower than 95 mm Hg. After stratification for centre, sex, and previous cardiovascular complications, 4695 patients were randomly assigned to nitrendipine 10-40 mg daily, with the possible addition of enalapril 5-20 mg daily and hydrochlorothiazide 12.5-25.0 mg daily, or matching placebos. Patients withdrawing from double-blind treatment were still followed up. We compared occurrence of major endpoints by intention to treat. At a median of 2 years’ follow-up, sitting systolic and diastolic blood pressures had fallen by 13 mm Hg and 2 mm Hg in the placebo group (n = 2297) and by 23 mm Hg and 7 mm Hg in the active treatment group (n = 2398). The between-group differences were systolic 10.1 mm Hg (95% CI 8.8-11.4) and diastolic, 4.5 mm Hg (3.9-5.1). Active treatment reduced the total rate of stroke from 13.7 to 7.9 endpoints per 1000 patient-years (42% reduction; p = 0.003). Non-fatal stroke decreased by 44% (p = 0.007). In the active treatment group, all fatal and non-fatal cardiac endpoints, including sudden death, declined by 26% (p = 0.03). Non-fatal cardiac endpoints decreased by 33% (p = 0.03) and all fatal and non-fatal cardiovascular endpoints by 31% (p < 0.001). Cardiovascular mortality was slightly lower on active treatment (-27%, p = 0.07), but all-cause mortality was not influenced (-14%; p = 0.22).

Alzheimer’s Disease Cholesterol-Lowering Treatment (ADCLT) trial

Clinical Question:
Is atorvastatin (Lipitor) therapy may be of benefit in patient with mild to moderate Alzheimer’s Disease?

Bottom Line:
Atorvastatin therapy may be of benefit in the treatment of mild-to-moderately affected AD patients, but the level of benefit produced may be predicated on earlier treatment, an individual’s apolipoprotein E genotype or whether the patient exhibits elevated cholesterol levels

Reference:
Circulating cholesterol levels, apolipoprotein E genotype and dementia severity influence the benefit of atorvastatin treatment in Alzheimer’s disease: results of the Alzheimer’s Disease Cholesterol-Lowering Treatment (ADCLT) trial.Sparks DL, Connor DJ, Sabbagh MN, Petersen RB, Lopez J, Browne P.Acta Neurol Scand Suppl. 2006;185:3-7.

Study Design:
Randomized Controlled Trial (Double Blind)

Synopsis:
Recent evidence suggests that treatment of mild-to-moderate Alzheimer’s disease (AD) with atorvastatin provides significant benefit on the Alzheimer Disease Assessment Scale-Cognitive (ADAS-cog) after 6 months. The authors determine if benefit on ADAS-cog performance produced by atorvastatin is influenced by severity of cognitive impairment, circulating cholesterol levels, or apolipoprotein E genotype. They did a double-blind, placebo-controlled, randomized (1:1) trial with a 1-year exposure to atorvastatin calcium or placebo. A single-site study at the clinical research center of the Sun Health Research Institute. Ninety-eight individuals with mild-to-moderate AD (MMSE score of 12-28) provided informed consent, and 67 were randomized. Stable dose use of cholinesterase inhibitors, estrogen and vitamin E was allowed, as was the use of many other medications in the treatment of co-morbidities. Participants using cholesterol-lowering medications or being treated for major depression or a psychiatric condition were excluded. Once daily atorvastatin calcium (80 mg; two 40 mg tablets) or placebo. A primary outcome measure was change ADAS-cog sub-scale score. Secondary outcome measures included scores on the MMSE, and circulating cholesterol levels. The Apolipoprotein E genotype was established for each participant. A significant positive effect on ADAS-cog performance occurred after 6 months of atorvastatin therapy compared with placebo. This positive effect was more prominent among individuals entering the trial with, (i) higher MMSE scores, (ii) cholesterol levels above 200 mg/dl or (iii) if they harbored an apolipoprotein-E-4 allele compared with participants not responding to atorvastatin treatment. Individuals in the placebo group tended to experience more pronounced deterioration if their cholesterol levels exceeded 200 mg/dl or they harbored an apolipoprotein-E-4 allele.

High-Dose Statin (Atorvastatin, Simvastatin, Rosuvastatin, etc.) After Stroke or TIA Effective for Secondary Prevention

A wealth of data supports the use of cholesterol-lowering statin medications for secondary prevention in patients with myocardial infarction. Patients in these trials have demonstrated not only a reduction in secondary cardiovascular events, but also a decreased risk of subsequent stroke and transient ischemic attack (TIA) in subgroup analyses. However, it still remains unclear if initiation of a statin after initial stroke or TIA will effectively prevent secondary cerebrovascular events. A recently published large trial attempted to address this issue and guide clinicians who are considering statin therapy in their patients who present with stroke or TIA.

The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial enrolled 4731 adults who suffered an ischemic or hemorrhagic stroke or TIA, diagnosed by a neurologist, one to six months prior to study entry. Patients with atrial fibrillation or proven cardiac sources of embolus were excluded, hoping to focus on a more atherosclerotic stroke population. Patients with known coronary heart disease were also excluded. Patients with an LDL level at baseline of 100 to 190 mg/dL were randomized in a double-blind fashion to 80 mg of atorvastatin daily or placebo with a primary end point of nonfatal or fatal stroke. The two study groups had similar LDL levels at study entry and did not have significant differences in their use of antiplatelet medications, antihypertensives, or warfarin throughout the course of the trial.

After a median follow up of nearly 5 years, the atorvastatin group demonstrated a 16.0% relative reduction in risk of subsequent nonfatal or fatal stroke (hazard ratio, 0.84; CI, 95%, interval, 0.71 to 0.99; p = .03). The number needed to treat with atorvastatin for 5 years to prevent one recurrent stroke was 46 patients (CI, 95%: 24 to 243 patients). Secondary end point analysis revealed a significant reduction in the combined risk of stroke and TIA (hazard ratio, 0.77; CI, 95%, interval, 0.67 to 0.88; p < .001) as well as in cardiovascular events such as myocardial infarction. There were no significant mortality differences between the two groups.

The number of patients in each group lost to follow up was similar as were the rates of serious adverse events. There were only five cases of rhabdomyolysis in the trial, and three occurred in patients assigned to the placebo group. Persistent transaminase elevation (defined as greater than three times normal) was more frequent in the statin group than in the placebo group (2.2% versus 0.5%, p < .001), but there were no episodes of liver failure observed in any of the patients in the trial.

Of the 88 patients experiencing at least one hemorrhagic stroke during the study, 55 were in the statin group and 33 were in the placebo group. Although this trial was not powered adequately to detect a difference in hemorrhage rates, these results agree with some previous studies that have revealed an increase in hemorrhagic stroke in patients with low LDL levels on statin therapy.

This well-designed randomized trial demonstrates that treating stroke or TIA patients with high-dose atorvastatin reduces the risk of recurrent stroke or TIA. The study population was limited to patients without known coronary artery disease and with baseline LDL levels of 100 to 190 mg/dL. The data support the view of stroke and TIA as coronary heart disease equivalents necessitating appropriate aggressive treatment of atherosclerotic risk factors such as hypercholesterolemia.

A few questions remain for clinicians deciding how best to treat patients with stroke and TIA. First, the dose and type of statin used in this trial was extremely high, and it is not clear if lower doses or alternative statin medications would have the same effect. Second, the relationship between low LDL levels and hemorrhagic stroke remains unclear. It is possible that statins alone or their lipid-lowering effects increase the risk of hemorrhagic stroke in some patients; until this is studied further, patients with hemorrhagic stroke should perhaps not have their LDL levels lowered to extremely low values, and they might not be ideal candidates for high-dose statin therapy. Finally, although the adverse event profile in this study was favorable in the treatment group, concerns regarding statin-induced myopathy and neuropathy remain, especially when statins are given at these high doses. Despite these limitations, this important study likely will change practice and now makes initiation of statin therapy standard-of-care in most patients with stroke or TIA.

Light tx for SAD effective short-term

Clinical Question:
In patients with seasonal affective disorder or other types of depression, is light therapy effective as sole therapy or as an adjunct therapy?

Bottom Line:
Many reports of the efficacy of light therapy are not based on rigorous study designs. This analysis of randomized, controlled trials suggests that bright light treatment and dawn simulation for seasonal affective disorder and bright light for nonseasonal depression are efficacious, with effect sizes equivalent to those in most antidepressant pharmacotherapy trials. Adopting standard approaches to light therapy’s specific issues (e.g., defining parameters of active versus placebo conditions) and incorporating rigorous designs (e.g., adequate group sizes, randomized assignment) are necessary to evaluate light therapy for mood disorders.

Reference:
Golden RN, Gaynes BN, Ekstrom RD, et al. The efficacy of light therapy in the treatment of mood disorders: A review and meta-analysis of the evidence. Am J Psychiatry 2005;162:656-62.

Study Design:
Systematic review

Synopsis:
The purpose of this study was to assess the evidence base for the efficacy of light therapy in treating mood disorders. The authors systematically searched PubMed (January 1975 to July 2003) to identify randomized, controlled trials of light therapy for mood disorders that fulfilled predefined criteria. These articles were abstracted, and data were synthesized by disease and intervention category. Only 13% of the studies met the inclusion criteria. Meta-analyses revealed that a significant reduction in depression symptom severity was associated with bright light treatment (eight studies, having an effect size of 0.84 and 95% confidence interval [CI] of 0.60 to 1.08) and dawn simulation in seasonal affective disorder (five studies; effect size=0.73, 95% CI=0.37 to 1.08) and with bright light treatment in nonseasonal depression (three studies; effect size=0.53, 95% CI=0.18 to 0.89). Bright light as an adjunct to antidepressant pharmacotherapy for nonseasonal depression was not effective (five studies; effect size=-0.01, 95% CI=-0.36 to 0.34).

Clinical decision rules useful for evaluating minor head injury

Clinical Question:
Which clinical decision rule — the Canadian CT Head Rule or the New Orleans Criteria — is the most useful in evaluating adults with minor head injury?

Bottom Line:
For patients with minor head injury and GCS score of 15, the CCHR and the NOC have equivalent high sensitivities for need for neurosurgical intervention and clinically important brain injury, but the CCHR has higher specificity for important clinical outcomes than does the NOC, and its use may result in reduced imaging rates.

Reference:
Stiell IG, Clement CM, Rowe BH, et al. Comparison of the Canadian CT Head Rule and the New Orleans Criteria in patients with minor head injury. JAMA 2005;294:1511-18.

Study Design:
Decision rule (validation)

Funding:
Government

Setting:
Emergency department

Synopsis:
Current use of cranial computed tomography (CT) for minor head injury is increasing rapidly, highly variable, and inefficient. The Canadian CT Head Rule (CCHR) and New Orleans Criteria (NOC) are previously developed clinical decision rules to guide CT use for patients with minor head injury and with Glasgow Coma Scale (GCS) scores of 13 to 15 for the CCHR and a score of 15 for the NOC. However, uncertainty about the clinical performance of these rules exists. To compare the clinical performance of these 2 decision rules for detecting the need for neurosurgical intervention and clinically important brain injury. In a prospective cohort study (June 2000-December 2002) that included 9 emergency departments in large Canadian community and university hospitals, the CCHR was evaluated in a convenience sample of 2707 adults who presented to the emergency department with blunt head trauma resulting in witnessed loss of consciousness, disorientation, or definite amnesia and a GCS score of 13 to 15. The CCHR and NOC were compared in a subgroup of 1822 adults with minor head injury and GCS score of 15. Neurosurgical intervention and clinically important brain injury evaluated by CT and a structured follow-up telephone interview. Among 1822 patients with GCS score of 15, 8 (0.4%) required neurosurgical intervention and 97 (5.3%) had clinically important brain injury. The NOC and the CCHR both had 100% sensitivity but the CCHR was more specific (76.3% vs 12.1%, P<.001) for predicting need for neurosurgical intervention. For clinically important brain injury, the CCHR and the NOC had similar sensitivity (100% vs 100%; 95% confidence interval [CI], 96%-100%) but the CCHR was more specific (50.6% vs 12.7%, P<.001), and would result in lower CT rates (52.1% vs 88.0%, P<.001). The kappa values for physician interpretation of the rules, CCHR vs NOC, were 0.85 vs 0.47. Physicians misinterpreted the rules as not requiring imaging for 4.0% of patients according to CCHR and 5.5% according to NOC (P = .04). Among all 2707 patients with a GCS score of 13 to 15, the CCHR had sensitivities of 100% (95% CI, 91%-100%) for 41 patients requiring neurosurgical intervention and 100% (95% CI, 98%-100%) for 231 patients with clinically important brain injury.