Lack of Relationship Between Chronic Upper Abdominal Symptoms and Gastric Function in Functional Dyspepsia

To determine the relationship between gastric function and upper abdominal sensations we studied sixty FD patients (43 female). All patients underwent three gastric function tests: 13C octanoic gastric emptying test, three-dimensional ultrasonography (proximal and distal gastric volume), and the nutrient drink test. Upper abdominal sensations experienced in daily life were scored using questionnaires. Impaired proximal gastric relaxation (23%) and a delayed gastric emptying (33%) are highly prevalent in FD patients; however, only a small overlap exists between the two pathophysiologic disorders (5%). No relationship was found between chronic upper abdominal symptoms and gastric function (proximal gastric relaxation, gastric emptying rate, or drinking capacity) (all P > 0.01). Proximal gastric relaxation or gastric emptying rate had no effect on maximum drinking capacity (P > 0.01). The lack of relationship between chronic upper abdominal sensations and gastric function questions the role of these pathophysiologic mechanisms in the generation of symptoms.
Introduction
Functional dyspepsia (FD) is a common disorder seen in daily clinical practice, characterized by the presence of pain or discomfort in the upper abdomen in the absence of organic, systemic, or metabolic disease [1]. Functional dyspeptic patients complain about a variety of symptoms, which are frequently intermittent, and mostly related to food intake [2]. For that reason, a subdivision of patients has been proposed, in order to clarify the heterogeneity of this disorder and to direct treatment options [3]. Attempts have been made to subdivide patients according to their symptoms; however, a large overlap of symptoms exists and many patients do not fit into one of the subgroups [1].
Currently, many efforts are being made to subdivide patients according to gastric (dys)function, and to find new ways of treating these proposed pathophysiologic disorders [4]. Three pathophysiologic mechanisms have been described as possible etiologic factors: (1) a delayed gastric emptying, (2) impaired proximal gastric accommodation, and (3) visceral hypersensitivity. Delayed gastric emptying is present in approximately 30% of FD patients, and may be one of the underlying mechanisms for symptoms (vomiting and postprandial fullness) [5]. Impaired proximal gastric relaxation may be an important etiologic factor in the pathophysiology of functional dyspepsia, considering the high prevalence of approximately 40% in FD patients, and a possible association with early satiety, weight loss, and fullness [6, 7]. Finally, an increased visceral sensitivity is highly frequent in FD patients, and even though difficult to measure, an important etiologic factor in the pathophysiology of FD [8]. However, when targeting specific pathophysiologic mechanisms by the use of pharmacologic agents, the effect on symptoms is questionable [6, 9, 10]. In other words, the relationship between specific upper abdominal sensations and the above-mentioned mechanisms remains to be matter of debate.
We conducted a study to assess the relationship between gastric function and upper abdominal sensations. Gastric emptying rate, proximal gastric relaxation, and maximum drinking capacity were assessed in FD patients. The symptoms experienced in daily life (chronic upper abdominal symptoms) were assessed and related to the primary outcome parameters of the gastric function tests. We hypothesised that chronic upper abdominal symptoms and specific pathophysiologic mechanisms have no correlation in functional dyspepsia.
Materials and methods
Patients
All patients visiting the outpatient clinics at our hospital, fulfilling the Rome II criteria for functional dyspepsia [1], were subjected to three non-invasive functional tests of the stomach. A total of 60 functional dyspeptic patients were prospectively evaluated; 43 female (median age 40 years; range 18–65) and 17 male (median age 37 years; range 21–64).
The inclusion criteria were (a) the presence of dyspeptic symptoms, assessed using the questionnaire described below; (b) no evidence of macroscopic inflammation of the esophageal mucosa or focal lesions of the esophagogastroduodenal mucosa at upper gastrointestinal endoscopy (performed within 1-year prior to inclusion); (c) no abnormalities seen during upper abdominal ultrasonography (performed within 1 year prior to inclusion); (d) absence of serious concomitant illness; and (e) the absence of major gastrointestinal surgery (excluding appendectomy).
The protocol was approved by the ethics committee of the University Medical Center Utrecht. All patients gave written informed consent for inclusion in the trial.
Chronic dyspeptic symptoms questionnaire
Each patient completed a reproducible dyspepsia questionnaire [5, 6, 11]. Patients were asked to score six different symptoms (pain or discomfort centered in the upper abdomen, early satiety, bloating in the upper abdomen, fullness, nausea, and vomiting) from 0 to 5 (0 = none, 1 = very mild; awareness of symptoms but easily tolerated, 2 = mild; tolerated without interference with usual activity, 3 = moderate; enough to cause some interference with usual activity, 4 = severe; enough to cause significant interference with usual activity, 5 = very severe; incapacitating with inability to work or do usual activity). For inclusion, two of these symptoms had to be scored as moderate, severe or very severe and these symptoms needed to be present for at least 12 weeks, not necessary consecutive, in the preceding 12 months.
Study protocol
All patients underwent three functional tests of the stomach on three separate days; the ¹³C-octanoic breath test, three-dimensional ultrasonography of the stomach, and a nutrient drink test. The order of the three study days was arbitrary. Each of the study days started at 08:00 h after an overnight fast of at least 10 h. The time interval between the tests was three days to 2 weeks. Patients were asked to discontinue any medication known to influence gastrointestinal motility or sensitivity for at least 7 days prior to the study, including PPI therapy. The use of narcotics, anticholinergic medication, serotonergic medication (including selective serotonin reuptake inhibitors), and antidepressants was considered an exclusion criterion. None of the patients were on NSAID therapy.
13C-octanoic breath test
The rate of gastric emptying was assessed using the 13C-octanoic breath test. The test meal consisted of two fried eggs, one slice of bread, 5 g margarine and 150 ml water (total caloric value of 294 kcal and a nutrient composition of 16 g protein, 16 g carbohydrate, 18 g fat) [12]. The egg yolk of one egg was labelled with 100 mg 13C-sodium-octanoic acid (598 μmol; Campro Scientific, Veenendaal, The Netherlands), dissolved in 1 ml distilled water. Breath samples were taken at baseline, before the meal and from start of ingestion of the meal every 2 min the first 30 min, every 5 min for the next 30 min and every 15 min thereafter up to 4 h.
Three-dimensional ultrasonography
Total-, proximal-, and distal gastric volumes were assessed before and after ingestion of a nutrient drink using 3D-US [13–16]. Ultrasonographic data were acquired in a sitting position, while fasting and at 5, 15, 30, 45, and 60 min after ingestion of a nutrient drink. The nutrient drink (500 ml) consisted of 200 ml lactose- and fiber-free milk drink, containing 12.0 g proteins, 11.6 g fat and 36.8 g carbohydrate (300 kcal) (Nutridrink, Nutricia, Zoetermeer, The Netherlands) mixed with 300 ml of water, and was ingested within 3 min.
The 3D imaging system consisted of an ultrasound scanner with a 3.5 MHz curved probe and a tracking system (Esaote-Pie Medical, Maastricht, The Netherlands). The tracking system consisted of a transmitter generating a spatially varying magnetic field and a small receiver, firmly attached to the ultrasound probe, containing three orthogonal coils to sense the magnetic field strength [17]. A standardized ultrasound-scanning pattern was used, starting at the left lateral subcostal margin and then moving distally towards the pylorus having the probe in a vertical position [14]. The 2D sagittal planes were used to draw the region of interest, corresponding to the inner layer of the stomach wall (the interface between the outer profile of the gastric wall mucosa and the liquid nutrition). A 3D reconstructed image of the stomach and the gastric volume was obtained using software with rendering and volume estimation capability (In Vivo ScanNT, Medcom GmbH, Darmstadt, Germany).
The proximal gastric volume was defined as the gastric volume between the diaphragm and a dividing plane 10 cm below the point where the fundic top reaches the diaphragm. Similarly, a distal part was separated, defined as the gastric region between the antral area (the sagittal ultrasound plane in which the antrum, the left liver lobe, the superior mesenteric vein and the abdominal aorta are seen simultaneously) and the gastroduodenal junction [18]. At every time point, we subtracted fasting total or partial gastric volume leaving the change in total or partial gastric volume. Proximal and distal gastric volume ratios were calculated by dividing proximal or distal gastric volume by total gastric volume. Recently, we defined impaired proximal relaxation as the average of the proximal gastric volume ratios of 5 and 15 min smaller than the lower limit of the 95% confidence interval (0.32–0.57) of healthy controls; 35 healthy controls (16 male; mean age 31 (18–53) years) [7]. All measurements were made by a single investigator (N.v.L.) who was blinded for the results of the gastric emptying test and the drink test.
Nutrient drink test
The nutrient drink test was used to measure the drinking capacity and the symptoms evoked by a nutrient drink [19, 20]. Patients were asked to ingest a nutrient drink (Nutridrink; 1.5 kcal/ml) at a constant rate of 15 ml/min. At 5-min intervals, they scored satiety using a graphic rating scale that combines verbal descriptors on a scale graded 0–5 (0 = no satiety, 5 = maximum satiety). The test ends when the subject reaches maximum satiety. In healthy controls, maximum satiety occurs after ingestion of 1005 ml (1508 kcal). The lower limit of normal was 653 ml (979 kcal) [19]. In the same study, FD patients ingested 361 ml (542 kcal) before reaching maximum satiety.
Statistical analysis
The main focus of our analysis was (a) to analyse a possible relationship between the rate of gastric emptying, total or partial gastric volumes after meal ingestion, and drinking capacity, and (b) to compare the outcome of the 13C-octanoic breath test, the 3D-US test, and the drink test with the symptoms of patients experienced during daily life (chronic symptoms).
The primary end points of the gastric function tests are dichotomous and continuous. The relationship between the outcomes of the three gastric function tests was studied using a Pearson’s correlation between continuous variables (half-emptying time, retentions after 120 min, fasting gastric volume, proximal gastric volume ratio, distal gastric volume ratio, and maximum drinking capacity). Secondly, patients were subdivided in two groups, according to postprandial proximal gastric relaxation (normal or impaired), and according to the rate of gastric emptying (normal or delayed), in order to compare multiple variables between the sub-groups using the Students’ t-test.
Chronic upper abdominal symptoms (ordinal variables) were compared between FD patients with normal- or delayed gastric emptying or a normal or impaired proximal gastric relaxation (dichotomous variable), using the χ2 test. Secondly, the relationship between chronic upper abdominal symptoms and half-emptying time, retention after 120 min, fasting gastric volume, proximal gastric volume ratio, distal gastric volume ratio, and maximum tolerated volume (continuous variable) was analysed using one-way analysis of variance (ANOVA).
We have analysed the effect of age, height, weight, BMI, and sex on the outcome of the gastric function tests and the chronic symptoms using a regression analysis. All variables were tested in single models and using multivariable analysis.
Due to the high number of comparisons made, we considered a P value of <0.01 as statistically significant. All statistical analysis was performed using commercially available software (SPSS 11.0 for Microsoft windows). For the χ2 test and the Students’ t-test, on the basis of a Cohen’s effect size of 0.8, a power of 0.80 was obtained with 60 subjects (considering α = 0.01) [21]. With the same number of subjects, there was good power (0.80) to detect an R value of 0.40 with an α = 0.01.
Results
Combined assessment of the 13C-octanoic breath test, 3D-US, and the nutrient drink test was performed in 60 FD patients. The frequency of upper abdominal sensations scored as moderate or higher was  upper abdominal pain (80%), early satiety (59%), bloating (77%), fullness (71%), and nausea (51%). Vomiting was present in 13% of patients (Table 1).
Table 1Frequency of severity grading for each of six dyspeptic symptoms in 60 dyspeptic patients (chronic symptoms)0 (None)1–2 (Very mild–mild)3 (Moderate)4–5 (Severe–very severe)Upper abdominal pain1 (2)11 (18)18 (30)30 (50)Early satiety7 (12)18 (30)19 (32)16 (27)Bloating4 (7)10 (17)27 (45)19 (32)Fullness2 (3)15 (25)26 (43)17 (28)Nausea10 (17)19 (32)14 (23)17 (28)Vomiting46 (77)6 (10)2 (3)6 (10)Numbers in parentheses represent row percentages
Gastric emptying and proximal gastric relaxation
Figure 1 shows the frequency of a delayed gastric emptying rate, defined as a half emptying time ≥120 min and/or a retention after 120 min ≥40%, and impaired proximal gastric relaxation, defined as an average proximal gastric volume ratio of 5 and 15 min postprandially ≤ 0.32 (95% CI healthy controls) in the patient group [7]. A delayed gastric emptying with a normal proximal gastric relaxation was found in 33% of patients. Impaired proximal gastric relaxation with a normal gastric emptying rate was observed in 23% of patients. In 38% of all patients, none of both pathophysiologic disorders were found. Finally, only a small overlap exists between the two pathophysiologic disorders (5% of patients). These numbers are in concordance with literature [5, 6].
Fig. 1Gastric emptying and proximal gastric relaxation in 60 FD patients: 33% of patients have a delayed gastric emptying and normal proximal gastric relaxation (black), 23% of patients have impaired proximal gastric relaxation and a normal gastric emptying rate (striped), 38% of patients have none of the pathophysiologic disorders (white), and 5% of patients have both disorders (grey)
Nutrient drink test
The average amount of nutridrink ingested before reaching maximum satiety was 399.8 (344–447) ml (600 kcal). Table 2 summarizes the results of the nutrient drink test. No effect of age or BMI on MTV and upper abdominal sensations was observed (all P > 0.01). Male patients had a maximum tolerated volume (MTV) of 500 (381–618), and female patients of 359 (301–417) (P = 0.017).
Table 2The effect of age, BMI, and sex on maximum tolerated volume (MTV) and the change in upper abdominal sensations after the nutrient drink testAgeBMISexβ0β1β0β1FemaleMaleMTV329 (160–499)1.7 (−2.2–5.6)363 (3–725)1.6 (−14 –18)359 (301–417)500 (381–618)Delta symptoms     Pain11 (0–35)0.02 (−0.5–0.6)24 (0–74)-0.5 (−3–2)10 (0–20)14 (0–28)    Fullness49 (23–76)-0.1 (−0.7–0.5)49 (0–100)-0.1 (−2–2)48 (37–59)42 (29–55)    Nausea46 (20–72)-0.5 (−1–0.1)28 (0–85)-0.2 (−3–2)21 (11–31)31 (12–50)    Hunger−28 (−50–0)0.09 (−0.4–0.6)−7 (−52–40)−0.8 (−3–1.2)−24 (−33  to  −15)−25 (−37 to −14)β0: intercept of the model. β1: slope of the corresponding variable. Numbers in parenthesis represent the 95% confidence interval of βI. MTV and delta symptoms in female and male patients are presented as mean (95% confidence interval for mean). No effect of age, BMI, or sex on MTV or the change in upper abdominal sensations after the nutrient drink test was observed (all P > 0.01)
Relationship between gastric emptying, total and partial gastric volume, and drinking capacity
Table 3 displays some of the patient characteristics in FD patients with normal or impaired proximal gastric relaxation and with normal or delayed gastric emptying. Age or BMI did not influence proximal gastric relaxation or the rate of gastric emptying. Patients with a normal gastric emptying rate had an MTV of 439 ml (359–519) whereas patients with a delayed gastric emptying had a MTV of 334 ml (279–389) (P = 0.032). MTV in patients with normal or impaired proximal relaxation was very similar (404 and 384 ml respectively). In patients with normal proximal gastric relaxation, an average fasting gastric volume of 50 ml (41–59) was determined, opposed to 34 ml (24–44) in patients with impaired proximal relaxation (P = 0.029). The fasting gastric volume in patients with normal or delayed gastric emptying was 44 and 47 ml, respectively.
Table 3Characteristics of FD patients, subdivided according to the extent of proximal gastric relaxation or the rate of gastric emptying (n = 60)Proximal gastric relaxationGastric emptyingNormal (n = 43)Impaired (n = 17)Normal (n = 37)Delayed (n = 23)Age41 (36–45)42 (35–49)40.9 (36–45)41 (35–48)BMI22 (21–23)23 (21–25)22 (21–23)22 (21–23)MTV (ml)404 (346–461)384 (237–530)439 (359–519)334 (279–389)Fasting gastric volume (ml)50 (41–59)34 (24–44)44 (33–55)47 (37–56)Data are presented as mean (95% confidence interval for mean). No effect of age and BMI on proximal gastric relaxation or gastric emptying was observed
Twenty out of 43 female patients had a delayed gastric emptying (47%) and 18% of all male patients had a delayed gastric emptying (P = 0.038). The prevalence of impaired proximal gastric relaxation in male and female patients was 21% and 35% respectively (not shown in the table).
A positive correlation was observed between the proximal gastric volume ratio (3D-US) and half emptying time (r = 0.32, P = 0.015) and the retention after 120 min (r = 0.30, P = 0.024) (13C breath test). No correlation was found between the distal gastric volume ratio and the main outcome parameters of the gastric emptying test.
Relationship between chronic symptoms and gastric function
No effect of age, sex, or BMI on any of the chronic upper abdominal sensations was observed, except that patients with a higher BMI or a higher weight scored lower on symptoms of early satiety (both P = 0.007). Figure 2 shows the chronic upper abdominal symptoms in FD patients with normal or delayed gastric emptying and normal or impaired proximal gastric relaxation. No differences were observed in the percentage of patients who scored any of the upper abdominal symptoms as moderate or higher between these groups (all P > 0.01). We did not find any correlation between half emptying time, retention after 120 min, proximal gastric volume ratio, distal gastric volume ratio, fasting gastric volume, and any of the chronic upper abdominal symptoms (all P > 0.01).
Fig. 2Chronic upper abdominal symptoms scored from 0 (nonexistent) to 5 (very severe; incapacitating with inability to work or do usual activity). The figure shows the number of the patients who scored three (moderate) or higher on the questionnaire (expressed as a percentage of the total) in subgroups with; (Fig. 1A) normal- (□) or delayed (■) gastric emptying, and (Fig. 1B) normal- (□) or impaired (■) proximal relaxation
Figure 2 depicts all FD patients categorized according to their chronic complaints; mild (1–2), moderate (3), and severe (4–5). No difference in maximum drinking capacity was observed between the three groups (all P > 0.01) (Fig. 3). Interestingly, patients who reported early satiety as moderate or higher have a comparable drinking capacity with patients who do not experience this symptom in daily life.
Fig. 3Nutrient drink test: maximum tolerated volume in FD patients, categorized according to the chronic symptoms. No difference in drinking capacity was observed between patients experiencing mild (1–2), moderate (3), or severe (4–5) pain, early satiety, fullness, or nausea in daily life (all P > 0.01)
Discussion
The following were the most important findings of this study: (1) no relationship was found between chronic upper abdominal symptoms and gastric function (proximal gastric relaxation, gastric emptying rate, or drinking capacity), (2) a third of all FD patients had a normal gastric emptying rate and a normal proximal gastric relaxation, and only a small overlap existed between the two pathophysiologic disorders (7%), and (3) there was an absence of any relationship between maximum drinking capacity and proximal gastric relaxation or gastric emptying rate.
The observation that approximately 40% of FD patients had a delayed gastric emptying, and approximately 30% of FD patients had impaired proximal gastric relaxation, is confirmatory of previous studies [5, 6]. The relative small overlap between the two pathophysiologic mechanisms may suggest that one abnormality excludes the other. However, no significant positive correlation between the proximal gastric volume ratio and half emptying time or retention after 120 min was found. The rate of gastric emptying is most likely dependent on many factors, including fundal, antral, pyloric, and duodenal motility [22]. For that reason, gastric emptying and postprandial gastric relaxation should be considered as two separate mechanisms [23].
For assessment of partial gastric volumes we used 3D-US as a noninvasive alternative for the barostat technique. Recently, a head-to-head comparison between the barostat and 3D-US was performed, in which it was shown that 3D-US was able to identify almost all patients with impaired accommodation assessed by barostat. It was, however, emphasized that the two techniques are not interchangeable, which is likely to be due to the difference in invasiveness of both techniques. Since there is no absolute concordance between the two techniques, we must preserve some reservations in generalizing the results of the current study.
The nutrient drink test has been suggested as a tool to measure meal-induced satiety, and as a non-invasive alternative for the detection of normal- or impaired accommodation of the stomach [6, 19]. Furthermore, a positive relationship between the rate of gastric emptying and the amount of Kcal ingested during the nutrient drink test has been described, thereby suggesting that the maximum tolerated volume is not only influenced by gastric accommodation [24]. However, many studies have shown conflicting results, displaying no relationship between drinking capacity and barostat or SPECT findings, [25, 26] and a negative relationship between gastric emptying rate and maximum tolerated volume [27].
Since the results from different studies do not correspond, it remains a mystery what it is we are testing with the nutrient drink test. The suggestion that the nutrient drink test can be used to discriminate between FD patients with normal or impaired visceral sensitivity is disputable [9]. In the current study, we did not observe any relationship between MTV and chronic upper abdominal symptoms or between MTV and proximal gastric relaxation or gastric emptying rate. Most studies do agree that the drink test differentiates between FD patients and healthy controls, as we have found in the present study. Notably, the average amount of nutridrink ingested until maximum satiety, was very similar to what others have found (approximately 360 ml) [19], which is below the 95% confidence interval of healthy controls. No effect of age or BMI on MTV was observed in the current study, however we did observe a modest effect of gender, although this did not reach statistical significance (P = 0.017) [20].
The nutrient drink test is also being used in pharmacological trials, and a resemblance between symptoms evoked by the meal challenge and symptoms experienced in daily life has been observed [27]. Recently, we have performed a double blind, placebo-controlled, crossover trial, in which the activity of a new drug was tested, using the outcome of the nutrient drink test as one of the end points in the study [28]. FD patients who participated in the pharmacological trial drank significantly more compared to the FD patients in the current study; 569 ± 90 ml and 360 ± 30 ml respectively (P < 0.001). A strong placebo effect and cognitive influences like motivation should therefore be considered as confounding factors. No differences in age, sex, BMI, chronic symptoms, or upper abdominal sensations experienced during the drink test were observed between the patients who participated in the pharmacological trial and those who did not.
In summary, the maximum drinking capacity of FD patients, seen at a tertiary referral practice, is not influenced by gastric emptying rate or proximal gastric relaxation. The question is raised what usefulness this test has, in terms of diagnosis or treatment options, in FD patients and as a tool to analyze gastric function or upper abdominal sensations. Since we did not find any relationship between upper abdominal symptoms and MTV, the nutrient drink test cannot be regarded as an alternative for measuring visceral perception, as can be done by gastric barostat. In our opinion, many subjective factors, like motivation, probably play an important disturbing factor in the outcome of the test.
In conclusion, in spite of a high prevalence of impaired proximal accommodation and delayed gastric emptying in FD patients, the lack of correlation between chronic upper abdominal sensations and gastric function questions the role of these pathophysiologic mechanisms in the generation of symptoms. Consequently, gastric function does not serve as a clear marker for the symptoms experienced by FD patients in daily life, and limited effect on symptoms may be expected when targeting these specific mechanisms. Finally, despite many efforts, no (measurable) motoric disorder can be appointed as a possible pathophysiologic mechanism underlying the presence of upper abdominal symptoms. Most likely, other factors like visceral perception play a vital role in functional dyspepsia.

upper abdominal symptoms
functional dyspepsia
gastric emptying
nutrient drink test
stomach
3d-ultrasonography


Age-Specific Search Strategies for Medline

Background Many clinicians and researchers are interested in patients of a specific age (childhood, geriatrics, and so on). Searching for age-specific publications in large bibliographic databases such as Medline is problematic because of inconsistencies in indexing, overlapping age categories, and the spread of the relevant literature over many journals. To our knowledge, no empirically tested age-specific search strategies exist for Medline.
Introduction
Clinicians and researchers seeking research reports for specific age categories, including generalists and those who are engaged in clinical specialties such as adult medicine, geriatric medicine, pediatric medicine, neonatal medicine, or obstetrics, need to target their literature searches so that the information they retrieve is relevant to their patient population. Difficulty in finding pertinent evidence contributes to the challenges	health professionals have in keeping up-to-date and practising evidence-based medicine [1-7].
Finding age-specific evidence in Medline is a difficult task for several key reasons. In large bibliographic databases such as Medline, optimal search retrieval for individual topics is hampered by the overwhelming amount of available information that is not pertinent to the question. When users search in Medline they have the potential to retrieve articles from any of the approximately 4800 journals that are currently indexed in the database. The size of this general purpose biomedical database coupled with imperfections in indexing [1-3] lead to a high risk of missing articles that are relevant to the topic of the search while at the same time retrieving many articles that are off target. Effective ways to refine the search may be helpful for those wanting to keep up-to-date and for those looking for an answer to a specific patient care question.
Searching in Medline for a specific patient population by selecting "age-specific" journals will not help because studies relevant to any age group are scattered through a wide range of journals, including general journals that cater to no particular age group. Moreover, in Medline, the indexing practices used to identify the ages of those involved in a study are so liberal that they create a very imprecise representation of the age categories of the participants within the study. Medline indexers apply all relevant age-specific index terms to an article regardless of how many participants fall within that category. Thus, if just one patient or participant in the study falls into a particular age category, that age-specific medical subject heading (MeSH) term will be applied. For example, if a researcher was interested in intercultural communication in family medicine around issues of newborn care, the study by Harmsen and colleagues [8] might be retrieved using the following index terms: infant, newborn; ethnic groups; communication; and family practice. However, looking at the patient population studied, only 0.9% of the participants were children under the age of 12 years—likely very few of these were newborns. The study included participants from many age categories, resulting in eight age-specific index terms being assigned to this article (infant, newborn; infant; child, preschool; child; adolescent; adult; middle aged; and aged). For searchers who are interested in communication around newborn issues, this article is likely not useful even though the indexing indicates that it is potentially relevant. These age-classification problems are compounded by the less than optimal search strategies used by clinicians, including their lack of knowledge about how to narrow searches without missing relevant information, and their uncertainty about when to stop searching [9,10].
To assist clinicians searching for studies on age-specific patient populations, we have developed and tested Medline search strategies for detecting studies for specific age categories as well as tested age-specific search terms pertinent to five age-related clinical specialties. In this paper, we report on the evaluation of the retrieval performance of age-specific search strategies in Medline compared with a manual review (the "gold standard" search) of each article in every issue of 161 journals in the year 2000.
Search strategies are useful tools when searching in large electronic databases. We previously developed search strategies for use in Medline to detect clinically relevant scientifically sound articles in the areas of causation, prognosis, treatment, and diagnosis [11-15]. After publishing our initial work on search strategy development [15], we were approached by neonatologists and gerontologists to develop age-specific search strategies because they expressed frustration with the inefficiency of the current system for finding content specific to their patient population. Using only the age-related MeSH terms when searching can be time-consuming because retrievals can be very large and imprecise. To our knowledge, no empirically developed age-specific search strategies have been previously reported for Medline.
Methods
The study compared the retrieval performance of age-specific search terms and phrases in Medline (accessed using Ovid) with a manual review of each article in every issue of 161 journal titles for the year 2000. The 161 journals were chosen over several years in an iterative process based on a hand search review of over 400 journals. The journals were recommended by clinicians, librarians, editors, and publishers and were chosen based on Science Citation Index impact factors and ongoing assessment of their yield of studies and reviews of scientific merit and clinical relevance [16] in the production of 4 evidence-based medicine secondary journals (ACP Journal Club, Evidence-Based Medicine, Evidence-Based Nursing, and Evidence-Based Mental Health). The 161 journals include content for the disciplines of internal medicine (eg, Annals of Internal Medicine), general medical practice (eg, BMJ, JAMA, and Lancet), mental health (eg, Archives of General Psychiatry, British Journal of Psychiatry), and general nursing practice (eg, Nursing Research).
Six research assistants hand searched the 161 journals for the year 2000 and collected data on age of the study participants according to our hand search categories defined in Table 1. This data collection was part of a larger study in which the research assistants applied methodological criteria to each article in each issue to determine if the article was methodologically sound for seven purpose categories (eg, treatment and diagnosis). All purpose category definitions and corresponding methodological rigor have been outlined in previous papers [4,17]. Research staff were rigorously calibrated for applying all these criteria, including the age classification of study participants, and interrater agreement for application of all criteria exceeded 80% beyond chance κ = 0.81; 95% CI = 0.79-0.84) [4].
Table 1
Comparison of hand searching and Medline MeSH classification of age categories
Hand Search Category
Our Definition
Medline MeSH Term Category
MeSH Definition
Fetus
Fetus
-
-
Newborn
Birth to 1 month
Infant, newborn
Birth to 1 month
Infant
> 1 month to < 24 months
Infant
1 to 23 months
Preschool
2 years to < 6 years
Child, preschool
2 to 5 years
Child
6 years to < 13 years
Child
6 to 12 years
Adolescent
13 years to < 19 years
Adolescent
13 to 18 years
Adult
19 years to < 45 years
Adult
19 to 44 years
Middle age
45 years to < 65 years
Middle aged
45 to 64 years
Aged
65 years to < 80 years
Aged
65 to 79 years
Aged 80
≥ 80 years
Aged, 80 and over
80 years and over
ND
Nondiscernible
-
-
MeSH terms and textwords related to age (eg, infant, child, adult) were downloaded from Medline and were treated as "diagnostic tests" for detecting studies with an age-specific population as determined by a hand search of the literature from 161 journals (the gold standard). The hand search data were obtained by reading each issue completely. The downloaded Medline data from the 161 journals included the retrieval sets for each of the individual terms. After these two data sources were obtained (ie, the Medline downloads and the hand search review), a database was created that included the matched merged content from these two sources. These Ovid retrieval sets were then manipulated by our own set of programs to calculate our outcome measures—the operating characteristics of each age-specific searching term (eg, sensitivities, specificities, and precision) for individual terms and for combinations of terms. When we merged the two data sets (Medline and hand search), we determined the match. If Medline included an item that was not indexed, we went back to the journal and scored it. If we had scored an item that was not in Medline, we removed it from the merged database. Therefore, the final merged database included only items that had hand search scores and Medline indexing. This merged database was used to develop the age-specific search strategies [17].
Borrowing from the concepts of diagnostic test evaluation and library science, we determined the sensitivity, specificity, precision, and accuracy of single- and multiple-term Medline searches. We considered these operating characteristics as the indicators of search term performance. Sensitivity for a given age-specific topic is defined as the proportion of relevant articles (ie, articles with the desired age-specific content) that are retrieved; specificity is the proportion of nonrelevant articles (ie, articles that are outside the desired age-specific content) not retrieved; precision is the proportion of retrieved articles that are relevant (a library science term that is equivalent to "positive predictive value" in diagnostic test evaluation); and accuracy is the proportion of all articles that are correctly classified (ie, overall proportion of relevant articles retrieved and nonrelevant articles not retrieved). Our hand search of the 161 journals indexed in Medline led to the classification of all articles in these journals for age-related content. Search terms were then tested to determine their performance in retrieving age-relevant articles while eliminating those that were nonrelevant. An automated process (which we developed and implemented using a computer program) was used to calculate the operating characteristics (performance) for each single and combination term in Medline. Formulae for calculating the operating characteristics (ie, sensitivity, specificity, precision, and accuracy) of searches are shown in Table 2.
Table 2
Formulae for calculating the sensitivity, specificity, precision, and accuracy of searches for detecting age-specific articles*
Hand Search
Detection of Search Terms
Meets Criteria
Does Not Meet Criteria
Detected
a
b
Not detected
c
d
a+c
b+d
*Sensitivity = a/(a + c); precision = a/(a + b); specificity = d/(b + d); accuracy = (a + d)/(a +b + c + d). All articles classified during the manual review of the literature, n = (a + b + c + d).
Individual search terms with sensitivity > 25% and specificity > 75% for a given age category were incorporated into the development of search strategies that included two or more terms. All combinations of terms used the Boolean "OR." For the development of multiple-term search strategies to either optimize sensitivity or specificity, we tested all two-term search strategies with sensitivity of at least 75% and specificity at least 50%.
To construct a comprehensive set of search terms, a list of MeSH terms and textwords was initially generated, and input was sought from clinicians and librarians in the United States and Canada through interviews with known searchers, requests at meetings and conferences, and requests to the National Library of Medicine. These experts were asked which terms or phrases they used when searching for age-specific studies, as well when searching for studies in specific purpose categories. Search terms could be MeSH terms, including publication types and subheadings, or textwords specific to age in titles and abstracts of articles. Various truncations were also applied to the textwords, phrases, and MeSH terms. We compiled a list of 543 age-specific terms (Multimedia Appendix). All terms were tested in Medline using the Ovid Technologies searching system.
Age categories for the hand search were modeled from the MeSH terms used to index age content. A comparison of hand search categories and MeSH term definitions is shown in Table 1. The major difference between the hand search age categories and the MeSH terms is in how they were applied. During the hand search, we classified the age of study participants in primary studies or review articles in the following way: select one age category, if possible, or up to three to represent where ≥ 50% of participants fell. This procedure is intended to more accurately represent the focus of age-category research of clinical relevance than the comprehensive indexing of all participants' ages provided by the Medline index terms (which may be more pertinent for nonclinical purposes).
We defined five age-specific specialty areas by collapsing our hand search age categories (see Table 1) and through discussions with clinicians from each specialty area about which definition most appropriately reflected the age of their patients in clinical practice: geriatric medicine (≥ 65 years of age), adult medicine (19 to < 65 years of age), pediatric medicine (> 1 month to < 19 years of age), neonatal medicine (birth to 1 month), and obstetrics (fetus).
Results
Tables 3 to 7 show the operating characteristics of top-performing combinations of terms with best sensitivity, best specificity, and best optimization of sensitivity and specificity while minimizing the difference between the two, for detecting studies on geriatric medicine, adult medicine, pediatric medicine, neonatal medicine, and obstetrics in Medline in 2000. Search strategies are reported using Ovid's search engine syntax for Medline (mp = multiple posting—term appears in title, abstract, or subject heading; sh = subject heading [MeSH term]; tw = textword—word or phrase appears in title or abstract; : = truncation; pt = publication type; exp = explode—a search term that automatically includes closely related MeSH terms; tu = therapeutic use as a subheading; xs = exploded subheading).
Geriatric Medicine
The single term "exp adult" yielded the best sensitivity (96.4%) with a specificity of 55.9% for retrieving articles about geriatric medicine. However, by using the next best sensitivity combination, "aged.sh. OR age:.tw.", a small sacrifice in sensitivity (1% absolute decrease) resulted in a much better specificity compared with the most sensitive term (absolute increase 14.4%) and improved precision (absolute increase 5.2%) and accuracy (absolute increase 13.3%). As expected, precision improved slightly when specificity was maximized (absolute increase 8.6%). The term that yielded the best optimization of sensitivity and specificity, "aged.sh.", resulted in 93.6% sensitivity and 82.7% specificity.
Table 3
Combination of terms with the best sensitivity, best specificity, and best optimization of sensitivity and specificity for detecting studies about geriatric medicine (≥ 65 years) in Medline in 2000
Search Strategy*
Operating Characteristics†
Sensitivity, %
(95% CI)
(n = 3309)
Specificity, %
(95% CI)
(n = 45719)
Precision, %‡
(95% CI)
Accuracy, %
(95% CI)
(n = 49028)
Best sensitivity(exp adult)
96.4(95.8-97.1)
55.9(55.5-56.4)
13.7(13.2-14.1)
58.7(58.2-59.1)
Next best sensitivity(aged.sh. OR age:.tw.)
95.4(94.7-96.1)
70.3(69.8-70.7)
18.9(18.2-19.4)
72.0(71.6-72.3)
Best specificity(aged, 80 and over.sh. OR of age.tw.)
63.3(61.7-65.0)
84.0(83.7-84.4)
22.3(21.5-23.1)
82.6(82.3-83.0)
Next best specificity(aged.sh.)
93.6(92.8-94.5)
82.7(82.4-83.1)
28.2(27.3-29.0)
83.5(83.1-83.8)
Best optimization of sensitivity and specificity(aged.sh.)
93.6(92.8-94.5)
82.7(82.4-83.1)
28.2(27.3-29.0)
83.5(83.1-83.8)
*Search strategies are reported using Ovid's search engine syntax for Medline (if a single search term is shown, this term outperformed two- and three-term combinations). Best sensitivity while keeping specificity ≥ 50%; Best specificity while keeping sensitivity ≥ 50%; Best Optimization of Sensitivity and Specificity is based on lowest possible absolute difference between sensitivity and specificity; exp = explode, a search term that automatically includes closely related indexing terms; sh = subject heading; : = truncation; tw = textword (word or phrase appears in title or abstract).
†Total database has 49028 articles, of which 3309 articles are relevant to geriatric medicine and 45719 are irrelevant to geriatric medicine.
‡n varies by row.
Adult Medicine
The three-term strategy "adult.mp. OR middle aged.sh. OR age:.tw." yielded the best sensitivity (94.9%) and had a specificity of 64.5% for retrieving articles about adult medicine. When specificity was maximized (85.2%) with the single term "middle aged.sh.", sensitivity lowered to 72.3%, but precision improved to 62.1% (absolute increase 14.8%) and accuracy improved as well (absolute increase 9.8%). The best optimization of sensitivity and specificity occurred with the combined terms "middle aged.sh. OR of age.tw.", with values approaching 79%.
Table 4
Combination of terms with the best sensitivity, best specificity, and best optimization of sensitivity and specificity for detecting studies about adult medicine (19 to < 65 years) in Medline in 2000
Search Strategy*
Operating Characteristics
†
Sensitivity, %
(95% CI)
(n = 12307)
Specificity, %
(95% CI)
(n = 39721)
Precision, %‡
(95% CI)
Accuracy, %
(95% CI)
(n = 49028)
Best sensitivity(adult.mp. OR middle aged.sh. OR age:.tw.)
94.9(94.5-95.3)
64.5(64.4-64.9)
47.3(46.6-47.8)
72.1(71.7-72.5)
Best specificity(middle aged.sh.)Next best specificity(adult.sh.)
72.3(71.5-73.1)75.3(74.6-76.1)
85.2(84.8-85.5)81.4(81.0-81.8)
62.1(61.3-62.8)57.6(56.8-58.4)
81.9(81.6-82.3)80.0(79.5-80.3)
Best optimization of sensitivity and specificity(middle aged.sh. OR of age.tw.)
78.7(78.0-79.4)
77.9(77.4-78.3)
54.4(53.7-55.1)
78.1(77.7-78.5)
*Search strategies are reported using Ovid's search engine syntax for Medline (if a single search term is shown, this term outperformed two- and three-term combinations). Best sensitivity while keeping specificity ≥ 50%; Best specificity while keeping sensitivity ≥ 50%; Best Optimization of Sensitivity and Specificity is based on lowest possible absolute difference between sensitivity and specificity; mp = multiple posting—term appears in title, abstract, or subject heading; sh = subject heading; : = truncation; tw = textword (word or phrase appears in title or abstract).
†Total database has 49028 articles, of which 12307 articles are relevant to adult medicine and 39721 are irrelevant to adult medicine.
‡n varies by row.
Pediatric Medicine
The three-term strategy "child:.mp. OR adolescent.mp. OR infan:.mp." yielded the best sensitivity of 98.0% with a specificity of 81.2% for retrieving articles about pediatric medicine. When specificity was maximized (97.1%) with the single term "children.tw.", a striking trade-off in sensitivity occurred as it was lowered to 58.2% (absolute decrease 39.8%). Yet, as expected, precision improved (absolute increase 30.9%). The three-term strategy "adolescent.tw. OR children.tw. OR child, preschool.sh." yielded the best optimization of sensitivity and specificity (89.3% and 87.3%, respectively).
Table 5
Combination of terms with the best sensitivity, best specificity, and best optimization of sensitivity and specificity for detecting studies about pediatric medicine (> 1 month to < 19 years) in Medline in 2000
Search Strategy*
Operating Characteristics†
Sensitivity, %
(95% CI)
(n = 2845)
Specificity, %
(95% CI)
(n = 46183)
Precision, %‡
(95% CI)
Accuracy, %
(95% CI)
(n = 49028)
Best sensitivity(child:.mp. OR adolescent.mp. OR infan:.mp.)
98.0(97.4-98.5)
81.2(81.1-81.4)
24.6(23.8-25.4)
82.4(82.1-82.8)
Best specificity(children.tw.)
58.2(56.4-60.0)
97.1(97.0-97.3)
55.5(53.7-57.2)
94.9(94.7-95.1)
Best optimization of sensitivity and specificity(adolescent.tw. OR children.tw. OR child, preschool.sh.)
89.3(88.1-90.4)
87.3(87.0-87.6)
30.3(29.3-31.3)
87.4(87.1-87.7)
*Search strategies are reported using Ovid's search engine syntax for Medline (if a single search term is shown, this term outperformed two- and three-term combinations). Best sensitivity while keeping specificity ≥ 50%; Best specificity while keeping sensitivity ≥ 50%; Best Optimization of Sensitivity and Specificity is based on lowest possible absolute difference between sensitivity and specificity; mp = multiple posting—term appears in title, abstract, or subject heading; : = truncation; tw = textword (word or phrase appears in title or abstract); sh = subject heading.
†Total database has 49028 articles, of which 2845 articles are relevant to pediatric medicine and 46183 are irrelevant to pediatric medicine.
‡n varies by row.
Neonatal Medicine
Best sensitivity (95.3%) was achieved by the three-term strategy "infan:.mp. OR child:.mp. OR gestation:.tw.", with a specificity of 83.6% for retrieving articles about neonatal medicine. An expected trade-off occurred in sensitivity (absolute decrease 41.7%) with the most specific term, "infants.tw." (98.7%). However, precision increased to 38.2% (absolute increase 30.8%) and accuracy reached 98.2%. The three-term strategy "infan:.mp. OR gestation:.tw. OR neonatal.tw." yielded the best optimization of sensitivity and specificity, reaching values of 93% (which were the highest among all five specialties).
Table 6
Combination of terms with the best sensitivity, best specificity, and best optimization of sensitivity and specificity for detecting studies about neonatal medicine (birth to 1 month) in Medline in 2000
Search Strategy*
Operating Characteristics†
Sensitivity, %
(95% CI)
(n = 663)
Specificity, %
(95% CI)
(n = 48365)
Precision, %‡
(95% CI)
Accuracy, %
(95% CI)
(n = 49028)
Best sensitivity(infan:.mp. OR child:.mp. OR gestation:.tw.)
95.3(93.7-96.9)
83.6(83.3-83.9)
7.4(6.8-7.9)
83.8(83.4-84.1)
Best specificity(infants.tw.)Next best specificity(infants.tw. OR neonatal.tw.)
53.6(52.6-60.2)67.7(64.0-71.1)
98.7(98.6-98.8)98.2(98.0-98.3)
38.2(34.9-41.0)33.7(31.0-36.0)
98.2(98.0-98.3)97.8(97.6-97.9)
Best optimization of sensitivity and specificity(infan:.mp. OR gestation:.tw. OR neonatal.tw.)
92.5(90.5-94.5)
92.6(92.4-92.8)
14.7(13.6-15.7)
92.6(92.4-92.8)
*Search strategies are reported using Ovid's search engine syntax for Medline (if a single search term is shown, this term outperformed two- and three-term combinations). Best sensitivity while keeping specificity ≥ 50%; Best specificity while keeping sensitivity ≥ 50%; Best Optimization of Sensitivity and Specificity is based on lowest possible absolute difference between sensitivity and specificity; mp = multiple posting—term appears in title, abstract, or subject heading; : = truncation; tw = textword (word or phrase appears in title or abstract).
†Total database has 49028 articles, of which 663 articles are relevant to neonatal medicine and 48365 are irrelevant to neonatal medicine.
‡n varies by row.
Obstetrics
The combination of terms "gestation:.tw. OR fetal.tw. OR pregnancy.tw." produced the best sensitivity of 82.0%, with a very high specificity of 97.1% for retrieving articles about obstetrics. The maximization of specificity (reaching almost 99%) with the single term "gestation:.tw." yielded a 1.8% increase in specificity but with a marked trade-off in sensitivity, which decreased to 52.0% (absolute decrease 30%).
Table 7
Combination of terms with the best sensitivity, best specificity, and best optimization of sensitivity and specificity for detecting studies about obstetrics (fetus) in Medline in 2000
Search Strategy*
Operating Characteristics†
Sensitivity, %
(95% CI)
(n = 516)
Specificity, %
(95% CI)
(n = 48512)
Precision, %‡
(95% CI)
Accuracy, %
(95% CI)
(n = 49028)
Best sensitivity(gestation:.tw. OR fetal.tw. OR pregnancy.tw.)
82.0(78.7-85.3)
97.1(97.0-97.3)
23.4(21.4-25.3)
97.0(96.9-97.1)
Best specificity(gestation:.tw.)
52.0(47.6-56.3)
98.9(98.8-99.0)
33.6(30.2-36.7)
98.4(98.3-98.5)
Best optimization of sensitivity and specificity(pregnancy.tw. OR fetal.tw. OR age:.tw.)
80.7(77.2-84.0)
79.3(78.9-79.7)
4.0(3.6-4.4)
79.3(79.0-79.7)
*Search strategies are reported using Ovid's search engine syntax for Medline (if a single search term is shown, this term outperformed two- and three-term combinations). Best sensitivity while keeping specificity ≥ 50%; Best specificity while keeping sensitivity ≥ 50%; Best Optimization of Sensitivity and Specificity is based on lowest possible absolute difference between sensitivity and specificity; : = truncation; tw = textword (word or phrase appears in title or abstract).
†Total database has 49028 articles, of which 516 articles are relevant to obstetrics and 48512 are irrelevant to obstetrics.
‡n varies by row.
Discussion
Our study shows that selected age-specific search strategies can achieve high retrieval of studies for age-specific populations. Our age-specific search strategies performed differently among the five specialties we investigated. The highest sensitivity and specificity were achieved for pediatric medicine (98% and 81.2%, respectively) and neonatal medicine (95.3% and 83.6%, respectively). This finding may be a result of these age groups being more precisely defined and that studies tend to be narrowly focused on them. Search strategies within obstetrics yielded a higher specificity (97.1%) than sensitivity (82%), indicating that this strategy was better at filtering out nonrelevant age-specific articles than retrieving them. The best performing strategy for optimizing sensitivity and specificity was achieved within neonatal medicine (92.5% and 92.6%, respectively). In all cases, precision was low, a consequence of searching in large multi-purpose databases. Future research is focusing on potential ways to improve precision without compromising sensitivity, for example, by searching in journal subsets.
A possible limitation to our study is the generalizability of our findings to other publication years as our data was collected in the year 2000. We believe, however, that our search strategies are robust because no major changes have been made to age-specific MeSH terms since the year 2000. Moreover, we have previously shown that search strategies developed in 1990 were robust when searching in 2000 [18]. Another potential limitation of our study is that our interrater agreement for classifying age content did not reach 100%. However, exceeding the level of agreement achieved in our study (> 80% beyond chance) is rarely done in diagnostic studies. The scope of journals investigated in our journal subset could be a limitation, but we have no indication that these search strategies would perform differently in other journal subsets aside from the precision values reported. Precision is affected by the prevalence of on-target articles within the database. Thus, our precision figures are presented as estimates of search strategy performance.
The utility of age-specific filters will vary according to the needs of clinicians and researchers who must weigh the consequences of using a sensitive or specific search. Although a sensitive search will not miss many relevant articles, such searches are less precise and entail time-consuming sorting through irrelevant articles. The narrower yield of a specific search will capture many relevant articles and take less weeding, but it has greater potential for missing key articles.
Search Examples
To illustrate the use of age-specific search strategies, if a geriatrician was looking for information about current treatment strategies for Huntington disease, she might begin her search by entering the content term "Huntington disease" in Medline, which would yield 5907 articles (Table 8).
Table 8
Example: best sensitivity (keeping specificity ≥ 50%) search strategies for detecting treatment studies in geriatric medicine (patients ≥ 65 years of age) in Medline (1996 to July week 3, 2005)
Search Strategy*
Content Term
Boolean Operator
Best Sensitivity Combination Strategy for Treatment Studies
Boolean Operator
Best Sensitivity Combination Strategy for Geriatric Medicine
Number of Articles
Huntington disease
-
-
-
-
5907
Huntington disease
AND
clinical trial.mp. OR clinical trial.pt. OR random:.mp. OR tu.xs.
-
-
901
Huntington disease
AND
clinical trial.mp. OR clinical trial.pt. OR random:.mp. OR tu.xs.
AND
exp adult†
483
*Search strategies are reported using Ovid's search engine syntax for Medline. mp = multiple posting—term appears in title, abstract, or subject heading; : = truncation; pt = publication type; tu = therapeutic use as a subheading; xs = exploded subheading; exp = explode—a search term that automatically includes closely related indexing terms.
†Outperformed two- and three-term combinations.
However, sifting through such a large number of articles would be time-consuming and many of these articles would not be relevant to treatment studies in geriatric medicine. By combining the content term "Huntington disease" with the most sensitive combination of terms for treatment studies (clinical trial.mp. OR clinical trial.pt. OR random:.mp. OR tu.xs.), the search can be narrowed to 901 articles. Further, by adding the most sensitive strategy for geriatric medicine (exp adult) to this search string with the Boolean operator AND, the search is refined to 483 articles, which is much more manageable than the original 5907 articles retrieved from searching the content term only. A sensitive search such as this would be an efficient beginning for researchers interested in conducting systematic reviews.
A more specific approach may be especially useful for physicians who do not have time to process an exhaustive search. In the above example, by combining the content word "Huntington disease" with the most specific search strategy for treatment studies [12], "randomized controlled trial.mp. OR randomized controlled trial.pt.", and the most specific search strategy for geriatric medicine, "aged, 80 and over.sh. OR age.tw.", the search yields five articles (Table 9). This is a dramatic reduction in the number of articles retrieved by searching the content term alone (5907 articles), but key articles can be missed.
Table 9
Example: best specificity (keeping sensitivity ≥ 50%) search strategies for detecting treatment studies in geriatric medicine (patients ≥ 65 years of age) in Medline (1996 to July week 3, 2005)
Search Strategy*
Content Term
Boolean Operator
Best Specificity Combination Strategy for Treatment Studies
Boolean Operator
Best Specificity Combination Strategy for Geriatric Medicine
Number of Articles
Huntington disease
-
-
-
-
5907
Huntington disease
AND
Randomized controlled trial.mp. OR randomized controlled trial.pt.
-
-
46
Huntington disease
AND
Randomized controlled trial.mp. OR randomized controlled trial.pt.
AND
aged, 80 and over.sh. OR of age.tw.
5
*Search strategies are reported using Ovid's search engine syntax for Medline. mp = multiple posting—term appears in title, abstract, or subject heading; pt = publication type; sh = subject heading; tw = textword (word or phrase appears in title or abstract).
Conclusion
Selected age-specific search strategies can enhance the retrieval of studies for clinicians and researchers who need information relevant for a well-defined age-category patient population. The optimal trade-off between sensitivity and specificity should be determined according to the needs of the searcher.

medline
medical subject headings
information storage and retrieval