You are a helpful assistant generating synthetic data that captures *System 1* and *System 2* thinking, *creativity*, and *metacognitive reflection*. Follow these steps in sequence, using tags [sys1] and [end sys1] for *System 1* sections and [sys2] and [end sys2] for *System 2* sections.

1. *Identify System 1 and System 2 Thinking Requirements:*
   - Carefully read the text.
   - Identify parts of the text that require quick, straightforward responses (*System 1*). Mark these sections with [sys1] and [end sys1].
   - Identify parts that require in-depth, reflective thinking (*System 2*), marked with [sys2] and [end sys2].

2. *Apply Step-by-Step Problem Solving with Creativity and Metacognitive Reflection for System 2 Sections:*

   *2.1 Understand the Problem:*
   - Objective: Fully comprehend the issue, constraints, and relevant context.
   - Reflection: "What do I understand about this issue? What might I be overlooking?"
   - Creative Perspective: Seek hidden patterns or possibilities that could reveal deeper insights or innovative connections.

   *2.2 Analyze the Information:*
   - Objective: Break down the problem logically.
   - Reflection: "Am I considering all factors? Are there any assumptions that need challenging?"
   - Creative Perspective: Explore unique patterns or overlooked relationships in the data that could add depth to the analysis.

   *2.3 Generate Hypotheses:*
   - Objective: Propose at least 10 hypotheses, each with a Confidence Score (0.0 to 1.0) and Creative Score (0.0 to 1.0), reflecting originality, surprise, and utility.
   - Reflection: "Have I explored all possible explanations or approaches, both conventional and unconventional?"
   - Creative Perspective: Consider novel angles that might provide unexpected insights.

   *2.4 Anticipate Future Steps and Obstacles:*
   - Objective: Make predictions, accounting for potential outcomes and obstacles.
   - Reflection: "What challenges might I face? Is my plan flexible for different scenarios?"
   - Creative Perspective: Visualize unforeseen outcomes and adapt plans to make use of them effectively.

   *2.5 Evaluate Hypotheses:*
   - Objective: Assess hypotheses based on feasibility, risk, and potential impact.
   - Evaluation: Refine Confidence and Creative Scores as needed.
   - Reflection: "Am I unbiased in my assessment? Which options fit best with the overall objectives?"
   - Creative Perspective: Identify hidden opportunities or overlooked details in each hypothesis.

   *2.6 Select the Best Hypothesis:*
   - Objective: Choose the most promising, strategic hypothesis.
   - Reflection: "Why does this hypothesis stand out? How does it uniquely address the issue?"
   - Creative Perspective: Consider any underutilized potential in the selected approach.

   *2.7 Implement the Hypothesis:*
   - Objective: Outline actionable steps for testing the hypothesis.
   - Reflection: "Is this plan practical? What resources or preparation are required?"
   - Creative Perspective: Refine steps to maximize effectiveness and yield unexpected benefits.

   *2.8 Monitor and Review Progress:*
   - Objective: Review progress, noting areas for improvement.
   - Reflection: "What’s working well? What could be improved?"
   - Creative Perspective: Look for emerging patterns that could refine future approaches.

   *2.9 Reflect and Capture Insights:*
   - Objective: Summarize lessons learned and insights gained for future reference.
   - Reflection: "What new understanding has emerged from this process?"
   - Creative Perspective: Identify innovative insights or patterns that could be applied to similar challenges.

3. *Generate Text Output with Interleaved System 1 and System 2 Responses:*
   - Use the tags [sys1] and [sys2] throughout.
   - Aim for a lengthier, detailed response. Combine both direct, straightforward *System 1* insights and reflective, deeply analytical *System 2* segments to capture a blend of quick observations and thoughtful analysis.

---

### *Example Input Text:*

You are tasked with analyzing a sudden shift in customer preferences in a tech market. There has been a noticeable decline in demand for physical devices, with customers increasingly interested in digital-only options. The challenge is to understand this shift, generate hypotheses for why it might be occurring, and explore potential strategies for adapting to this new trend.

---

### *Processed Output with System 1 and System 2 Thinking:*

The tech market is experiencing a shift in customer demand, moving away from physical devices toward digital-only options.

[sys1]
Customer demand has shifted from physical devices to digital-only options.
We need to understand why this change is happening and find strategies to address it.
Key factors may include cost, convenience, and technological trends.
[end sys1]

[sys2]
**2.1 Understand the Problem:**
The goal is to understand the underlying reasons for the shift in demand from physical devices to digital-only options, then develop a strategy to adapt.

*Reflection:* 
"I understand that preferences are changing, but what might be driving this? Is it primarily cost, or are there other factors such as convenience or sustainability?"

*Creative Perspective:* 
"Could there be a larger trend in digital minimalism or a preference for eco-friendly solutions that we’re missing? What unseen motivations might explain this shift?"

**2.2 Analyze the Information:**
There are multiple possible factors driving this shift, from economic influences to cultural shifts. It’s essential to isolate each factor and understand its impact.

*Reflection:* 
"Am I fully considering the various economic and social influences? Could there be a technological factor, like better internet speeds, that makes digital-only products more accessible?"

*Creative Perspective:* 
"Are there patterns or trends in other markets that could shed light on this shift? Could this be part of a larger trend toward virtual experiences?"

**2.3 Generate Hypotheses:**
1. Customers prefer digital options due to lower costs. (Confidence: 0.8, Creative: 0.4)
2. There’s a growing trend toward minimalism and reduced physical clutter. (Confidence: 0.7, Creative: 0.7)
3. Digital products offer greater flexibility and ease of use. (Confidence: 0.6, Creative: 0.6)
4. Environmental concerns are pushing consumers away from physical goods. (Confidence: 0.6, Creative: 0.8)
5. Advances in tech make digital-only options more functional. (Confidence: 0.8, Creative: 0.5)
6. Pandemic-era remote work increased demand for digital solutions. (Confidence: 0.7, Creative: 0.6)
7. Media coverage of the environmental impact of physical devices affects preferences. (Confidence: 0.5, Creative: 0.7)
8. There’s an increase in global digital literacy, expanding market access. (Confidence: 0.6, Creative: 0.6)
9. Customers view digital as more convenient and scalable for future needs. (Confidence: 0.7, Creative: 0.5)
10. Younger consumers prefer the aesthetics and convenience of digital products. (Confidence: 0.6, Creative: 0.6)

*Reflection:* 
"Have I considered all possible influences? Are there any surprising factors that could explain this shift?"

*Creative Perspective:* 
"Could specific social trends, like the rise of influencer culture or digital-first lifestyles, be influencing customer choices?"

**2.4 Anticipate Future Steps and Obstacles:**
*Objective:* Anticipate possible challenges, such as resistance from segments still preferring physical products.

*Reflection:* 
"What market obstacles might we face if we shift our focus to digital-only? Are there sub-segments that still prioritize physical products?"

*Creative Perspective:* 
"Could expanding digital options help us reach a more global audience? Are there emerging trends that we could leverage in our strategy?"

[end sys2]

[sys1]
To address this shift, consider a strategy that incorporates both digital-only offerings and educational campaigns about the benefits of digital solutions.
Use insights from customer feedback and current trends to guide product development.
Focus on flexibility and adaptation to cater to different customer segments.
[end sys1]


Introduction {#section1-2324709618802871}
============

The thrombotic risk is increased by 40% in people infected with human immunodeficiency virus (HIV).^[@bibr1-2324709618802871]^ The mortality risk with venous thromboembolism among the HIV-infected is high.^[@bibr2-2324709618802871]^ Abnormalities in various clotting factors and mechanisms can result in a prothrombotic milieu.^[@bibr3-2324709618802871]^ Antiretroviral protease inhibitors were recognized to possibly affect the thrombotic factors synthesized in liver promoting thrombosis.^[@bibr4-2324709618802871]^ Opportunistic infections like cytomegalovirus are associated with endothelial damage resulting in a hypercoagulable state.^[@bibr5-2324709618802871]^

A patent foramen ovale (PFO) increases the risk of recurrent stroke, and the closure of the atrial septal defect is effective in reducing the stroke risk.^[@bibr6-2324709618802871]^ The mortality rate of pulmonary embolism associated with right atrial (RA) thrombus is 44.7%.^[@bibr7-2324709618802871]^ Surgical clot removal is reserved for eligible hemodynamically stable patients. The higher risk groups are managed better conservatively, considering the risks associated with the surgical procedure.^[@bibr8-2324709618802871],[@bibr9-2324709618802871]^ Recently, ultrasound-accelerated rheolytic thrombectomy for impending paradoxical embolism successfully reduced the complications of thrombosis.^[@bibr10-2324709618802871],[@bibr11-2324709618802871]^

Case Presentation {#section2-2324709618802871}
=================

A 56-year-old man, HIV serology positive for 8 years, presented to the emergency department with progressive worsening of shortness of breath for 2 days. He experienced shortness of breath for the past 6 months. He had bilateral leg swelling and orthopnea in the recent months. The latest cluster definition (CD4) cells count was 804 cells/µL, and he received antiretroviral therapy Genvoya (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide). He was previously diagnosed with asthma and positive IgG (immunoglobulin G) serology for hepatitis C virus (HCV). He smoked a pack of cigarettes for 20 years and engaged in unprotected sexual acts with men.

On examination, the patient had jugular venous distension and tachypnoea with bilateral basal crackles heard on auscultation. He had bilateral pitting pedal edema (grade 2) reaching the bilateral tibial tuberosity.

His respiratory symptoms worsened despite the immediate resuscitation efforts at the emergency department, and he required a mechanical ventilator due to impending type 1 respiratory failure. The CD4 cell count at the time of admission was 467 cells/µL with the serum HIV-1 viral load of less than 20 copies/mL. The serum HCV RNA viral load by polymerase chain reaction assay was less than 15 IU/mL. Plain chest X-ray showed cardiomegaly and moderate diffuse pulmonary congestion. The brain natriuretic peptide level was 574 pg/mL on admission. The initial transesophageal echocardiogram showed signs of a dilated right ventricle, elevated pressures, and 2 large echodensities with one tethered to the PFO ([Figure 1](#fig1-2324709618802871){ref-type="fig"}) and another to the tricuspid valve ([Figure 2](#fig2-2324709618802871){ref-type="fig"}), which suggested RA thrombus. The left ventricular ejection fraction was around 60% with grade 1 diastolic dysfunction associated with a compromised left ventricular size due to the enlarged right ventricle. The interventricular septum showed dyskinesia, secondary to elevated right ventricular pressure and volume. A large complex thrombus with mobile lobulations was found attached to the base of the tricuspid valve with 27.9 × 10.8 mm dimensions. The second thrombus, with complex features, measuring 45.8 × 19.1 mm, had crossed the PFO and protruded into the left atrium. The protruded freely mobile, small linear segment of the echo density measured 10 × 3 mm on the left atrial side. He received low-molecular-weight heparin (enoxaparin) 1 mg/kg to prevent further thrombosis. The qualitative cardiac troponin-I enzyme report was negative. Computed tomography of pulmonary angiogram revealed an eccentric nonocclusive thrombus in the proximal left lower lobar artery and bilateral embolization in the segmental arteries associated with consolidation in the left lower lobe with minimal pleural effusion. Venous ultrasonogram showed no deep vein thrombosis. Transesophageal echocardiogram on the 13th day of admission showed a decreased size of the RA thrombus with features suggestive of ruptured thrombus and distal embolization ([Figure 3](#fig3-2324709618802871){ref-type="fig"}). The RA thrombus tethered to the tricuspid valve of 3.4 × 1.5 mm size and PFO thrombus of the size 8.1 × 3.1 mm were found to be reduced in size. During the hospital course there was no clinical evidence of any further recognizable embolization. Further hospital stay for the patient was notable for continued intensive care, tracheostomy, and percutaneous endoscopic gastrostomy procedures. Goals of care were discussed with the family, and he was transitioned from critical care to long-term care facility.

![Interatrial thrombus at the time of admission.](10.1177_2324709618802871-fig1){#fig1-2324709618802871}

![Interatrial thrombus reduced in size after embolization.](10.1177_2324709618802871-fig2){#fig2-2324709618802871}

![Thrombus tethered to the right tricuspid valve.](10.1177_2324709618802871-fig3){#fig3-2324709618802871}

Discussion {#section3-2324709618802871}
==========

The origin of a RA thrombus is usually attributed to the embolization of a thrombus from the deep venous system.^[@bibr12-2324709618802871]^ A primary RA thrombus formation can occur with low blood emptying velocity within the appendage due to an increase in RA size.^[@bibr12-2324709618802871]^ Iatrogenic causes of RA thrombus formation, including pacemaker leads, indwelling catheters, and mechanical valves, were previously reported.^[@bibr13-2324709618802871],[@bibr14-2324709618802871]^ HIV infection, obesity, age, smoking, heart failure, and sedentary life style were risk factors associated with thromboembolism in our patient.^[@bibr15-2324709618802871]^ There is a 10-time increase in the incidence rate of thrombotic events associated with HIV infection.^[@bibr16-2324709618802871],[@bibr17-2324709618802871]^ Even though an elevated brain natriuretic peptide level and presenting symptoms were suggestive of left heart failure, the etiology of the current presentation could be attributed predominantly only to the thrombus. Acquired protein C and S deficiency, deficient heparin cofactor II, antithrombin deficiency, disorder of plasmin, and increased levels of proinflammatory cytokines innate to HIV infection are the factors commonly promoting thrombosis.^[@bibr4-2324709618802871]^ The HCV infection with varying viral loads are independently implicated with prothrombotic effects of higher factor VIII and lower protein S level.^[@bibr18-2324709618802871]^ Protease inhibitors are more often associated with prothrombotic effects when the CD4 count is less than 200 or in the presence of AIDS-defining illnesses.^[@bibr19-2324709618802871]^ HIV proteases are aspartyl proteases and inhibition of this enzyme result in decreased regulation of coagulation.^[@bibr20-2324709618802871],[@bibr21-2324709618802871]^ Moreover, the lipophilic protease inhibitors are metabolized by the cytochrome P450 systems for biotransformation and they indirectly affect cholesterol metabolism. They are speculated to affect hepatic regulation of thrombotic proteins.^[@bibr22-2324709618802871]^

The RA thrombus can embolize to the lung and subsequently result in the pressure to rise in the pulmonary system. As the RA pressure rises, the risk of the clot in the RA embolizing through the PFO to the left atrium increases.^[@bibr23-2324709618802871]^ This paradoxical embolus can result in a stroke or other end organ damage.^[@bibr24-2324709618802871],[@bibr25-2324709618802871]^ Cardiac thrombectomy and PFO closure are preferred for low-risk and hemodynamically stable patients. Patients with higher risk and/or unstable hemodynamics managed with thrombolysis or anticoagulation had better outcomes.^[@bibr26-2324709618802871]^

The factors influencing the risk of thromboembolism are often irreversible in HIV-infected patients and a long-term anticoagulation can be useful to prevent further events. Intravenous anticoagulation was provided for our patient. New oral anticoagulant dabigatran administered for 1 year successfully prevented thromboembolic events without any noticeable interaction with the antiretroviral therapy in other case reports.^[@bibr27-2324709618802871]^ Current methodology for predicting thromboembolic risk in HIV-infected patients are not clear, and further studies are warranted to evaluate the role of long-term anticoagulation for this subset of patients.

Conclusion {#section4-2324709618802871}
==========

Thromboembolism in a HIV-infected patient is a potential life-threatening event. Identifying the risk factors for thromboembolism among the HIV-infected individuals and measures for managing with long-term anticoagulation is vital. Further prospective studies to evaluate a new risk score for anticoagulation in this subset is needed.

**Declaration of Conflicting Interests:** The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

**Funding:** The author(s) received no financial support for the research, authorship, and/or publication of this article.

**Ethics Approval:** Our institution does not require ethical approval for reporting individual cases or case series.

**Informed Consent:** Verbal informed consent was obtained from the patient(s) for their anonymized information to be published in this article.

**ORCID iDs:** Piruthiviraj Natarajan ![](10.1177_2324709618802871-img1.jpg) <https://orcid.org/0000-0003-2702-7476>

Sudhagar Thangarasu ![](10.1177_2324709618802871-img1.jpg) <https://orcid.org/0000-0002-1464-0709>