Objective: Medical decision-making is often uncertain. The positive predictive value (PPV) and negative predictive value (NPV) are conditional probabilities characterizing diagnostic tests and assessing diagnostic interventions in clinical medicine and epidemiology. The PPV is the probability that a patient has a specified disease, given a positive test result for that disease. The NPV is the probability that a patient does not have the disease, given a negative test result for that disease. Both values depend on disease incidence or prevalence, which may be highly uncertain for unfamiliar diseases, epidemics, etc. Probability distributions for this uncertainty are usually unavailable. We develop a non-probabilistic method for interpreting PPV and NPV with uncertain prevalence.
Methods: Uncertainty in PPV and NPV is managed with the non-probabilistic concept of robustness in info-gap theory. Robustness of PPV or NPV estimates is the greatest uncertainty (in prevalence) at which the estimate’s error is acceptable.
Results: Four properties are demonstrated. Zeroing: best estimates of PPV or NPV have no robustness to uncertain prevalence; best estimates are unreliable for interpreting diagnostic tests. Trade-off: robustness increases as error increases; this trade-off identifies robustly reliable error in PPV or NPV. Preference reversal: sometimes sub-optimal PPV or NPV estimates are more robust to uncertain incidence or prevalence than optimal estimates, motivating reversal of preference from the putative optimum to the sub-optimal estimate. Trade-off between specificity and robustness to uncertainty: the robustness increases as test-specificity decreases. These four properties underlie the interpretation of PPV and NPV.
Conclusions: The PPV and NPV assess diagnostic tests, but are sensitive to lack of knowledge that generates non-probabilistic uncertain prevalence and must be supplemented with robustness analysis. When uncertainties abound, as with unfamiliar diseases, assessing robustness is critical to avoiding erroneous decisions.
Pancytopenia is defined as a reduction in red blood cells, white blood cells, and platelets, and can pose as a diagnostic challenge due to the multitude of causes. Myxedema coma is the manifestation of severe untreated hypothyroidism. This case report presents a rare instance of myxedema coma-associated pancytopenia in a 53-year-old man with a history of untreated hypothyroidism. The patient presented with altered mental status and vital instability, and on further workup was found to have pancytopenia. During his hospital stay his symptomatic hypothyroidism was identified, and he was treated with intravenous levothyroxine, hydrocortisone, and supportive care. The patient’s clinical status improved gradually, with normalized blood counts upon discharge. This case underscores the significance of considering myxedema coma in the differential diagnosis of pancytopenia, especially in older patients with limited healthcare access. Increased awareness of this association can aid clinicians in timely diagnosis and management, preventing potential complications associated with untreated hypothyroidism.
Background and Objective: Chronic low back pain disability (CLBPD) is a syndrome that includes pain, disability, emotional impairments, and social problems. The study was conducted to examine the effect of an inpatient rehabilitation program on the performance of everyday life tasks (daily activities), and report on pain in CLBPD patients with primary activities of daily living (ADL) deficits.
Methods: In a retrospective cohort study, demographic and clinical data were retrieved from records of inpatients admitted consecutively to the program. Scores of the Spinal Pain Independence Measure (SPIM) and of changes in reported pain levels were used to assess improvement in the performance of daily activities and pain reduction. T-tests were used to assess the significance of score changes. Spearman’s correlations and analysis of variance were used to assess relationships of SPIM gain and affecting factors.
Results: Ninety-nine patients were included. Daily task performance improved in 71 patients (71.7%). The SPIM score increased from 48.7 (SD 16.3) at admission to the rehabilitation program to 57.8 (SD 12.5) at discharge (P<0.001). The SPIM score at admission negatively affected SPIM gain (P<0.001). The SPIM gain was significant for admission SPIM scores of 50 or lower (P<0.05), but differences in SPIM scores were not as noticeable for patients with admission SPIM scores above 50. Relief in pain was reported in 59 patients (59.6%) and was not associated with function.
Conclusions: The multidisciplinary rehabilitation program, which improved function and provided limited pain relief in inpatients with CLBPD primary ADL deficits, can be effective for the most severe CLBPD cases.
Objective: A single layer of tightly spaced cells, known as the endothelium, rests on the posterior side of the cornea. This endothelium regulates the stroma’s relative dehydration, which is essential for corneal clarity. Cell therapy is an innovative method being used to repair various corneal abnormalities. Mesenchymal stem cells (MSCs) are now one of the most significant types of stem cells scientists have studied. This study aimed to evaluate the role of MSCs for corneal endothelial regeneration.
Methods: A systematic review was performed by searching for articles from reputable databases with many study-type references, including PubMed, Cochrane Library, Science Direct, and Google Scholar, up to January 2024. The resulting data were displayed using the 2020 PRISMA flowchart and evaluated using the PRISMA 2020 checklist. Most of the included studies were in vivo and used topical application and anterior chamber injection as the administration routes.
Results: Based on the findings of this review, MSCs increased corneal endothelial cell density, improved the defect area and corneal transparency, facilitated endothelial cell regeneration and wound healing, and decreased neovascularization and corneal pro-inflammatory cytokines as compared to controls.
Conclusion: Administration of MSCs into the anterior chamber could increase regeneration and proliferation of corneal endothelial tissue.
Background: Hyperinsulinemia and insulin resistance occurs in obese patients with primary hypertension independent of diabetes and obesity. This study was aimed at assessing serum fasting insulin levels, the homeostatic model assessment for insulin resistance (HOMA-IR), and serum lipid levels in non-obese patients with primary hypertension when compared to normotensive subjects.
Methods: This observational study comprised 100 patients over 18 years of age, divided into two groups. The hypertensive group comprised non-obese patients with primary hypertension (n=50); the normotensive group comprised normotensive age- and sex-matched individuals (n=50). Patients with diabetes, impaired fasting glucose, obesity, and other causative factors of insulin resistance were excluded from the study. Serum fasting insulin levels and fasting lipid profiles were measured, and insulin resistance was calculated using HOMA-IR. These data were compared between the two groups. Pearson’s correlation coefficient was used to assess the extent of a linear relationship between HOMA-IR and to evaluate the association between HOMA-IR and systolic and diastolic blood pressures.
Results: Mean serum fasting insulin levels (mIU/L), mean HOMA-IR values, and fasting triglyceride levels (mg/dL) were significantly higher in the hypertensive versus normotensive patients (10.32 versus 6.46, P<0.001; 1.35 versus 0.84, P<0.001; 113.70 versus 97.04, P=0.005, respectively). The HOMA-IR levels were associated with systolic blood pressure (r value 0.764, P=0.0005).
Conclusion: We observed significantly higher fasting insulin levels, serum triglyceride levels, and HOMA-IR reflecting hyperinsulinemia and possibly an insulin-resistant state among primary hypertension patients with no other causally linked factors for insulin resistance. We observed a significant correlation between systolic blood pressure and HOMA-IR.
Background: Early thyroid cancers have excellent long-term outcomes, yet the word “cancer” draws unnecessary apprehension. This study aimed to define when the recommendations for observation and surveillance may be extended to early thyroid cancers at the population level.
Methods: Non-metastasized thyroid cancers ≤40 mm diameter were identified from the 1975–2016 Surveillance, Epidemiology and End Results (SEER) database. Causes of death were compared across demographic data. Disease-specific outcomes were compared to the age-adjusted healthy United States (US) population. Survival estimates were computed using Kaplan–Meier and compared using the Cox proportional hazard model. Dynamic benchmarks impacting disease-specific overall survival were determined by decision tree modeling and tested by the Cox model.
Results: Of the 28,728 thyroid cancers included in this study, 98.4% underwent some form of thyroid-specific treatment and were followed for a maximum of 10.9 years. This group had a 4.3% mortality rate at the end of follow-up (10.9 years maximum), with 13 times more deaths attributed to competing risks rather than thyroid cancer (stage T1a versus stage T1b, P=1.000; T1 versus T2, P<0.001). Among the untreated T1a or T1b tumors, the risk of disease-specific death was 21 times lower than death due to other causes. There was no significant difference between T1a and T1b tumors nor across sex. The age-adjusted risk of death for the healthy US population was higher than the population with thyroid cancer. Dynamic categorization demonstrated worsening outcomes up to 73 years, uninfluenced by sex or tumor size. For patients over 73 years of age, only tumors >26 mm impacted outcomes.
Conclusion: Based on the current data, T1a and T1b nodules have similar survival outcomes and are not significantly impacted even when left untreated. Multi-institutional prospective studies are needed to confirm these findings so that current observation and surveillance recommendations can be extended to certain T1 thyroid nodules.
Background: Patellar instability comprises a group of pathologies that allow the patella to move out of its trajectory within the trochlear groove during walking. Symptomatic patients who need surgery commonly undergo soft tissue procedures such as medial patellofemoral ligament repair to strengthen the ligaments that hold the patella in place. However, soft-tissue repairs may be insufficient in patients suffering from patellar maltracking, which is characterized by an unbalanced gliding of the patella within its route. In these patients, a different approach is advised. We aim to provide the mid-term clinical outcomes of the Fulkerson distal realignment operation in selected patients with non-traumatic patellar maltracking.
Methods: The clinical outcomes of the Fulkerson distal realignment operation performed in 22 knees of 21 patients were evaluated by a self-administered subjective International Knee Documentation Committee (IKDC) score and the Tegner–Lysholm knee scoring scale.
Results: Before surgery, the median IKDC score was 52, and the median Tegner–Lysholm score was 56. Following surgery (mean follow-up 48 months, range 24–156), the median IKDC and the Tegner–Lysholm scores were 67 and 88, respectively. The improvement was statistically significant (P=0.001 and P=0.002 for IKDC and Tegner–Lysholm scores, respectively). Associated procedures included patella microfracture due to grade III–IV cartilage lesion (International Cartilage Repair Society grading system) in four patients, retinacular releases in three patients, medial capsular augmentations in two patients, and medial patellofemoral ligament reconstruction in two patients. One patient with Ehlers–Danlos disease required excessive medialization of the tibial tuberosity. Surgery-related complications occurred in three patients.
Discussion: Surgical correction of patellar maltracking with Fulkerson distal realignment combined with associated procedures in individual patients was associated with an increase in subjective and functional clinical scores at medium-term follow-up. Particular attention should address pathologies associated with patellar maltracking and managed accordingly.
Level of evidence: 4c (case series).
Background: With the availability of coronavirus disease 2019 (COVID-19) vaccine, concerns have been raised regarding pre-vaccination seroprevalence in healthcare workers (HCW). This study examines the seroprevalence of HCW at an Israeli tertiary medical center before first BNT162b2 vaccination.
Methods: This was a retrospective observational study. Before vaccination, HCW at our center were offered serological testing. Data on their epidemiological, workplace, and quarantine history were collect¬ed. The SARS-CoV-2 IgG assay was performed pre-vaccination.
Results: A total of 4,519 (82.5%) of the HCW were tested. Of these, 210 were seropositive; 101 had no known history of COVID-19. Of the 101 asymptomatic HCW, only 3 (3%) had worked at COVID-19 depart¬ments, and 70 (69.3%) had not been previously quarantined. Positive serology was similarly distributed across age groups, and about 40% had no children. Nearly half of the HCW tested were administrative and service staff. Overall, seropositive tests were associated with having no children (OR 1.42, 95% CI 1.06–1.89; P=0.0218), history of having been quarantined without proof of disease (OR 6.04, 95% CI 4.55–8.01; P<0.001), and Arab ethnicity (OR 3.36, 95% CI 2.54–4.43; P<0.001). Seropositivity was also more prevalent in members of the administration compared to other sectors, medical and paramedical, who are exposed to patients in their daily work (OR 1.365, 95% CI 1.02–1.82; P=0.04).
Conclusions: The low percentage of asymptomatic COVID-19 among our HCW may reflect the high compliance to personal protective equipment use despite treating hundreds of COVID-19 patients. The relatively high number of childless seropositive HCW could reflect misconceptions regarding children as a main source of infection, leading to carelessness regarding the need for appropriate out-of-hospital protection.
Breast cancer is a common malignancy and a common cause of cancer-related mortality in women. Pre-treatment workup of breast cancer does not routinely include positron emission tomography scans. We aimed to review cases of women with breast cancer and a synchronous second primary malignancy. We present three cases of women with non-metastatic cancer in whom a synchronous second primary malignancy was found. Synchronous, second primary malignancies which were identified included rectal cancer, gastrointestinal stromal tumor, and non-small cell lung cancer. All second primary malignancies were identified by a PET-CT scan. In conclusion, PET-CT may be used for detection of secondary primary malignancies in select breast cancer patients.
Objectives: Anti-osteoporotic drugs (AOD) are essential for secondary prevention of osteoporotic fracture (OF) in patients with established osteoporosis. However, data about AOD utilization rates are scarce among patients with OF. This study was therefore aimed at determining the AOD utilization rates among those particularly vulnerable patients.
Materials and Methods: This cross-sectional study followed the medical records of patients with OF starting from their first OF diagnosis date. Each patient’s preventive osteoporosis treatments (vitamin D, calcium+vitamin D) and AOD utilization rate were recorded for a 12-month period following OF diagnosis.
Results: A total of 210 patients (168 females, mean age: 67.8±11.9 years; 42 males, mean age 62.4±16.1 years) were enrolled in the study. Of these, 65.7% (n=138) did not use any medication for primary protection against osteoporosis before OF diagnosis. The ratio of patients not using any type of medication for secondary prevention after OF increased from 26.5% to 51% during a 12-month period. In addition, by one year following diagnosis, AOD usage rate had decreased from 62.3% to 41.3%.
Conclusion: The AOD usage rates for secondary prevention of OF were insufficient, and cessation rates were high. Identification of factors associated with decreased AOD utility rates will provide important information for guiding patient follow-up in order to reduce the occurrence of OF.
