Review of null hypothesis significance testing in the ophthalmic literature: are most ‘significant’ P values false positives?

P values associated with null hypothesis significance testing (NHST) are almost universal in the ophthalmic literature. A P value < 0.05 is traditionally considered ‘significant’. This concept may deflect further thought about the veracity of the results. P values influence the publishability of the data and have flow‐on effects for funding success and the direction of future research. Despite their importance, the problems inherent in P values have been recognized since their inception, and in more recent years have been increasingly highlighted in some scientific fields. In this review, we aim to bring the problems associated with P values and NHST to the attention of the ophthalmic research community. We do not offer a universal solution to the problem of determining the veracity of a scientific claim; however, we demonstrate the need for caution in interpreting ‘significant’ P values by performing a Bayesian re‐analysis of t‐tests in the ophthalmic literature.     

Serotonin transporter gene polymorphism in irritable bowel syndrome

OBJECTIVES: Serotonin is a key mediator of intestinal peristalsis, and after it is secreted, it is effectively cleansed from the neuronal gap by means of a high affinity substance called serotonin transporter (SERT), which depends on the Na+ and Cl- ions localized in the presynaptic neuronal membranes. The aim of this study was to investigate SERT polymorphism in patients with irritable bowel syndrome (IBS). METHODS: SERT gene polymorphism was assessed by polymerase chain reaction on DNA chains obtained from leukocytes in serum samples from 54 patients diagnosed with IBS and 91 healthy subjects. The polymorphism of two regions (variable number tandem repeats and the SERT gene-linked polymorphic region [5-HTTLPR]) of SERT was assessed. RESULTS: SERT polymorphisms were found to be similar in healthy subjects and IBS patients (p > 0.05). IBS patients were divided into three groups: diarrhea predominant (n = 18), constipation predominant (n = 26), and alternating diarrhea and constipation (n = 10). These groups were compared with respect to gene polymorphism, and it was found that the 5-HTTLPR allele S/S genotype occurred with greater frequency in the constipation predominant group than in the other two subgroups (p < 0.05), and L/S genotype frequency in the diarrhea predominant group was higher than those in the constipation and control groups. CONCLUSIONS: No relationship was found between IBS and SERT gene polymorphism. It is conceivable that the presence of the S/S genotype in IBS patients carries an increased risk of the constipation predominant type of IBS, whereas the presence of the 5-HTTLPR allele L/S genotype carries an increased risk of the diarrhea predominant type.     

Portal vein thrombosis in cirrhotics: related with anticardiolipin antibodies?

BACKGROUND/AIMS: To evaluate the relationship of antiphospholipid antibodies and portal vein thrombosis in cirrhotics. METHODOLOGY: 22 cirrhotics without portal vein thrombosis (Group I), 18 with portal vein thrombosis (Group II) and 20 healthy controls (Group III) were enrolled. Anticardiolipin IgG and IgM antibody concentrations were measured by ELISA and lupus anticoagulant by clotting. Groups were compared according to sex, age, etiology of cirrhosis, prior intraabdominal surgery, Child groups, anticardiolipin IgG, IgM and lupus anticoagulant. Then for all the 40 cirrhotics (Group IV) correlation was tested between anticardiolipin IgM, IgG, lupus anticoagulant and Child groups, etiology of cirrhosis, sex and prior surgery. RESULTS: In Group I, anticardiolipin IgG concentration was 15.3 (15.9) GPL)/mL and IgM was 8.6 (6.5) MPL/mL. In 6 (27.27%) anticardiolipin IgG, in 6 (27.27%) IgM and in 2 (9.09%) both were high. Lupus anticoagulant was positive in 7 (31.81%). In Group II anticardiolipin IgG concentration was 26.3 (14.7) GPL/mL and IgM was 15.1 (7.2) MPL/mL. In 10 (55.55%) anticardiolipin IgG, in 13 (72.22%) IgM and in 9 (50%) both were high. Lupus anticoagulant was positive in 5 (27.77%). In Group III lupus anticoagulant was positive in 1 (0.5%). Anticardiolipin IgG was 10.3 (5.9) GPL/mL, IgM 5 (3.6) MPL/mL anticardiolipin IgM level was high in 1 (0.5%). Group I and II were similar with respect to lupus anticoagulant, Child groups, prior intraabdominal surgery and etiology of cirrhosis. For anticardiolipin IgG and IgM there was a significant difference between Group I and II, I and III and II and III. In Group IV there was no correlation between prior abdominal surgery, Child groups, sex, etiology and anticardiolipin IgG, IgM or lupus anticoagulant. CONCLUSIONS: Anticardiolipin antibody concentrations were significantly higher in cirrhotics with portal vein thrombosis. Thus anticardiolipin antibodies may play a role in the development of portal vein thrombosis in cirrhosis.     

PECAM-1 gene polymorphisms and soluble PECAM-1 level in rheumatoid arthritis and systemic lupus erythematosus patients: any link with clinical atherosclerotic events?

Genetic polymorphisms of platelet endothelial cell adhesion molecule-1 (PECAM-1) were found to play roles in atherosclerotic events. We determined PECAM-1 polymorphisms, soluble PECAM-1, and CD40L levels in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and evaluated their associations with clinical atherosclerotic complications. We included 100 RA patients, 81 SLE patients, and 94 healthy controls. The clinical features about the patients were obtained from medical records. Past cardiovascular complications were recorded. The most frequent gene polymorphisms of PECAM-1 were studied in our genetics laboratory. Soluble PECAM-1 and CD40L levels in serum were determined with ELISA. The frequencies of 373C (rs668) and 1688A (rs12953) alleles were higher in RA patients when compared to controls (p values, 0.028 and 0.016). RA and SLE patients had significantly higher allele frequencies for 2008A (rs1131012) when compared to controls (p values, 0.016 and 0.001). SLE patients had significantly more frequent AA genotype for rs1131012 polymorphism than RA patients and controls (p values, 0.007 and <0.001). Soluble PECAM-1 level was significantly higher in RA patients than in SLE patients and healthy controls (p values <0.001). Atherosclerotic complications were more frequent in SLE patients with AG genotype (rs12953) than those with AA genotype (p?=?0.021). SLE patients with CC genotype (rs668) had a significantly lower frequency of atherosclerotic complications than those with CG genotype (p?=?0.045). Nevertheless, in multivariate analysis, there was no association between genotype and atherosclerotic complications. We found associations between various PECAM-1 polymorphisms in RA and SLE; PECAM-1 and soluble CD40 ligand (sCD40L) levels were significantly higher in RA patients than in SLE and control groups. PECAM-1 polymorphisms in SLE were protective against atherosclerotic complications.     

Quadruple salivary duct diversion for drooling in cerebral palsy

Drooling complicates many neurologic disorders including cerebral palsy. It is socially debilitating for the patient and very tedious for the caregiver. Surgical treatment consists mainly of ablative (excision/ligation) or physiological (diversion) methods; combined techniques have also been proposed. We have applied bilateral diversion of both submandibular and parotid ducts in 12 cerebral palsy patients (age range, 7-15 years). Preoperative drooling severity was grade 4/5 in 10 cases and grade 5/5 in 2 of the cases. All patients underwent physiotherapy for a minimum of 6 months and were consulted with a dentist, otolaryngologist, and a speech therapist before surgery. No bleeding, hematoma, or infection has been observed in any of the patients. Two patients had early postoperative tongue edema that regressed with conservative treatment. All patients except one regressed to grade 2/5 drooling by the first postoperative month. In 1 patient who had previously been classified as grade 5/5, surgery provided limited improvement with only 1 grade of step-down. Satisfactory results for the patients and their families could be achieved and sustained for a median 18 months (7-20 months) of follow-up. In conclusion, the quadruple duct diversion method is an effective physiological surgical method in the control of drooling in cerebral palsy.