The risk of oesophago-gastric cancer in symptomatic patients in primary care: a large case–control study using electronic records

Background:

Over 15 000 new oesophago-gastric cancers are diagnosed annually in the United Kingdom, with most being advanced disease. We identified and quantified features of this cancer in primary care.

Methods:

Case–control study using electronic primary-care records of the UK patients aged ⩾40 years was performed. Cases with primary oesophago-gastric cancer were matched to controls on age, sex and practice. Putative features of cancer were identified in the year before diagnosis. Odds ratios (ORs) were calculated for these features using conditional logistic regression, and positive predictive values (PPVs) were calculated.

Results:

A total of 7471 cases and 32 877 controls were studied. Sixteen features were independently associated with oesophago-gastric cancer (all P<0.001): dysphagia, OR 139 (95% confidence interval 112–173); reflux, 5.7 (4.8–6.8); abdominal pain, 2.6 (2.3–3.0); epigastric pain, 8.8 (7.0–11.0); dyspepsia, 6 (5.1–7.1); nausea and/or vomiting, 4.9 (4.0–6.0); constipation, 1.5 (1.2–1.7); chest pain, 1.6 (1.4–1.9); weight loss, 8.9 (7.1–11.2); thrombocytosis, 2.4 (2.0–2.9); low haemoglobin, 2.4 (2.1–2.7); low MCV, 5.2 (4.2–6.4); high inflammatory markers, 1.7 (1.4–2.0); raised hepatic enzymes, 1.3 (1.2–1.5); high white cell count, 1.4 (1.2–1.7); and high cholesterol, 0.8 (0.7–0.8). The only PPV >5% in patients ⩾55 years was for dysphagia. In patients <55 years, all PPVs were <1%.

Conclusion:

Symptoms of oesophago-gastric cancer reported in secondary care were also important in primary care. The results should inform guidance and commissioning policy for upper GI endoscopy.     

Postural configuration does not alter unperturbed or perturbed reach movement kinematics

This study investigated whether postural configuration has a significant effect upon the kinematics of arm movements when humans performed unconstrained reach movements to visual targets. Eight subjects were required to reach to static visual targets (unperturbed REACH movements) or correct reach movements when the position of a target unexpectedly changed during the execution of a planned movement (perturbed reaches, or online corrections, OC). Subjects were required to execute REACH and OC movements in sitting and standing (STAND) positions. The height of the targets, distance from the right shoulder (acromion) and eccentricity in terms of the body midline were standardized between the two postural conditions before movements begun. Unperturbed REACH movements were executed to a central target placed at 130 % of outstretched arm length, along the midline (0°). Perturbed (OC) movements involved subjects initiating an arm movement to the 0° target upon its illumination. Two hundred milliseconds after the onset of the hand movement, the 0° target was extinguished and the target at 60° to the right of the midline (still at 130 % outstretched arm distance) illuminated. Subjects had to correct their reach movements online to the new target. Results demonstrated that, despite evident differences in postural kinematics between the four experimental conditions (e.g. pelvis obliquity and trunk/pelvis rotation), postural configuration had little or no effect upon the endpoint kinematics of the finger. Most importantly, the STAND position, with its greater postural constraints, did not affect the time taken to initiate an OC, nor did it lengthen the time taken to complete the REACH or OC movements. Our results suggest, therefore, that postural constraints are accounted for by the central nervous system when executing complex arm reaching movements.     

Clinical features of metastatic cancer in primary care: a case–control study using medical records

Background

How metastatic cancer initially presents is largely unknown.

Aim

To identify clinical features of metastatic cancer in primary care.

Design and setting

Case–control study in 11 general practices in Devon, UK.

Method

Cases of patients who had died with metastatic breast, colorectal, or prostate cancer were selected. In addition, two control groups were formed of patients with the same primary cancer but without metastases (‘cancer controls’) and patients without cancer (‘healthy controls’), matched for age, sex, and practice. All symptoms, signs, and laboratory test abnormalities in the year before metastasis were identified. The primary analysis used conditional logistic regression.

Results

In total, 162 cases, 152 cancer controls, and 145 healthy controls were studied. Common symptoms associated with cancer were: vomiting, 40 (25%) cases and 13 (9%) cancer controls (multivariable odds ratio [OR] 3.5, 95% confidence interval [CI] = 1.3 to 9.4, P = 0.011); low back pain, 38 (24%) cases and 17 (11%) cancer controls (OR 2.5, 95% CI = 1.1 to 5.6, P = 0.032); loss of appetite, 32 (20%) cases and nine (6%) cancer controls (OR 4.0, 95% CI = 1.2 to 13.2, P = 0.021); and shoulder pain, 27 (17%) cases and eight (5%) cancer controls (OR 5.3, 95% CI = 1.6 to 18, P = 0.007). Groin pain was uncommon, but strongly associated (16 [10%] cases and one [1%] cancer control [OR 10, 95% CI = 1.2 to 82, P = 0.032]), as was pleural disease (nine [6%] cases and one [1%] cancer control [OR 10, 95% CI = 1.1 to 92, P = 0.038]).

Conclusion

These features of disseminated cancer have been reported before in studies from secondary care, but the scarcity of specific symptoms (such as local pain) and the fairly common occurrence of non-specific symptoms (vomiting and loss of appetite) is important and may explain delays in the diagnosis of metastases.     

Imatinib mesylate resistance through BCR-ABL independence in chronic myelogenous leukemia

Imatinib mesylate (IM) binds to the BCR-ABL protein, inhibiting its kinase activity and effectively controlling diseases driven by this kinase. IM resistance has been associated with kinase mutations or increased BCR-ABL expression. However, disease progression may be mediated by other mechanisms that render tumor cells independent of BCR-ABL. To demonstrate this potential, IM-resistant cells were found in chronic myelogenous leukemia patients with continuous BCR-ABL gene expression but undetectable BCR-ABL protein expression. These cells were unresponsive to IM and acquired BCR-ABL-independent signaling characteristics. IM resistance in some patients may be mediated through loss of kinase target dependence.     

Neck muscle fatigue and postural control in patients with whiplash injury.

OBJECTIVES: To examine if patients with whiplash injury show identifiable increases in neck muscle fatigability and associated increase in postural body sway after contractions of dorsal neck muscles, and if physiotherapy treatment reduces these effects. METHODS: Sway was measured during stance in 13 patients before and after 5 min of isometric dorsal neck muscle contractions and after recovery, pre- and post-physiotherapy, using a force platform. Amplitude and median frequency of neck muscle EMG were calculated during the contracting period. After each stance trial, patients gave a subjective score of sway. RESULTS: Pre-treatment, seven patients showed EMG signs of fatigue (increases in amplitude, decreases in median frequency) and increases in sway (eyes closed) after contractions. The other patients showed neither fatigue nor increased sway. Post-treatment, no signs of fatigue or imbalance were recorded in all patients, for the same levels of muscle contraction. CONCLUSIONS: As in normal human subjects, increases in sway are associated with signs of neck muscle fatigue in some whiplash injury patients. Physiotherapy decreases the susceptibility to fatigue of neck muscles and is an effective choice of treatment of subjective instability and sway. SIGNIFICANCE: This study demonstrates a pathophysiological link between neck muscle fatigue and impaired postural control, and also that physiotherapy can relieve symptoms and signs of impaired neck muscle function by reducing muscle fatigability.     

Spread of infection, in an animal model, after intramedullary nailing of an infected external fixator pin track.

Implant sepsis. due to previous external fixator pin track infection, is the most common complication of secondary intramedullary (IM) nailing of the tibia. We have developed an animal model, which allows different treatment methods to be studied. Using an established ovine model of a pin track infection, Staphylococcus aureus was used to infect the external fixator pins, two weeks prior to reamed IM nailing. In the control group, the animals were killed at a mean of 10.5 days following nailing, when widespread infection was evident, with septic arthritis, abscess formation, and infection of the entire length of the tibia in all six animals. In the treatment group, before IM nailing, the pin sites were debrided, and both local and systemic antibiotics were administered. All surgical wounds healed without evidence of infection, 4 of the 6 animals survived for 28 days, and bacteria were only isolated from 1 of the 6 implants. Treatment was successful at reducing, but not eliminating, infection after secondary nailing.     

“Just like talking to someone about like shit in your life and stuff,and they help you”: Hopes and expectations for therapy among depressed adolescents

Objective: To explore hopes and expectations for therapy among a clinical population of depressed adolescents. Method: As part of a randomized clinical trial, 77 adolescents aged 11–17, with moderate to severe depression, were interviewed using a semi-structured interview schedule. The interviews were analysed qualitatively using framework analysis. Results: The findings are reported around five themes: “the difficulty of imagining what will happen in therapy,” “the ‘talking cure,’” “the therapist as doctor,” “therapy as a relationship,” and “regaining the old self or developing new capacities.” Conclusions: Differing expectations are likely to have implications for the way young people engage with treatment, and failure to identify these expectations may lead to a risk of treatment breakdown.     

Ballistic research techniques: visualizing gunshot wounding patterns

International Journal of Legal Medicine - There are difficulties associated with mapping gunshot wound (GSW) patterns within opaque models. Depending on the damage measurement parameters required,...     

Avermectins, New Family of Potent Anthelmintic Agents: Producing Organism and Fermentation

The avermectins are a complex of chemically related agents which exhibit extraordinarily potent anthelmintic activity. They are produced by a novel species of actinomycete, NRRL 8165, which we have named Streptomyces avermitilis. The morphological and cultural characteristics which differentiate the producing organism from other species are described. The avermectins have been identified as a series of macrocyclic lactone derivatives which, in contrast to the macrolide or polyene antibiotics, lack significant antibacterial or antifungal activity. The avermectin complex is fully active against the gastrointestinal nematode Nematospiroides dubius when fed to infected mice for 6 days at 0.0002% of the diet. Fermentation development, including medium modification and strain selection, resulted in increasing the broth yields from 9 to 500 mug/ml.