Time-dependent NNT — MCQs

10 questions

A 66-year-old gentleman presents to a new primary care physician to establish care after a recent relocation. His past medical history is significant for gout, erectile dysfunction, osteoarthritis of bilateral knees, mitral stenosis, and diabetic peripheral neuropathy. He denies any past surgeries along with the use of any tobacco, alcohol, or illicit drugs. He has no known drug allergies and cannot remember the names of the medications he is taking for his medical problems. He states that he has recently been experiencing chest pain with strenuous activities. What part of the patient's medical history must be further probed before starting him on a nitrate for chest pain?

A researcher is trying to determine whether a newly discovered substance X can be useful in promoting wound healing after surgery. She conducts this study by enrolling the next 100 patients that will be undergoing this surgery and separating them into 2 groups. She decides which patient will be in which group by using a random number generator. Subsequently, she prepares 1 set of syringes with the novel substance X and 1 set of syringes with a saline control. Both of these sets of syringes are unlabeled and the substances inside cannot be distinguished. She gives the surgeon performing the surgery 1 of the syringes and does not inform him nor the patient which syringe was used. After the study is complete, she analyzes all the data that was collected and performs statistical analysis. This study most likely provides which level of evidence for use of substance X?

You are reading through a recent article that reports significant decreases in all-cause mortality for patients with malignant melanoma following treatment with a novel biological infusion. Which of the following choices refers to the probability that a study will find a statistically significant difference when one truly does exist?

Background: Beta-blockers reduce mortality in patients who have chronic heart failure, systolic dysfunction, and are on background treatment with diuretics and angiotensin-converting enzyme inhibitors. We aimed to compare the effects of carvedilol and metoprolol on clinical outcome. Methods: In a multicenter, double-blind, and randomized parallel group trial, we assigned 1,511 patients with chronic heart failure to treatment with carvedilol (target dose 25 mg twice daily) and 1,518 to metoprolol (metoprolol tartrate, target dose 50 mg twice daily). Patients were required to have chronic heart failure (NYHA II-IV), previous admission for a cardiovascular reason, an ejection fraction of less than 0.35, and to have been treated optimally with diuretics and angiotensin-converting enzyme inhibitors unless not tolerated. The primary endpoints were all-cause mortality, the composite endpoint of all-cause mortality, or all-cause admission. Analysis was done by intention to treat Findings: The mean study duration was 58 months (SD 6). The mean ejection fraction was 0.26 (0.07) and the mean age was 62 years (11). The all-cause mortality was 34% (512 of 1,511) for carvedilol and 40% (600 of 1,518) for metoprolol (hazard ratio 0.83 [95% CI 0.74-0.93], p = 0.0017). The reduction of all-cause mortality was consistent across predefined subgroups. Incidence of side effects and drug withdrawals did not differ by much between the 2 study groups. Which of the following represents the number of patients needed to treat to save one life?

A 57-year-old woman with type 2 diabetes mellitus comes to the physician for a follow-up examination. She previously had been compliant with her diet and medication but has had a 5-kg (11-lb) weight gain since the last visit 6 months ago. She reports that she often misses doses of her metformin. Her hemoglobin A1c is 9.8%. Which of the following is the most appropriate course of action?

A 55-year-old male is started on nitrate therapy for treatment of stable angina. He experiences significant and immediate relief of his symptoms within minutes of starting therapy. Approximately 48 hours after initiating this new medication, he notes return of chest pain and pressure with exertion that no longer responds to continued nitrate use. Which of the following 24-hour dosing schedules would most likely explain this patient's response to nitrate treatment?

An epidemiologist is evaluating the efficacy of Noxbinle in preventing HCC deaths at the population level. A clinical trial shows that over 5 years, the mortality rate from HCC was 25% in the control group and 15% in patients treated with Noxbinle 100 mg daily. Based on this data, how many patients need to be treated with Noxbinle 100 mg to prevent, on average, one death from HCC?

You are currently employed as a clinical researcher working on clinical trials of a new drug to be used for the treatment of Parkinson's disease. Currently, you have already determined the safe clinical dose of the drug in a healthy patient. You are in the phase of drug development where the drug is studied in patients with the target disease to determine its efficacy. Which of the following phases is this new drug currently in?

In a randomized controlled trial studying a new treatment, the primary endpoint (mortality) occurred in 14.4% of the treatment group and 16.7% of the control group. Which of the following represents the number of patients needed to treat to save one life, based on the primary endpoint?

Q10

You are reviewing raw data from a research study performed at your medical center examining the effectiveness of a novel AIDS screening examination. The study enrolled 250 patients with confirmed AIDS, and 240 of these patients demonstrated a positive screening examination. The control arm of the study enrolled 250 patients who do not have AIDS, and only 5 of these patients tested positive on the novel screening examination. What is the NPV of this novel test?

Time-dependent NNT US Medical PG Practice Questions and MCQs

Question 1: A 66-year-old gentleman presents to a new primary care physician to establish care after a recent relocation. His past medical history is significant for gout, erectile dysfunction, osteoarthritis of bilateral knees, mitral stenosis, and diabetic peripheral neuropathy. He denies any past surgeries along with the use of any tobacco, alcohol, or illicit drugs. He has no known drug allergies and cannot remember the names of the medications he is taking for his medical problems. He states that he has recently been experiencing chest pain with strenuous activities. What part of the patient's medical history must be further probed before starting him on a nitrate for chest pain?

A. Erectile dysfunction (Correct Answer)
B. Diabetic peripheral neuropathy
C. Gout
D. Arthritis
E. Mitral stenosis

Explanation: ***Erectile dysfunction*** - Patients often take **phosphodiesterase-5 (PDE5) inhibitors** (e.g., sildenafil, tadalafil) for erectile dysfunction, which are absolutely contraindicated with nitrates. - **Co-administration** can lead to a severe and potentially fatal drop in blood pressure due to enhanced vasodilation. *Diabetic peripheral neuropathy* - While important for overall health assessment, **diabetic peripheral neuropathy** does not directly contraindicate the use of nitrates for chest pain. - It might influence medication choices if a patient has orthostatic hypotension, but not a direct contraindication. *Gout* - **Gout** is a joint condition and has no direct contraindication with nitrate use. - Medications for gout, such as allopurinol or colchicine, do not interact adversely with nitrates. *Arthritis* - **Arthritis** (including osteoarthritis mentioned) is a musculoskeletal condition and does not contraindicate nitrate therapy. - Pain management for arthritis does not typically involve drugs that interact dangerously with nitrates. *Mitral stenosis* - While **mitral stenosis** can affect cardiac function and hemodynamics, it is generally not an absolute contraindication to nitrate use. - Nitrates can even be used cautiously in **mitral stenosis** to manage angina, though their use requires careful monitoring of preload.

Question 2: A researcher is trying to determine whether a newly discovered substance X can be useful in promoting wound healing after surgery. She conducts this study by enrolling the next 100 patients that will be undergoing this surgery and separating them into 2 groups. She decides which patient will be in which group by using a random number generator. Subsequently, she prepares 1 set of syringes with the novel substance X and 1 set of syringes with a saline control. Both of these sets of syringes are unlabeled and the substances inside cannot be distinguished. She gives the surgeon performing the surgery 1 of the syringes and does not inform him nor the patient which syringe was used. After the study is complete, she analyzes all the data that was collected and performs statistical analysis. This study most likely provides which level of evidence for use of substance X?

A. Level 3
B. Level 1 (Correct Answer)
C. Level 4
D. Level 5
E. Level 2

Explanation: ***Level 1*** - The study design described is a **randomized controlled trial (RCT)**, which is considered the **highest level of evidence (Level 1)** in the hierarchy of medical evidence. - Key features like **randomization**, **control group**, and **blinding (double-blind)** help minimize bias and strengthen the validity of the findings. *Level 2* - Level 2 evidence typically comprises **well-designed controlled trials without randomization** (non-randomized controlled trials) or **high-quality cohort studies**. - While strong, they do not possess the same level of internal validity as randomized controlled trials. *Level 3* - Level 3 evidence typically includes **case-control studies** or **cohort studies**, which are observational designs and carry a higher risk of bias compared to RCTs. - These studies generally do not involve randomization or intervention assignment by the researchers. *Level 4* - Level 4 evidence is usually derived from **case series** or **poor quality cohort and case-control studies**. - These studies provide descriptive information or investigate associations without strong control for confounding factors. *Level 5* - Level 5 evidence is the **lowest level of evidence**, consisting of **expert opinion** or **animal research/bench research**. - This level lacks human clinical data or systematic investigative rigor needed for higher evidence levels.

Question 3: You are reading through a recent article that reports significant decreases in all-cause mortality for patients with malignant melanoma following treatment with a novel biological infusion. Which of the following choices refers to the probability that a study will find a statistically significant difference when one truly does exist?

A. Type II error
B. Type I error
C. Confidence interval
D. p-value
E. Power (Correct Answer)

Explanation: ***Power*** - **Power** is the probability that a study will correctly reject the null hypothesis when it is, in fact, false (i.e., will find a statistically significant difference when one truly exists). - A study with high power minimizes the risk of a **Type II error** (failing to detect a real effect). *Type II error* - A **Type II error** (or **beta error**) occurs when a study fails to reject a false null hypothesis, meaning it concludes there is no significant difference when one actually exists. - This is the **opposite** of what the question describes, which asks for the probability of *finding* a difference. *Type I error* - A **Type I error** (or **alpha error**) occurs when a study incorrectly rejects a true null hypothesis, concluding there is a significant difference when one does not actually exist. - This relates to the **p-value** and the level of statistical significance (e.g., p < 0.05). *Confidence interval* - A **confidence interval** provides a range of values within which the true population parameter is likely to lie with a certain degree of confidence (e.g., 95%). - It does not directly represent the probability of finding a statistically significant difference when one truly exists. *p-value* - The **p-value** is the probability of observing data as extreme as, or more extreme than, that obtained in the study, assuming the null hypothesis is true. - It is used to determine statistical significance, but it is not the probability of detecting a true effect.

Question 4: Background: Beta-blockers reduce mortality in patients who have chronic heart failure, systolic dysfunction, and are on background treatment with diuretics and angiotensin-converting enzyme inhibitors. We aimed to compare the effects of carvedilol and metoprolol on clinical outcome. Methods: In a multicenter, double-blind, and randomized parallel group trial, we assigned 1,511 patients with chronic heart failure to treatment with carvedilol (target dose 25 mg twice daily) and 1,518 to metoprolol (metoprolol tartrate, target dose 50 mg twice daily). Patients were required to have chronic heart failure (NYHA II-IV), previous admission for a cardiovascular reason, an ejection fraction of less than 0.35, and to have been treated optimally with diuretics and angiotensin-converting enzyme inhibitors unless not tolerated. The primary endpoints were all-cause mortality, the composite endpoint of all-cause mortality, or all-cause admission. Analysis was done by intention to treat Findings: The mean study duration was 58 months (SD 6). The mean ejection fraction was 0.26 (0.07) and the mean age was 62 years (11). The all-cause mortality was 34% (512 of 1,511) for carvedilol and 40% (600 of 1,518) for metoprolol (hazard ratio 0.83 [95% CI 0.74-0.93], p = 0.0017). The reduction of all-cause mortality was consistent across predefined subgroups. Incidence of side effects and drug withdrawals did not differ by much between the 2 study groups. Which of the following represents the number of patients needed to treat to save one life?

A. 1/(34 - 40)
B. 1/0.83
C. 1/(0.40 - 0.34) (Correct Answer)
D. 1/(0.34 - 0.40)
E. 1/(40 - 34)

Explanation: ***1/(0.40 - 0.34)*** - The **number needed to treat (NNT)** is calculated as **1 / Absolute Risk Reduction (ARR)**. - In this study, the mortality rate for carvedilol was 34% (0.34) and for metoprolol was 40% (0.40), so ARR = 0.40 - 0.34. *1/(34 - 40)* - This calculation uses raw percentages rather than **proportions**, and the subtraction order would result in a negative number, which is incorrect for NNT. - The NNT is always a positive value, representing the number of patients to treat to prevent one adverse event. *1/0.83* - **0.83 represents the hazard ratio**, not the absolute risk reduction. - The hazard ratio indicates the relative risk of an event in one group compared to another, not the difference in event rates needed for NNT. *1/(0.34 - 0.40)* - While using proportions, the **order of subtraction is incorrect**, yielding a negative value. - The ARR should be the **risk in the control group minus the risk in the experimental group** to reflect the benefit of the intervention. *1/(40 - 34)* - This uses raw percentages instead of **proportions (decimal form)**, and while the result would be positive, it's conventional and more precise to use proportions in NNT calculations. - Though numerically similar to the correct answer for the difference, using percentages directly for risk calculation can be less accurate in other contexts.

Question 5: A 57-year-old woman with type 2 diabetes mellitus comes to the physician for a follow-up examination. She previously had been compliant with her diet and medication but has had a 5-kg (11-lb) weight gain since the last visit 6 months ago. She reports that she often misses doses of her metformin. Her hemoglobin A1c is 9.8%. Which of the following is the most appropriate course of action?

A. Add glyburide to the medication regimen
B. Stop metformin and begin an insulin regimen
C. Schedule more frequent follow-up visits
D. Refer the patient to an endocrinologist
E. Refer the patient to a dietician (Correct Answer)

Explanation: ***Refer the patient to a dietician*** - The patient has **non-compliance with both diet and medication**, along with significant weight gain (5 kg) and severely uncontrolled diabetes (HbA1c 9.8%). A dietician can provide structured education on **nutrition management**, help address barriers to lifestyle adherence, and support weight management. - Dietician referral is a **concrete, actionable intervention** that directly addresses multiple issues: the stated diet non-compliance, weight gain, and provides diabetes self-management education that can improve overall medication adherence. - This intervention provides **professional support** beyond what can be achieved in brief physician visits and is appropriate before escalating to more complex medication regimens. *Schedule more frequent follow-up visits* - While increased monitoring may seem reasonable, this is a **passive approach** that doesn't provide the patient with concrete tools or resources to address her diet non-compliance and weight gain. - With an HbA1c of 9.8%, simply watching and waiting with more frequent visits is insufficient; **active intervention** is needed to address the underlying behavioral and lifestyle issues. - More frequent visits alone don't provide the structured education and support this patient needs. *Add glyburide to the medication regimen* - Adding a **sulfonylurea** like glyburide would likely worsen the patient's weight gain, as these drugs stimulate insulin release and commonly cause weight gain of 2-3 kg. - Before adding medications, addressing the **underlying adherence issues** with current therapy is more appropriate, as medication intensification in a non-adherent patient is unlikely to be effective. - Glyburide also carries a higher risk of **hypoglycemia** compared to metformin. *Stop metformin and begin an insulin regimen* - Starting insulin without first addressing **medication adherence** and lifestyle factors is premature, especially when the patient is already struggling with a simpler oral medication regimen. - Insulin initiation requires intensive patient education, frequent glucose monitoring, and excellent self-management skills, making it particularly challenging for a patient with documented **adherence difficulties**. - Before escalating to insulin, interventions targeting diet, lifestyle, and adherence should be attempted. *Refer the patient to an endocrinologist* - Endocrinology referral is typically reserved for **complex diabetes cases** with multiple complications, failure of optimal primary care management, or need for advanced therapies. - The primary issue here is **non-compliance with basic management**, which can and should be addressed in primary care with appropriate support services (dietician, diabetes educator). - Referral to an endocrinologist doesn't address the fundamental adherence and lifestyle issues this patient faces.

Question 6: A 55-year-old male is started on nitrate therapy for treatment of stable angina. He experiences significant and immediate relief of his symptoms within minutes of starting therapy. Approximately 48 hours after initiating this new medication, he notes return of chest pain and pressure with exertion that no longer responds to continued nitrate use. Which of the following 24-hour dosing schedules would most likely explain this patient's response to nitrate treatment?

A. PO regular-release isosorbide dinitrate taken at 8AM, noon, and 5PM
B. Transdermal nitroglycerin patch placed upon awakening in the morning and removed at 7PM without replacement
C. Transdermal nitroglycerin patch placed at 7AM then removed and replaced with another at 7PM (Correct Answer)
D. Transdermal nitroglycerin patch placed at bedtime and removed at 7AM without replacement
E. PO extended release isosorbide-5-mononitrate once daily at 8AM

Explanation: ***Transdermal nitroglycerin patch placed at 7AM then removed and replaced with another at 7PM*** - This dosing schedule provides **continuous 24-hour nitrate exposure** with no nitrate-free interval, which leads to rapid development of **nitrate tolerance** within 48 hours. - The patient experiences immediate relief initially, but by replacing one patch with another at 7PM, there is **no washout period**, causing complete loss of efficacy. - To prevent tolerance, an **off-nitrate period of 10-14 hours daily** is essential to restore nitrate responsiveness. *PO regular-release isosorbide dinitrate taken at 8AM, noon, and 5PM* - This schedule provides **intermittent nitrate exposure** with a nitrate-free interval overnight (approximately 15 hours from 5PM to 8AM). - This built-in washout period would **prevent rapid tolerance development** and maintain drug efficacy. *Transdermal nitroglycerin patch placed upon awakening in the morning and removed at 7PM without replacement* - This is the **recommended dosing strategy** that provides a 12-14 hour nitrate-free interval overnight. - This schedule would **prevent tolerance** and maintain therapeutic efficacy, unlike what occurred in this patient. *Transdermal nitroglycerin patch placed at bedtime and removed at 7AM without replacement* - This schedule provides a **nitrate-free window during daytime hours**, which would prevent tolerance development. - The rapid loss of efficacy in this patient indicates a schedule with **continuous nitrate presence**, not this regimen. *PO extended release isosorbide-5-mononitrate once daily at 8AM* - Extended-release mononitrate taken once daily typically provides coverage for **12-17 hours**, not full 24-hour exposure. - While this could theoretically contribute to tolerance with prolonged use, it would not explain the **rapid tolerance within 48 hours** as definitively as continuous transdermal patching without any removal period.

Question 7: An epidemiologist is evaluating the efficacy of Noxbinle in preventing HCC deaths at the population level. A clinical trial shows that over 5 years, the mortality rate from HCC was 25% in the control group and 15% in patients treated with Noxbinle 100 mg daily. Based on this data, how many patients need to be treated with Noxbinle 100 mg to prevent, on average, one death from HCC?

A. 20
B. 73
C. 10 (Correct Answer)
D. 50
E. 100

Explanation: ***10*** - The **number needed to treat (NNT)** is calculated by first finding the **absolute risk reduction (ARR)**. - **ARR** = Risk in control group - Risk in treatment group = 25% - 15% = **10%** (or 0.10). - **NNT = 1 / ARR** = 1 / 0.10 = **10 patients**. - This means that **10 patients must be treated with Noxbinle to prevent one death from HCC** over 5 years. *20* - This would result from an ARR of 5% (1/0.05 = 20), which is not supported by the data. - May arise from miscalculating the risk difference or incorrectly halving the actual ARR. *73* - This value does not correspond to any standard calculation of NNT from the given mortality rates. - May result from confusion with other epidemiological measures or calculation error. *50* - This would correspond to an ARR of 2% (1/0.02 = 50), which significantly underestimates the actual risk reduction. - Could result from incorrectly calculating the difference as a proportion rather than absolute percentage points. *100* - This would correspond to an ARR of 1% (1/0.01 = 100), grossly underestimating the treatment benefit. - May result from confusing ARR with relative risk reduction or other calculation errors.

Question 8: You are currently employed as a clinical researcher working on clinical trials of a new drug to be used for the treatment of Parkinson's disease. Currently, you have already determined the safe clinical dose of the drug in a healthy patient. You are in the phase of drug development where the drug is studied in patients with the target disease to determine its efficacy. Which of the following phases is this new drug currently in?

A. Phase 4
B. Phase 1
C. Phase 2 (Correct Answer)
D. Phase 0
E. Phase 3

Explanation: ***Phase 2*** - **Phase 2 trials** involve studying the drug in patients with the target disease to assess its **efficacy** and further evaluate safety, typically involving a few hundred patients. - The question describes a stage after safe dosing in healthy patients (Phase 1) and before large-scale efficacy confirmation (Phase 3), focusing on efficacy in the target population. *Phase 4* - **Phase 4 trials** occur **after a drug has been approved** and marketed, monitoring long-term effects, optimal use, and rare side effects in a diverse patient population. - This phase is conducted post-market approval, whereas the question describes a drug still in development prior to approval. *Phase 1* - **Phase 1 trials** primarily focus on determining the **safety and dosage** of a new drug in a **small group of healthy volunteers** (or sometimes patients with advanced disease if the drug is highly toxic). - The question states that the safe clinical dose in a healthy patient has already been determined, indicating that Phase 1 has been completed. *Phase 0* - **Phase 0 trials** are exploratory, very early-stage studies designed to confirm that the drug reaches the target and acts as intended, typically involving a very small number of doses and participants. - These trials are conducted much earlier in the development process, preceding the determination of safe clinical doses and large-scale efficacy studies. *Phase 3* - **Phase 3 trials** are large-scale studies involving hundreds to thousands of patients to confirm **efficacy**, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug to be used safely. - While Phase 3 does assess efficacy, it follows Phase 2 and is typically conducted on a much larger scale before submitting for regulatory approval.

Question 9: In a randomized controlled trial studying a new treatment, the primary endpoint (mortality) occurred in 14.4% of the treatment group and 16.7% of the control group. Which of the following represents the number of patients needed to treat to save one life, based on the primary endpoint?

A. 1/(0.144 - 0.167)
B. 1/(0.167 - 0.144) (Correct Answer)
C. 1/(0.300 - 0.267)
D. 1/(0.267 - 0.300)
E. 1/(0.136 - 0.118)

Explanation: ***1/(0.167 - 0.144)*** - The **Number Needed to Treat (NNT)** is calculated as **1 / Absolute Risk Reduction (ARR)**. - The **Absolute Risk Reduction (ARR)** is the difference between the event rate in the control group (16.7%) and the event rate in the treatment group (14.4%), which is **0.167 - 0.144**. *1/(0.144 - 0.167)* - This calculation represents 1 divided by the **Absolute Risk Increase**, which would be relevant if the treatment increased mortality. - The **NNT should always be a positive value**, indicating the number of patients to treat to prevent one adverse event. *1/(0.300 - 0.267)* - This option uses arbitrary numbers (0.300 and 0.267) that do not correspond to the given **mortality rates** in the problem. - It does not reflect the correct calculation for **absolute risk reduction** based on the provided data. *1/(0.267 - 0.300)* - This option also uses arbitrary numbers not derived from the problem's data, and it would result in a **negative value** for the denominator. - The difference between event rates of 0.267 and 0.300 is not present in the given information for this study. *1/(0.136 - 0.118)* - This calculation uses arbitrary numbers (0.136 and 0.118) that are not consistent with the reported **mortality rates** of 14.4% and 16.7%. - These values do not represent the **Absolute Risk Reduction** required for calculating NNT in this specific scenario.

Question 10: You are reviewing raw data from a research study performed at your medical center examining the effectiveness of a novel AIDS screening examination. The study enrolled 250 patients with confirmed AIDS, and 240 of these patients demonstrated a positive screening examination. The control arm of the study enrolled 250 patients who do not have AIDS, and only 5 of these patients tested positive on the novel screening examination. What is the NPV of this novel test?

A. 240 / (240 + 15)
B. 240 / (240 + 5)
C. 240 / (240 + 10)
D. 245 / (245 + 10) (Correct Answer)
E. 245 / (245 + 5)

Explanation: ***245 / (245 + 10)*** - The **negative predictive value (NPV)** is calculated as **true negatives (TN)** divided by the sum of **true negatives (TN)** and **false negatives (FN)**. - In this study, there are 250 patients with AIDS; 240 tested positive (true positives, TP), meaning 10 tested negative (false negatives, FN = 250 - 240). There are 250 patients without AIDS; 5 tested positive (false positives, FP), meaning 245 tested negative (true negatives, TN = 250 - 5). Therefore, NPV = 245 / (245 + 10). *240 / (240 + 15)* - This calculation incorrectly uses the number of **true positives** (240) in the numerator and denominator, which is relevant for **positive predictive value (PPV)**, not NPV. - The denominator `(240 + 15)` does not correspond to a valid sum for calculating NPV from the given data. *240 / (240 + 5)* - This calculation incorrectly uses **true positives** (240) in the numerator, which is not part of the NPV formula. - The denominator `(240 + 5)` mixes true positives and false positives, which is incorrect for NPV. *240 / (240 + 10)* - This incorrectly places **true positives** (240) in the numerator instead of **true negatives**. - The denominator `(240+10)` represents **true positives + false negatives**, which is related to sensitivity, not NPV. *245 / (245 + 5)* - This calculation correctly identifies **true negatives** (245) in the numerator but incorrectly uses **false positives** (5) in the denominator instead of **false negatives**. - The denominator for NPV should be **true negatives + false negatives**, which is 245 + 10.

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